@article{Bahr2011,

title = {Standardized Electrolyte Supplementation and Fluid Management Improves Survival During Amphotericin Therapy for Cryptococcal Meningitis in Resource-Limited Settings},

author = {Nathan C. Bahr and Melissa A. Rolfes and Abdu Musubire and Henry Nabeta and Darlisha A. Williams and Joshua Rhein and Andrew Kambugu and David B. Meya and David R. Boulware},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Standardized-Electrolyte-Supplementation-and.pdf},

doi = { 10.1093/ofid/ofu070},

year  = {2011},

date = {2011-08-25},

journal = {Open Forum Infectious Diseases},

volume = {1},

number = {2},

abstract = {Background

.

Amphotericin B is the preferred treatment for cryptococcal meningitis, but it has cumulative severe

side effects, including nephrotoxicity, hypokalemia, and hypomagnesemia. Amphotericin-induced severe hypokale-

mia may predispose the patient to cardiac arrhythmias and death, and there is very little data available regarding

these toxicities in resource-limited settings. We hypothesized that standardized electrolyte management during

amphotericin therapy is essential to minimize toxicity and optimize survival in sub-Saharan Africa.

Methods

.

Human immunode

fi

ciency virus-infected, antiretroviral therapy naive adults with cryptococcal men-

ingitis were prospectively enrolled at Mulago Hospital in Kampala, Uganda in 3 sequential cohorts with amphoter-

icin B deoxycholate induction treatment. Intravenous

fl

uid use was intermittent in 2001

–

2002, and universal in

2006

–

2012. In 2001

–

2009, serum potassium (K

+

) was monitored on days 1, 7, and 14 of treatment with replacement

(K

+

,Mg

2+

) per clinician discretion. In 2011

–

2012, K

+

was measured on days 1, 5, and approximately every 48 hours

thereafter with universal electrolyte (K

+

,Mg

2+

) supplementation and standardized replacement. Clinical outcomes

were retrospectively compared between

fl

uid and electrolyte management strategies.

Results

.

With limited intravenous

fl

uids, the 14-day survival was 49% in 2001

–

2002. With universal intravenous

fl

uids, the 30-day survival improved to 62% in 2006

–

2010 (

P

= .003). In 2011

–

2012, with universal supplementation

of

fl

uids and electrolytes, 30-day cumulative survival improved to 78% (

P

= .021 vs 2006

–

2010 cohort). The cumu-

lative incidence of severe hypokalemia (<2.5 mEq/L) decreased from 38% in 2010 to 8.5% in 2011

–

2012 with uni-

versal supplementation (

P

< .001).

Conclusions

.

Improved survival was seen in a resource-limited setting with proactive

fl

uid and electrolyte man-

agement (K

+

,Mg

2+

), as part of comprehensive amphotericin-based cryptococcal therapy},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Abouyannsis2011,

title = {Development and validation of systems for rational use of viral load testing in adults receiving first-line antiretroviral treatment in sub-Saharan Africa},

author = {Michael Abouyannsis and Joris Menten and Agnes Kiragga and Lutgarde Lynen and Gavin Robertson and Barbara Castelnuovo and Yukari C. Manabe and Steven J. Reymonds and Lesley Roberts},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Development-and-validation-of-systems....pdf},

doi = {10.1097/QAD.0b013e328349a414},

year  = {2011},

date = {2011-08-25},

journal = {AIDS (London, England)},

volume = {25},

number = {113},

pages = {1627-35},

abstract = {BACKGROUND:



World Health Organization (WHO) immunological and clinical criteria for monitoring first-line antiretroviral treatment (ART) offer low accuracy for predicting viral failure. Targeting viral load assays to those at high risk has been recommended and a system to do this has been developed in Cambodia. Systems for use in sub-Saharan African populations were evaluated.

METHODS:



A new Ugandan-based scoring system for targeting viral load assays was developed from data from the first 4 years of a Ugandan cohort (N = 559) receiving first-line ART. The accuracy of this, the Cambodian system and the WHO criteria to predict viral failure, through targeting viral load assays, were compared in a separate population of 496 Ugandans.

RESULTS:



The new Ugandan scoring system included CD4 cell count, mean cell volume, adherence, and HIV-associated clinical events as predictors of viral failure. In the validation population, the Ugandan system undertook viral load assays in 61 (12.3%) cases offering 20.5% sensitivity and 100% positive predictive value (PPV) to predict viral failure. The Cambodian system undertook viral load assays in 33 (6.7%) cases producing 23.1% sensitivity and 90.0% PPV. WHO criteria recommended viral load assays in 72 (14.5%) cases offering 30.8% sensitivity and 100% PPV.

CONCLUSION:



Locally developed algorithms based on clinical and immunological criteria may offer little additional accuracy over WHO criteria for targeting viral load assays. When possible, confirming viral load before switching therapy is recommended. Scoring systems are more flexible than WHO criteria in allowing ART providers to choose the proportion of the population that undergo targeted viral load testing.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{O’Reilly2011,

title = {Risk factors and seroprevalence of hepatitis C among patients hospitalized at Mulago hospital, Uganda},

author = {J.I. O’Reilly and P.Ocama and C.K.Opio and A. Alfred and E.Paintsil and E. Seremba and A.N. Sofair

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/RiskFactorsandSeroprevalenceofHepatitisCamong-PatientsHospitalizedatMulagoHospitalUganda.pdf

},

doi = {10.1155/2011/598341},

year  = {2011},

date = {2011-08-09},

journal = {Journal of Tropical Medicine},

abstract = {The emergence of hepatitis C virus (HCV) and its associated sequelae in Africa is a cause for significant concern. Human immunodeficiency virus (HIV) positive patients are at an increased risk of contracting HCV infection due to similar risk factors and modes of transmission. We investigated the seroprevalence of hepatitis C in hospitalized HIV-positive and HIV-negative patients in Mulago Hospital, an academic hospital in Uganda. Blood samples were first tested for HCV antibodies, and positive tests were confirmed with HCV RNA PCR. We enrolled five hundred patients, half HIV-positive and half HIV negative. Overall, 13/500 patients (2.6%) tested positive for HCV antibodies. There was no difference in HCV antibody detection among HIV-positive and HIV-negative patients. Out of all risk factors examined, only an age greater than 50 years was associated with HCV infection. Traditional risk factors for concurrent HIV and HCV transmission, such as intravenous drug use, were exceedingly rare in Uganda. Only 3 of 13 patients with detectable HCV antibodies were confirmed by HCV RNA detection. This result concurs with recent studies noting poor performance of HCV antibody testing when using African sera. These tests should be validated in the local population before implementation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bakeera-Kitaka2011,

title = {Tuberculosis in human immunodefi  ciency virus infected  Ugandan children starting on antiretroviral therapy},

author = {S. Bakeera-Kitaka and A. Conesa-Botella and A. Dhabangi and A. Maganda and A. Kekitiinwa and R. Colebunders and D. R. Boulware

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Tuberculosis-in-human-immunodeficiency-virus-infected-Ugandan-children-starting-on-antiretoviral.pdf},

doi = {10.5588/ijtld.10.0538},

year  = {2011},

date = {2011-08-01},

journal = {2011-08-01},

volume = {15},

number = {8},

abstract = {OBJECTIVE: To identify the incidence of tuberculosis (TB) in human immunodeficiency virus (HIV) infected children in a resource-limited setting before and after initiation of antiretroviral therapy (ART), and to assess the impact of TB screening by tuberculin skin testing and clinical history.



METHODS: A retrospective cohort study of 1806 HIV-infected children and adolescents (age <18 years) initiating ART from 2003 to 1 July 2006 in Kampala, Uganda. A TB screening program was instituted clinic-wide in January 2006.



RESULTS: Of 311 (17.2%) HIV-infected children, 171 had been diagnosed with TB before and 140 after ART initiation. During the first 100 days of ART, risk of a new TB diagnosis was 2.7-fold higher compared to the pre-ART period (RR 2.7, 95%CI 2.1–3.5, P < 0.001). After 100 days of ART, the TB incidence rate decreased to below pre-ART levels (RR 0.41, 95%CI 0.30–0.54, P = 0.002). After TB screening was instituted in 2006, the proportion of new TB cases diagnosed after starting ART decreased by 70% (95%CI 51–82, P < 0.001), abating the early excess risk.



CONCLUSIONS: TB is common among African children and adolescents initiating ART in sub-Saharan Africa. More aggressive screening for active TB before starting ART can diminish the rate of TB during immune reconstitution. Future studies are needed to determine optimal screening practices for HIV-infected children. },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{P2011,

title = {Hepatitis B virus and HIV infection among patients with primary hepatocellular carcinoma in Kampala, Uganda},

author = {Ocama P and Opio KC and Kagimu M and Seremba E and Wabinga H and Colebunders R},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Hepatitis-B-virus-and-HIV-infection-among-patients-with-primary....pdf},

year  = {2011},

date = {2011-08-01},

journal = {African health science},

abstract = {BACKGROUND:



Hepatitis B virus (HBV) is the commonest cause of primary hepatocellular (PHC) carcinoma worldwide. Co-infection with the HIV leads to more rapid progression of liver disease.

OBJECTIVES:



We described prevalence of HBV and HIV among patients with PHC admitted to Mulago Hospital, Kampala, Uganda.

METHODS:



We assessed all patients admitted to the gastrointestinal service of Mulago hospital with a diagnosis of PHC for HBV and HIV infection.

RESULTS:



From March to June 2008, we recruited 15 patients. Nine (60%) were male; the overall median age was 32 years (IQR 15 -67), with median ages for male and female 33 and 36 years respectively. Alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and AFP were all elevated with median values of 57.5 IU/L, 222 IU/L, 392 IU/L and 362 ng/ml respectively (IQR 14-145, 49-393, 165-1294 and 7-480). Eight (53%) patients were from North and Northeastern Uganda. The HBsAg was reactive in 13(87%) patients and HIV in 3(20%), all of whom were also co-infected with HBV.

CONCLUSION:



There is high prevalence of HBV and HBV/HIV co-infection among patients with PHC in Uganda with high mortality. Reduction in incidence and mortality due to PHC in Uganda will require urgent large scale HBV vaccination},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Stabinski2011b,

title = {High Prevalence of Liver Fibrosis Associated with HIV Infection: A Cross-Sectional Study in Rural Rakai, Uganda},

author = {Lara Stabinski and Steven J. Reynolds and Ponsiano Ocama and Oliver Laeyendecker and Iga Boaz and Anthony Ndyanabo and Valerian Kiggundu and Ron H. Gray and Maria Wawer and ChloeThio and David L. Thomas and Thomas C. Quinn and 

Gregory D. Kirk

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/High-Prevalence-of-Liver-Fibrosis-Associated-with-HIV-Infection.pdf},

doi = {10.3851/IMP1783.},

year  = {2011},

date = {2011-08-01},

journal = {Antiviral Therapy},

volume = {16},

number = {3},

pages = {405-11},

abstract = {BACKGROUND:



Liver disease is a leading cause of mortality among HIV-infected persons in the United States and Europe. However, data regarding the effects of HIV and antiretroviral therapy (ART) on liver disease in Africa are sparse.

METHODS:



A total of 500 HIV-infected participants in an HIV care programme in rural Rakai, Uganda were frequency-matched by age, gender and site to 500 HIV-uninfected participants in a population cohort. All participants underwent transient elastography (FibroScan(®)) to quantify liver stiffness measurements (LSM) and identify participants with significant liver fibrosis, defined as LSM≥9.3 kPa (≈ Metavir F≥2). Risk factors for liver fibrosis were identified by estimating adjusted prevalence risk ratios (adjPRR) and 95% CI using modified Poisson multivariate regression.

RESULTS:



The prevalence of hepatitis B coinfection in the study population was 5%. The prevalence of significant fibrosis was 17% among HIV-infected and 11% in HIV-uninfected participants (P=0.008). HIV infection was associated with a 50% increase in liver fibrosis (adjPRR 1.5, 95% CI 1.1-2.1; P=0.010). Fibrosis was also associated with male gender (adjPRR 1.4, 95% CI 1.0-1.9; P=0.045), herbal medicine use (adjPRR 2.0, 95% CI 1.2-3.3; P=0.005), heavy alcohol consumption (adjPRR 2.3, 95% CI 1.3-3.9; P=0.005), occupational fishing (adjPRR 2.5, 95% CI 1.2-5.3; P=0.019) and chronic HBV infection (adjPRR 1.7, 95% CI 1.0-3.1; P=0.058). Among HIV-infected participants, ART reduced fibrosis risk (adjPRR 0.6, 95% CI 0.4-1.0; P=0.030).

CONCLUSIONS:



The burden of liver fibrosis among HIV-infected rural Ugandans is high. These data suggest that liver disease may represent a significant cause of HIV-related morbidity and mortality in Africa.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Wiersma2011b,

title = {Treatment of chronic hepatitis B virus infection in resource-constrained settings: expert panel consensus},

author = {Wiersma, ST and McMahon, B and Pawlotsky, JM and Thio, CL and Thursz, M and Lim, SG and Ocama, P and Esmat, G and Maimuna, M and Bell, D and Vitoria, M and Eramova, I and Lavanchy, D and Dusheiko, G and World Health Organization Department of Immunization, Vaccines and Biologicals.},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Treatment-of-chronic-hepatitis-B-virus-infection-in-resource-constrained-settings-expert-panel-consensus.pdf},

doi = {10.1111/j.1478-3231.2010.02373.x.},

year  = {2011},

date = {2011-07-07},

journal = {Liver International },

volume = {31},

number = {6},

pages = {755-61},

abstract = {Most of the estimated 350 million people with chronic hepatitis B virus (HBV) infection live in resource‐constrained settings. Up to 25% of those persons will die prematurely of hepatocellular carcinoma (HCC) or cirrhosis. Universal hepatitis B immunization programmes that target infants will have an impact on HBV‐related deaths several decades after their introduction. Antiviral agents active against HBV are available; treatment of HBV infection in those who need it has been shown to reduce the risk of HCC and death. It is estimated that 20–30% of persons with HBV infection could benefit from treatment. However, drugs active against HBV are not widely available or utilized in persons infected with HBV. Currently recommended antiviral agents used for treatment of human immunodeficiency virus (HIV) infection do not adequately suppress HBV, which is of great concern for the estimated 10% of the HIV‐infected persons in Africa who are co‐infected with HBV. Progressive liver disease has been shown to occur in co‐infected persons whose HBV infection is not suppressed. In view of these concerns, an informal World Health Organization consultation of experts concluded that: chronic HBV is a major public health problem in emerging nations; all HIV‐infected persons should be screened for HBV infection; HIV/HBV co‐infected persons should be treated with therapies active against both viruses and that reduce the risk of resistance; standards for the management of chronic HBV infection should be adapted to resource‐constrained settings. In addition, a research agendum was developed focusing on issues related to prevention and treatment of chronic HBV in resource‐constrained settings.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Yoo2011,

title = {Clinical significance of normal chest radiographs among HIV- seropositive patients with suspected tuberculosis in Uganda},

author = {Samuel D. Yoo and Adithya Cattamanchi and Saskia den Boon and William Worodria and Harriet Kisembo and Laurence Huang and J. Lucian Davis},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Clinical-significance-of-normal-chest-radiographs-among-HIV-seprositive-patients....pdf},

doi = {10.1111/j.1440-1843.2011.01981.x},

year  = {2011},

date = {2011-07-01},

journal = {Respirology},

volume = {16},

number = {5},

pages = {836-41},

abstract = {BACKGROUND AND OBJECTIVE:



The frequency, aetiologies and outcomes of normal chest radiographs (CXRs) among HIV-seropositive patients with suspected pulmonary tuberculosis (TB) have been infrequently described.

METHODS:



Consecutive HIV-seropositive adults hospitalized for cough of ≥2 weeks duration at Mulago Hospital (Kampala, Uganda), between September 2007 and July 2008, were enrolled. Baseline CXRs were obtained on admission. Patients with sputum smears that were negative for acid-fast bacilli (AFB) were referred for bronchoscopy with bronchoalveolar lavage (BAL). BAL fluid was examined for mycobacteria, Pneumocystis jirovecii and other fungi. Patients were followed for 2 months after enrolment.

RESULTS:



Of the 334 patients, 54 (16%) had normal CXRs. These patients were younger (median age 30 vs 34 years, P = 0.002), had lower counts of CD4+ T lymphocytes (median 13 vs 57 cells/µL, P < 0.001), and were less likely to be smear positive for AFB (17% vs 39%, P = 0.002) than those with abnormal CXRs. Pulmonary TB was the most frequent diagnosis (44%) among those with normal CXRs, followed by unknown diagnoses, pulmonary aspergillosis and pulmonary cryptococcosis. The frequency of normal CXRs was 12% among pulmonary TB patients. There was a trend towards increased 2-month mortality among patients with normal CXRs compared to those with abnormal CXRs (40% vs 29%, P = 0.15).

CONCLUSIONS:



Normal CXR findings were common among HIV-seropositive patients with suspected TB, especially those who were young, those with low CD4+ T cell counts and those with sputum smears that were negative for AFB. Mortality was high among those with normal CXRs. Normal CXR findings should not preclude further diagnostic evaluation in this population.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Gesesew2011,

title = {Predictors of mortality in a cohort of tuberculosis/HIV co-infected patients in Southwest Ethiopia},

author = {Hailay Gesesew and Birtukan Tsehayneh and Desalegn Massa and Amanuel Gebremedhin and Hafte Kahsay and Lillian Mwanri

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Predictors-of-mortality-in-a-cohort-of-tuberculosis....pdf},

doi = {10.1186/s40249-016-0202-1},

year  = {2011},

date = {2011-06-13},

journal = {BMC Infectious Diseases and Poverty},

abstract = {Background:

Tuberculosis/HIV co-infection is a bidirectional and synergistic combination of two very important

pathogens in public health. To date, there have been limited clinical data regarding mortality rates among

tuberculosis/HIV co-infected patients and the impact of a

ntiretroviral therapy on clinical outcomes in Ethiopia.

This study assessed the incidence and predictors of tuberculosis/HIV co-infection mortality in Southwest

Ethiopia.

Methods:

A retrospective cohort study collated tuberculosi

s/HIV data from Jimma University Teaching Hospital

for the period of September 2010 and August 2012. The data analysis used proportional hazards cox

regression model at

P

value of

≤

0.05 in the final model.

Results:

Fifty-five (20.2 %) patients died during the stud

y period and 272 study participants contributed 3

082.7 person month observations. Facto

rs including: being aged between 35

–

44 years (AHR = 2.9; 95 %

CI

:

1.08

–

7.6), being a female sex worker (AHR = 9.1; 95 %

CI

:2.7

–

30.7), being bed ridden as functional status

(AHR = 3.2; 95 %

CI

:1.2

–

8.7), and being at World Health Organization HIV disease stages 2 (AHR = 0.2;

95 %

CI

:0.06

–

0.5),3(AHR=0.3;95%

CI

:0.1

–

0.8) and 4(AHR = 0.2; 95 %

CI

:0.04

–

0.55) were significant

predictors of mortality for tuberc

ulosis/HIV co-infected patients.

Conclusions:

Contrary to our expectations, the World Health Organization (WHO) HIV disease stage 1 was

found to be a significant predictor of mortality. Hi

gher mortality rates were observed in WHO disease

stage 1 patients compared to pa

tients in stages 2, 3 and 4. The current study also confirmed and

reaffirmed known significant predictors of the mortality for tuberculosis/HIV co-infected patients including

being 35

–

44 years, being a female sex worker and being bed

ridden functional status. The occurrence of

high death rate among tuberculosis/HIV co-infecte

d cases needs actions to reduce this poor outcome.

Keywords:

Tuberculosis, HIV, Co-infection, Mortalit

y, Survival, Retrospective cohort, Ethiopia},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Huang2011,

title = {HIV-Associated Pneumocystis Pneumonia},

author = {Laurence Huang and Adithya Cattamanchi and J. Lucian Davis and Saskia den Boon and Joseph Kovacs and Steven Meshnick and Robert F. Miller and Peter D. Walzer and William Worodria and Henry Masur},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/HIV-Associated.pdf},

year  = {2011},

date = {2011-06-01},

volume = {8},

number = {3},

pages = {294-300},

abstract = {During the past 30 years, major advances have been made in our

understanding of HIV/AIDS and

Pneumocystis

pneumonia (PCP), but

significant gaps remain.

Pneumocystis

is classified as a fungus and is

host-species specific, but an understanding of its reservoir, mode of

transmission, and pathogenesis is incomplete. PCP remains a fre-

quent AIDS-defining diagnosis and is a frequent opportunistic

pneumonia in the United States and in Europe, but comparable

epidemiologic data from other areas of the world that are burdened

with HIV/AIDS are limited.

Pneumocystis

cannot be cultured, and

bronchoscopy with bronchoalveolar lavage is the gold standard

procedure to diagnose PCP, but noninvasive diagnostic tests and

biomarkers show promise that must be validated. Trimethoprim-

sulfamethoxazole is the recommended first-line treatment and

prophylaxis regimen, but putative trimethoprim-sulfamethoxazole

drug resistance is an emerging concern. The International HIV-

associated Opportunistic Pneumonias (IHOP) study was established

to address these knowledge gaps. This review describes recent

advances in the pathogenesis, epidemiology, diagnosis, and man-

agement of HIV-associated PCP and ongoing areas of clinical and

translational research that are part of the IHOP study and the

Longitudinal Studies of HIV-associated Lung Infections and Compli-

cations (Lung HIV)},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Elbireer2011,

title = {Tuberculosis treatment default among HIV-TB co-infected patients in urban Uganda},

author = {Sawsan Elbireer and David Guwatudde and Peter Mudiope and Juliet Nabbuye-Sekandi and Yukari C. Manabe

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Elbireer_et_al-2011-Tropical_Medicine_26_International_Health.pdf},

doi = {10.1111/j.1365-3156.2011.02800.x},

year  = {2011},

date = {2011-05-18},

journal = {Tropical Medicine and International Health},

volume = {16},

number = {8},

pages = {981-7},

abstract = {OBJECTIVE:



To identify health facility and patient-specific factors associated with TB treatment default in HIV-infected patients, in a TB clinic on the campus of Mulago National Referral Hospital in Kampala, Uganda.

METHODS:



Unmatched case-control study between March and May 2009. Cases were TB patients known to have defaulted on their anti-TB treatment, defined as a TB patient who had documented discontinuation of TB medication for two or more consecutive months due to reasons other than physician's advice and who did not access care at another facility. Controls were TB patients who completed 8 months of anti-TB treatment without interruption of two or more months. Data on health facility-specific factors and individual characteristics were collected using semi-structured questionnaires.

RESULTS:



Factors associated with defaulting from TB treatment were: distance from home to clinic (OR 2.22; 1.21-4.06); long waiting time at the clinic (OR 4.18; 2.18-8.02); poor drug availability (OR 4.75; 2.29-9.84); conduct of staff (OR 2.72; 1.02-7.25); lack of opportunity to express feelings (OR 3.47; 1.67-7.21). Other patient-related factors were lack of health education, i.e. not being aware of the duration of treatment or the risk of discontinuing it (OR 5.31; 1.94-14.57); not knowing that TB can be cured (OR 44.11; 13.66-142.41); length of TB treatment (OR 10.77; 5.18-22.41), and side effects of treatment OR 5.53 (2.25-13.61).

CONCLUSIONS:



Defaulting is influenced by health systems, staff factors, and patient misinformation. Health education on TB directed at patients combined with staff sensitization could help to improve adherence to TB treatment.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Stabinski2011,

title = {Hepatitis B virus and sexual behavior in Rakai, Uganda},

author = {Lara Stabinski and Steven J. Reynolds and Ponsiano Ocama and Oliver Laeyendecker and David Serwadda and Ron H. Gray and Maria Wawer and David L. Thomas and Thomas C. Quinn and Gregory D. Kirk},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Hepatitis-B-Virus-and-Sexual-Behavior-in-Rakai-Uganda.pdfhttps://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.22051},

doi = {doi.org/10.1002/jmv.22051},

year  = {2011},

date = {2011-05-01},

journal = {Journal of Medical Virology},

volume = {83},

number = {5},

pages = {796-800},

abstract = {HIV and hepatitis B virus (HBV) co‐infection poses important public health considerations in resource‐limited settings. Demographic data and sera from adult participants of the Rakai Health Sciences Program Cohort in Southwestern Uganda were examined to determine HBV seroprevalence patterns in this area of high HIV endemicity prior to the introduction of anti‐retroviral therapy. Commercially available EIAs were used to detect prevalent HBV infection (positive for HBV core antibody [anti‐HBc] and/or positive HBV surface antigen [HBsAg]), and chronic infection (positive for HBsAg). Of 438 participants, 181 (41%) had prevalent HBV infection while 21 (5%) were infected chronically. Fourteen percent of participants were infected with HIV. Fifty three percent showed evidence of prevalent HBV infection compared to 40% among participants infected with HIV (P = 0.067). Seven percent of participants infected with HIV were HBsAg positive compared to 4% among participants not infected with HIV (P = 0.403). The prevalence of prevalent HBV infection was 55% in adults aged >50 years old, and 11% in persons under 20 years. In multivariable analysis, older age, HIV status, and serologic syphilis were significantly associated with prevalent HBV infection. Transfusion status and receipt of injections were not significantly associated with HBV infection. Contrary to expectations that HBV exposure in Uganda occurred chiefly during childhood, prevalent HBV infection was found to increase with age and was associated sexually transmitted diseases (HIV and syphilis.) Therefore vaccination against HBV, particularly susceptible adults with HIV or at risk of HIV/STDs should be a priority. J. Med. Virol. 83:796–800, 2011. © 2011 Wiley‐Liss, Inc. },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Prendergast2011,

title = {Hospitalization for severe malnutrition among HIV-infected children starting antiretroviral therapy},

author = {Andrew Prendergast and Mutsa F. Bwakura-Dangarembizi and Adrian D. Cook and Sabrina Bakeera-Kitaka and Eva Natukunda and Patricia Nahirya Ntege and Kusum J. Nathoo and Christine Karungi and Joseph Lutaakome and Adeodata Kekitiinwa and Diana M. Gibb

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Hospitalization_for_severe_malnutrition_among.8.pdf},

doi = { 10.1097/QAD.0b013e328345e56b},

year  = {2011},

date = {2011-04-24},

journal = {AIDS (London, England)},

volume = {25},

number = {7},

pages = {951-6},

abstract = {OBJECTIVE:



To describe early hospitalization for severe malnutrition in HIV-infected children initiating antiretroviral therapy (ART).

DESIGN:



Randomized trial of induction-maintenance and monitoring strategies in HIV-infected children.

SETTING:



Three tertiary hospitals in Uganda and one in Zimbabwe.

PARTICIPANTS:



1207 HIV-infected children, median age 6 years (range, 3 months to 17 years).

INTERVENTION:



Abacavir, lamivudine and nevirapine or efavirenz were given; children in induction-maintenance arms also received zidovudine to week 36. Pre-ART inpatient/outpatient nutritional rehabilitation for children with baseline severe malnutrition.

MAIN OUTCOME MEASURES:



: Hospitalization for severe malnutrition and change in CD4 cell percentage by week 12 after ART. Mortality and change in weight-for-age Z-score (WAZ) by week 24 after ART.

RESULTS:



Thirty-nine of 1207 (3.2%) children were hospitalized for severe malnutrition (20 with oedema), median 28 days [interquartile range (IQR) 14, 36] after ART for marasmus and 26 days (IQR 14, 56) after ART for kwashiorkor. Hospitalized children had lower baseline and greater 24-week rise in WAZ than nonhospitalized children (P < 0.001). Twenty-nine of 39 (74%) children admitted for severe malnutrition had underlying infections. Of 220 children with advanced disease (baseline WAZ and CD4 cell Z-scores both <-3), 7.3% [95% confidence interval (CI) 3.8, 10.7] developed kwashiorkor and 3.6% (95% CI 1.2, 6.1) developed marasmus by week 12. CD4 cell percentage rise was similar among groups (P = 0.37). Twenty-four-week mortality was 32, 20 and 1.7% among children hospitalized with marasmus, kwashiorkor and not hospitalized, respectively, (P < 0.001).

CONCLUSION:



One in nine children with advanced HIV required early hospitalization for severe malnutrition after ART, with a 15-fold increase in 6-month mortality compared with nonhospitalized children. Integration of HIV/malnutrition services and further research to determine optimal ART timing, role of supplementary feeding and antimicrobial prophylaxis are urgently required.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Yoo2011b,

title = {Clinical significance of normal chest radiographs among HIV- seropositive patients with suspected tuberculosis in Uganda},

author = {Samuel D. Yoo and Adithya Cattamanchi and Saskia den Boon and William Worodria and Harriet Kisembo and Laurence Huang and 

J. Lucian Davis},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Clinical-significance-of-normal-chest-radiographs-among-HIVseropositive-patients-with-suspected-tuberculosis-in-Uganda.pdf},

doi = {10.1111/j.1440-1843.2011.01981.x},

year  = {2011},

date = {2011-04-22},

journal = {Respirology},

volume = {16},

number = {5},

pages = {836-41},

abstract = {BACKGROUND AND OBJECTIVE:



The frequency, aetiologies and outcomes of normal chest radiographs (CXRs) among HIV-seropositive patients with suspected pulmonary tuberculosis (TB) have been infrequently described.

METHODS:



Consecutive HIV-seropositive adults hospitalized for cough of ≥2 weeks duration at Mulago Hospital (Kampala, Uganda), between September 2007 and July 2008, were enrolled. Baseline CXRs were obtained on admission. Patients with sputum smears that were negative for acid-fast bacilli (AFB) were referred for bronchoscopy with bronchoalveolar lavage (BAL). BAL fluid was examined for mycobacteria, Pneumocystis jirovecii and other fungi. Patients were followed for 2 months after enrolment.

RESULTS:



Of the 334 patients, 54 (16%) had normal CXRs. These patients were younger (median age 30 vs 34 years, P = 0.002), had lower counts of CD4+ T lymphocytes (median 13 vs 57 cells/µL, P < 0.001), and were less likely to be smear positive for AFB (17% vs 39%, P = 0.002) than those with abnormal CXRs. Pulmonary TB was the most frequent diagnosis (44%) among those with normal CXRs, followed by unknown diagnoses, pulmonary aspergillosis and pulmonary cryptococcosis. The frequency of normal CXRs was 12% among pulmonary TB patients. There was a trend towards increased 2-month mortality among patients with normal CXRs compared to those with abnormal CXRs (40% vs 29%, P = 0.15).

CONCLUSIONS:



Normal CXR findings were common among HIV-seropositive patients with suspected TB, especially those who were young, those with low CD4+ T cell counts and those with sputum smears that were negative for AFB. Mortality was high among those with normal CXRs. Normal CXR findings should not preclude further diagnostic evaluation in this population},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Castelnuovo2011,

title = {Evaluation of WHO Criteria for Viral Failure in Patients on Antiretroviral Treatment in Resource-Limited Settings},

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

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Evaluation-of-WHO-Criteria-for-Viral-Failure-in-Patients....pdf},

doi = {10.1155/2011/736938},

year  = {2011},

date = {2011-04-10},

journal = {AIDS Research and Treatment},

abstract = {Our objective was to evaluate outcomes in patients with sustained viral suppression compared to those with episodes of viremia.

METHODS:



In a prospective cohort of patients started on ART in Uganda and followed for 48 months, patients were categorized according to viral load (VL): (1) sustained-suppression: (VL ≤1,000 copies/mL) (2) VL 1,001-10,000, or (3) VL >10,000.

RESULTS:



Fifty-Three (11.2%) and 84 (17.8%) patients had a first episode of intermediate and high viremia, respectively. Patients with sustained suppression had better CD4+ T cell count increases over time compared to viremic patients (P < .001). The majority of patients with viremia achieved viral suppression when the measurement was repeated. Only 39.6% of patients with intermediate and 19.1% with high viremia eventually needed to be switched to second line (P = .008).

CONCLUSIONS:



The use of at least one repeat measurement rather than a single VL measurement could avert from 60% to 80% of unnecessary switches.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Boehme2011,

title = {Feasibility, diagnostic accuracy, and effectiveness of decentralised use of the Xpert MTB/RIF test for diagnosis of tuberculosis and multidrug resistance: a multicentre implementation study},

author = {Catharina C Boehme and Mark P Nicol and Pamela Nabeta and Joy S Michael and Eduardo Gotuzzo and Rasim Tahirli and Ma Tarcela Gler and Robert Blakemore and William Worodria and Christen Gray and Laurence Huang and Tatiana Cac

eres and Rafail Mehdiyev and Lawrence Raymond and Andrew Whitelaw and Kalaiselvan Sagadevan and Heather Alexander and Heidi Albert and Frank Cobelens and Helen Cox and David Alland and Mark D Perkins},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Feasibility-diagnostic-accuracy....pdf},

doi = {10.1016/S0140-6736(11)60438-8.},

year  = {2011},

date = {2011-04-08},

journal = {Lancent},

volume = {377},

number = {9776},

pages = {1495-505},

abstract = {BACKGROUND:



The Xpert MTB/RIF test (Cepheid, Sunnyvale, CA, USA) can detect tuberculosis and its multidrug-resistant form with very high sensitivity and specificity in controlled studies, but no performance data exist from district and subdistrict health facilities in tuberculosis-endemic countries. We aimed to assess operational feasibility, accuracy, and effectiveness of implementation in such settings.

METHODS:



We assessed adults (≥18 years) with suspected tuberculosis or multidrug-resistant tuberculosis consecutively presenting with cough lasting at least 2 weeks to urban health centres in South Africa, Peru, and India, drug-resistance screening facilities in Azerbaijan and the Philippines, and an emergency room in Uganda. Patients were excluded from the main analyses if their second sputum sample was collected more than 1 week after the first sample, or if no valid reference standard or MTB/RIF test was available. We compared one-off direct MTB/RIF testing in nine microscopy laboratories adjacent to study sites with 2-3 sputum smears and 1-3 cultures, dependent on site, and drug-susceptibility testing. We assessed indicators of robustness including indeterminate rate and between-site performance, and compared time to detection, reporting, and treatment, and patient dropouts for the techniques used.

FINDINGS:



We enrolled 6648 participants between Aug 11, 2009, and June 26, 2010. One-off MTB/RIF testing detected 933 (90·3%) of 1033 culture-confirmed cases of tuberculosis, compared with 699 (67·1%) of 1041 for microscopy. MTB/RIF test sensitivity was 76·9% in smear-negative, culture-positive patients (296 of 385 samples), and 99·0% specific (2846 of 2876 non-tuberculosis samples). MTB/RIF test sensitivity for rifampicin resistance was 94·4% (236 of 250) and specificity was 98·3% (796 of 810). Unlike microscopy, MTB/RIF test sensitivity was not significantly lower in patients with HIV co-infection. Median time to detection of tuberculosis for the MTB/RIF test was 0 days (IQR 0-1), compared with 1 day (0-1) for microscopy, 30 days (23-43) for solid culture, and 16 days (13-21) for liquid culture. Median time to detection of resistance was 20 days (10-26) for line-probe assay and 106 days (30-124) for conventional drug-susceptibility testing. Use of the MTB/RIF test reduced median time to treatment for smear-negative tuberculosis from 56 days (39-81) to 5 days (2-8). The indeterminate rate of MTB/RIF testing was 2·4% (126 of 5321 samples) compared with 4·6% (441 of 9690) for cultures.

INTERPRETATION:



The MTB/RIF test can effectively be used in low-resource settings to simplify patients' access to early and accurate diagnosis, thereby potentially decreasing morbidity associated with diagnostic delay, dropout and mistreatment.

FUNDING:



Foundation for Innovative New Diagnostics, Bill & Melinda Gates Foundation, European and Developing Countries Clinical Trials Partnership (TA2007.40200.009), Wellcome Trust (085251/B/08/Z), and UK Department for International Development},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Nakanjako2011,

title = {Low prevalence of Plasmodium  falciparum antigenaemia among asymptomatic HAART- treated adults in an urban cohort in Uganda},

author = {Damalie Nakanjako and Agnes N Kiragga and Barbara Castelnuovo and Daniel J Kyabayinze and Moses R Kamya

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Low-prevalence-.pdf},

doi = {10.1186/1475-2875-10-66},

year  = {2011},

date = {2011-03-22},

journal = {Malaria Journal},

abstract = {BACKGROUND:



Presumptive treatment of malaria is common practice in malaria endemic resource-limited settings. With the changing epidemiology of malaria and the introduction of artemisinin-based combination therapy (ACT), there is increasing need for parasite-based malaria case management to prevent unnecessary use of anti-malarial medicines, improve patient care in parasite-positive patients and identify parasite-negative patients in whom another diagnosis must be sought. Although parasitological confirmation by microscopy or alternatively by malaria rapid diagnostic tests (RDTs) is recommended in all patients suspected of malaria before treatment, gaps remain in the implementation of this policy in resource-limited settings. There is need to evaluate the use of RDTs among highly active anti-retroviral therapy (HAART)-treated people living with HIV (PLHIV).

METHODS:



Within an urban prospective observational research cohort of 559 PLHIV initiated on HAART and cotrimoxazole prophylaxis between April, 2004 and April, 2005, 128 patients with sustained HIV-RNA viral load < 400 copies/ml for four years were evaluated, in a cross-sectional study, for asymptomatic malaria infection using a histidine-rich protein-2 (HRP-2) RDT to detect Plasmodium falciparum antigen in peripheral blood. Patients with positive RDT results had microscopy performed to determine the parasite densities and were followed for clinical signs and symptoms during the subsequent six months.

RESULTS:



Of the 128 asymptomatic patients screened, only 5 (4%) had asymptomatic P. falciparum antigenaemia. All the patients with positive HRP2 RDT results showed malaria parasites on thick film with parasite densities ranging from 02-15 malaria parasites per high power field. None of the patients with positive RDT results reported signs and symptoms of malaria infection during the subsequent six months.

CONCLUSIONS:



In an urban area of low to moderate stable malaria transmission, there was low HRP2 P. falciparum antigenaemia among PLHIV after long-term HAART and cotrimoxazole prophylaxis. Parasite-based malaria diagnosis (PMD) is recommended among PLHIV that are on long-term anti-retroviral therapy. RDTs should be utilized to expand PMD in similar settings where microscopy is unavailable.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Nankumbi2011,

title = {The impact on nurses and nurse managers of introducing PEPFAR clinical services in urban government clinics in Uganda},

author = {Joyce Nankumbi and Sara Groves and Elli Leontsini and Nambusi Kyegombe and Alex Coutinho and Yuka Manabe},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/The-impact-on-nurses-and-nurse-managers-....pdf},

doi = {10.1186/1472-698X-11-S1-S8},

year  = {2011},

date = {2011-03-19},

journal = {BMC International Health and Human Rights},

volume = {11},

number = {1},

abstract = {Background:

Improving provider performance is central to strengthening health services in developing countries.

Because of critical shortages of physicians, many clinics in sub-Saharan Africa are led by nurses. In addition to

clinical skills, nurse managers need practical managerial skills and adequate resources to ensure procurement of

essential supplies, quality assurance implementation, and productive work environment. Giving nurses more

autonomy in their work empowers them in the workplace and has shown to create positive influence on work

attitudes and behaviors. The Infectious Disease Institute, an affiliate of Makerere University College of Health

Science, in an effort to expand the needed HIV services in the Ugandan capital, established a community-university

partnership with the Ministry of Health to implement an innovative model to build capacity in HIV service delivery.

This paper evaluates the impact on the nurses from this innovative program to provide more health care in six

nurse managed Kampala City Council (KCC) Clinics.

Methods:

A mixed method approach was used. The descriptive study collected key informant interviews from the

six nurse managers, and administered a questionnaire to 20 staff nurses between September and December 2009.

Key themes were manually identified from the interviews, and the questionnaire data were analyzed using SPSS.

Results:

Introducing new HIV services into six KCC clinics was positive for the nurses. They identified the project as

successful because of perceived improved environment, increase in useful in-service training, new competence to

manage patients and staff, improved physical infrastructure, provision of more direct patient care, motivation to

improve the clinic because the project acted on their suggestions, and involvement in role expansion. All of these

helped empower the nurses, improving quality of care and increasing job satisfaction.

Conclusions:

This community-university HIV innovative model was successful from the point of view of the nurses

and nurse managers. This model shows promise in increasing effective, quality health service; HIV and other

programs can build capacity and empower nurses and nurse managers to directly implement such services. It also

demonstrates how MakCHS can be instrumental through partnerships in designing and testing effective strategies,

building human health resources and improving Ugandan health outcomes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Matsubayashi2011,

title = {RESEARCH Open Access The effects of an HIV project on HIV and non-HIV services at local government clinics in urban Kampala},

author = {Toru Matsubayashi and Yukari C Manabe and Allan Etonu and Nambusi Kyegombe and Alex Muganzi and Alex Coutinho and David H Peters

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/The-effects-of-HIV-and-non-HIV-services-at-local-goverment-at-local-government-clinics-in-urban-kampala.pdf},

doi = {10.1186/1472-698X-11-S1-S9},

year  = {2011},

date = {2011-03-09},

journal = {BMC International Health and Human Rights},

volume = {11},

number = {1},

abstract = {Background:

HIV/AIDS is a major public health concern in Uganda. There is widespread consensus that weak

health systems hamper the effective provision of HIV/AIDS services. In recent years, the ways in which HIV/AIDS-

focused programs interact with the delivery of other health services is often discussed, but the evidence as to

whether HIV/AIDS programs strengthen or distort overall health services is limited. The aim of this study was to

examine the effect of a PEPFAR-funded HIV/AIDS program on six government-run general clinics in Kampala.

Methods:

Longitudinal information on the delivery of health services was collected at each clinic. Monthly changes in

the volume of HIV and non-HIV services were analyzed by using multilevel models to examine the effect of an HIV/AIDS

program on health service delivery. We also conducted a cross-sectional survey utilizing patient exit interviews to

compare perceptions of the experiences of patients receiving HIV care and those receiving non-HIV care.

Results:

All HIV service indicators showed a positive change after the HIV program began. In particular, the

number of HIV lab tests (10.58, 95% Confidence Interval (C.I.): 5.92, 15.23) and the number of pregnant women

diagnosed with HIV tests (0.52, 95%C.I.: 0.15, 0.90) increased significantly after the introduction of the project. For

non-HIV/AIDS health services, TB lab tests (1.19, 95%C.I.: 0.25, 2.14) and diagnoses (0.34, 95%C.I.: 0.05, 0.64) increased

significantly. Noticeable increases in trends were identified in pediatric care, including immunization (52.43, 95%C.I.:

32.42, 74.43), malaria lab tests (1.21, 95%C.I.: 0.67, 1.75), malaria diagnoses (7.10, 95%C.I.: 0.73, 13.46), and skin

disease diagnoses (4.92, 95%C.I.: 2.19, 7.65). Patients

’

overall impressions were positive in both the HIV and non-HIV

groups, with more than 90% responding favorably about their experiences.

Conclusions:

This study shows that when a collaboration is established to strengthen existing health systems, in

addition to providing HIV/AIDS services in a setting in which other primary health care is being delivered, there are

positive effects not only on HIV/AIDS services, but also on many other essential services. There was no evidence

that the HIV program had any deleterious effects on health services offered at the clinics studied.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Wiersma2011c,

title = {Treatment of chronic hepatitis B virus infection in resource‐constrained settings: expert panel consensus},

author = {Steven T. Wiersma and Brian McMahon and Jean-Michel Pawlotsky and Chloe L. Thio and Mark Thursz and Seng Gee Lim   and Ponsiano Ocama and Gamal Esmat and Mendy Maimuna and David Bell and Marco Vitoria and Irina Eramova and Daniel Lavanchy and Geoff Dusheiko

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Wiersma_et_al-2011-Liver_International-1.pdf},

doi = {10.1111/j.1478-3231.2010.02373.x},

year  = {2011},

date = {2011-02-15},

journal = {Liver International},

volume = {31},

number = {6},

pages = {755-61},

abstract = {Most of the estimated 350 million people with chronic hepatitis B virus (HBV) infection live in resource-constrained settings. Up to 25% of those persons will die prematurely of hepatocellular carcinoma (HCC) or cirrhosis. Universal hepatitis B immunization programmes that target infants will have an impact on HBV-related deaths several decades after their introduction. Antiviral agents active against HBV are available; treatment of HBV infection in those who need it has been shown to reduce the risk of HCC and death. It is estimated that 20-30% of persons with HBV infection could benefit from treatment. However, drugs active against HBV are not widely available or utilized in persons infected with HBV. Currently recommended antiviral agents used for treatment of human immunodeficiency virus (HIV) infection do not adequately suppress HBV, which is of great concern for the estimated 10% of the HIV-infected persons in Africa who are co-infected with HBV. Progressive liver disease has been shown to occur in co-infected persons whose HBV infection is not suppressed. In view of these concerns, an informal World Health Organization consultation of experts concluded that: chronic HBV is a major public health problem in emerging nations; all HIV-infected persons should be screened for HBV infection; HIV/HBV co-infected persons should be treated with therapies active against both viruses and that reduce the risk of resistance; standards for the management of chronic HBV infection should be adapted to resource-constrained settings. In addition, a research agendum was developed focusing on issues related to prevention and treatment of chronic HBV in resource-constrained settings.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Wiersma2011,

title = {Treatment of chronic hepatitis B virus infection in resource-constrained settings: expert panel consensus.},

author = {Steven T. Wiersma and Brian McMahon and Jean-Michel Pawlotsky and Chloe L. Thio and Mark Thursz and Seng Gee Lim and Ponsiano Ocama and Gamal Esmat and Mendy Maimuna and David Bell and Marco Vitoria and Irina Eramova and Daniel Lavanchy and Geoff Dusheiko},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Wiersma_et_al-2011-Liver_International.pdf},

doi = { 10.1111/j.1478-3231.2010.02373.x},

year  = {2011},

date = {2011-02-15},

journal = {Liver International},

volume = {31},

number = {6},

pages = {755-61},

abstract = {Most of the estimated 350 million people with chronic hepatitis B virus (HBV) infection live in resource-constrained settings. Up to 25% of those persons will die prematurely of hepatocellular carcinoma (HCC) or cirrhosis. Universal hepatitis B immunization programmes that target infants will have an impact on HBV-related deaths several decades after their introduction. Antiviral agents active against HBV are available; treatment of HBV infection in those who need it has been shown to reduce the risk of HCC and death. It is estimated that 20-30% of persons with HBV infection could benefit from treatment. However, drugs active against HBV are not widely available or utilized in persons infected with HBV. Currently recommended antiviral agents used for treatment of human immunodeficiency virus (HIV) infection do not adequately suppress HBV, which is of great concern for the estimated 10% of the HIV-infected persons in Africa who are co-infected with HBV. Progressive liver disease has been shown to occur in co-infected persons whose HBV infection is not suppressed. In view of these concerns, an informal World Health Organization consultation of experts concluded that: chronic HBV is a major public health problem in emerging nations; all HIV-infected persons should be screened for HBV infection; HIV/HBV co-infected persons should be treated with therapies active against both viruses and that reduce the risk of resistance; standards for the management of chronic HBV infection should be adapted to resource-constrained settings. In addition, a research agendum was developed focusing on issues related to prevention and treatment of chronic HBV in resource-constrained settings.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Byakika-Kibwika2011,

title = {Artemether-Lumefantrine Combination Therapy for Treatment of Uncomplicated Malaria: The Potential for Complex Interactions with Antiretroviral Drugs in HIV-Infected Individuals},

author = {Pauline Byakika-Kibwika and Mohammed Lamorde and Harriet Mayanja-Kizza and SayeKhoo and ConceptaMerry and Jean-Pierre Vangeertruyden},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Artemether-Lumefantrine-Combination-Therapy....pdf},

year  = {2011},

date = {2011-02-11},

journal = {Malaria Reaserch and Treatment},

abstract = {Treatment of malaria in HIV-infected individuals receiving antiretroviral therapy (ART) poses significant challenges. Artemether lumefantrine (AL) is one of the artemisisnin-based combination therapies recommended for treatment of malaria. The drug combination is highly efficacious against sensitive and multidrug resistant falciparum malaria. Both artemether and lumefantrine aremetabolizedbyhepaticcytochromeP450(CYP450)enzymes which metabolize the protease inhibitors (PIs) and non nucleoside reverse transcriptase inhibitors (NNRTIs) used for HIV treatment. Co administration of NNRTIs and PIs with AL could potentially cause complex pharmacokinetic drug interactions. NNRTI by inducing CYP450 3A4 enzyme and PIs by inhibiting CYP450 3A4 enzymes could influence both artemether and lumefantrine concentrations and their active metabolites dihydroartemisinin and desbutyl-lumefantrine, predisposing patients to poor treatment response, toxicity, and risk for development of resistance. There are scanty data on these interactions and their consequences. Pharmacokinetic studies to evaluate these interactions in the target populations are urgently needed},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Nakanjako2011b,

title = {High T-cell immune activation and immune exhaustion among individuals with suboptimal CD4 recovery after 4 years of antiretroviral therapy in an African cohort},

author = {Damalie Nakanjako and Isaac Ssewanyana and Harriet Mayanja-Kizza and Agnes Kiragga and Robert Colebunders and Yukari C Manabe and Rose Nabatanzi and Moses R Kamya and Huyen Cao

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/High-T-cell-immune-activation-and-immune-exhaustion-among-individuals-with-suboptimal-CD4-recovery-after-4-years-of-antiretroviral-therapy-in-an-African-cohort-.pdf},

doi = {10.1186/1471-2334-11-43},

year  = {2011},

date = {2011-02-08},

journal = {BMC Infectious Diseases},

abstract = {BACKGROUND:



Antiretroviral therapy (ART) partially corrects immune dysfunction associated with HIV infection. The levels of T-cell immune activation and exhaustion after long-term, suppressive ART and their correlation with CD4 T-cell count reconstitution among ART-treated patients in African cohorts have not been extensively evaluated.

METHODS:



T-cell activation (CD38+HLA-DR+) and immune exhaustion (PD-1+) were measured in a prospective cohort of patients initiated on ART; 128 patient samples were evaluated and subcategorized by CD4 reconstitution after long-term suppressive treatment: Suboptimal [median CD4 count increase 129 (-43-199) cells/μl], N = 34 ], optimal [282 (200-415) cells/μl, N = 64] and super-optimal [528 (416-878) cells/μl, N = 30].

RESULTS:



Both CD4+ and CD8 T-cell activation was significantly higher among suboptimal CD4 T-cell responders compared to super-optimal responders. In a multivariate model, CD4+CD38+HLADR+ T-cells were associated with suboptimal CD4 reconstitution [AOR, 5.7 (95% CI, 1.4-23, P = 0.014)]. T-cell exhaustion (CD4+PD1+ and CD8+PD1+) was higher among suboptimal relative to optimal (P < 0.001) and super-optimal responders (P < 0.001). T-cell exhaustion was significantly associated with suboptimal responders [AOR, 1.5 (95%CI, 1.1-2.1), P = 0.022].

CONCLUSION:



T-cell activation and exhaustion persist among HIV-infected patients despite long-term, sustained HIV-RNA viral suppression. These immune abnormalities were associated with suboptimal CD4 reconstitution and their regulation may modify immune recovery among suboptimal responders to ART.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kiragga2011,

title = {RESEARCH Open Access Quality of data collection in a large HIV observational clinic database in sub-Saharan Africa: implications for clinical research and audit of care},

author = {Agnes N Kiragga and Barbara Castelnuovo and Petra Schaefer and Timothy Muwonge and Philippa J Easterbrook},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Quality-of-data-collection-in-a-large-HIV-observational-clinic-database-in-sub-Saharan-Africa.pdf},

doi = {10.1186/1758-2652-14-3},

year  = {2011},

date = {2011-01-20},

journal = {Journal of the Intrernational AIDS society},

abstract = {BACKGROUND:



Observational HIV clinic databases are now widely used to answer key questions related to HIV care and treatment, but there has been no systematic evaluation of their quality of data. Our objective was to evaluate the completeness and accuracy of recording of key data HIV items in a large routine observational HIV clinic database.

METHODS:



We looked at the number and rate of opportunistic infections (OIs) per 100 person years at risk in the 24 months following antiretroviral therapy (ART) initiation in 559 patients who initiated ART in 2004-2005 and enrolled into a research cohort. We compared this with data in a routine clinic database for the same 559 patients, and a further 1233 patients who initiated ART in the same period. The Research Cohort database was considered as the reference "gold standard" for the assessment of data accuracy. A crude percentage of underreporting of OIs in the clinic database was calculated based on the difference between the OI rates reported in both databases.We reviewed 100 clinic patient medical records to assess the accuracy of recording of key data items of OIs, ART toxicities and ART regimen changes.

RESULTS:



The overall incidence rate per 100 person years at risk for the initial OI in the 559 patients in the research cohort and clinic databases was 24.1 (95% CI: 20.5-28.2) and 13.2 (95% CI: 10.8-16.2) respectively, and 10.4 (95% CI: 9.1-11.9) for the 1233 clinic patients. This represents a 1.8- and 2.3-fold higher rate of events in the research cohort database compared with the same 599 patients and 1233 patients in the routine clinic database, or a 45.1% and 56.8% rate of underreporting, respectively. The combined error rate of missing and incorrect items from the medical records' review was 67% for OIs, 52% for ART-related toxicities, and 83% and 58% for ART discontinuation and modification, respectively.

CONCLUSIONS:



There is a high rate of underreporting of OIs in a routine HIV clinic database. This has important implications for the use and interpretation of routine observational databases for research and audit, and highlights the need for regular data validation of these databases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kiragga2011b,

title = {Quality of data collection in a large HIV observational clinic database in sub-Saharan Africa: implications for clinical research and audit of care},

author = {Agnes N Kiragga and Barbara Castelnuovo and Petra Schaefer and Timothy Muwonge and Philippa J Easterbrook},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Quality-of-data-collection-in-a-large-HIV-observational-clinic-database-in-sub-Saharan-Africa.pdf},

doi = {10.1186/1758-2652-14-3},

year  = {2011},

date = {2011-01-20},

journal = {Journal of the Intrernational AIDS society},

abstract = {BACKGROUND:



Observational HIV clinic databases are now widely used to answer key questions related to HIV care and treatment, but there has been no systematic evaluation of their quality of data. Our objective was to evaluate the completeness and accuracy of recording of key data HIV items in a large routine observational HIV clinic database.

METHODS:



We looked at the number and rate of opportunistic infections (OIs) per 100 person years at risk in the 24 months following antiretroviral therapy (ART) initiation in 559 patients who initiated ART in 2004-2005 and enrolled into a research cohort. We compared this with data in a routine clinic database for the same 559 patients, and a further 1233 patients who initiated ART in the same period. The Research Cohort database was considered as the reference "gold standard" for the assessment of data accuracy. A crude percentage of underreporting of OIs in the clinic database was calculated based on the difference between the OI rates reported in both databases.We reviewed 100 clinic patient medical records to assess the accuracy of recording of key data items of OIs, ART toxicities and ART regimen changes.

RESULTS:



The overall incidence rate per 100 person years at risk for the initial OI in the 559 patients in the research cohort and clinic databases was 24.1 (95% CI: 20.5-28.2) and 13.2 (95% CI: 10.8-16.2) respectively, and 10.4 (95% CI: 9.1-11.9) for the 1233 clinic patients. This represents a 1.8- and 2.3-fold higher rate of events in the research cohort database compared with the same 599 patients and 1233 patients in the routine clinic database, or a 45.1% and 56.8% rate of underreporting, respectively. The combined error rate of missing and incorrect items from the medical records' review was 67% for OIs, 52% for ART-related toxicities, and 83% and 58% for ART discontinuation and modification, respectively.

CONCLUSIONS:



There is a high rate of underreporting of OIs in a routine HIV clinic database. This has important implications for the use and interpretation of routine observational databases for research and audit, and highlights the need for regular data validation of these databases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Lamorde2011b,

title = {Nevirapine pharmacokinetics when initiated at 200 mg or 400 mg daily in HIV-1 and tuberculosis co-infected Ugandan adults on rifampicin},

author = {Mohammed Lamorde and Pauline Byakika-Kibwika and Violet Okaba-Kayom and Mairin Ryan and Peter Coakley and Marta Boffito and Rhoda Namakula and Francis Kalemeera and Robert Colebunders and David Back and Saye Khoo and Concepta Merry

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Nevirapine-pharmacokinetics-when-initiated-at-200-mg-or-400-mg-daily-in-HIV-1....pdf},

doi = {10.1093/jac/dkq411},

year  = {2011},

date = {2011-01-01},

journal = {Journal of Antimicrobial Chemotherapy},

volume = {66},

number = {1},

pages = {180-3},

abstract = {BACKGROUND:



rifampicin lowers nevirapine plasma concentrations by inducing cytochrome P450. However, few data are available on this interaction during the lead-in period of nevirapine treatment.

METHODS:



eighteen HIV-1/tuberculosis co-infected adults receiving rifampicin daily as part of anti-tuberculosis therapy were evenly randomized to nevirapine initiation by dose escalation (NVP200) or nevirapine initiation at 200 mg twice daily (NVP400). Subjects underwent 12 h intensive pharmacokinetic sampling on Days 7, 14 and 21 of nevirapine treatment. A minimum effective concentration (MEC) of 3000 ng/mL was used to interpret nevirapine concentrations 12 h after dosing (C(12)).

TRIAL REGISTRATION NUMBER:



NCT00617643 (www.clinicaltrials.gov).

RESULTS:



day 7 geometric mean nevirapine C(12) [90% confidence interval (CI)] was 1504 (1127-2115) ng/mL and 3148 (2451-4687) ng/mL in the NVP200 and NVP400 arms, respectively (P < 0.01). Nevirapine C(12) on Days 14 and 21 was similar. On Day 21, nevirapine concentration in 64% of patients was below the MEC. On Day 7, geometric mean area under the curve (AUC(0-12)) was lower in the NVP200 arm, 25 223 (90% CI, 21 978-29 695) ng·h/mL versus 43 195 (35 607-57 035) ng·h/mL in the NVP400 arm (P  <  0.01). Similarly, on Day 14, nevirapine AUC(0-12) was lower in the NVP200 arm 23 668 (18 253-32 218) ng·h/mL versus the NVP400 arm 44 918 (36 264-62 769) ng·h/mL (P = 0.03).

CONCLUSIONS:



in co-treated patients, nevirapine concentrations were below the MEC during initiation with dose escalation. Nevirapine initiation at the maintenance dose of 200 mg twice daily is preferred. Sub-therapeutic nevirapine concentrations were common at Day 21 with either regimen. Evaluation of higher nevirapine maintenance doses may be considered},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{xiao2011multib,

title = {A multi-label classifier for predicting the subcellular localization of gram-negative bacterial proteins with both single and multiple sites},

author = {Xuan Xiao and Zhi-Cheng Wu and Kuo-Chen Chou},

year  = {2011},

date = {2011-01-01},

journal = {PloS one},

volume = {6},

number = {6},

pages = {e20592},

publisher = {Public Library of Science San Francisco, USA},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{xiao2011multi,

title = {A multi-label classifier for predicting the subcellular localization of gram-negative bacterial proteins with both single and multiple sites},

author = {Xuan Xiao and Zhi-Cheng Wu and Kuo-Chen Chou},

year  = {2011},

date = {2011-01-01},

journal = {PloS one},

volume = {6},

number = {6},

pages = {e20592},

publisher = {Public Library of Science San Francisco, USA},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Byakika-Kibwika2011c,

title = {Cardiac Conduction Safety during Co-administration of Artemether-Lumefantrine and Lopinavir/Ritonavir in HIV-Infected Ugandan Adults},

author = {Pauline Byakika-Kibwika and Mohammed Lamorde and PeterLwabi and Wilson B. Nyakoojo and Violet Okaba-Kayom and Harriet Mayanja-Kizza and Marta Boffito and EllyKatabira and David Back and Saye Khoo and Concepta Merry},

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

year  = {2011},

date = {2011-00-31},

abstract = {WeaimedtoassesscardiacconductionsafetyofcoadministrationoftheCYP3A4inhibitorlopinavir/ritonavir(LPV/r) and the CYP3A4 substrate artemether-lumefantrine (AL) in HIV-positive Ugandans. Methods. Open-label safety study of HIVpositive adults administered single-dose AL (80/400mg) alone or with LPV/r (400/100mg). Cardiac function was monitored using continuous electrocardiograph (ECG). Results. Thirty-two patients were enrolled; 16 taking LPV/r -based ART and 16 ART na¨ıve. All took single doseAL. No serious adverse events were observed. ECG parameters in millisecondsremained within normal limits. QTc measurements did not change significantly over 72 hours although were higher in LPV/r arm at 24 (424 versus 406; P = .02) and 72 hours (424 versus 408; P = .004) after AL intake. Conclusion. Coadministration of single dose of AL with LPV/r was safe; however, safety of six-doseAL regimen with LPV/r shouldbe investigated.

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Albert2010,

title = {Performance of Three LED-Based Fluorescence Microscopy Systems for Detection of Tuberculosis in Uganda},

author = {Heidi Albert and Yukari Manabe and George Lukyamuzi and Patrick Ademun and Sheena Mukkada and Barnabas and Nyesiga and Moses Joloba and C. N. Paramasivan and Mark D Perkins

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Performance-of-Three-LED-Based-Fluorescence.pdf},

doi = {10.1371/journal.pone.0015206},

year  = {2010},

date = {2010-12-28},

journal = {PloS One},

volume = {5},

number = {12},

abstract = {BACKGROUND:



Direct smear microscopy using Ziehl-Neelsen (ZN) staining is the mainstay of tuberculosis (TB) diagnosis in most high burden countries, but is limited by low sensitivity in routine practice, particularly in high human immunodeficiency virus (HIV) prevalence settings.

METHODS:



We compared the performance of three commercial light emitting diode (LED)-based microscopy systems (Primostar™ iLED, Lumin™ and AFTER®) for fluorescent detection of Mycobacterium tuberculosis with ZN microscopy on slides prepared from sputum of TB suspects. Examination time for LED-based fluorescent microscopy (LED FM) and ZN slides was also compared, and a qualitative user appraisal of the LED FM systems was carried out.

RESULTS:



LED FM was between 5.6 and 9.4% more sensitive than ZN microscopy, although the difference was not statistically significant. There was no significant difference in the sensitivity or specificity of the three LED FM systems, although the specificity of Fraen AFTER was somewhat lower than the other LED FM methods. Examination time for LED FM was 2 and 4 times less than for ZN microscopy. LED FM was highly acceptable to Ugandan technologists, although differences in operational performance of the three systems were reported.

CONCLUSIONS:



LED FM compares favourably with ZN microscopy, with equivalent specificity and a modest increase in sensitivity. Screening of slides was substantially quicker using LED FM than ZN, and LED FM was rated highly by laboratory technologists. Available commercial systems have different operational characteristics which should be considered prior to programmatic implementation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Boulware2010,

title = {Clinical Features and Serum Biomarkers in HIV Immune Reconstitution Inflammatory Syndrome after Cryptococcal Meningitis: A Prospective Cohort Study},

author = {David R. Boulware and David B. Meya and Tracy L. Bergemann and Darin L. Wiesner and Joshua Rhein and Abdu Musubire and Sarah J. Lee and Andrew Kambugu and Edward N. Janoff and Paul R. Bohjanen

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Clinical-Features-and-Serum-Biomarkers.pdf},

doi = {10.1371/journal.pmed.1000384},

year  = {2010},

date = {2010-12-21},

journal = {PloS Medicine},

volume = {7},

number = {12},

abstract = {BACKGROUND:



Although antiretroviral therapy (ART) improves survival in persons with cryptococcal meningitis (CM) and AIDS, ART frequently elicits HIV immune reconstitution inflammatory syndrome (IRIS), an exaggerated and frequently deadly inflammatory reaction that complicates recovery from immunodeficiency. The pathogenesis of IRIS is poorly understood and prediction of IRIS is not possible.

METHODS AND FINDINGS:



We prospectively followed 101 ART-naïve Ugandans with AIDS and recent CM for one year after initiating ART, and used Luminex multiplex assays to compare serum cytokine levels in participants who did or did not develop IRIS. IRIS occurred in 45% of participants with recent CM on ART, including 30% with central nervous system (CNS) manifestations. The median time to CM-IRIS was 8.8 wk on ART. Overall mortality on ART was 36% with IRIS and 21% without IRIS. CM-IRIS was independently associated with death (HR = 2.3, 95% CI 1.1-5.1, p = 0.04). Patients experiencing subsequent CM-IRIS had 4-fold higher median serum cryptococcal antigen (CRAG) levels pre-ART (p = 0.006). Higher pre-ART levels of interleukin (IL)-4 and IL-17 as well as lower tumor necrosis factor (TNF)-α, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and vascular endothelial growth factor (VEGF) predicted future IRIS in multivariate analyses (area under the curve [AUC] = 0.82). An algorithm based on seven pre-ART serum biomarkers was a robust tool for stratifying high (83%), moderate (48%), and low risk (23%) for IRIS in the cohort. After ART was initiated, increasing levels of C-reactive protein (CRP), D-dimer, IL-6, IL-7, IL-13, G-CSF, or IL-1RA were associated with increasing hazard of IRIS by time-to-event analysis (each p≤0.001). At the time of IRIS onset, multiple proinflammatory cytokine responses were present, including CRP and IL-6. Mortality was predicted by pre-ART increasing IL-17, decreasing GM-CSF, and CRP level >32 mg/l (highest quartile). Pre-ART CRP level >32 mg/l alone was associated with future death (OR = 8.3, 95% CI 2.7-25.6, p<0.001).

CONCLUSIONS:



Pre-ART increases in Th(17) and Th(2) responses (e.g., IL-17, IL-4) and lack of proinflammatory cytokine responses (e.g., TNF-α, G-CSF, GM-CSF, VEGF) predispose individuals to subsequent IRIS, perhaps as biomarkers of immune dysfunction and poor initial clearance of CRAG. Although requiring validation, these biomarkers might be an objective tool to stratify the risk of CM-IRIS and death, and could be used clinically to guide when to start ART or use prophylactic interventions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Worodria2010,

title = {Antiretroviral Treatment-Associated Tuberculosis in a Prospective Cohort of HIV-Infected Patients Starting ART},

author = {William Worodria,

1,2, 3, 4

Marguerite Massinga-Loembe and Harriet Mayanja-Kizza and Jane Namaganda and Andrew Kambugu and Yukari C. Manabe and Luc Kestens and Robert Colebunders

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Antiretroviral-Treatment-Associated-Tuberculosis-in-a-Prospective-cohort-of-HIV-Infected-Patients-Starting-ART-1.pdf},

doi = { 10.1155/2011/758350},

year  = {2010},

date = {2010-12-08},

journal = {Clinical and Development Immunology},

abstract = {Commencement of antiretroviral treatment (ART) in severely immunosuppressed HIV-infected persons is associated with unmasking of subclinical disease. The subset of patients that are diagnosed with tuberculosis (TB) disease while on ART have been classified as ART-associated TB. Few studies have reported the incidence of ART-associated TB and unmasking TB-IRIS according to the International Network for the Study of HIV-Associated IRIS (INSHI) consensus definition. To determine the incidence and predictors of ART-associated TB, we screened 219 patients commencing ART at the Infectious Diseases Clinic in Kampala, Uganda for TB by symptoms, sputum microscopy, and chest X-rays and followed them for one year. Fourteen (6.4%) patients were diagnosed with TB during followup. Eight (3.8%) patients had ART-associated TB (incidence rate of 4.3 per 100 person years); of these, three patients fulfilled INSHI criteria for unmasking TB-associated IRIS (incidence rate of 1.6 per 100 person years). A body mass index of less than 18.5 kg/m(2) BMI (HR 5.85 95% CI 1.24-27.46, P = .025) and a C-reactive protein greater than 5 mg/L (HR 8.23 95% CI 1.36-38.33, P = .020) were risk factors for ART-associated TB at multivariate analysis. In conclusion, with systematic TB screening (including culture and chest X-ray), the incidence of ART-associated TB is relatively low in settings with high HIV and TB prevalence.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Boulware2010c,

title = {Antiretroviral Therapy Down-regulates Innate Antiviral Response Genes in Patients with AIDS in Sub-Saharan Africa},

author = {David R. Boulware and David B. Meya and Tracy L.Bergemann and Darlisha Williams and Irina A. Vlasova-St. Louis and Josh Rhein Jack Staddon and Andrew Kambugu and Edward N. Janoff and Paul R. Bohjanen, },

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Antiretroviral-Therapy-Down-regulates-Innate-Antiviral-Response-Genes.pdf},

doi = { 10.1097/QAI.0b013e3181ef4963},

year  = {2010},

date = {2010-12-01},

journal = {Journal of Acquired Immune Dificiency syndrome},

volume = {55},

number = {4},

pages = {428-38},

abstract = {OBJECTIVE:



HIV pathogenesis is characterized by destructive imbalances between virus-mediated immune damage, antiviral immune responses, and immune activation. We characterized the effects of successful antiretroviral therapy (ART) to identify the breadth and patterns of HIV-associated gene expression.

METHODS:



In a prospective observational, longitudinal cohort study of 10 ART-naive Ugandans with AIDS (median 30 CD4/μL), we measured mRNA gene profiles in peripheral blood using Affymetrix U133_Plus2.0 microarrays at 0, 2, 4, 8, and 24 weeks after ART initiation.

RESULTS:



We identified 160 mRNA transcripts that were consistently down-regulated and 48 that were up-regulated after ART at each point over 24 weeks based on linear regression modeling (adjusted P < 0.05), Of these 208 transcripts, approximately half represent heretofore unrecognized ART-responsive genes and one-third have no known function. The down-regulated genes with known function encoded mediators of innate antiviral responses, including antiviral restriction factors, pattern recognition receptors, and interferon response proteins, and mediators of immune activation, cellular proliferation, and apoptosis.

CONCLUSIONS:



By using ART to block the viral stimulus, we identified transcripts involved in innate antiviral immunity, including antiviral restriction factors and pattern recognition receptors, that were not previously known to be induced by HIV infection},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Wiersma2010,

title = {Treatment of chronic hepatitis B virus infec tion in resource-constrained settings: expert panel consensus},

author = {Steven T. Wiersma and Brian McMahon and Jean-Michel Pawlotsky and Chloe L. Thio and Mark Thursz and Seng Gee Lim and Ponsiano Ocama and Gamal Esmat and Mendy Maimuna and David Bell and Marco Vitoria and Irina Eramova and Daniel Lavanchy and Geoff Dusheiko

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Treatment-of-chronic-hepatitis-B-virus-infec-tion-in-resource-constrained-setting-.pdf },

doi = { 10.1111/j.1478-3231.2010.02373.x},

year  = {2010},

date = {2010-11-28},

journal = {Liver International},

volume = {31},

number = {6},

pages = {755-61},

abstract = {Most of the estimated 350 million people with chronic hepatitis B virus (HBV) infection live in resource-constrained settings. Up to 25% of those persons will die prematurely of hepatocellular carcinoma (HCC) or cirrhosis. Universal hepatitis B immunization programmes that target infants will have an impact on HBV-related deaths several decades after their introduction. Antiviral agents active against HBV are available; treatment of HBV infection in those who need it has been shown to reduce the risk of HCC and death. It is estimated that 20-30% of persons with HBV infection could benefit from treatment. However, drugs active against HBV are not widely available or utilized in persons infected with HBV. Currently recommended antiviral agents used for treatment of human immunodeficiency virus (HIV) infection do not adequately suppress HBV, which is of great concern for the estimated 10% of the HIV-infected persons in Africa who are co-infected with HBV. Progressive liver disease has been shown to occur in co-infected persons whose HBV infection is not suppressed. In view of these concerns, an informal World Health Organization consultation of experts concluded that: chronic HBV is a major public health problem in emerging nations; all HIV-infected persons should be screened for HBV infection; HIV/HBV co-infected persons should be treated with therapies active against both viruses and that reduce the risk of resistance; standards for the management of chronic HBV infection should be adapted to resource-constrained settings. In addition, a research agendum was developed focusing on issues related to prevention and treatment of chronic HBV in resource-constrained settings.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Meya2010,

title = {Reflexive Laboratory-Based Cryptococcal Antigen Screening and Preemptive Fluconazole Therapy for Cryptococcal Antigenemia in HIV-Infected Individuals With CD4 <100 Cells/µL: A Stepped-Wedge, Cluster-Randomized Trial},

author = {David B. Meya, Agnes N. Kiragga, Elizabeth Nalintya, Bozena M. Morawski, Radha Rajasingham, Benjamin J. Park, Anthony Mubiru, Jonathan E. Kaplan, Yukari C. Manabe and David R. Boulware, ORCAS study team},

doi = {doi: 10.1097/QAI.0000000000001894},

year  = {2010},

date = {2010-11-05},

journal = {Journal of Acquired Immune Deficiency Syndromes (1999)},

volume = {80},

number = {2},

pages = {182–189},

abstract = {Background:



HIV-infected persons with cryptococcal antigenemia (CrAg) are at high risk for meningitis or death. We evaluated the effect of CrAg screening and preemptive fluconazole therapy, adjunctive to antiretroviral therapy (ART), on 6-month survival among persons with advanced HIV/AIDS.



Methods:



We enrolled HIV-infected, ART-naive participants with <100 CD4 cells/µL, in a stepped-wedge, cluster-randomized trial from July 2012 to December 2014 at 17 Ugandan clinics. Clinics participated in a prospective observational phase, followed by an interventional phase with laboratory-based, reflexive CrAg screening of residual CD4 count plasma. Asymptomatic CrAg+ participants received preemptive fluconazole therapy. We assessed 6-month survival using Cox-regression, adjusting for nadir CD4, calendar time, and stepped-wedge steps.



Results:



We included 1280 observational and 2108 interventional participants, of whom 9.3% (195/2108) were CrAg+. CD4-, time-, and stepped-wedge–adjusted analyses demonstrated no difference in survival in the observational vs the interventional arms (hazard ratio = 1.34; 95% confidence interval: 0.86 to 2.10; P = 0.20). Fewer participants initiated ART in the interventional (73%) versus the observational phase (82%, P < 0.001). When ART initiation was modeled as a time-dependent covariate or confounder, survival did not differ. However, 6-month mortality of participants with CrAg titers <1:160 and CrAg-negative patients did not differ. Patients with CrAg titers ≥1:160 had 2.6-fold higher 6-month mortality than patients with titers <1:160.



Conclusions:



We observed no overall survival benefit of the CrAg screen-and-treat intervention. However, preemptive antifungal therapy for asymptomatic cryptococcosis seemed to be effective in patients with CrAg titer <1:160. A more aggressive approach is required for persons with CrAg titer ≥1:160.



Key Words: 

cryptococcus, HIV, fluconazole, preventative therapy, cryptococcal meningitis, clinical trial},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Kiragga2010,

title = {Baseline severe anaemia should not preclude use of zidovudine in antiretroviral-eligible patients in resource-limited settings},

author = {Agnes N Kiragga and Barbara Castelnuovo and Damalie Nakanjako and Yukari C Manabe},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Baseline-severe-anaemia-should-not-preclude-use-of-zidovudine....pdf},

doi = {10.1186/1758-2652-13-42},

year  = {2010},

date = {2010-11-03},

journal = {Journal of the Intrernational AIDS society},

abstract = {

Background



Stavudine is no longer recommended as part of first-line therapy for patients initiating antiretroviral therapy (ART) in Uganda. Most patients are currently initiated on zidovudine-containing regimens, which can induce anaemia. We investigated the risk factors for early severe anaemia in the first six months of ART initiation.

Methods



We defined baseline (ART initiation) anaemia as haemoglobin (Hb) ≤9.5 g/dL, baseline severe anaemia as Hb ≤8 g/dL, and early severe anaemia as Hb ≤8 g/dL within six months of ART initiation. Risk factors for the development of early severe anaemia were analyzed using a multivariable logistic regression model.

Results



In total, 5494 patients initiated ART, 821 (15%) had baseline anaemia, and 296 (5%) had baseline severe anaemia. Early severe anaemia occurred in 109 (4%) of 3105 patients who had at least one Hb measurement in the first six months on ART. Patients with baseline anaemia had a larger increase in Hb (median g/dL [IQR]) within the first six months compared with non-anaemic patients (2.9 [1.7, 4.6] vs. 0.7 [-0.2, 1.7], p < 0.0001). Having a new tuberculosis episode OR 3.69 (95% CI 1.64 - 8.32), MCV <80fL OR 1.60 (95% CI 1.01- 2.52) and baseline severe anaemia OR 5.27 (95% CI 3.00 - 9.26) were associated with early severe anaemia. Initiation on a zidovudine-based regimen was not associated with an increased risk of early severe anaemia.

Conclusions



Among patients in an urban HIV clinic in Uganda, severe anaemia is modestly prevalent at ART initiation and improves with ART in the majority of patients. These data suggest that baseline severe anaemia should not be used as a criterion for avoiding the use of zidovudine in patients initiating ART in resource-limited settings.

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kadowa2010,

title = {Factors influencing disclosure of HIV positive status in Mityana district of Uganda},

author = {Isaac Kadowa and Fred Nuwaha},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Factors-influencing-discosure-of-HIV-positive-Status-in-Mityana-district-of-Uganda.pdf},

year  = {2010},

date = {2010-10-01},

journal = {African Health Sciences},

volume = {9},

number = {1},

pages = {26-33},

abstract = {Background:

 Disclosure of HIV positive sero-status to sexual partners, friends or relatives is useful for prevention and care.

Identifying factors associated with disclosure is a research priority as a high proportion of persons living with HIV/AIDS (PHA

) never

disclose.

Objective:

 To identify factors associated with disclosure among PHAs in Mityana district of Uganda.

Methods: 

Using a case control design, we compared 139 PHAs who had disclosed to 139 PHA who had not disclosed regarding

socio demographic characteristics, sexual behaviour, individual experiences and perceptions about disclosure, as well as on hea

lth

facility/community correlates of disclosure.

Results: 

The independent factors that favour disclosure are not fearing negative outcomes of disclosure adjusted odds ratio (AOR)

7.00, 95 % confidence interval (95% CI) 3.03-16.95, having communication skills to disclose (AOR 12.08, 95% CI 4.94-29.51),

having initiated anti-retroviral therapy (AOR 7.51, 95%

CI 3.42-16.49), not having tested for HIV during ante-natal clinic (AOR

5.07, 95%

CI 1.95-13.10), receiving ongoing counselling (AOR 4.33, 95%

CI 1.50-12.51) and having ever seen a PHA publicly

disclose his/her HIV status AOR 2.73, 95%

 CI 1.24-6.02).

Conclusions

PHAs that have not initiated anti-retroviral therapy (ART), test for HIV in ante-natal clinic and fear negative outcomes need m

ore

help in disclosure. Measures that empower PHA to disclose such as those that lead to improved communication skills should be

reinforced during ongoing counselling},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Boulware2010d,

title = {Paucity of initial cerebrospinal fluid inflammation in cryptococcal meningitis is associated with subsequent immune reconstitution inflammatory syndrome},

author = {David R. Boulware and Shulamith C. Bonham and David B. Meya and Darin L. Wiesner and Gregory S. Park and Andrew Kambugu and Edward N. Janoff and Paul R Bohjanen},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Paucity-of-initial-cerebrospinal-fluid-inflammation-in-cryptococcal-meningitis-is-associated-with-subsequent-immune-reconstitution-inflammatory-syndrome.pdf},

doi = {10.1086/655785.},

year  = {2010},

date = {2010-09-15},

journal = {The Journal of Infectious Diseases},

volume = {206},

number = {6},

pages = {962-70},

abstract = {BACKGROUND:

Cryptococcal meningitis (CM)-related immune reconstitution inflammatory syndrome (IRIS) complicates antiretroviral therapy (ART) in 20%-40% of ART-naive persons with AIDS and prior CM. Pathogenesis is unknown.

METHODS:

We compared initial cerebrospinal fluid (CSF) cultures, inflammatory markers, and cytokine profiles in ART-naive patients with AIDS who did or did not subsequently develop IRIS after starting ART. We also compared results obtained at IRIS events or CM relapse.

RESULTS:

Of 85 subjects with CM, 33 (39%) developed CM-related IRIS and 5 (6%) developed culture-positive CM relapse. At CM diagnosis, subjects subsequently developing IRIS had less inflammation, with decreased CSF leukocytes, protein, interferon-gamma, interleukin-6, interleukin-8, and tumor necrosis factor-alpha, compared with subjects not developing IRIS (P<.05, for each). Initial CSF white blood cell counts < or =25 cells/microL and protein levels < or =50 mg/dL were associated with development of IRIS (odds ratio, 7.2 [95% confidence interval, 2.7-18.7]; P<.001). Compared with baseline levels, we identified CSF elevations of interferon-gamma, tumor necrosis factor-alpha, granulocyte colony-stimulating factor, vascular-endothelial growth factor, and eotaxin (CCL11) (P<.05, for each) at the time of IRIS but minimal inflammatory changes in those with CM relapse.

CONCLUSIONS:

Patients who subsequently develop CM-related IRIS exhibit less initial CSF inflammation at the time of CM diagnosis, compared with those who do not develop IRIS. The inflammatory CSF cytokine profiles observed at time of IRIS can distinguish IRIS from CM relapse.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Katusiime2010,

title = {Immune Reconstitution Inflammatory Syndrome among Adolescents: A Report of Cases in a Resource-Limited Setting (Uganda). },

author = {Christine Katusiime and Ponsiano Ocama and Andrew Kambugu},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Immune-Reconstitution-Inflammatory-Syndrome-among-Adolescents.pdf},

year  = {2010},

date = {2010-09-01},

journal = {Southern African Journal of HIV Medicine},

abstract = {The immune reconstitution inflammatory syndrome (IRIS) is a frequent early complication of antiretroviral therapy (ART), particularly in patients who commence ART with low CD4 counts and established opportunistic infections. IRIS in HIV-infected patients results from a pathological inflammatory response to pre-existing infective, host or other antigens, alive or dead, causing clinical deterioration after initiating ART.1 The most common forms of IRIS occur in association with mycobacterial and herpesvirus infections.2 

Adolescents and young adults comprise an increasing proportion of new HIV infections both in developing and developed countries, and little is known regarding HIV IRIS in this group. As the ART roll-out has gathered pace since 2004 in resource-limited settings, adolescent IRIS has emerged as a clinical challenge. We describe adolescent/young adult patients who presented to our clinic with IRIS events.

METHODS The study was performed at the Adult Infectious Diseases Institute (IDI) at Mulago Hospital, Kampala, Uganda. The AIDC is part of the Makerere University Infectious Diseases Institute and provides HIV care, including free ART, to HIV-infected patients with a CD4+ count <200 cells/µl or with World Health Organization stage IV disease. The study was approved by the ethics panel and the Institutional Review Board since this was a case series. Among our adolescent/ young adult cohort aged 16 - 24 years of about 480, we have seen 6 cases of IRIS, including cryptococcal meningitis IRIS, Kaposi’s sarcoma IRIS, herpes zoster IRIS, pulmonary tuberculosis IRIS and 2 cases of 

oral candidiasis IRIS within the past 12 months. The incidence of IRIS after initiation of HAART was 1.25%. The median age of presentation was 22 years and the median CD4+ count before commencing ART 65 cells/ µl. IRIS presented a median of 6 weeks from the start of HAART (range 3 - 16 weeks). 

Mycobacteria are by far the most common pathogens associated with IRIS in HIV-infected patients.3-7 Other infections that have been associated with IRIS events include varicella zoster, herpes simplex, meningeal cryptococcosis, hepatitis, cytomegalovirus retinitis, progressive multifocal leuco-encephalopathy and intestinal parasites. While the majority of IRIS events are infectious in nature, auto-immune IRIS reactions have also been described in adults.8

DISCUSSION IRIS is a condition seen in some cases of AIDS or immunosuppression, in which the immune system begins to recover but then responds to a previously acquired opportunistic infection with an overwhelming inflammatory response that paradoxically makes the symptoms of infection worse.9 It is thought that the immunopathological response initiated by HAART restores the immune response against pathogenic antigens.10 There is paradoxical worsening of preexisting infectious processes following initiation of HAART in HIV-infected individuals.9

 

These cases highlight the risks faced during immune reconstitution in adolescent and young adult patients who commence ART with advanced immunosuppression. 

IMMUNE },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Katusiime2010b,

title = {A Case of Palatal Perforation caused by Toxoplasmosis},

author = {Christine Katusiime and Ponsiano Ocama and Andrew Kambugu},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/A-Case-of-Palatal-Perforation-caused-by-Toxoplasmosis.pdf},

year  = {2010},

date = {2010-09-01},

journal = {Southern African Journal of HIV Medicine},

abstract = {HIV infection has several oral manifestations, including oral candidiasis and oral hairy leucoplakia. Occasionally unusual presentations requiring rigorous investigations are seen, and in these cases the diagnosis sometimes remains a dilemma owing to limited investigation facilities.1-3 We present the case of a patient who presented with a puzzling oral lesion},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ocama2010b,

title = {Low frequency of liver enzyme elevation in HIV-infected patients attending a large urban treatment centre in Uganda},

author = {P Ocama and B. Castelnuovo and M R Kamya and G D Kirk and S J and Reynolds and A Kiragga and R Colebunders and 

D L Thomas},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Low-frequency-of-liver-enzyme-elevation-in-HIV-infected-patients-attending-a-large-urban-treatment-centre-in-Uganda.pdf},

doi = {10.1258/ijsa.2010.010027},

year  = {2010},

date = {2010-08-01},

journal = {International Journal of STD and AIDS},

volume = {21},

number = {8},

pages = {553-7},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kyabayinze2010,

title = {Use of RDTs to improve malaria diagnosis and fever  case management at primary health care facilities  in Uganda},

author = {Daniel J Kyabayinze and Caroline Asiimwe and Damalie Nakanjako and Jane Nabakooza and Helen Counihan and James K Tibenderana},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Use-of-RDTs-to-improve-malaria-diagnosis-and-fever-case-management-at-primary-health-care-facilities-in-Ugand.pdf},

doi = { 10.1186/1475-2875-9-200},

year  = {2010},

date = {2010-07-12},

journal = {Malaria Journal},

abstract = {BACKGROUND:



Early and accurate diagnosis of malaria followed by prompt treatment reduces the risk of severe disease in malaria endemic regions. Presumptive treatment of malaria is widely practised where microscopy or rapid diagnostic tests (RDTs) are not readily available. With the introduction of artemisinin-based combination therapy (ACT) for treatment of malaria in many low-resource settings, there is need to target treatment to patients with parasitologically confirmed malaria in order to improve quality of care, reduce over consumption of anti-malarials, reduce drug pressure and in turn delay development and spread of drug resistance. This study evaluated the effect of malaria RDTs on health workers' anti-malarial drug (AMD) prescriptions among outpatients at low level health care facilities (LLHCF) within different malaria epidemiological settings in Uganda.

METHODS:



All health workers (HWs) in 21 selected intervention (where RDTs were deployed) LLHF were invited for training on the use RDTs. All HWs were trained to use RDTs for parasitological diagnosis of all suspected malaria cases irrespective of age. Five LLHCFs with clinical diagnosis (CD only) were included for comparison. Subsequently AMD prescriptions were compared using both a 'pre-post' and 'intervention-control' analysis designs. In-depth interviews of the HWs were conducted to explore any factors that influence AMD prescription practices.

RESULTS:



A total of 166,131 out-patient attendances (OPD) were evaluated at 21 intervention LLHCFs. Overall use of RDTs resulted in a 38% point reduction in AMD prescriptions. There was a two-fold reduction (RR 0.62, 95% CI 0.55-0.70) in AMD prescription with the greatest reduction in the hypo-endemic setting (RR 0.46 95% CI 0.51-0.53) but no significant change in the urban setting (RR1.01, p-value=0.820). Over 90% of all eligible OPD patients were offered a test. An average of 30% (range 25%-35%) of the RDT-negative fever patients received AMD prescriptions. When the test result was negative, children under five years of age were two to three times more likely (OR 2.6 p-value<0.001) to receive anti-malarial prescriptions relative to older age group. Of the 63 HWs interviewed 92% believed that a positive RDT result confirmed malaria, while only 49% believed that a negative RDT result excluded malaria infection.

CONCLUSION:



Use of RDTs resulted in a 2-fold reduction in anti-malarial drug prescription at LLHCFs. The study demonstrated that RDT use is feasible at LLHCFs, and can lead to better targetting of malaria treatment. Nationwide deployment of RDTs in a systematic manner should be prioritised in order to improve fever case management. The process should include plans to educate HWs about the utility of RDTs in order to maximize acceptance and uptake of the diagnostic tools and thereby leading to the benefits of parasitological diagnosis of malaria.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Lamorde2010e,

title = {Medicinal plants used by traditional medicine practitioners for the treatment of HIV/AIDS and related conditions in Uganda.},

author = {Mohammed Lamorde and John R.S. Tabuti and Celestino Obua and Collins Kukunda-Byobona and Hindam Lanyero and Pauline Byakika-Kibwika and Godfrey S. Bbosa and Aloysius Lubega and Jasper Ogwal-Okeng and Mairin Ryan and Paul J. Waako and Concepta Merry},

doi = {10.1016/j.jep.2010.04.004.},

year  = {2010},

date = {2010-07-06},

journal = {Journal of Ethnopharmacology},

volume = {130},

number = {1},

pages = {43-53},

abstract = {INTRODUCTION AND OBJECTIVES:

In Uganda, there are over one million people with HIV/AIDS. When advanced, this disease is characterized by life-threatening opportunistic infections. As the formal health sector struggles to confront this epidemic, new medicines from traditional sources are needed to complement control efforts. This study was conducted to document herbal medicines used in the treatment of HIV/AIDS and related opportunistic infections, and to document the existing knowledge, attitudes and practices related to HIV/AIDS recognition, control and treatment in Sembabule, Kamuli, Kabale and Gulu districts in Uganda.

METHODS:

In this study, 25 traditional medicine practitioners (TMPs) were interviewed using structured questionnaires.

RESULTS:

The TMPs could recognize important signs and symptoms of HIV/AIDS and its associated opportunistic infections. The majority of practitioners treated patients who were already receiving allopathic medicines including antiretroviral drugs (ARVs) prescribed by allopathic practitioners. There were 103 species of medicinal plants identified in this survey. Priority plants identified include Aloe spp., Erythrina abyssinica, Sarcocephalus latifolius, Psorospermum febrifugum, Mangifera indica and Warburgia salutaris. There was low consensus among TMPs on the plants used. Decoctions of multiple plant species were commonly used except in Gulu where mono-preparations were common. Plant parts frequently used were leaves (33%), stem bark (23%) and root bark (18%). About 80% of preparations were administered orally in variable doses over varied time periods. The TMP had insufficient knowledge about packaging and preservation techniques.

CONCLUSIONS:

Numerous medicinal plants for treatment of HIV/AIDS patients were identified in the four districts surveyed and the role of these plants in the management of opportunistic infections warrants further investigation as these plants may have a role in Uganda's public health approach to HIV/AIDS control.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}