@article{Picat2013,

title = {Predicting Patterns of Long-Term CD4 Reconstitution in HIV-Infected Children Starting Antiretroviral Therapy in Sub-Saharan Africa: A Cohort-Based Modelling Study},

author = {Marie-Quitterie Picat and Joanna Lewis and Victor Musiime nd Andrew Prendergast and Kusum Nathoo and Addy Kekitiinwa and Patricia Nahirya Ntege and Diana M. Gibb and Rodolphe Thiebaut and A. Sarah Walker and Nigel Klein and Robin Callard an the ARROW Trial Team},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Predicting-patterns-of-Long-Term-CD4-Reconstitution....pdf},

doi = {10.1371/journal.pmed.1001542},

year  = {2013},

date = {2013-10-01},

journal = {PloS Medicine},

volume = {10},

number = {10},

abstract = {BACKGROUND:



Long-term immune reconstitution on antiretroviral therapy (ART) has important implications for HIV-infected children, who increasingly survive into adulthood. Children's response to ART differs from adults', and better descriptive and predictive models of reconstitution are needed to guide policy and direct research. We present statistical models characterising, qualitatively and quantitatively, patterns of long-term CD4 recovery.

METHODS AND FINDINGS:



CD4 counts every 12 wk over a median (interquartile range) of 4.0 (3.7, 4.4) y in 1,206 HIV-infected children, aged 0.4-17.6 y, starting ART in the Antiretroviral Research for Watoto trial (ISRCTN 24791884) were analysed in an exploratory analysis supplementary to the trial's pre-specified outcomes. Most (n = 914; 76%) children's CD4 counts rose quickly on ART to a constant age-corrected level. Using nonlinear mixed-effects models, higher long-term CD4 counts were predicted for children starting ART younger, and with higher CD4 counts (p<0.001). These results suggest that current World Health Organization-recommended CD4 thresholds for starting ART in children ≥5 y will result in lower CD4 counts in older children when they become adults, such that vertically infected children who remain ART-naïve beyond 10 y of age are unlikely ever to normalise CD4 count, regardless of CD4 count at ART initiation. CD4 profiles with four qualitatively distinct reconstitution patterns were seen in the remaining 292 (24%) children. Study limitations included incomplete viral load data, and that the uncertainty in allocating children to distinct reconstitution groups was not modelled.

CONCLUSIONS:



Although younger ART-naïve children are at high risk of disease progression, they have good potential for achieving high CD4 counts on ART in later life provided ART is initiated following current World Health Organization (WHO), Paediatric European Network for Treatment of AIDS, or US Centers for Disease Control and Prevention guidelines. In contrast, to maximise CD4 reconstitution in treatment-naïve children >10 y, ART should ideally be considered even if there is a low risk of immediate disease progression. Further exploration of the immunological mechanisms for these CD4 recovery profiles should help guide management of paediatric HIV infection and optimise children's immunological development. Please see later in the article for the Editors' Summary.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Nakiwogga-Muwanga2013b,

title = {Inadequate Monitoring in Advanced Stages of Disease with Lack of Supportive Counseling Increases Attrition among Patients on Antiretroviral Treatment at a Large Urban Clinic in Uganda},

author = {Alice Nakiwogga-Muwanga and Stella Alamo-Talisuna and Joseph Musaazi and Andrew Kambugu and P. Ssekawungu and Elly Katabira and Robert Colebunders},

url = {http://journals.sagepub.com/doi/pdf/10.1177/2325957413501719},

year  = {2013},

date = {2013-09-30},

journal = {journal of the International Association of Providers of AIDS Care},

volume = {13},

number = {6},

pages = {547-54},

abstract = {BACKGROUND:



The purpose of this case-control study was to identify risk factors for loss to follow-up (LTFU).

METHODS:



Cases and controls were selected from HIV-positive patients, aged 18 years and older, on antiretroviral therapy (ART) at the Infectious Diseases Clinic (IDC) in January 2008. As cases, we selected 209 patients who in 2008 did not return to the clinic within 90 days of their scheduled appointment date. As controls, we randomly selected 626 patients from the 5872 patients who were following up at the end of December 2008.

RESULTS:



In multivariable logistic regression analysis, urban or semiurban residence, World Health Organization disease stage III or IV at ART initiation, a median CD4 count at last visit <200 cells/mm(3), tuberculosis (TB) in the 6 months before the last visit, absence of counseling before ART initiation, and no disclosure of HIV status were associated with LTFU.

CONCLUSION:



This study demonstrates the importance of close patient monitoring in advanced stages of disease, supportive counseling for patients initiating ART, extra psychosocial support for patients with TB and HIV coinfection, assisting patients with disclosure, and setting up a good referral system to retain patients on ART},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Haberer2013,

title = {Adherence to Antiretroviral Prophylaxis for HIV Prevention: A Substudy Cohort within a Clinical Trial of Serodiscordant Couples in East Africa},

author = {Jessica E. Haberer and Jared M. Baeten and James Campbell and Jonathan Wangisi and Elly Katabira and Allan Ronald and Elioda Tumwesigye and Christina Psaros and Steven A. Safren and Norma C. Ware and Katherine K. Thomas and Deborah Donnell and Meighan Krows and Lara Kidoguchi and Connie Celum and David R. Bangsberg},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Adherence-to-Antiretroviral-Prophylaxis-for-HIV-preservation....pdf},

doi = {1001511. Epub 2013 Sep 10},

year  = {2013},

date = {2013-09-10},

journal = {PloS Medicine},

volume = {10},

number = {9},

abstract = {BACKGROUND:



Randomized clinical trials of oral antiretroviral pre-exposure prophylaxis (PrEP) for HIV prevention have widely divergent efficacy estimates, ranging from 0% to 75%. These discrepancies are likely due to differences in adherence. To our knowledge, no studies to date have examined the impact of improving adherence through monitoring and/or intervention, which may increase PrEP efficacy, or reported on objective behavioral measures of adherence, which can inform PrEP effectiveness and implementation.

METHODS AND FINDINGS:



Within the Partners PrEP Study (a randomized placebo-controlled trial of oral tenofovir and emtricitabine/tenofovir among HIV-uninfected members of serodiscordant couples in Kenya and Uganda), we collected objective measures of PrEP adherence using unannounced home-based pill counts and electronic pill bottle monitoring. Participants received individual and couples-based adherence counseling at PrEP initiation and throughout the study; counseling was intensified if unannounced pill count adherence fell to <80%. Participants were followed monthly to provide study medication, adherence counseling, and HIV testing. A total of 1,147 HIV-uninfected participants were enrolled: 53% were male, median age was 34 years, and median partnership duration was 8.5 years. Fourteen HIV infections occurred among adherence study participants--all of whom were assigned to placebo (PrEP efficacy = 100%, 95% confidence interval 83.7%-100%, p<0.001). Median adherence was 99.1% (interquartile range [IQR] 96.9%-100%) by unannounced pill counts and 97.2% (90.6%-100%) by electronic monitoring over 807 person-years. Report of no sex or sex with another person besides the study partner, younger age, and heavy alcohol use were associated with <80% adherence; the first 6 months of PrEP use and polygamous marriage were associated with >80% adherence. Study limitations include potential shortcomings of the adherence measures and use of a convenience sample within the substudy cohort.

CONCLUSIONS:



The high PrEP adherence achieved in the setting of active adherence monitoring and counseling support was associated with a high degree of protection from HIV acquisition by the HIV-uninfected partner in heterosexual serodiscordant couples. Low PrEP adherence was associated with sexual behavior, alcohol use, younger age, and length of PrEP use. Please see later in the article for the Editors' Summary.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Albert2013,

title = {Operational Implementation of LED Fluorescence Microscopy in Screening Tuberculosis Suspects in an Urban HIV Clinic in Uganda},

author = {Heidi Albert and Lydia Nakiyingi and Joseph Sempa and Olive Mbabazi and Sheena Mukkada and Barnabas Nyesiga and Mark D. Perkins and Yukari C. Manabe

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Operational-Implementation-of-LED-Fluorescence....pdf},

doi = {10.1371/journal.pone.0072556},

year  = {2013},

date = {2013-09-06},

journal = {PloS One},

volume = {8},

number = {9},

abstract = {BACKGROUND:



Light emitting diode (LED) fluorescence microscopy (FM) is an affordable, technology targeted for use in resource-limited settings and recommended for widespread roll-out by the World Health Organization (WHO). We sought to compare the operational performance of three LED FM methods compared to light microscopy in a cohort of HIV-positive tuberculosis (TB) suspects at an urban clinic in a high TB burden country.

METHODS:



Two spot specimens collected from TB suspects were included in the study. Smears were stained using auramine O method and read after blinding by three LED-based FM methods by trained laboratory technicians in the Infectious Diseases Institutelaboratory. Leftover portions of the refrigerated sputum specimens were transported to the FIND Tuberculosis Research Laboratory for Ziehl Neelsen (ZN) smear preparation and reading by experienced technologist as well as liquid and solid culture.

RESULTS:



174 of 627 (27.8%) specimens collected yielded one or more positive mycobacterial cultures. 94.3% (164/174) were M. tuberculosis complex. LED FM was between 7.3-11.0% more sensitive compared to ZN microscopy. Of the 592 specimens examined by all microscopy methods, there was no significant difference in sensitivity between the three LED FM methods. The specificity of the LED FM methods was between 6.1% and 7.7% lower than ZN microscopy (P<0.001), although exclusion of the single poor reader resulted in over 98% specificity for all FM methods.

CONCLUSIONS:



Laboratory technicians in routine settings can be trained to use FM which is more sensitive than ZN microscopy. Despite rigorous proficiency testing, there were operator-dependent accuracy issues which highlight the critical need for intensive quality assurance procedures during LED FM implementation. The low sensitivity of FM for HIV-positive individuals particularly those with low CD4 T cell counts, will limit the number of additional patients found by LED FM in countries with high rates of HIV co-infection.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Sempa2013,

title = {Among Patients with Sustained Viral Suppression in a Resource-Limited Setting, CD4 Gains Are Continuous Although Gender-Based Differences Occur},

author = {Joseph B. Sempa and Agnes N. Kiragga and Barbara Castelnuovo and Moses R. Kamya and Yukari C. Manabe

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Among-patients-with-sustained-viral-suppresion-in-a-resource-limitted-setting....pdf},

doi = {10.1371/journal.pone.0073190},

year  = {2013},

date = {2013-08-27},

journal = {PloS One},

volume = {8},

number = {8},

abstract = {INTRODUCTION:



There is conflicting data on long-term CD4 immune recovery after combination antiretroviral therapy (ART) in resource-limited settings. Virologic suppression is rarely documented in cohorts from sub-Saharan Africa so objective evidence of adherence is biologically unsubstantiated. We sought to investigate long-term patterns of immune recovery in Ugandan patients on ART with sustained viral suppression.

METHODS:



A prospective cohort of patients starting ART between April, 2004 and April, 2005 at the Infectious Diseases Institute with sustained viral suppression (viral load ≤ 400 copies/ml at month 6 and 12) while on first-line ART. Propensity scores were used to adjust for treatment allocation (nevirapine or efavirenz) at ART initiation. Data were analyzed using Kaplan Meier methods and cross-sectional time series regression.

RESULTS:



Three hundred and fifty-six patients were included in the analysis.71.6% were female, 87% in WHO stage 3 or 4, median age was 37 years, (IQR:32-43), and median CD4 count was 108 cells/µL, (IQR:35-174) at ART start. At multivariable analysis, lower immune recovery (measured by change in CD4 from ART start at each time interval) was associated with male-gender (-59, 95% CI: 90, -28, P<0.001), baseline CD4 count of 101-200 cells/µL (-35, 95% CI: 62, -9, P=0.009) and >200 (-64, 95% CI: 101, -26, P=0.001), and use of AZT at baseline (-47, 95% CI: -74, -20, P=0.001). Median time to reach >400 cells/µL was longer in males (197.4 weeks, IQR:119.9-312.0), compared to females (144.7 weeks, IQR:96.6-219.7, P<0.001). The cumulative probability of attaining CD4 >400 cells/µL over 7 years was higher in females compared to males (P<0.001).

CONCLUSIONS:



There was long-term, continuous, immunologic recovery up to 7 years after ART initiation in an urban Ugandan cohort. Virologically suppressed women had better sustained immune recovery than men. Men take longer to immune reconstitute and have a lower probability of reaching a CD4 cell count >400 cells/µL. The biologic mechanisms of these gender differences need further exploration.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kiwuwa-Muyingo2013,

title = {Dynamic logistic regression model and population attributable fraction to investigate the association between adherence, missed visits and mortality: a study of HIV-infected adults surviving the first year of ART},

author = {Sylvia Kiwuwa-Muyingo and Hannu Oja and Ann Sarah Walker and Pauliina Ilmonen and Jonathan Levin and Ivan Mambule and AndrewReid and Peter Mugyenyi and ,JimTodd and DART Trial team},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Dynamic-logistic-regression-model....pdf},

doi = { 10.1186/1471-2334-13-395},

year  = {2013},

date = {2013-08-27},

journal = {BMC Infectious Diseases},

volume = {13},

abstract = {BACKGROUND:



Adherence is one of the most important determinants of viral suppression and drug resistance in HIV-infected people receiving antiretroviral therapy (ART).

METHODS:



We examined the association between long-term mortality and poor adherence to ART in DART trial participants in Uganda and Zimbabwe randomly assigned to receive laboratory and clinical monitoring (LCM), or clinically driven monitoring (CDM). Since over 50% of all deaths in the DART trial occurred during the first year on ART, we focussed on participants continuing ART for 12 months to investigate the implications of longer-term adherence to treatment on mortality. Participants' ART adherence was assessed by pill counts and structured questionnaires at 4-weekly clinic visits. We studied the effect of recent adherence history on the risk of death at the individual level (odds ratios from dynamic logistic regression model), and on mortality at the population level (population attributable fraction based on this model). Analyses were conducted separately for both randomization groups, adjusted for relevant confounding factors. Adherence behaviour was also confounded by a partial factorial randomization comparing structured treatment interruptions (STI) with continuous ART (CT).

RESULTS:



In the CDM arm a significant association was found between poor adherence to ART in the previous 3-9 months with increased mortality risk. In the LCM arm the association was not significant. The odds ratios for mortality in participants with poor adherence against those with optimal adherence was 1.30 (95% CI 0.78,2.10) in the LCM arm and 2.18 (1.47,3.22) in the CDM arm. The estimated proportions of deaths that could have been avoided with optimal adherence (population attributable fraction) in the LCM and CDM groups during the 5 years follow-up period were 16.0% (95% CI 0.7%,31.6%) and 33.1% (20.5%,44.8%), correspondingly.

CONCLUSIONS:



Recurrent poor adherence determined even through simple measures is associated with high mortality both at individual level as well as at the ART programme level. The number of lives saved through effective interventions to improve adherence could be considerable particularly for individuals monitored without using CD4 cell counts. The findings have important implications for clinical practice and for developing interventions to enhance adherence},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Robertson2013,

title = {Cryptococcus neoformans Ex Vivo Capsule Size Is Associated With Intracranial Pressure and Host Immune Response in HIV-associated Cryptococcal Meningitis},

author = {Emma J. Robertson and Grace Najjuka and Melissa A. Rolfes and Andrew Akampurira and Neena Jain and Janani Anantharanjit and Maximilian von Hohenberg and Manlio Tassieri and Allan Carlsson and David B. Meya and Thomas S. Harrison and Bettina C. Fries and David R. Boulware and Tihana Bicanic },

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Cryptococcus-neoformans-Ex-Vivo-Capsule-Size-Is-Associated-With-Intracranial-Pressure-and-Host-Immune-Response-in-HIV-associated-Cryptococcal-Meningitis.pdf},

doi = {https://doi.org/10.1093/infdis/jit435},

year  = {2013},

date = {2013-08-14},

journal = {The Journal of the Infectious Diseases},

volume = {209},

number = {1},

pages = {74-82},

abstract = {Abstract



Background. The Cryptococcus neoformans polysaccharide capsule is a well-characterized virulence factor with immunomodulatory properties. The organism and/or shed capsule is postulated to raise intracranial pressure (ICP) in cryptococcal meningitis (CM) by mechanical obstruction of cerebrospinal fluid (CSF) outflow. Little is known regarding capsule phenotype in human cryptococcosis. We investigated the relationship of ex vivo CSF capsular phenotype with ICP and CSF immune response, as well as in vitro phenotype.



Methods. In total, 134 human immunodeficiency virus (HIV)-infected Ugandan adults with CM had serial lumbar punctures with measurement of CSF opening pressures, quantitative cultures, ex vivo capsule size and shedding, viscosity, and CSF cytokines; 108 had complete data. Induced capsular size and shedding were measured in vitro for 48 C. neoformans isolates.



Results. Cryptococcal strains producing larger ex vivo capsules in the baseline (pretreatment) CSF correlated with higher ICP (P = .02), slower rate of fungal clearance (P = .02), and paucity of CSF inflammation, including decreased CSF white blood cell (WBC) count (P < .001), interleukin (IL)-4 (P = .02), IL-6 (P = .01), IL-7 (P = .04), IL-8 (P = .03), and interferon γ (P = .03). CSF capsule shedding did not correlate with ICP. On multivariable analysis, capsule size remained independently associated with ICP. Ex vivo capsular size and shedding did not correlate with that of the same isolates grown in vitro.



Conclusions. Cryptococcal capsule size ex vivo is an important contributor to virulence in human cryptococcal meningitis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ochola2013,

title = {High burden of hepatitis B infection in Northern Uganda: results of a population-based survey},

author = {Emmanuel Ochola and Ponsiano Ocama and Christopher G Orach and Ziadah K Nankinga and Joan N Kalyango and Willi McFarland and Charles Karamagi},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/High-burden-of-hepatitis-B-infection-in-Northern-Uganda....pdf},

doi = {1186/1471-2458-13-727},

year  = {2013},

date = {2013-08-07},

journal = {BMC Public Health},

volume = {13},

abstract = {BACKGROUND:



Worldwide 2 billion people are exposed to hepatitis B infection, 350 million have chronic infection, 65 million in sub-Saharan Africa. Uganda is highly endemic with 10% national prevalence of hepatitis B infection, rates varying across the country from 4% in the southwest and 25% in the Northeast. Childhood vaccination was rolled out in 2002, the effect of which on the burden of hepatitis B has not been examined. We determined the prevalence and risk factors for hepatitis B infection in the Northern Uganda Municipality of Gulu.

METHODS:



We carried out a cross-sectional, population-based survey. The study population included those found at home at the time of recruitment. Data on demographics, wealth index, cultural and behavioral factors, vaccination and health education on hepatitis B were collected. Hepatitis B infection (Hepatitis B surface antigen positive) and lifetime exposure (anti-hepatitis B core antibody positive) were measured. Analysis was done in 2 age groups, 1-14 years, 14 years and more. Associations between predictors and HBV infection were assessed.

RESULTS:



Information on 790 respondents were analyzed. Overall, 139/790 (17.6%) had hepatitis B infection and 572/790 (72.4%) lifetime exposure. In the younger age group 16/73 (21.9%) had hepatitis B infection and 35/73 (48%) lifetime exposure. Increasing wealth was protective for infection (OR 0.46 per quartile, 95% CI=0.26-0.82, p=0.009), while older age was protective for lifetime exposure (OR 2.70 per age group, 95% CI 1.03-7.07, p=0.043). In the older age group, overall hepatitis B infection was seen in 123/717 (17.2%) and lifetime exposure in 537/717 (74.9%). The female sex (OR 0.63, 95% CI=0.42-0.98, p=0.032) and increasing age (OR 0.76 per age group, 95% CI=0.64-0.91, p=0.003) were factors associated with infection. For lifetime exposure, increasing number of lifetime sexual partners was a risk factor (OR 1.19 per partner category, 95% CI=1.04-1.38, p=0.012).

CONCLUSIONS:



We found a high prevalence of hepatitis B infection and lifetime exposures to hepatitis B in this northern Uganda Municipality. Targeted vaccination of susceptible adults and improving existing childhood vaccinations and provision of treatment for those with infection will play roles in reducing the high prevalence rates seen in the population.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Jacob2013,

title = {Mycobacterium tuberculosis Bacteremia in a Cohort of HIV-Infected Patients Hospitalized with Severe Sepsis in Uganda–High Frequency, Low Clinical Sand Derivation of a Clinical Prediction Score},

author = {Shevin T. Jacob and Patricia B. Pavlinac and Lydia Nakiyingi and Patrick Banura and Jared M. Baeten and Karen Morgan and Amalia Magaret and Yuka Manabe and Steven J. Reynolds and W. Conrad Lilea and Anna Wald and Moses L. Joloba and Harriet Mayanja-Kizza and W. Michael Scheld},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Mycobacterium-tuberculosis-Bacteremia-in-a-cohort-of-HIV-Infected-patients-hospitalised-with-severe-sepsis-in-Uganda-High-Frequency...-1.pdf},

year  = {2013},

date = {2013-08-05},

journal = {PloS One},

abstract = {Background: When manifested as Mycobacterium  tuberculosis (MTB) bacteremia, disseminated MTB infection clinically mimics other serious blood stream infections often hindering early diagnosis and initiation of potentially life-saving anti- tuberculosis therapy. In a cohort of hospitalized HIV-infected Ugandan patients with severe sepsis, we report the frequency, management and outcomes of patients with MTB bacteremia and propose a risk score based on clinical predictors of MTB bacteremia. Methods: We prospectively enrolled adult patients with severe sepsis at two Ugandan hospitals and obtained blood cultures for MTB identification. Multivariable logistic regression modeling was used to determine predictors of MTB bacteremia and to inform the stratification of patients into MTB bacteremia risk categories based on relevant patient characteristics. Results: Among 368 HIV-infected patients with a syndrome of severe sepsis, eighty-six (23%) had MTB bacteremia. Patients with MTB bacteremia had a significantly lower median CD4 count (17 vs 64 lymphocytes/mm 3 ,p , 0.001) and a higher 30- day mortality (53% vs 32%, p = 0.001) than patients without MTB bacteremia. A minority of patients with MTB bacteremia underwent standard MTB diagnostic testing (24%) or received empiric anti-tuberculosis therapy (15%). Independent factors associated with MTB bacteremia included male sex, increased heart rate, low CD4 count, absence of highly active anti- retroviral therapy, chief complaint of fever, low serum sodium and low hemoglobin. A risk score derived from a model containing these independent predictors had good predictive accuracy [area under the curve = 0.85, 95% CI 0.80–0.89]. Conclusions: Nearly 1 in 4 adult HIV-infected patients hospitalized with severe sepsis in 2 Ugandan hospitals had MTB bacteremia. Among patients in whom MTB was suspected, standard tests for diagnosing pulmonary MTB were inaccurate for correctly classifying patients with or without bloodstream MTB infection. A MTB bacteremia risk score can improve early diagnosis of MTB bacteremia particularly in settings with increased HIV and MTB co-infection.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Musiime2013,

title = {Bacteremia, Causative Agents and Antimicrobial Susceptibility Among HIV-1–infected Children on Antiretroviral Therapy in Uganda and Zimbabwe},

author = {Musiime, Victor; Cook, Adrian; Bakeera-Kitaka, Sabrina; Vhembo, Tichaona; Lutakome, Joseph; Keishanyu, Rosette; Prendergast, Andrew J. DPhil; Lubwama, Sam; Robertson, Val; Hughes, Peter; Nathoo, Kusum; Munderi, Paula; Klein, Nigel; Musoke, Philippa; Gibb, Diana M. on Behalf of the ARROW Trial Team},

doi = {doi: 10.1097/INF.0b013e31828c3991},

year  = {2013},

date = {2013-08-01},

journal = {The Pediatric Infectious Disease Journal},

volume = {32},

number = {8},

pages = {856-862},

abstract = {Background: 



Bacteremia is common in HIV-infected children in Africa, including after start of antiretroviral therapy (ART), but there are limited data on causative pathogens and their antimicrobial sensitivity patterns in this population.



Methods: 



We analyzed data on blood cultures taken from HIV-infected children developing acute febrile illness after enrollment to the Antiretroviral Research for Watoto (ARROW) clinical trial in Uganda and Zimbabwe. Patterns of bacterial pathogens and their antimicrobial susceptibilities were determined and bacteremia rates calculated over time from ART initiation.



Results: 



A total of 848 blood cultures were obtained from 461 children, of which 123 (14.5%) from 105 children (median age 3.5 years, 51% girls) were culture positive, including 75 (8.8%) with clearly pathogenic organisms. The event rates for positive cultures with clearly pathogenic organisms after 0–1, 2–3, 4–11 and ≥12 months on ART were 13.3, 11.4, 2.1 and 0.3 per 1000 person-months of follow-up, respectively. The pathogens isolated (n; %) were Streptococcus pneumoniae (36; 28.3%), Staphylococcus aureus (11; 8.7%), Klebsiella pneumoniae (6; 4.7%), Pseudomonas aeruginosa (6; 4.7%), Salmonella spp (6; 4.7%), Escherichia coli (5; 3.9%), Haemophilus influenzae (1; 0.8%) and fungal spp (4; 3.1%). Other bacteria of doubtful pathogenicity (n = 52; 42%) were also isolated. Most isolates tested were highly (80–100%) susceptible to ceftriaxone, cefotaxime and ciprofloxacin; very few (~5%) were susceptible to cotrimoxazole; S. pneumoniae had high susceptibility to amoxicillin/ampicillin (80%).



Conclusions: 



Rates of proven bacteremia were >20-fold higher immediately after starting ART compared with 12 months later in African HIV-infected children. S. pneumoniae was most commonly isolated, suggesting need for pneumococcal vaccination and effective prophylactic antibiotics.

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kibirige2013,

title = {Vitamin D deficiency among adult patients with tuberculosis: a cross sectional study from a national referral hospital in Uganda},

author = {Davis Kibirige and Edrisa Mutebi and Richard Ssekitoleko and William Worodria and Harriet Mayanja-Kizza

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Vitamin-D-deficiency-among-adult-patients-with-tuberculisis.pdf},

doi = {10.1186/1756-0500-6-293},

year  = {2013},

date = {2013-07-25},

journal = {BMC Research Notes},

volume = {6},

abstract = {BACKGROUND:



Vitamin D deficiency has been reported among patients with tuberculosis in Africa despite abundant sunshine. Vitamin D plays a fundamental role in improving anti tuberculosis immunity, reducing progression and severity of TB in humans.

METHODS:



In this descriptive cross sectional study, 260 hospitalized adults with a confirmed diagnosis of TB were enrolled into the study from the pulmonology wards of Mulago national referral and teaching hospital, Uganda. The serum concentrations of 25-hydroxyvitamin D or 25 (OH) D were determined by an electrochemilumniscence immunoassay. Vitamin D deficiency, vitamin D insufficiency, severe and very severe vitamin D deficiency were defined as serum 25(OH) D concentrations of ≤ 20 ng/ml, 21-29 ng/ml, < 10 ng/ml and <5 ng/ml respectively.

RESULTS:



Majority of the study participants were males (146, 56.2%) and < 35 years (154, 59.2%). The mean age ± SD was 34.7 ± 9.5 years. Two hundred eight (80%) patients were HIV co-infected with a median CD4 count of 68 cells/mm3 (IQR: 17-165). The prevalence of vitamin D deficiency, vitamin D insufficiency, severe and very severe vitamin D deficiency among the hospitalized adult tuberculosis patients was 44.2%, 23.5%, 13.5% and 4.2% respectively. The median (IQR) vitamin D concentration in ng/ml was 22.55 (14.59-33.31).

CONCLUSION:



Vitamin D deficiency is very common among hospitalized adult tuberculosis patients in Uganda especially in patients with hypoalbuminemia, anemia, HIV co-infected patients with CD4 count <200cells/mm3 and hypocalcemia corrected for serum albumin levels.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Nakiwogga-Muwanga2013d,

title = {Factors before enrolment are associated with being removed from a Pharmacy-only Refill Programme at a large urban HIV/AIDS clinic, Uganda},

author = {A Nakiwogga-Muwanga and E Katabira and A Kiragga and A Kambugu and E Nakibuuka-Lubwama and YC Manabe and ST Alamo and R Colebunders},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Factors-before-enrolment-are-associated-with....pdf},

doi = {10.1177/0956462413492715},

year  = {2013},

date = {2013-07-19},

journal = {International Journal of STD and AIDS},

volume = {25},

number = {2},

pages = {105-112 },

abstract = {A Pharmacy-only Refill  Programme (PRP) a type of task shifting in which stable HIV-positive patients are managed

through pharmacy-only visits instead of physician visits. We performed a study to identify factors for being removed from

the PRP in order to establish better referral criteria. The study was performed at the Infectious Disease Clinic (IDC) in

Kampala, Uganda. We selected a random sample of 588 patients from 2431 patients on antiretroviral therapy referred to

the PRP at least 12 months before commencement of the PRP evaluation. We compared the characteristics of patients

who during 12 months of follow-up were removed from the PRP with those who continued to be followed up. Data

were abstracted from the IDC data base, the pharmacy register and the patient clinical notes. Of 588 patients, 106 (18%)

were removed from the PRP. In multivariate analysis, less than 100% self-reported adherence to antiretroviral therapy,

missing at least one scheduled appointment in the six months before referral to the PRP and being on a lopinavir/

ritonavir-containing regimen were independently associated with being removed from the PRP. Criteria for referring

patients to a PRP should focus on antiretroviral therapy adherence and appointment keeping. Patients on a lopinavir/

ritonavir-containing regimen should not be targeted for a PRP. On the other hand a PRP is an efficient strategy that

targets stable adherent patients in clinics with high patient load},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tran2013,

title = {Modulation of the complement system in monocytes contributes to tuberculosis-associated immune reconstitution inflammatory syndrome},

author = {Tran, Huyen T.T.; Van den Bergh, Rafaela; Loembé, Marguerite M.; Worodria, Williamd; Mayanja-Kizza, Harrietd; Colebunders, Roberte; Mascart, Françoise; Stordeur, Patrick; Kestens, Lucc; De Baetselier, Patrick; Raes, Geerta for the TB-IRIS study group},

doi = {doi: 10.1097/QAD.0b013e328361648b},

year  = {2013},

date = {2013-07-17},

journal = {AIDS},

volume = {27},

number = {11},

pages = {1725-1734},

abstract = {Objective: 



Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a common complication in HIV-TB co-infected patients receiving combined antiretroviral therapy (cART). This study investigated a putative contribution of monocytes to the development of TB-IRIS.



Design: 



A prospective study was designed to compare gene expression between patients who developed TB-IRIS with matched non-TB-IRIS controls.



Methods: 



We performed a hypothesis-generating transcriptome analysis on monocytes of HIV-TB co-infected patients. Identified pathways were subsequently analysed in patients’ monocytes before and shortly after cART initiation, in a technically independent set-up (nCounter). Additionally, protein expression and enzymatic activities of specific factors were assessed at the systemic level.



Results: 



Pathway analysis of microarray datasets and focused gene expression study revealed that, even before initiation of cART, the complement system is dysregulated in HIV–TB co-infected patients who are predisposed to developing TB-IRIS. Detailed analysis revealed differences between TB-IRIS patients and matched non-TB-IRIS cases, at the level of the balance between the effector C1Q and the inhibitor C1-INH, both before and 2 weeks after cART initiation. These differences were mirrored by increases in the downstream pro-inflammatory complement factor C5 over the course of 2 weeks of cART. Our results suggest that inappropriate control of complement activation could be associated with the ‘flaring up’ of inflammation observed during TB-IRIS.



Conclusion: 



The current study reveals a contribution of monocytes and the complement system to TB-IRIS development. An intriguing possibility is that the development of TB-IRIS may depend partially on the relative balance between C1Q and C1-INH.

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Nakiwogga-Muwanga2013,

title = {A Pharmacy-Only Refill Program at a Large HIV Clinic in Uganda: Experience and Satisfaction of Patients},

author = {Alice Nakiwogga-Muwanga and Elly Katabira and Joseph Sempa and Andrew Kambugu and Esther Nakibuuka-Lubwama and Mohammed Lamorde and Joseph Mawejje and Robert Colebunders},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/A-Pharmacy-Only-Refill-Program-at-a-LargeA-Pharmacy-Only-Refill-Program-at-a-Large-llinic-in-Uganda.pdf},

doi = {10.1177/2325957413488179},

year  = {2013},

date = {2013-07-15},

journal = {journal of the International Association of Providers of AIDS Care},

volume = {13},

number = {3},

pages = {264-8},

abstract = {Background:

The purpose of this study was to assess patients’ experience and satisfaction with pharmacy-only refill program (PRP)

and to compare those who were removed from the PRP with those still in the program.

Methods:

A sample of 446 patients was

selected from 1503 patients on antiretroviral therapy that had been enrolled in the PRP for at least 24 months. The study used

interviewer-administered questionnaires to assess patients’ experience and satisfaction with PRP.

Results:

Of the 446 patients,

133 (29.8%) were removed from the PRP. By multivariate analysis, it was found that wanting to see a clinician before their

scheduled clinic visit, Christian religion, and not understanding why they were enrolled in PRP were associated with having

been removed from the PRP. Patients felt that the greatest benefit from the program was the time that they saved to do

other activities. Patients preferred to collect their medication every 3 months instead of every month.

Conclusion:

All

patients interviewed scored the program high, and all recommended that the PRP should continue. Stable patients prefer to

see clinicians less frequently and visit clinic less often},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Morawski2013,

title = {Accuracy of Pima Point-of-Care CD4 Analyzer In Routine Use in Public Health Clinics in Uganda},

author = {Bozena M Morawski and David B. Meya and David R Boulware},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Accuracy-of-Pima-point-of-care-CD4-analyzer-in-routine-use-in-Public-health-clinics-in-Uganda.pdf},

doi = {10.1097/QAI.0b013e3182928f27},

year  = {2013},

date = {2013-07-01},

journal = {Journalof Acquired Immune  Deficiency Syndrome},

volume = {63},

number = {3},

pages = {113-5},

abstract = {We read with interest the article by Larson et al.,

1

 and we would like to summarize findings

of point-of-care CD4 testing in a multi-site, real-world setting at seven Kampala Capital

City Authority (KCCA) health facilities in Uganda under general clinic conditions.

Venous blood samples (n=225) were run onsite by trained clinic staff using the Pima

™

Analyser (Alere). Excess portions of the same plasma specimen were sent to the Makerere

University-Johns Hopkins University (MU-JHU) laboratory for testing within 24 hours via a

BD FACSCalibur

™

 flow cytometer. The MU-JHU lab is accredited by the College of

American Pathologists and participates in external quality assurance testing. Daily

calibrations are performed with commercial controls. The sampled population was 80%

female, and comprised of HIV-infected persons whose median age was 27},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Nakanjako2013,

title = {Impaired T-cell proliferation among HAART-treated adults with suboptimal CD4 recovery in an African cohort},

author = {Damalie Nakanjako, Isaac Ssewanyana, Rose Nabatanzi, Agnes Kiragga, Moses R Kamya, Huyen Cao & Harriet Mayanja-Kizza },

doi = {https://doi.org/10.1186/1471-2172-14-26},

year  = {2013},

date = {2013-06-20},

journal = {BMC Immunology volume},

volume = {14},

number = {(1):26},

abstract = {Background



Most HIV-infected subjects exhibit a progressive rise in CD4 T-cell counts after initiation of highly active antiretroviral therapy (HAART). However, a subset of individuals exhibit very poor CD4 T-cell recovery despite effective control of HIV-RNA viraemia. We evaluated CD4 T-cell proliferation among suboptimal responders and its correlation with CD4 T-cell activation.



Methods



The magnitude of CD4 increase (difference between absolute CD4 counts at baseline and absolute CD4 counts at 4 years of ART) was grouped into 4 quartiles for the 211 patients with sustained HIV-RNA viral suppression. Cases of ‘Suboptimal immune responders’ included patients within the lowest quartile [Median CD4 increase 165 (Range −43-298) cells/μl; n=52] and a comparison group of ‘Optimal immune responders’ was defined as patients within the highest quartile of CD4 increase [Median CD4 increase 528 (Range 417–878) cells/μl; n=52]. Frozen PBMC were thawed and analysed from a convenient sample of 39 suboptimal responders and 48 optimal responders after 4 years of suppressive antiretroviral therapy. T-cell activation was measured by proportions of T-cells expressing surface marker CD38 and HLADR (CD4+CD38+HLA-DR+ and CD8+CD38+HLA-DR+ cells). T-cell proliferation was determined by the extent of carboxyfluorescein diacetate succinimidyl ester (CFSE) dye dilution on culture day 5 of PBMCs in the presence of antigen (SEB, PPD, CMVpp65, GagA and GagD). Samples were analyzed on a FACS Calibur flow cytometer and flow data was analyzed using FlowJo and GraphPad.



Results



Overall, CD4 T-cell proliferation on stimulation with SEB, PPD, CMVpp65, Gag A and Gag D.antigens, was lower among suboptimal than optimal responders; this was significant for SEB (CD4+ p=0.003; CD8+ p=0.048) and PPD antigens (CD8+ p=0.038). Among suboptimal responders, T-cell proliferation decreased with increasing immune activation (Negative correlation; slope = −0.13±−0.11) but not among optimal responders.



Conclusion



T-cell immune activation and exhaustion were associated with poor proliferation among suboptimal responders to HAART despite sustained viral suppression. We recommend studies to further understand the mechanisms leading to impaired T-cell function among suboptimal responders as well as the potential role of immune modulation in optimizing CD4 count and functional recovery after HAART.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Nankabirwa2013,

title = {Asymptomatic Plasmodium Infection and Cognition among Primary Schoolchildren in a High Malaria Transmission Setting in Uganda},

author = {Joaniter Nankabirwa and Bonnie Wandera and Noah Kiwanuka and Sarah G. Staedke and Moses R. Kamya, and Simon J. Brooker},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Asymptomatic...-1.pdf},

doi = {10.4269/ajtmh.12-0633},

year  = {2013},

date = {2013-06-01},

journal = {American Journal of Tropical Medicine and Hygiene},

volume = {88},

number = {6},

pages = {1102-8},

abstract = {Asymptomatic parasitemia is common among schoolchildren living in areas of high malaria transmission, yet little is known about its effect on cognitive function in these settings. To investigate associations between asymptomatic parasitemia, anemia, and cognition among primary schoolchildren living in a high malaria transmission setting, we studied 740 children enrolled in a clinical trial in Tororo, Uganda. Parasitemia, measured by thick blood smears, was present in 30% of the children. Infected children had lower test scores for abstract reasoning (adjusted mean difference [AMD] -0.6, 95% confidence interval [CI] -1.01 to -0.21) and sustained attention (AMD -1.6 95% CI -2.40 to -0.81) compared with uninfected children. There was also evidence for a dose-response relationship between parasite density and scores for sustained attention. No associations were observed between anemia and either test of cognition. Schoolchildren in high transmission settings may experience cognitive benefits, from interventions aimed at reducing the prevalence of asymptomatic parasitemia.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Andama2013,

title = {Prevalence and Outcomes of Cryptococcal Antigenemia in HIV- seropositive Patients Hospitalized for Suspected Tuberculosis in Uganda},

author = {A.O. Andama and S. den Boon and D. Meya and A. Cattamanchi and W. Worodria and J.L. Davis and N.D. Walter and S.D. Yoo and N. Kalema and B. Haller and L. Huang on behalf of the International HIV-associated Opportunistic Pneumonias (IHOP) Study},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Prevalence-and-Outcomes-of-Cryptococcal-Antigenemia-....pdf},

doi = {10.1097/QAI.0b013e3182926f95},

year  = {2013},

date = {2013-06-01},

journal = {Journal of Acquired Imune Dificiency syndrome},

volume = {63},

number = {2},

pages = {189–194},

abstract = {Background—

Cryptococcal infection occurs in HIV-seropositive patients and is associated with

high mortality. However, limited information is available on the prevalence and outcomes of

cryptococcal antigenemia among hospitalized HIV-seropositive patients in sub-Saharan Africa.

Objectives—

To determine the prevalence of and risk factors for cryptococcal antigenemia

among HIV-seropositive patients presenting to Mulago Hospital (Kampala, Uganda) with

unexplained cough ≥2 weeks and suspected TB, and also to determine if antigenemia is associated

with an increased mortality.

Methods—

Between September 2009 and September 2010, we enrolled consecutive HIV-

seropositive adults hospitalized at Mulago Hospital with cough ≥2 weeks and suspected TB.

Banked serum was tested for cryptococcal antigen. We compared demographic, clinical

characteristics and 2-month mortality in patients with and without cryptococcal antigenemia.

Results—

Of 563 HIV-seropositive patients, 32 (5.7%) were CrAg-positive. None had

Cryptococcus neoformans

 detected on fungal culture of BAL fluid (n=116). CrAg-positive

patients had a lower median CD4-count compared to CrAg-negative patients (25 vs. 55 cells/uL,

p=0.02) and a substantial proportion of CrAg-positive patients also had concurrent TB (31%). A

positive CrAg test was not associated with increased mortality during the 2-month follow-up

period (HR: 0.99, 95% CI: 0.63–1.54, p=0.95) after adjusting for CD4 count and ART use at

enrollment and/or follow-up.

Conclusions—

Occult cryptococcal antigenemia occurs commonly among hospitalized HIV-

seropositive patients with suspected TB. CrAg testing should be considered in hospitalized, HIV seropositive patients with CD4 count <50 cells/uL, coupled with longer follow-up to evaluate the

diagnostic value of CrAg and therapeutic interventions in patients with asymptomatic cryptococcal

antigenemia.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Duffy2013,

title = {Reach and Cost-Effectiveness of the PrePex Device for Safe Male Circumcision in Uganda},

author = {Kevin Duffy and Moses Galukande and Nick Wooding and Monica Dea and Alex Coutinho},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Reach-and-Cost-Effectiveness-of-the-PrePex-Device-for-Safe-Male-Circumcision-in-Uganda.pdf},

doi = {10.1371/journal.pone.0063134},

year  = {2013},

date = {2013-05-13},

journal = {PloS One},

volume = {8},

number = {5},

abstract = {INTRODUCTION:



Modelling, supported by the USAID Health Policy Initiative and UNAIDS, performed in 2011, indicated that Uganda would need to perform 4.2 million medical male circumcisions (MMCs) to reach 80% prevalence. Since 2010 Uganda has completed 380,000 circumcisions, and has set a national target of 1 million for 2013.

OBJECTIVE:



To evaluate the relative reach and cost-effectiveness of PrePex compared to the current surgical SMC method and to determine the effect that this might have in helping to achieve the Uganda national SMC targets.

METHODS:



A cross-sectional descriptive cost-analysis study conducted at International Hospital Kampala over ten weeks from August to October 2012. Data collected during the performance of 625 circumcisions using PrePex was compared to data previously collected from 10,000 circumcisions using a surgical circumcision method at the same site. Ethical approval was obtained.

RESULTS:



The moderate adverse events (AE) ratio when using the PrePex device was 2% and no severe adverse events were encountered, which is comparable to the surgical method, thus the AE rate has no effect on the reach or cost-effectiveness of PrePex. The unit cost to perform one circumcision using PrePex is $30.55, 35% ($7.90) higher than the current surgical method, but the PrePex method improves operator efficiency by 60%, meaning that a team can perform 24 completed circumcisions compared to 15 by the surgical method. The cost-effectiveness of PrePex, comparing the cost of performing circumcisions to the future cost savings of potentially averted HIV infections, is just 2% less than the current surgical method, at a device cost price of $20.

CONCLUSION:



PrePex is a viable SMC tool for scale-up with unrivalled potential for superior reach, however national targets can only be met with effective demand creation and availability of trained human resource.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Jones-Lopez2013,

title = {Cough Aerosols of Mycobacterium tuberculosis Predict New Infection},

author = {Edward C. Jones-Lopez and Olive Namugga and Francis Mumbowa and Martin Ssebidandi and Olive Mbabazi and Stephanie Moine and Gerald Mboowa and Matthew P. Fox and Nancy Reilly and Irene Ayakaka and Soyeon Kim and Alphonse Okwera and Moses Joloba and Kevin P. Fennelly

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Cough-Aerosols-of-mycobacterium-tuberculosis-predict-new-infection....pdf},

doi = {10.1164/rccm.201208-1422OC},

year  = {2013},

date = {2013-05-01},

journal = {American Journal of Respiratory and Critical Care Medicine},

volume = {187},

number = {9},

pages = {1007-15},

abstract = {RATIONALE:



Airborne transmission of Mycobacterium tuberculosis results from incompletely characterized host, bacterial, and environmental factors. Sputum smear microscopy is associated with considerable variability in transmission.

OBJECTIVES:



To evaluate the use of cough-generated aerosols of M. tuberculosis to predict recent transmission.

METHODS:



Patients with pulmonary tuberculosis (TB) underwent a standard evaluation and collection of cough aerosol cultures of M. tuberculosis. We assessed household contacts for new M. tuberculosis infection. We used multivariable logistic regression analysis with cluster adjustment to analyze predictors of new infection.

MEASUREMENTS AND MAIN RESULTS:



From May 2009 to January 2011, we enrolled 96 sputum culture-positive index TB cases and their 442 contacts. Only 43 (45%) patients with TB yielded M. tuberculosis in aerosols. Contacts of patients with TB who produced high aerosols (≥10 CFU) were more likely to have a new infection compared with contacts from low-aerosol (1-9 CFU) and aerosol-negative cases (69%, 25%, and 30%, respectively; P = 0.009). A high-aerosol patient with TB was the only predictor of new M. tuberculosis infection in unadjusted (odds ratio, 5.18; 95% confidence interval, 1.52-17.61) and adjusted analyses (odds ratio, 4.81; 95% confidence interval, 1.20-19.23). Contacts of patients with TB with no aerosols versus low and high aerosols had differential tuberculin skin test and interferon-γ release assay responses.

CONCLUSIONS:



Cough aerosols of M. tuberculosis are produced by a minority of patients with TB but predict transmission better than sputum smear microscopy or culture. Cough aerosols may help identify the most infectious patients with TB and thus improve the cost-effectiveness of TB control programs.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Musubire2013,

title = {Diagnosis and Management of Cryptococcal Relapse},

author = {Abdu K Musubire and David R Boulware and David B Meya and Joshua Rhein

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Diagnosis-and-Management-of-Cryptococcal-Relapse.pdf},

year  = {2013},

date = {2013-04-29},

journal = {Journal of AIDS & Clilnical Resaerch},

volume = {3},

number = {3},

abstract = {Despite improvements in the antifungal regimens and the roll out of antiretroviral therapy (ART) in sub-Saharan Africa, mortality due to cryptococcal meningitis remains high. Relapse of an initially successfully treated infection contributes to this mortality and is often a clinical dilemma in differentiating between paradoxical immune reconstitution inflammatory syndrome (IRIS) and culture-positive relapse or treatment failure. Herein, we present a clinical case scenario and review the case definitions, differential diagnosis, and management of relapse with an emphasis on the current diagnostic and management strategies. We also highlight the challenges of resistance testing and management of refractory relapse cases. The risk of relapse is influenced by: 1) the choice of induction therapy, with higher mortality risk with fluconazole monotherapy which can select for resistance; 2) non-adherence to or lack of secondary prophylaxis; 3) failure of linkage-to-care or retention-in-care of HIV ART programs.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Team2013,

title = {Routine versus clinically driven laboratory monitoring and first-line antiretroviral therapy strategies in African children with HIV (ARROW): a 5-year open-label randomised factorial trial},

author = {ARROW Trail Team},

url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3641608/},

doi = {10.1016/S0140-6736(12)62198-9},

year  = {2013},

date = {2013-04-10},

journal = {Lancent},

volume = {381},

number = {9875},

pages = {1391-1403},

abstract = {BACKGROUND:



No trials have investigated routine laboratory monitoring for children with HIV, nor four-drug induction strategies to increase durability of first-line antiretroviral therapy (ART).

METHODS:



In this open-label parallel-group trial, Ugandan and Zimbabwean children or adolescents with HIV, aged 3 months to 17 years and eligible for ART, were randomly assigned in a factorial design. Randomisation was to either clinically driven monitoring or routine laboratory and clinical monitoring for toxicity (haematology and biochemistry) and efficacy (CD4 cell counts; non-inferiority monitoring randomisation); and simultaneously to standard three-drug or to four-drug induction first-line ART, in three groups: three-drug treatment (non-nucleoside reverse transcriptase inhibitor [NNRTI], lamivudine, abacavir; group A) versus four-drug induction (NNRTI, lamivudine, abacavir, zidovudine; groups B and C), decreasing after week 36 to three-drug NNRTI, lamivudine, plus abacavir (group B) or lamivudine, abacavir, plus zidovudine (group C; superiority ART-strategy randomisation). For patients assigned to routine laboratory monitoring, results were returned every 12 weeks to clinicians; for clinically driven monitoring, toxicity results were only returned for requested clinical reasons or if grade 4. Children switched to second-line ART for WHO stage 3 or 4 events or (routine laboratory monitoring only) age-dependent WHO CD4 criteria. Randomisation used computer-generated sequentially numbered tables incorporated securely within the database. Primary efficacy endpoints were new WHO stage 4 events or death for monitoring and change in CD4 percentage at 72 and 144 weeks for ART-strategy randomisations; the co-primary toxicity endpoint was grade 3 or 4 adverse events. Analysis was by intention to treat. This trial is registered, ISRCTN24791884.

FINDINGS:



1206 children were randomly assigned to clinically driven (n=606) versus routine laboratory monitoring (n=600), and groups A (n=397), B (n=404), and C (n=405). 47 (8%) children on clinically driven monitoring versus 39 (7%) on routine laboratory monitoring had a new WHO stage 4 event or died (hazard ratio [HR] 1·13, 95% CI 0·73-1·73, p=0·59; non-inferiority criterion met). However, in years 2-5, rates were higher in children on clinically driven monitoring (1·3 vs 0·4 per 100 child-years, difference 0·99, 0·37-1·60, p=0·002). One or more grade 3 or 4 adverse events occurred in 283 (47%) children on clinically driven versus 282 (47%) on routine laboratory monitoring (HR 0·98, 0·83-1·16, p=0·83). Mean CD4 percentage change did not differ between ART groups at week 72 (16·5% [SD 8·6] vs 17·1% [8·5] vs 17·3% [8·0], p=0·33) or week 144 (p=0·69), but four-drug groups (B, C) were superior to three-drug group A at week 36 (12·4% [7·2] vs 14·1% [7·1] vs 14·6% [7·3], p<0·0001). Excess grade 3 or 4 events in groups B (one or more events reported by 157 [40%] children in A, 190 [47%] in B; HR [B:A] 1·32, 1·07-1·63) and C (218 [54%] children in C; HR [C:A] 1·58, 1·29-1·94; global p=0·0001) were driven by asymptomatic neutropenia in zidovudine-containing groups (B, C; 86 group A, 133 group B, 184 group C), but resulted in drug substitutions in only zero versus two versus four children, respectively.

INTERPRETATION:



NNRTI plus NRTI-based three-drug or four-drug ART can be given across childhood without routine toxicity monitoring; CD4 monitoring provided clinical benefit after the first year on ART, but event rates were very low and long-term survival high, suggesting ART rollout should take priority. CD4 benefits from four-drug induction were not durable, but three-NRTI long-term maintenance was immunologically and clinically similar to NNRTI-based ART and could be valuable during tuberculosis co-treatment.

FUNDING:



UK Medical Research Council, the UK Department for International Development; drugs donated and viral load assays funded by ViiV Healthcare and GlaxoSmithKline},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tapley2013,

title = {Mobile Digital Fluorescence Microscopy for Diagnosis of Tuberculosis},

author = {Asa Tapley and Neil Switz and Clay Reber and J. Lucian Davis and Cecily Miller and John Baptist Matovu and William Worodria and Laurence Huang Daniel A. Fletcher and Adithya Cattamanchi

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Mobile-Digital-Fluorescence-Microscopy-for-Diagnosis-of-Tuberculosis.pdf},

doi = {10.1128/JCM.03432-12},

year  = {2013},

date = {2013-04-03},

journal = {Journal of Clinical Microbiology},

volume = {51},

number = {16},

pages = {1774-8},

abstract = {Access to sputum smear microscopy in high-tuberculosis (TB)-burden regions is limited by a scarcity of microscopes and experienced technicians. We evaluated the accuracy of CellScope, a novel digital fluorescence microscope that may expand access to microscopy. The study utilized smear microscopy slides prepared from sputum specimens submitted by consecutive adults with ≥ 2 weeks of cough who were admitted to Mulago Hospital (Kampala, Uganda). Conventional light-emitting diode (LED) fluorescence microscopy (FM) and mycobacterial culture were performed by experienced technicians. Two U.S.-based postgraduate researchers without prior microscopy experience restained, imaged, and interpreted the slides using CellScope. We assessed whether sensitivity and specificity of CellScope-based LED FM was noninferior to conventional LED FM by using a preselected margin of inferiority of 15%. Of 525 patients included, 72% were HIV seropositive and 39% had culture-confirmed TB. The proportions of positive results were similar with CellScope and conventional LED FM (34% versus 32%, respectively; P = 0.32), and agreement was substantial. CellScope accuracy was within the noninferiority margin for both sensitivity (63% versus 70%; difference, -7%; 95% confidence interval [CI], -13% to -1%) and specificity (85% versus 92%; difference, -7%; 95% CI, -12% to -3%). A subanalysis of 43 slides evaluated by each CellScope reader found substantial interreader reliability (custom-weighted kappa, 0.65) and variable intrareader reliability (custom-weighted kappa, 0.11 versus 0.48). CellScope offers promise for expanding microscopy services. Future studies should evaluate the device when operated by health workers in low-resource settings, the feasibility of image transmission and analysis by experienced microscopists, and the accuracy of automated image analysis algorithms.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Redd2013,

title = {Liver Stiffness Is Associated With Monocyte Activation in HIV-Infected Ugandans Without Viral Hepatitis},

author = {Andrew D. Redd and Sarah K. Wendel and Mary K. Grabowski and Ponsiano Ocama and Valerian Kiggundu and Francis Bbosa and Iga Boaz and Ashwin Balagopal and Steven J. Reynolds and Ronald H. Gray and David Serwadda and Gregory D. Kirk and Thomas C. Quinn and Lara Stabinski},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Liver-Stiffness-Is-Associated-With-Monocyte-Activation....pdf},

doi = {10.1089/AID.2013.0004},

year  = {2013},

date = {2013-04-03},

journal = {AIDS Resaerch and Human Retroviruses},

volume = {29},

number = {7},

pages = {1026-30},

abstract = {A high prevalence of liver stiffness, as determined by elevated transient elastography liver stiffness measurement, was previously found in a cohort of HIV-infected Ugandans in the absence of chronic viral hepatitis. Given the role of immune activation and microbial translocation in models of liver disease, a shared immune mechanism was hypothesized in the same cohort without other overt causes of liver disease. This study examined whether HIV-related liver stiffness was associated with markers of immune activation or microbial translocation (MT). A retrospective case-control study of subjects with evidence of liver stiffness as defined by a transient elastography stiffness measurement ≥9.3 kPa (cases=133) and normal controls (n=133) from Rakai, Uganda was performed. Cases were matched to controls by age, gender, HIV, hepatitis B virus (HBV), and highly active antiretroviral therapy (HAART) status. Lipopolysaccharide (LPS), endotoxin IgM antibody, soluble CD14 (sCD14), C-reactive protein (CRP), and D-dimer levels were measured. Conditional logistic regression was used to estimate adjusted matched odds ratios (adjMOR) and 95% confidence intervals. Higher sCD14 levels were associated with a 19% increased odds of liver stiffness (adjMOR=1.19, p=0.002). In HIV-infected individuals, higher sCD14 levels were associated with a 54% increased odds of having liver stiffness (adjMOR=1.54, p<0.001); however, the opposite was observed in HIV-negative individuals (adjMOR=0.57, p=0.001). No other biomarker was significantly associated with liver stiffness, and only one subject was found to have detectable LPS. Liver stiffness in HIV-infected Ugandans is associated with increased sCD14 indicative of monocyte activation in the absence of viral hepatitis or microbial translocation, and suggests that HIV may be directly involved in liver disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Sun2013,

title = {Cost-Utility of Lateral-Flow Urine Lipoarabinomannan for Tuberculosis Diagnosis in HIV-infected African Adults},

author = {Di Sun and Susan Dorman and Maunank Shah and Yukari C. Manabe and V. Mischka

Moodley Mark P. Nicol and David W. Dowdy},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Cost-Utility-of-Lateral-Flow-Urine-Lipoarabinomannan-for-tuberculosis-diagnosis-in-HIV-infected-African-adults.pdf},

doi = {doi: 10.5588/ijtld.12.0627},

year  = {2013},

date = {2013-04-01},

journal = {International journal of Tuberculosis and Lung Disease},

volume = {17},

number = {4},

pages = {552-8},

abstract = {OBJECTIVE:



To evaluate the cost-effectiveness of a lateral-flow urine lipoarabinomannan (LAM) test when added to existing strategies for tuberculosis (TB) diagnosis in human immunodeficiency virus infected adults (CD4(+) T-cell counts < 100 cells/l) with symptoms of active TB.

DESIGN:



Decision-analytic cost-utility model, with the primary outcome being the incremental cost-effectiveness ratio, expressed in 2010 US dollars per disability-adjusted life year (DALY) averted from the perspective of a public sector TB control program.

RESULTS AND CONCLUSION:



For every 1000 patients tested, adding lateral-flow urine LAM generated 80 incremental appropriate anti-tuberculosis treatments and averted 224 DALYs. Estimated cost utility was US$353 per DALY averted (95% uncertainty range $192$1161) in South Africa and $86 per DALY averted (95% uncertainty range $49$239) in Uganda, reflecting the lower treatment costs in Uganda. Cost utility was most sensitive to assay specificity, cost of anti-tuberculosis treatment, life expectancy after TB cure and cohort TB prevalence, but did not rise above $1500 per DALY averted in South Africa under any one-way sensitivity analysis. The probability of acceptability was >99.8% at a per-DALY willingness-to-pay threshold equal to the per capita gross domestic product in South Africa ($7275) and Uganda ($509)},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Fogel2013,

title = {Impact of Maternal and Infant Antiretroviral Drug Regimens on Drug Resistance in HIV-Infected Breastfeeding Infants},

author = {Jessica M. Fogel and Anthony Mwatha and Paul Richardson and Elizabeth R. Brown and Tsungai Chipato and Michel Alexandre and Dhayendre Moodley and Ali Elbireer and Mark Mirochnick and Kathleen George and Lynne M. Mofenson and Sheryl Zwerski and Hoosen M. Coovadia and Susan H.Eshleman},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Impact-of-Maternal-and-Infant-Antiretroviral-Drug....pdf},

doi = { 10.1097/INF.0b013e31827f44ee},

year  = {2013},

date = {2013-04-01},

journal = {Pediatric Infectious Diseases Journal},

volume = {32},

number = {4},

pages = {164-9},

abstract = {BACKGROUND:



The HIV Prevention Trials Network (HPTN) 046 trial evaluated the efficacy of extended infant nevirapine (NVP) administration for prevention of HIV transmission through breastfeeding. Infants received daily NVP up to 6 weeks of age. HIV-uninfected infants (the intent-to-treat group) received daily NVP or placebo up to 6 months of age. We analyzed emergence of NVP resistance in infants who acquired HIV infection despite prophylaxis.

METHODS:



HIV genotyping was performed using the ViroSeq HIV Genotyping System. Medians and proportions were used to summarize data. Two-sided Fisher exact tests were used to evaluate associations between categorical variables.

RESULTS:



NVP resistance was detected in 12 (92.3%) of 13 infants who were HIV-infected by 6 weeks and in 7 (28%) of 25 infants who were HIV-uninfected at 6 weeks and HIV-infected at 6 months of age (6/8 = 75% in the NVP arm, 1/17 = 5.9% in the placebo arm, P = 0.001). Among those 25 infants, 4 had mothers who initiated an antiretroviral treatment regimen by 6 months postpartum. In all 4 cases, the treatment regimen included a non-nucleoside reverse transcriptase inhibitor (NVP or efavirenz). NVP resistance was detected in all 4 of those infants by 6 months of age (4/4 = 100%). In contrast, only 3 (14.2%) of the remaining 21 HIV-infected infants whose mothers did not initiate antiretroviral treatment developed NVP resistance (P = 0.003).

CONCLUSIONS:



Extended NVP prophylaxis significantly increased the risk of NVP resistance in infants who acquired HIV infection after 6 weeks of age. Treatment of maternal HIV infection was also associated with emergence of NVP resistance in HIV-infected, breastfed infants.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tukei2013,

title = {Virologic, immunologic and clinical response of infants to antiretroviral therapy in Kampala, Uganda},

author = {Vincent J Tukei and Miriam Murungi and Alice R Asiimwe and Daniella Migisha and Albert Maganda and Sabrina Bakeera-Kitaka and Israel Kalyesubula and Philippa Musoke and Adeodata Kekitiinwa

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Virologic-immunologic-and-clinical-response-of-infants...-in-Kampala-Uganda.pdf},

doi = { 10.1186/1471-2431-13-42},

year  = {2013},

date = {2013-03-27},

journal = {BMC Pediatrics},

abstract = {BACKGROUND:



Antiretroviral therapy (ART) is known to save lives. Among HIV-infected infants living in resource constrained settings, the short and long term benefits of ART are only partially known. This study was designed to determine the virologic, immunologic and clinical outcomes of antiretroviral therapy in a cohort of HIV-infected infants receiving care from an outpatient clinic in Kampala, Uganda.

METHODS:



A prospective cohort of HIV-infected infants receiving treatment at the Baylor-Uganda clinic was analyzed. Patients were diagnosed, enrolled and followed up at the clinic. HIV viral load, CD4 cell counts and clinical progress were assessed during follow-up. Descriptive statistical analysis and logistic regression modeling to determine predictors of treatment success were conducted.

RESULTS:



Of 91 HIV-infected infants enrolled into the cohort, 53 (58.2%) infants were female; 43 (47.3%) were 6 months of age or younger, and 50 (55.6%) had advanced HIV/AIDS disease (Clinical stage 3 or 4). Eighty four infants started ART and 78 (92.9%) completed 6 months of treatments. Fifty six (71.8%) infants attained virologic suppression by month-6 of ART, and at month-12 of ART, the cumulative probability of attaining viral suppression was 83.1%. None of the baseline infant factors (age, sex, WHO stage, CD4 cell percent, weight for age, or height for age z-score) predicted treatment success. There was an increase in CD4 cells from a baseline mean of 23% to 30% at month-6 of treatment (p<0.001) and by month-24 of ART, the mean CD4 percent was 36%. A total of 7 patients died while on ART and another 7 experienced adverse events that were related to treatment.

CONCLUSION:



Our results show that, even among very young patients from resource constrained settings, ART dramatically suppresses HIV replication, allows immune recovery and clinical improvement, and is safe. However, baseline characteristics do not predict recovery in this age group.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Lamorde2013,

title = {Lower artemether, dihydroartemisinin and lumefantrine concentrations during rifampicin-based tuberculosis treatment},

author = {Mohammed Lamorde and Pauline Byakika-Kibwikaa and Jonathan Mayito and Lillian Nabukeeraa and Mairin Ryan and Warunee Hanpithakpong and Gilbert Lefe `vree and David J. Back and Saye H. Khoo and Concepta Merrya},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Lower_artemether_dihydroartemisinin_and.12.pdf},

doi = {10.1097/QAD.0b013e32835cae3b},

year  = {2013},

date = {2013-03-27},

journal = {AIDS (London, England)},

volume = {27},

number = {6},

pages = {961-5},

abstract = {OBJECTIVE:



To investigate the pharmacokinetics of artemether, dihydroartemisinin and lumefantrine during rifampicin intake and after stopping rifampicin.

STUDY DESIGN:



An open-label, two-phase, longitudinal drug interaction study with patients serving as their own controls.

METHODS:



We recruited HIV-1-seropositive Ugandan adults who were receiving rifampicin-based tuberculosis treatment and who did not have malaria. Pharmacokinetic sampling after six doses of artemether-lumefantrine was performed during rifampicin-based tuberculosis treatment (phase 1) and repeated at least 3 weeks after stopping rifampicin-based tuberculosis treatment (phase 2).

RESULTS:



Six and five patients completed phases 1 and 2, respectively. Median age and weight were 30 years and 64 kg. Artemether and dihydroartemisinin area under the concentration-time curve (AUC(0-12h)) were significantly lower by 89% [geometric mean ratio (GMR) 90% confidence interval (CI) 0.11, 0.05-0.26] and 85% (0.15, 0.10-0.23), respectively, during rifampicin-based treatment when compared to AUC(0-12h) after stopping rifampicin intake. Similarly, artemether and dihydroartemisinin C(max) were 83% (0.17, 0.08-0.39) and 78% (0.22, 0.15-0.33) lower, respectively, during rifampicin treatment. For artemether, mean (±SD) C(12) was 0.5(±1.0) and 5.9(±2.5) ng/ml in phases 1 and 2, respectively. Corresponding values for dihydroartemisinin (DHA) were 0.3(±0.4) and 4.7(±2.0) ng/ml, respectively. Day 8 lumefantrine concentration was significantly lower by 84% (GMR 90% CI 0.16, 0.09-0.27), and AUC(Day3-Day25) was significantly lower by 68% (GMR 90% CI 0.32, 0.21-0.49) during rifampicin-based treatment when compared to exposure values after stopping rifampicin.

CONCLUSION:



Pharmacokinetic parameters for artemether-lumefantrine were markedly lower during rifampicin-based tuberculosis treatment. Artemether-lumefantrine should not be co-administered with rifampicin.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Seden2013b,

title = {Drug-drug interactions between antiretrovirals and drugs used in the management of neglected tropical diseases: important considerations in the WHO 2020 Roadmap and London Declaration on Neglected Tropical Diseases.},

author = {Kay Seden and Saye Khoo and David Back and Natalie Prevatt and Mohammed Lamorde and Pauline Byakika-Kibwika Jonathan Mayito and Mairin Ryan and Concepta Merry},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Drug_drug_interactions_between_antiretrovirals_and.1.pdf},

doi = {10.1097/QAD.0b013e32835ca9b4},

year  = {2013},

date = {2013-03-13},

journal = {African Health Sciences},

volume = {27},

number = {5},

pages = {675-86},

abstract = {The group of infections known as the neglected tropical diseases (NTDs) collectively affect one billion people worldwide, equivalent to one-sixth of the world's population. The NTDs cause severe physical and emotional morbidity, and have a profound effect on cycles of poverty; it is estimated that NTDs account for 534 000 deaths per year. NTDs such as soil-transmitted helminth infections and the vector-borne protozoal infections leishmaniasis and trypanosomiasis occur predominantly in the most economically disadvantaged and marginalized communities. It is estimated that all low-income countries harbour at least five of the NTDs simultaneously. NTDs are neglected because they do not individually rank highly in terms of mortality data, and because they affect populations with little political voice. There is considerable geographic overlap between areas with high prevalence of NTDs and HIV, raising the possibility of complex polypharmacy and drug-drug interactions. Antiretrovirals pose a particularly high risk for potential drug-drug interactions, which may be pharmacokinetic or pharmacodynamic in nature and can result in raising or lowering plasma or tissue concentrations of co-prescribed drugs. Elevated drug concentrations may be associated with drug toxicity and lower drug concentrations may be associated with therapeutic failure. The aim of this paper is to review the currently available data on interactions between antiretrovirals and drugs used in the management of NTDs. It is intended to serve as a resource for policy makers and clinicians caring for these patients, and to support the recent WHO 2020 Roadmap and the 2012 London Declaration on NTDs.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Sekadde2013,

title = {Evaluation of the Xpert MTB/RIF test for the diagnosis of childhood pulmonary tuberculosis in Uganda: a cross-sectional diagnostic study},

author = {Moorine Penninah Sekadde and Eric Wobudeya and Moses L Joloba and Willy Ssengooba and Harriet Kisembo and Sabrina Bakeera-Kitaka and Philippa Musoke},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Evaluation-of-the-Xpert....pdf},

doi = { 10.1186/1471-2334-13-133.},

year  = {2013},

date = {2013-03-12},

journal = {BMC Infectious Diseases},

abstract = {BACKGROUND:



The diagnosis of childhood tuberculosis remains a challenge worldwide. The Xpert MTB/RIF test, a rapid mycobacteria tuberculosis diagnostic tool, was recommended for use in children based on data from adult studies. We evaluated the performance of the Xpert MTB/RIF test for the diagnosis of childhood pulmonary tuberculosis using one induced sputum sample and described clinical characteristics associated with a positive Xpert MTB/RIF test. The sputum culture on both Lowenstein-Jensen (LJ) and Mycobacteria Growth Indicator Tube (MGIT) was the gold standard.

METHODS:



We consecutively enrolled 250 Ugandan children aged 2 months to 12 years with suspected pulmonary tuberculosis between January 2011 and January 2012 into a cross-sectional diagnostic study at a tertiary care facility in Uganda.

RESULTS:



We excluded data from 15 children (13 contaminated culture and 2 indeterminate MTB/RIF test results) and analysed 235 records. The Xpert MTB/RIF test had a sensitivity of 79.4% (95% CI 63.2 - 89.7) and a specificity of 96.5% (95% CI 93 - 98.3). The Xpert MTB/RIF test identified 13 of the 14 (92.9%) smear positive-culture positive and 14 of the 20 (70%) smear negative -culture positive cases. The Xpert MTB/RIF identified twice as many cases as the smear microscopy (79.4% Vs 41.2%). Age > 5 years (OR 3.3, 95% CI 1.4 - 7.4, p value 0.005), a history of Tuberculosis (TB) contact (OR 2.4, 95% CI 1.1 - 5.2, p value 0.03), and a positive tuberculin skin test (OR 4.1, 95% CI 1.7 - 10, p value 0.02) was associated with a positive Xpert MTB/RIF test. The median time to TB detection was 49.5 days (IQR 38.4-61.2) for LJ, and 6 days (IQR 5 - 11.5) for MGIT culture and 2 hours for the Xpert MTB/RIF test.

CONCLUSION:



The Xpert MTB/RIF test on one sputum sample rapidly and correctly identified the majority of children with culture confirmed pulmonary tuberculosis with high specificity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Durski2013,

title = {Cost-effective Diagnostic Checklists for Meningitis in Resource Limited Settings},

author = {Kara N. Durski and Karen M. Kuntz and Kosuke Yasukawa and Beth A. Virnig and David B. Meya and 

David R. Boulware,},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Cost-effective-Diagnostic-Checklists-for-Meningitis-in-Resource.pdf},

doi = {10.1097/QAI.0b013e31828e1e56},

year  = {2013},

date = {2013-03-05},

journal = {Journal of Acquired Imune Dificiency syndrome},

volume = {63},

number = {3},

pages = {101-8},

abstract = {BACKGROUND:



Checklists can standardize patient care, reduce errors, and improve health outcomes. For meningitis in resource-limited settings, with high patient loads and limited financial resources, central nervous system diagnostic algorithms may be useful to guide diagnosis and treatment. However, the cost effectiveness of such algorithms is unknown.

METHODS:



We used decision analysis methodology to evaluate the costs, diagnostic yield, and cost effectiveness of diagnostic strategies for adults with suspected meningitis in resource-limited settings with moderate/high HIV prevalence. We considered 3 strategies: (1) comprehensive "shotgun" approach of utilizing all routine tests; (2) "stepwise" strategy with tests performed in a specific order with additional tuberculosis (TB) diagnostics; (3) "minimalist" strategy of sequential ordering of high-yield tests only. Each strategy resulted in 1 of 4 meningitis diagnoses: bacterial (4%), cryptococcal (59%), TB (8%), or other (aseptic) meningitis (29%). In model development, we utilized prevalence data from 2 Ugandan sites and published data on test performance. We validated the strategies with data from Malawi, South Africa, and Zimbabwe.

RESULTS:



The current comprehensive testing strategy resulted in 93.3% correct meningitis diagnoses costing $32.00 per patient. A stepwise strategy had 93.8% correct diagnoses costing an average of $9.72 per patient, and a minimalist strategy had 91.1% correct diagnoses costing an average of $6.17 per patient. The incremental cost-effectiveness ratio was $133 per additional correct diagnosis for the stepwise over minimalist strategy.

CONCLUSIONS:



Through strategically choosing the order and type of testing coupled with disease prevalence rates, algorithms can deliver more care more efficiently. The algorithms presented herein are generalizable to East Africa and Southern Africa.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kirenga2013,

title = {Chronic respiratory diseases in a tertiary  healthcare facility in Uganda},

author = {B J Kirenga and L Nakiyingi and W Worodria and M Okot-Nwang},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Chronic-respiratory-diseases-.....pdf},

year  = {2013},

date = {2013-03-02},

journal = { African Journal of Respiratory Medicine},

number = {8},

pages = {2},

abstract = {Globally it is being increasingly recognised that non-

communicable diseases (NCDs) constitute a neglected 

epidemic, especially in low- and  middle-income coun

-

tries. Chronic respiratory diseases (CRDs) are among 

the most common NCDs but their burden is unknown 

in many low- and middle-income countries. 

We conducted a retrospective analysis of data col

-

lected on hospitalised patients in a pulmonary ward 

of  Mulago  National  Referral  Hospital,  between  De

-

cember  2010  and  August  2011.   The  objective  of  this  

analysis was to determine the proportion, mortality, 

and average length of stay of patients with CRDs in a 

tertiary healthcare facility in Uganda.  Demographic 

characteristics, final diagnosis, vital status at discharge, 

and the average length of stay were extracted from 

the inpatient database. Proportions of the diagnoses, 

mortality, and average length of stay of  the admitted 

patients were calculated.

Five  hundred  and  fifty  eight  (558)  patients  were  

admitt ed during the study period; 58.2% were male. 

The mean age was 37.4 years (17.4 SD). The average 

length of stay was 5.6 days (8.4 SD). Fifty-one patients 

(9.0%) had CRD; of these asthma was the most frequent.

Eighty  (14.1%)  of  the  admitted  patients  died  dur

-

ing  hospitalisation;  5  (9.8%)  of  them  were  patients  

with CRD and  73 (14.5%) had communicable disease. 

Communicable respiratory diseases still account for 

the majority of inpatients in Mulago hospital and are 

associated  with  high  mortality  but  admission  rates  

and mortality associated with CRD, though lower than 

that of communicable respiratory diseases, are higher 

than in developed settings and causes of death among 

patients with CRDs.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{HMetal2013,

title = {The African Middle Eastern Society for Digestive Oncology mission against viral hepatitis and hepatocellular carcinoma},

author = {Mudawi HMetal},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/The-African-Middle-Eastern-Society-for-Digestive-Oncology-mission-against-viral-hepatitis-and-hepatocellar-carcinoma.pdf},

doi = { 10.1016/j.ajg.2012.12.003},

year  = {2013},

date = {2013-03-01},

journal = {Arab Journal of Gastroenteerology},

volume = {14},

number = {1},

pages = {31-3},

abstract = {Until the 1980s, gastroenterology was considered as a part of

internal medicine. Since the 1990s gastroenterology included

hepatology. Digestive cancers are the most common cancers

worldwide with 3 million new cases each year. Affected organs in-

clude the liver, pancreas, oesophagus, stomach, colon and rectum.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kirenga2013b,

title = {Tuberculin skin test conversion among HIV patients on  antiretroviral therapy in Uganda},

author = {B. J. Kirenga and W. Worodria and M. Massinga-Loembe and T. Nalwoga and Y. C. Manabe and L. Kestens and R. Colebunders and H. Mayanja-Kizza},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Tuberculin-skin-test-conversion-among-HIV-patients-on-antiretrviral-therapy-in-Uganda.pdf},

doi = {10.5588/ijtld.12.0298},

year  = {2013},

date = {2013-03-01},

journal = {International journal of Tuberculosis and Lung Disease},

volume = {17},

number = {3},

pages = {336-41},

abstract = {ETTING:



A human immunodeficiency virus (HIV) clinic in a setting of high tuberculosis (TB) and HIV prevalence.

OBJECTIVE:



To study the incidence of and factors associated with tuberculin skin test (TST) conversion in HIV patients on antiretroviral therapy (ART).

DESIGN:



Prospective cohort study of TST-negative, ART-naïve HIV patients (CD4 cell count < 250 cells/l) without active TB. TST was repeated at 2 months and, if negative, at 6 months. TST positivity was defined as an induration of ≥5 mm. Clinical examination, chest X-ray and CD4 cell counts were performed at baseline and follow-up. Proportions and incidence of TST conversion were calculated, and logistic regression analyses were performed.

RESULTS:



Of the 142 patients, 105 (75.5%) were females. The mean age was 35.9 years (standard deviation 8.1) and the median CD4 cell count was 119 cells/l (interquartile range 42168). The incidence of TST conversion was 30.2/100 person years (95%CI 19.546.8). Conversion was not associated with clinical, CD4 cell count or chest radiography findings.

CONCLUSIONS:



A high incidence of TST conversion was observed, supporting the World Health Organization recommendation to provide isoniazid preventive therapy (IPT) to all HIV patients in high TB prevalence settings. If case-control programmes choose to provide IPT only to TST-positive patients, repeat TST should be considered following initiation of ART},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tumwesigye2013,

title = {Policy development, implementation and evaluation by the AIDS control program in Uganda: a review of the processes},

author = {Benson T Tumwesigye and Damalie Nakanjako and Rhoda Wanyenze and Zainab Akol and Nelson Sewankambo},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Policy-development-implementation....pdf},

doi = { 10.1186/1478-4505-11-7},

year  = {2013},

date = {2013-02-23},

journal = {Health Research Policy and Systems},

volume = {11},

number = {1},

abstract = {BACKGROUND:



The AIDS Control Program (ACP) in Uganda has spearheaded the national health sector HIV response for the last three decades. ACP has developed, revised and implemented various HIV prevention, care and treatment policies in order to keep interventions relevant to the changing dynamics of the HIV epidemic. However, the ACP team and partners remain concerned about the lengthy policy development processes. This study documented the policy development and revision processes to identify strengths and weaknesses in order to inform adjustments as Uganda embraces the move to 'zero' HIV infections.

METHODS:



Data was collected through a review of the relevant policy documents and key informant interviews with the five program officers involved in the recently developed Safe Male Circumcision (SMC) policy and the recently revised HIV Counseling and Testing (HCT) policy. Qualitative data was analyzed manually using pre-determined themes.

RESULTS:



Development and revision of the SMC and HCT policies followed similar processes that included a series of meetings between senior management and a selected technical working group. However, the gaps included: i) inadequate awareness of the existence of national policy development and management guidelines; ii) limited engagement of the policy analysis unit in the policy development/revision processes; iii) inadequate tracking and evaluation of the policies before revision or development of new related policies; iv) lack of specific protocols/standard operating procedures (SOPs); and, v) limited indigenous funding for the entire policy development processes which contributed to non-adherence to the anticipated timelines.

CONCLUSIONS:



Policy development and revision of the SMC and HCT policies followed similar processes. Gaps identified included lack of protocols/SOPs for the processes and limited indigenous funding to support adherence to anticipated timelines. We recommend active involvement of the policy analysis unit in all policy processes. Specific protocols/SOPs for development, analysis, revision, implementation, monitoring, evaluation and impact assessment processes should be developed prior to commencement of the activities.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Okumu2013,

title = {Effect of emergency major abdominal surgery on CD4 cell count among HIV positive patients in a sub Saharan Africa tertiary hospital - a prospective study},

author = {Gabriel Okumu and Patson Makobore and Sam Kaggwa and Andrew Kambugu and Moses Galukande

},

url = {file:///C:/Users/MNASSA~1/AppData/Local/Temp/1471-2482-13-4.pdf},

doi = { 10.1186/1471-2482-13-4},

year  = {2013},

date = {2013-02-13},

journal = {BMC Surgery },

volume = {13},

abstract = {BACKGROUND:



Surgery plays a key role in HIV palliative care, specifically in the diagnosis and treatment of HIV related and non-related conditions. Yet major surgery depresses the immune system. Whereas the surgical consequences of HIV infection are well described, there is a paucity of published data, in resource-limited settings, on the effects of major surgery on the immune system. The purpose of this study was to determine the effect of major abdominal surgery on CD4 count in HIV positive and HIV negative patients after emergency major surgery.

METHODS:



A prospective cohort study was done for patients who underwent emergency major abdominal surgery. Their peri-operative CD4 counts were done for both HIV- and HIV + patients. Median CD4s were used in analysis.Mann Whitney test of significance was used for continuous data and Fisher' exact test used for categorical data. IRB approval was obtained.

RESULTS:



A total of 101 patients were recruited, 25 HIV positive and 76 HIV negative. The median CD4 cell reduction was higher in the HIV negative group (-68 cells) than HIV positive group (-29 cells) (p = 0.480).There was a general increase in the median CD4 change by 72 cells for the HIV positives and 95 cells for the HIV negatives (p = 0.44). CD4 change rose in both the HIV positive and negative groups by 27 cells for the HIV positives and 28 cells for the HIV negatives (p = 0.94). Relative Risk was 0.96, {CI 0.60 - 1.53}.

CONCLUSION:



Major emergency abdominal surgery had no significant effect on CD4 cell count among HIV positive patients},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kumwenda2013,

title = {Distribution of haematological and chemical pathology values among infants in Malawi and Uganda},

author = {Newton I. Kumwenda and Tiwonge Khonje and Linda Mipando and Kondwani Nkanaunena and Pauline Katundu Irene Lubega and Ali Elbireer and Steve Bolton and Danstan Bagenda and Michael Mubiru and Mary Glenn Fowler and Taha E. Taha

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Distribution-of-haematological-and-chemical-pathology-valus-among-infantss-in-Malawi-and-Uganda.pdf},

doi = { 10.1179/2046905512Y.0000000034},

year  = {2013},

date = {2013-02-13},

journal = {Pediatrics and International child Health},

volume = {32},

number = {4},

pages = {213-27},

abstract = {BACKGROUND:



Data on paediatric reference laboratory values are limited for sub-Saharan Africa.

OBJECTIVE:



To describe the distribution of haematological and chemical pathology values among healthy infants from Malawi and Uganda.

METHODS:



A cross-sectional study was conducted among healthy infants, 0-6 months old, born to HIV-uninfected mothers recruited from two settings in Blantyre, Malawi and Kampala, Uganda. Chemical pathology and haematology parameters were determined using standard methods on blood samples. Descriptive analyses by age-group were performed based on 2004 Division of AIDS Toxicity Table age categories. Mean values and interquartile ranges were compared by site and age-group.

RESULTS:



A total of 541 infants were included altogether, 294 from Malawi and 247 from Uganda. Overall, the mean laboratory values were comparable between the two sites. Mean alkaline phosphatase levels were lower among infants aged ≤21 days while aspartate aminotransferase, creatinine, total bilirubin and gamma-glutamyl transferase were higher in those aged 0-7 days than in older infants. Mean haematocrit, haemoglobin and neutrophil counts were higher in the younger age-groups (<35 days) and overall were lower than US norms. Red and white blood cell counts tended to decrease after birth but increased after ∼2 months of age. Mean basophil counts were higher in Malawi than in Uganda in infants aged 0-1 and 2-7 days; mean counts for eosinophils (for age groups 8-21 or older) and platelets (for all age groups) were higher in Ugandan than in Malawian infants. Absolute lymphocyte counts increased with infant age.

CONCLUSION:



The chemical pathology and haematological values in healthy infants born to HIV-uninfected mothers were comparable in Malawi and Uganda and can serve as useful reference values in these settings.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Hermans2013,

title = {Risk of tuberculosis after antiretroviral treatment  initiation: a comparison between efavirenz and  nevirapine using inverse probability weighting},

author = {Sabine M Hermans and Yukari C Manabe and Agnes N Kiragga and Andy IM Hoepelman and Joep MA Lange and Frank van Leth

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Risk-of-tuberculosis-after-antiretroviral-treatment-initiation....pdf},

doi = {10.3851/IMP2525},

year  = {2013},

date = {2013-02-01},

journal = {Antiviral Therapy},

volume = {18},

number = {4},

pages = {615-22},

abstract = {BACKGROUND:



There is a high incidence of tuberculosis (TB) early after antiretroviral therapy (ART) initiation. This historical cohort study evaluated the association of efavirenz (EFV) compared to nevirapine (NVP) with post-ART TB among patients initiated on first-line ART from 2005 to 2009 in a large, urban HIV clinic in Uganda.

METHODS:



Hazard ratios (HR) for developing TB were computed using multivariable Cox proportional hazards models with inverse weighting of the probability of being prescribed NVP or EFV (calculated by a multivariable logistic regression model), stratifying by baseline CD4+ T-cell count. Adjustment for time-updated CD4+ T-cell count, restriction of the analysis to patients remaining in follow-up and a TB-free survival analysis were performed as sensitivity analyses.

RESULTS:



ART was initiated in 5,797 patients; 66% were women with a mean age of 37 years (SD 9) and a median baseline CD4+ T-cell count of 117 cells/mm3 (IQR 43-182). Overall, 60% (n = 3,484) were initiated on NVP and 40% (n = 2,313) on EFV. In the first 2 years of ART, 377 patients developed TB. The use of EFV compared to NVP was independently associated with higher TB incidence in patients with a baseline CD4+ T-cell count < 100 cells/mm3 (HR 2.05 [95% CI 1.29, 3.27]; P = 0.003), but not at higher CD4+ T-cell counts (HR 0.71 [95% CI 0.39, 1.31]; P = 0.428). These estimates were robust to all sensitivity analyses.

CONCLUSIONS:



There was a higher incidence of TB in patients with baseline CD4+ T-cell counts < 100 cells/mm3 initiated on EFV compared to those initiated on NVP. Further research in a trial setting or a larger multisite observational cohort is needed to confirm these findings.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Nakasujja2013,

title = {Randomized trial of minocycline in the treatment of HIV-associated cognitive impairment},

author = {Noeline Nakasujja and Sachiko Miyahara and Scott Evans and Anthony Lee and Seggane Musisi and Elly Katabira and Kevin Robertson and Allan Ronald and David B. Clifford and Ned Sacktor},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Randomized-trial-of-minocycline....pdf},

doi = {10.1212/WNL.0b013e31827b9121},

year  = {2013},

date = {2013-01-24},

journal = {Nuerology},

volume = {80},

number = {2},

pages = {196-202},

abstract = {OBJECTIVE:



To evaluate the efficacy and safety of minocycline in the management of HIV-associated cognitive impairment.

METHODS:



We enrolled HIV-positive participants with a CD4 count of 250 to 500 cells/μL in a randomized, double-blind, placebo-controlled study. They received 100 mg of minocycline or matching placebo orally every 12 hours for 24 weeks. Cognitive function was measured using the Uganda neuropsychological test battery summary measure (U NP Sum) and the Memorial Sloan-Kettering (MSK) scale. The primary efficacy measure was the 24-week change in an average of 9 standardized U NP Sum z scores.

RESULTS:



Seventy-three participants were enrolled. Of these, 90% were female, 49% were between the ages 30 and 39 years, and 74% had 6 or more years of education. One participant had MSK score of stage 1 (i.e., mild HIV dementia), and 72 participants had MSK stage 0.5 (i.e., equivocal or subclinical dementia) at the baseline evaluation. The minocycline effect on the 24-week change of the U NP Sum compared with placebo was 0.03 (95% confidence interval -0.51, 0.46; p = 0.37).

CONCLUSION:



Minocycline was safe and well tolerated in HIV-positive individuals. However, it did not improve HIV-associated cognitive impairment.

CLASSIFICATION OF EVIDENCE:



This study provides Class II evidence that 100 mg of minocycline given orally every 12 hours for 24 weeks had no significant effect compared with placebo in the improvement of cognitive function in antiretroviral therapy-naive, HIV-positive patients},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Wagner2013,

title = {The Impact of ART on the Economic Outcomes of People Living with HIV/AIDS},

author = {Annet Nannungi Glenn Wagner and Bonnie Ghosh-Dastidar

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/ART2013-362972.pdf},

doi = { 10.1155/2013/362972},

year  = {2013},

date = {2013-01-09},

journal = {AIDS Research and Treatment},

abstract = {BACKGROUND:



Clinical benefits of ART are well documented, but less is known about its effects on economic outcomes such as work status and income in sub-Saharan Africa.

METHODS:



Data were examined from 482 adult clients entering HIV care (257 starting ART; 225 not yet eligible for ART) in Kampala, Uganda. Self-reported data on work status and income were assessed at baseline, months 6 and 12. Multivariate analysis examined the effects of ART over time, controlling for change in physical health functioning and baseline covariates.

RESULTS:



Fewer ART patients worked at baseline compared to non-ART patients (25.5% versus 34.2%); 48.8% of those not working at baseline were now working at month 6, and 50% at month 12, with similar improvement in both the ART and non-ART groups. However, multivariate analysis revealed that the ART group experienced greater improvement over time. Average weekly income did not differ between the groups at baseline nor change significantly over time, among those who were working; being male gender and having any secondary education were predictive of higher income.

CONCLUSIONS:



ART was associated with greater improvement in work status, even after controlling for change in physical health functioning, suggesting other factors associated with ART may influence work.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kamya2013b,

title = {The effect of HIV on malaria in the context of the current standard of care for HIV-infected populations in Africa},

author = {Moses R Kamya and Pauline Byakika-Kibwika and Anne F Gasasira and Diane Havlir and Philip J. Rosenthal and Grant Dorsey and Jane Achan

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/The-effect-of-HIV-on-malaria-in-the-context-of-the-current....pdf},

year  = {2013},

date = {2013-01-03},

journal = {Future Virology},

volume = {7},

number = {7},

pages = {699-708.},

abstract = {HIV infection affects the clinical pattern of malaria. There is emerging evidence to suggest that previously documented interactions may be modified by recently scaled-up HIV and malaria interventions. Prophylaxis with trimethoprim-sulfamethoxazole (TS) in combination with use of insecticide-treated nets can markedly decrease the incidence of malaria in HIV-infected pregnant and nonpregnant adults and children even in the setting of antifolate resistance-conferring mutations that are currently common in Africa. Nonetheless, additional interventions are needed to protect HIV-infected people that reside in high-malaria-transmission areas. Artemether-lumefantrine and dihydroartemisinin-piperaquine are highly efficacious and safe for the treatment of uncomplicated malaria in HIV-infected persons. Coadministration of antiretroviral and antimalarial drugs creates the potential for pharmacokinetic drug interactions that may increase (causing enhancement of malaria treatment efficacy and post-treatment prophylaxis and/or unanticipated toxicity) or reduce (creating risk for treatment failure) antimalarial drug exposure. Further studies are needed to elucidate potentially important pharmacokinetic interactions between commonly used antimalarials, antiretrovirals and TS and their clinical implications. Data on the benefits of long-term TS prophylaxis among HIV patients on antiretroviral therapy who have achieved immune-reconstitution are limited. Studies to address these questions are ongoing or planned, and the results should provide the evidence base required to guide the prevention and treatment of malaria in HIV-infected patients},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Reynolds2012,

title = {Virologic versus immunologic monitoring and the rate of accumulated genotypic resistance to first-line antiretroviral drugs in Uganda},

author = {Steven J Reynolds and Hakim Sendagire and Kevin Newell and Barbara Castelnuovo and Immaculate Nankya and Moses Kamya and Thomas C Quinn and Yukari C Manabe and Andrew Kambugu},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Virologic-Versus-immunologic....pdf},

doi = {10.1186/1471-2334-12-381},

year  = {2012},

date = {2012-12-27},

journal = {BMC Infectious Diseases},

abstract = {BACKGROUND:



Viral load monitoring (VLM) to identify individuals failing antiretroviral therapy (ART) is not widely available in resource-limited settings. We compared the genotypic resistance patterns between clients with VLM versus immunological monitoring (IM).

METHODS:



Between 2004-2008, 559 ART naïve clients were enrolled in a prospective cohort, initiated on ART, and monitored with viral load (VL) and CD4+ cell counts every 6 months (VLM group). From February 2008 through June 2009, 998 clients on ART for 36-40 months (corresponding to the follow-up time of the VLM group) at the same clinic and monitored with CD4+ cell counts every 6 months were recruited into a cross sectional study (IM group). Samples from VLM clients at 12, 24 and 36 months and IM clients at 36-40 months with VL > 2000 copies/ml underwent genotypic drug resistance testing.

RESULTS:



Baseline characteristics were similar. Virologic failure (VL > 400 copies/ml) at 12, 24 and 36 months in the VLM group were 12%, 6% and 8% respectively, and in the IM group 10% at 36-40 months. Samples from 39 VLM and 70 IM clients were genotyped. 23/39 (59%) clients in the VLM group (at 12, 24 or 36 months) compared to 63/70 (90%) in the IM group, (P < 0.0001) had at least 1 non-nucleoside reverse transcriptase mutation. 19/39 (49%) of VLM clients had an M184V mutation compared to 61/70 (87%) in the IM group (P < 0.0001). Only 2/39 (5%) of VLM clients developed thymidine analogue mutations compared to 34/70 (49%) of IM clients (P < 0.0001).

CONCLUSIONS:



Routine VL monitoring reduced the rate of accumulated genotypic resistance to commonly used ART in Uganda.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Blount2012,

title = {Serologic Responses to Recombinant Pneumocystis jirovecii Major Surface Glycoprotein among Ugandan Patients with Respiratory Symptoms},

author = {Robert J. Blount and Leah G. Jarlsberg aqnd Kieran R. Daly and William Worodria and J. Lucian Davia and 

Adithya Cattamanchi and Kpandja Djawa and Alfred Andama and Judith Koch and Peter D. Walzer and Laurence Huang on behalf of the International HIV-Associated Opportunistic Pneumonias

(IHOP) Study},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Serologic-Responses-to-Recombinant....pdf},

doi = {10.1371/journal.pone.0051545},

year  = {2012},

date = {2012-12-21},

journal = {PloS One},

volume = {7},

number = {12},

abstract = {BACKGROUND:



Little is known about the serologic responses to Pneumocystis jirovecii major surface glycoprotein (Msg) antigen in African cohorts, or the IgM responses to Msg in HIV-positive and HIV-negative persons with respiratory symptoms.

METHODS:



We conducted a prospective study of 550 patients, both HIV-positive (n = 467) and HIV-negative (n = 83), hospitalized with cough ≥2 weeks in Kampala, Uganda, to evaluate the association between HIV status, CD4 cell count, and other clinical predictors and antibody responses to P. jirovecii. We utilized ELISA to measure the IgM and IgG serologic responses to three overlapping recombinant fragments that span the P. jirovecii major surface glycoprotein: MsgA (amino terminus), MsgB (middle portion) and MsgC1 (carboxyl terminus), and to three variations of MsgC1 (MsgC3, MsgC8 and MsgC9).

RESULTS:



HIV-positive patients demonstrated significantly lower IgM antibody responses to MsgC1, MsgC3, MsgC8 and MsgC9 compared to HIV-negative patients. We found the same pattern of low IgM antibody responses to MsgC1, MsgC3, MsgC8 and MsgC9 among HIV-positive patients with a CD4 cell count <200 cells/µl compared to those with a CD4 cell count ≥200 cells/µl. HIV-positive patients on PCP prophylaxis had significantly lower IgM responses to MsgC3 and MsgC9, and lower IgG responses to MsgA, MsgC1, MsgC3, and MsgC8. In contrast, cigarette smoking was associated with increased IgM antibody responses to MsgC1 and MsgC3 but was not associated with IgG responses. We evaluated IgM and IgG as predictors of mortality. Lower IgM responses to MsgC3 and MsgC8 were both associated with increased in-hospital mortality.

CONCLUSIONS:



HIV infection and degree of immunosuppression are associated with reduced IgM responses to Msg. In addition, low IgM responses to MsgC3 and MsgC8 are associated with increased mortality.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Wiens2012,

title = {Adherence to Antiretroviral Therapy in HIV-Positive Adolescents in Uganda Assessed by Multiple Methods},

author = {Matthew O. Wiens, Stuart MacLeod, Victor Musiime, Mark Ssenyonga, Ruth Kizza, Sabrina Bakeera-Kitaka, Richard Odoi-Adome & Francis Ssali },

doi = {https://doi.org/10.1007/BF03262238},

year  = {2012},

date = {2012-12-18},

journal = {Pediatric Drugs },

volume = {14},

pages = {331–335},

abstract = {Background



The effectiveness of traditional adherence measurements used in adolescent populations is difficult to assess. Antiretroviral (ARV) adherence research among adolescents living with HIV in resource-constrained countries is particularly challenging and little evidence is available.



Objectives



The primary objective of this study was to determine the feasibility of a large-scale, long-term study using electronic adherence monitoring in Uganda. The secondary objective was to compare accuracy of pill count (PC) and self-report (SR) adherence with electronic medication vials (eCAPs™).



Methods



Adolescents receiving ARV therapy at the Joint Clinical Research Centre in Kampala, Uganda, were recruited. ARVs were dispensed in eCAPs™ for 1 year. Person-pill-days (PPDs) [1 day where adherence was measured for one medication in one patient] were calculated and a weighted paired t-test was used to compare the levels of adherence among subjects for three different adherence measurement methods.



Results



Fifteen patients were included: 40% were female, mean age was 14 years, mean baseline CD4+ cell count was 244 cells/μL, and average treatment duration was 9 months at study entry. Overall, 4721 PPDs were observed. Some eCAPs™ required replacement during the study resulting in some data loss. Consent rate was high (94%) but was slow due to age limit cut-points.



Overall adherence for SR was 99%, PC was 97% and eCAP™ was 88% (p<0.05 for all comparisons). 93%, 67% and 23% of patients had an adherence of greater than 95% as measured by SR, PC and eCAP™ methods, respectively.



Conclusions



A large-scale adherence study in Uganda would be feasible using a more robust electronic monitoring system. Adherence measurements produced by PCs and self-reporting methods appear to overestimate adherence measured electronically.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Castelnuovo2012,

title = {Implementation of Provider-Based Electronic Medical Records and Improvement of the Quality of Data in a Large HIV Program in Sub-Saharan Africa},

author = {Barbara Castelnuovo and Agnes Kiragga and Victor Afayo and Malisa Ncube and Richard Orama and Stephen Magero and Peter Okwi and Yukari C. Manabe and Andrew Kambugu},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Implementation-of-Provider-Based-Electronic-Medical-records-and-improvrment-of....pdf},

doi = { 10.1371/journal.pone.0051631},

year  = {2012},

date = {2012-12-17},

journal = {PloS One},

volume = {7},

number = {12},

abstract = {INTRODUCTION:



Starting in June 2010 the Infectious Diseases Institute (IDI) clinic (a large urban HIV out-patient facility) switched to provider-based Electronic Medical Records (EMR) from paper EMR entered in the database by data-entry clerks. Standardized clinics forms were eliminated but providers still fill free text clinical notes in physical patients' files. The objective of this study was to compare the rate of errors in the database before and after the introduction of the provider-based EMR.

METHODS AND FINDINGS:



Data in the database pre and post provider-based EMR was compared with the information in the patients' files and classified as correct, incorrect, and missing. We calculated the proportion of incorrect, missing and total error for key variables (toxicities, opportunistic infections, reasons for treatment change and interruption). Proportions of total errors were compared using chi-square test. A survey of the users of the EMR was also conducted. We compared data from 2,382 visits (from 100 individuals) of a retrospective validation conducted in 2007 with 34,957 visits (from 10,920 individuals) of a prospective validation conducted in April-August 2011. The total proportion of errors decreased from 66.5% in 2007 to 2.1% in 2011 for opportunistic infections, from 51.9% to 3.5% for ART toxicity, from 82.8% to 12.5% for reasons for ART interruption and from 94.1% to 0.9% for reasons for ART switch (all P<0.0001). The survey showed that 83% of the providers agreed that provider-based EMR led to improvement of clinical care, 80% reported improved access to patients' records, and 80% appreciated the automation of providers' tasks.

CONCLUSIONS:



The introduction of provider-based EMR improved the quality of data collected with a significant reduction in missing and incorrect information. The majority of providers and clients expressed satisfaction with the new system. We recommend the use of provider-based EMR in large HIV programs in Sub-Saharan Africa.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tumwesigye2012,

title = {Alcohol consumption and risky sexual behaviour in the fishing communities: evidence from two fish landing sites on Lake Victoria in Uganda},

author = {Nazarius M Tumwesigye and Lynn Atuyambe and Rhoda K Wanyenze and Simon PS Kibira and Qing Li and Fred Wabwire-Mangen and Glenn Wagner

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Alcohol-comsumption-and-risky-behaviorin-the-fishing-communities.pdf},

doi = {10.1186/1471-2458-12-1069},

year  = {2012},

date = {2012-12-11},

journal = {BMC Public Health},

volume = {12},

abstract = {BACKGROUND:



The fishing communities are among population groups that are most at risk of HIV infection, with some studies putting the HIV prevalence at 5 to 10 times higher than in the general population. Alcohol consumption has been identified as one of the major drivers of the sexual risk behaviour in the fishing communities. This paper investigates the relationship between alcohol consumption patterns and risky behaviour in two fishing communities on Lake Victoria.

METHODS:



Face-to-face interviews were conducted among 303 men and 172 women at the fish landing sites; categorised into fishermen, traders of fish or fish products and other merchandise, and service providers such as casual labourers and waitresses in bars and hotels, including 12 female sexual workers. Stratified random sampling methodology was used to select study units. Multivariable analysis was conducted to assess independent relationship between alcohol consumption and sexual risky behaviour. Measures of alcohol consumption included the alcohol use disorder test score (AUDIT), having gotten drunk in previous 30 days, drinking at least 2 times a week while measures for risky behaviour included engaging in transactional sex, inconsistent condom use, having sex with non-regular partner and having multiple sexual partners.

RESULTS:



The level of harmful use of alcohol in the two fishing communities was quite high as 62% of the male and 52% of the female drinkers had got drunk in previous 30 days. The level of risky sexual behaviour was equally high as 63% of the men and 59% of the women had unprotected sex at last sexual event. Of the 3 occupations fishermen had the highest levels of harmful use of alcohol and risky sexual behaviour followed by service providers judging from values of most indicators. The kind of alcohol consumption variables correlated with risky sexual behaviour variables, varied by occupation. Frequent alcohol consumption, higher AUDIT score, having got drunk, longer drinking hours and drinking any day of the week were strongly correlated with engaging in transactional sex among fishermen but fewer of the factors exhibited the same correlation among traders and service providers. Fishermen who drank 2 or more times a week were 7.9 times more likely to have had transactional sex (95% CI: 2.05-30.24) compared to those who never drank alcohol. A similar pattern was observed for traders and service providers at the landing sites. Inconsistent condom use or none use of condoms was not significantly correlated with any of the alcohol consumption indicator variables in multivariate analysis except for day of drinking among men.

CONCLUSION:



Alcohol consumption is strongly correlated with having multiple sexual partners, sex with non-regular partner and engagement in transactional sex but not with consistent condom use at fish landing sites. However, the pattern and strength of this correlation differs by occupation. HIV risk reduction programs targeting the fishing communities should address alcohol consumption, particularly alcohol consumption before sexual contact. Different occupations may need different interventions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Butler2012,

title = {Long Term 5-Year Survival of Persons with Cryptococcal Meningitis or Asymptomatic Subclinical Antigenemia in Uganda},

author = {Elissa K. Butler and David R. Boulware and Paul R. Bohjanen and David B. Meya

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Long-Term-5-Year-Survival-of-Persons-with-Cryptococcal-menegitis....pdf},

doi = {10.1371/journal.pone.0051291},

year  = {2012},

date = {2012-12-10},

journal = {PloS One},

volume = {7},

number = {12},

abstract = {Data presented previously as an abstract at the 2011 CUGH Global Health Conference in Montreal, Canada on 15 Nov 2011. The long-term survival of HIV-infected persons with symptomatic cryptococcal meningitis and asymptomatic, subclinical cryptococcal antigenemia (CRAG+) is unknown. We prospectively enrolled 25 asymptomatic, antiretroviral therapy (ART)-naïve CRAG+ Ugandans with CD4<100 cells/mcL who received pre-emptive fluconazole treatment (CRAG+ cohort) and 189 ART-naïve Ugandans with symptomatic cryptococcal meningitis treated with amphotericin (CM cohort). The 10-week survival was 84% (95%CI: 70-98%) in the CRAG+ cohort and 57% (95%CI: 50%-64%) in the CM cohort. The CRAG+ cohort had improved five-year survival of 76% (95%CI: 59%-93%) compared to 42% (95%CI: 35%-50%) in the CM cohort (P = 0.001). The two cohorts had similar immunosuppression pre-ART with median CD4 counts of 15 vs. 21 CD4/mcL in the CRAG+ and CM cohorts, respectively (P = 0.45). Despite substantial early mortality, subsequent 5-year survival of persons surviving 6-months was excellent (>88%), demonstrating that long term survival is possible in resource-limited settings. Pre-ART CRAG screening with preemptive fluconazole treatment and improved CM treatment(s) are needed to reduce AIDS-attributable mortality due to cryptococcosis which remains 20-25% in sub-Saharan Africa},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Auerbach2012,

title = {Traditional Herbal Medicine Use Associated with Liver Fibrosis in Rural Rakai, Uganda},

author = {Brandon J. Auerbach and Steven J. Reynolds and Mohammed Lamorde and Concepta Merry and Collins Kukunda-Byobona and Ponsiano Ocama and Aggrey S. Semeere and Anthony Ndyanabo and Iga Boaz and Valerian Kiggundu and Fred Nalugoda and Ron H. Gray and Maria J. Wawer and David L. Thomas and Gregory D. Kirk and Thomas C. Quinn and Lara Stabinsk},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Traditional-Herbal-Medicine-Use-Associated-with-Liver-fibrosis-in-rural-Rakai-Uganda.pdf},

doi = {10.1371/journal.pone.0041737},

year  = {2012},

date = {2012-11-27},

journal = {PloS One},

volume = {7},

number = {11},

abstract = {BACKGROUND:



Traditional herbal medicines are commonly used in sub-Saharan Africa and some herbs are known to be hepatotoxic. However little is known about the effect of herbal medicines on liver disease in sub-Saharan Africa.

METHODS:



500 HIV-infected participants in a rural HIV care program in Rakai, Uganda, were frequency matched to 500 HIV-uninfected participants. Participants were asked about traditional herbal medicine use and assessed for other potential risk factors for liver disease. All participants underwent transient elastography (FibroScan®) to quantify liver fibrosis. The association between herb use and significant liver fibrosis was measured with adjusted prevalence risk ratios (adjPRR) and 95% confidence intervals (CI) using modified Poisson multivariable logistic regression.

RESULTS:



19 unique herbs from 13 plant families were used by 42/1000 of all participants, including 9/500 HIV-infected participants. The three most-used plant families were Asteraceae, Fabaceae, and Lamiaceae. Among all participants, use of any herb (adjPRR = 2.2, 95% CI 1.3-3.5, p = 0.002), herbs from the Asteraceae family (adjPRR = 5.0, 95% CI 2.9-8.7, p<0.001), and herbs from the Lamiaceae family (adjPRR = 3.4, 95% CI 1.2-9.2, p = 0.017) were associated with significant liver fibrosis. Among HIV infected participants, use of any herb (adjPRR = 2.3, 95% CI 1.0-5.0, p = 0.044) and use of herbs from the Asteraceae family (adjPRR = 5.0, 95% CI 1.7-14.7, p = 0.004) were associated with increased liver fibrosis.

CONCLUSIONS:



Traditional herbal medicine use was independently associated with a substantial increase in significant liver fibrosis in both HIV-infected and HIV-uninfected study participants. Pharmacokinetic and prospective clinical studies are needed to inform herb safety recommendations in sub-Saharan Africa. Counseling about herb use should be part of routine health counseling and counseling of HIV-infected persons in Uganda.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Guwatudde2012,

title = {Multivitamin supplementation in HIV infected adults initiating antiretroviral therapy in Uganda: the protocol for a randomized double blinded placebo controlled efficacy trial},

author = {David Guwatudde and Amara E Ezeamama and Danstan Bagenda and Rachel Kyeyune and Fred Wabwire-Mangen and Henry Wamani and Ferdinand Mugusi and Donna Spiegelman and Molin Wang and Yukari C Manabe and

Wafaie W Fawzi

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Multivitamin-supplemention-in-HIV-infected-adults-intiating-antretroviral-therapy-in-Uganda.pdf},

doi = {10.1186/1471-2334-12-304},

year  = {2012},

date = {2012-11-15},

journal = {15},

volume = {1},

abstract = {Background:

Use of multivitamin supplements during the pre-HAART era has been found to reduce viral load,

enhance immune response, and generally improve clinical outcomes among HIV-infected adults. However, immune

reconstitution is incomplete and significant mortality and opportunistic infections occur in spite of HAART. There is

insufficient research information on whether multivitamin supplementation may be beneficial as adjunct therapy for

HIV-infected individuals taking HAART. We propose to evaluate the efficacy of a single recommended daily

allowance (RDA) of micronutrients (including vitamins B-complex, C, and E) in slowing disease progression among

HIV-infected adults receiving HAART in Uganda.

Methods/Design:

We are using a randomized, double-blind, placebo-controlled trial study design. Eligible patients

are HIV-positive adults aged at least 18 years, and are randomized to receive either a placebo; or multivitamins that

include a single RDA of the following vitamins: 1.4 mg B1, 1.4 mg B2, 1.9 mg B6, 2.6 mcg B12, 18 mg niacin, 70 mg C,

10 mg E, and 0.4 mg folic acid. Participants are followed for up to 18 months with evaluations at baseline, 6, 12 and

18 months. The study is primarily powered to examine the effects on immune reconstitution, weight gain, and

quality of life. In addition, we will examine the effects on other secondary outcomes including the risks of

development of new or recurrent disease progression event, including all-cause mortality; ARV regimen change from

first- to second-line therapy; and other adverse events as indicated by incident peripheral neuropathy, severe anemia,

or diarrhea.

Discussions:

The conduct of this trial provides an opportunity to evaluate the potential benefits of this affordable

adjunct therapy (multivitamin supplementation) among HIV-infected adults receiving HAART in a developing country

setting.

Trial registration:

Clinical Trial Registration-URL: www.clinicaltrials.gov. Unique identifier: NCT01228578

Keywords:

HIV infected adults, HAART, Micronutrient supplementation, Nutrition, Randomized double-blind placebo-

controlled trial, Trial protocol, Uganda, Sub-Saharan Africa},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Hermans2012,

title = {Unrecognised tuberculosis at antiretroviral therapy initiation is associated with lower CD4+ T cell recovery},

author = {Sabine M. Hermans and Frank van Leth and Agnes N. Kiragga and Andy I. M. Hoepelman and Joep M. A. Lange and Yukari C. Manabe},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Hermans_et_al-2012-Tropical_Medicine_26_International_Health.pdf},

doi = { 10.1111/tmi.12001},

year  = {2012},

date = {2012-11-06},

journal = {Tropical Medicine and International Health},

volume = {17},

number = {12},

pages = {1527-33},

abstract = {OBJECTIVES:



To investigate whether an unrecognised diagnosis of tuberculosis (TB) at the start of antiretroviral therapy (ART) influences subsequent CD4+ T cell (CD4) count recovery in an urban HIV clinic in Uganda.

METHODS:



In a retrospective cohort study, a multivariable polynomial mixed effects model was used to estimate CD4 recovery in the first 96 weeks of ART in two groups of patients: prevalent TB (started ART while on TB treatment), unrecognised TB (developed TB within 6 months after start ART).

RESULTS:



Included were 511 patients with a median baseline CD4 count of 57 cells/mm(3) (interquartile range: 22-130), of whom 368 (72%) had prevalent TB and 143 (28%) had unrecognised TB. Compared with prevalent TB, unrecognised TB was associated with lower CD4 count recovery at 96 weeks: -22.3 cells/mm(3) (95% confidence interval -43.2 to -1.5, P = 0.036). These estimates were adjusted for gender, age, baseline CD4 count and the use of zidovudine-based regimen.

CONCLUSIONS:



Unrecognised TB at the time of ART initiation resulted in impaired CD4 recovery compared with TB treated before ART initiation. More vigilant screening with more sensitive and rapid TB diagnostics prior to ART initiation is needed to decrease the risk of ART-associated TB and sub-optimal immune reconstitution.},

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