@article{Sekaggya2016,

title = {Challenges in achieving a target international normalized ratio for deep vein thrombosis among HIV-infected patients with tuberculosis: a case series. BMC Hematol},

author = {C. Sekaggya and D. Nalwanga and A. Von Braun and R. Nakijoba A. Kambugu and J. Fehr and M. Lamorde and B. Castelnuovo},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Challenges-in-achieving-a-target-international-normalized-ratio-for-deep-vein-thrombosis-among-HIV-infected-patients-with-tuberculosis-a-case-series.pdf},

doi = { 10.1186/s12878-016-0056-6},

year  = {2016},

date = {2016-06-04},

journal = {BMC Hematology},

volume = {16},

abstract = {BACKGROUND:



Tuberculosis (TB) and HIV are among the risk factors for deep vein thrombosis (DVT). There are several challenges in the management of DVT patients with TB-HIV co-infection including drug-drug interactions and non-adherence due to pill burden.

METHODS:



HIV infected patients starting treatment for TB were identified and followed up two weekly. Cases of DVT were diagnosed with Doppler ultrasound and patients were initiated on oral anticoagulation with warfarin and followed up with repeated INR measurements and warfarin dose adjustment.

RESULTS:



We describe 7 cases of TB and HIV-infected patients in Uganda diagnosed with DVT and started on anticoagulation therapy. Their median age was 30 (IQR: 27-39) years and 86 % were male. All patients had co-medication with cotrimoxazole, tenofovir, lamivudine and efavirenz and some were on fluconazole. The therapeutic range of the International Normalization Ratio (INR) was difficult to attain and unpredictable with some patients being under-anticoagulated and others over-anticoagulated. The mean Time in Therapeutic Range (TTR) for patients who had all scheduled INR measurements in the first 12 weeks was 33.3 %. Only one patient among those with all the scheduled INR measurements had achieved a therapeutic INR by 2 weeks. Four out of seven (57 %) of the patients had at least one INR above the therapeutic range which required treatment interruption. None of the patients had major bleeding.

CONCLUSION:



We recommend more frequent monitoring and timely dose adjustment of the INR, as well as studies on alternative strategies for the treatment of DVT in TB-HIV co-infected patients.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kiragga2016,

title = {Implementation and Operational Research: Impact of Nurse-Targeted Care on HIV Outcomes Among Immunocompromised Persons: A Before-After Study in Uganda.},

author = {Agnes N. Kiragga and Elizabeth Nalintya and Bozena M. Morawski and Joanita Kigozi and Benjamin J. Park and Jonathan E. Kaplan and David R. Boulware and David B. Meya and Yukari C. Manabe 

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Implementation-and-Operational-Research-Impact-of-Nurse-Targeted-Care-on-HIV-Outcomes-Among-Immunocompromised-Persons-A-Before-After-Study-in-Uganda..pdf},

doi = {10.1097/QAI.0000000000001002},

year  = {2016},

date = {2016-06-01},

journal = {Journal of Acquired Immune Defficiency Syndrome},

volume = {72},

number = {2},

pages = {32-36},

abstract = {Improving HIV outcomes among severely immunocompromised HIV-infected persons who have increased morbidity and mortality remains an important issue in sub-Saharan Africa. We sought to evaluate the impact of targeted clinic-based nurse care on antiretroviral therapy (ART) initiation and retention among severely immunocompromised HIV-infected persons.

METHODS:



The study included ART-naive patients with CD4 counts <100 cells per microliter registered in seven urban clinics in Kampala, Uganda. Data were retrospectively collected on patients enrolled from July to December 2011 (routine care cohort). Between July 2012 and September 2013, 1 additional nurse per clinic was hired (nurse counselor cohort) to identify new patients, expedite ART initiation, and trace those who were lost to follow-up. We compared time to ART initiation and 6-month retention in care between cohorts and used a generalized linear model to estimate the relative risk of retention.

RESULTS:



The study included 258 patients in the routine care cohort and 593 in the nurse counselor cohort. The proportion of patients who initiated ART increased from 190 (73.6%) in the routine care cohort to 506 (85.3%) in the nurse counselor cohort (P < 0.001). At 6 months, 62% of the routine care cohort were retained in care versus 76% in the nurse counselor cohort (P = 0.001). A 21% increase in the likelihood of retention in the nurse counselor cohort (relative risk: 1.21, 95% CI: 1.09 to 1.34) compared with the routine care cohort was observed.

CONCLUSIONS:



Implementation of targeted nurse-led care of severely immunocompromised HIV-infected patients in public outpatient health care facilities resulted in decreased time to ART initiation and increased retention.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Semeere2016b,

title = {A prospective ascertainment of cancer incidence in sub‐Saharan Africa: The case of Kaposi sarcoma},

author = {Aggrey Semeere and Megan Wenger and Naftali Busakhala and Nathan Buziba and Mwebesa Bwana and Winnie Muyindike and Erin Amerson and Toby Maurer and Timothy Mc Calmont and Philip LeBoit and Beverly Musick and Constantin Yiannoutsos and Robert Lukande and Barbara Castelnuovo and Miriam Laker-Oketta and Andrew Kambugu David Glidden and Kara Wools-Kaloustian and Jeffrey Martin},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/A-prospective-ascertainment-of-cancer-incidence-in-sub-Saharan-Africa-The-case-of-Kaposi-sarcoma..pdf},

doi = {10.1002/cam4.618},

year  = {2016},

date = {2016-05-28},

journal = {Cancer Medicine},

volume = {5},

number = {5},

pages = {914-928},

abstract = {In resource- limited areas, such as sub- Saharan Africa, problems in accurate cancer case ascertainment and enumeration of the at- risk population make it difficult to estimate cancer incidence. We took advantage of a large well- enumerated healthcare system to estimate the incidence of Kaposi sarcoma (KS), a cancer which has become prominent in the HIV era and whose incidence may be changing with the rollout of antiretroviral therapy (ART). To achieve this, we evaluated HIV- infected adults receiving care between 2007 and 2012 at any of three medical centers in Kenya and Uganda that participate in the East Africa International Epidemiologic Databases to Evaluate AIDS (IeDEA) Consortium. Through IeDEA, clinicians received training in KS recognition and biopsy equipment. We found that the overall prevalence of KS among 102,945 HIV- infected adults upon clinic enrollment was 1.4%; it declined over time at the largest site. Among 140,552 patients followed for 319,632 person- years, the age- standardized incidence rate was 334/100,000 person- years (95% CI: 314– 354/100,000 person- years). Incidence decreased over time and was lower in women, persons on ART, and those with higher CD4 counts. The incidence rate among patients on ART with a CD4 count >350 cells/mm3 was 32/100,000 person- years (95% CI: 14–70/100,000 person- years). Despite reductions over time coincident with the expansion of ART, KS incidence among HIV- infected adults in East Africa equals or exceeds the most common cancers in resource- replete settings. In resource- limited settings, strategic efforts to improve cancer diagnosis in combination with already well- enumerated at- risk denominators can make healthcare systems attractive platforms for estimating cancer incidence.

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Wandera2016,

title = {Efficacy of a Single, Brief Alcohol Reduction Intervention among Men and Women Living with HIV/AIDS and Using Alcohol in Kampala, Uganda: A Randomized Trial},

author = {Bonnie Wandera and Nazarius M Tumwesigye and Joaniter I Nankabirwa and David K Mafigiri and Rosalind Parkes-Rantashi and Saidi Kapiga and Judith Hahn and Ajay K Sethi

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Efficacy-of-a-Single-Brief-Alcohol-Reduction-Intervention-among-Men-and-Women-Living-with-HIVAIDS-and-Using-Alcohol-in-Kampala-Uganda-A-Randomized-Trial.pdf},

doi = {10.1177/2325957416649669},

year  = {2016},

date = {2016-05-23},

journal = {Journal of International Association pf Providers of AIDS Care},

volume = {16},

number = {3},

pages = {276-258},

abstract = {Objective—We evaluated the efficacy of a brief motivational intervention (MI) counseling in reducing alcohol consumption among persons living with HIV/AIDS (PLWHA) in KampalaUganda.

Methods—PLWHA attending an outpatient HIV clinic with alcohol disorders identification testConsumption component (AUDIT-C) score ≥3 points were randomized to either standardized positive prevention counseling alone or in combination with alcohol brief MI counseling. Mean change in AUDIT-C scores over 6 months were compared by treatment arm.

RESULTS—The mean (SD) AUDIT-C scores were 6.3(2.3) and 6.8(2.3), for control and MI arms (p=0.1) at baseline and change in mean AUDIT-C score was not statistically different between the treatment arms over the 6 months follow up time (P=0.8).

CONCLUSION—There was a non-differential reduction in alcohol consumption in both intervention and control arms. Standard positive prevention counseling should be provided to all PLWHA who use alcohol. Studies with more than one counseling session need to be evaluated},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Fife2016,

title = {Transient Increase in Herpes Simplex Virus Type 2 (HSV-2)–Associated Genital Ulcers Following Initiation of Antiretroviral Therapy in HIV/HSV-2–Coinfected Individuals },

author = {Kenneth H. Fife and Kenneth Mugwanya and Katherine K. Thomas and Jared M. Baeten and Connie Celum and Elizabeth Bukusi and Guy de Bruyn and Andrew Mujugira and Bellington Vwalika and Anna Wald and Jairam R. Lingappa for the Partners in Prevention HSV/HIV Transmission Study Team },

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Transient-Increase-in-Herpes-Simplex-Virus-Type-2-HSV-2-Associated-Genital-Ulcers-Following-Initiation-of-Antiretroviral-Therapy-in-HIVHSV-2-Coinfected-Individuals..pdf},

doi = {10.1093/infdis/jiv765},

year  = {2016},

date = {2016-05-15},

journal = {Journal of Infectious Diseases},

volume = {213},

number = {10},

pages = {1573-1578},

abstract = {BACKGROUND:



Immune reconstitution inflammatory syndrome (IRIS) in human immunodeficiency virus (HIV)-infected persons beginning antiretroviral therapy (ART) has been incompletely characterized for herpes simplex virus type 2 (HSV-2).

METHODS:



We evaluated genital ulcer disease (GUD) and HSV-2-associated GUD at quarterly visits or when spontaneously reported at monthly visits in 3381 HIV/HSV-2-coinfected individuals in a placebo-controlled trial of suppressive acyclovir therapy to prevent HIV transmission, 349 of whom initiated ART during the study. Incidence was calculated for months before and after ART initiation, and incidence rate ratios (IRRs) were calculated.

RESULTS:



GUD incidence increased from 15.0 episodes per 100 person-years before ART to 26.9 episodes per 100 person-years in the first full quarter after ART initiation (IRR, 1.83;P= .03), and the incidence of HSV-2-associated GUD increased from 8.1 to 19.0 episodes per 100 person-years (IRR, 2.20;P= .02). Subsequently, the incidence of GUD was similar to that before ART, although the numbers were small. Persons receiving suppressive acyclovir had fewer GUD episodes, but the IRR after beginning ART was similar in the acyclovir and placebo groups.

CONCLUSIONS:



Initiation of ART in HIV/HSV-2-coinfected persons is associated with a transient increase in GUD and HSV-2 GUD. Acyclovir reduces the incidence of GUD but does not prevent an increase in GUD incidence during the first quarter following initiation of ART.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Sempa2016,

title = {Reevaluating Cumulative HIV-1 Viral Load as a Prognostic Predictor: Predicting Opportunistic Infection Incidence and Mortality in a Ugandan Cohort.},

author = {Joseph B. Sempa and Jonathan Dushoff and Michael J. Daniels and Barbara Castelnuovo and AgnesN.Kiragga and Martin Nieuwoudt and Steven E. Bellan

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Reevaluating-Cumulative-HIV-1-Viral-Load-as-a-Prognostic-Predictor-Predicting-Opportunistic-Infection-Incidence-and-Mortality-in-a-Ugandan-Cohort.pdf},

doi = { 10.1093/aje/kwv303.},

year  = {2016},

date = {2016-05-05},

journal = {Journal of American Epidemiology},

volume = {184},

number = {1},

pages = {67-77},

abstract = {Recent studies have evaluated cumulative human immunodeficiency virus type 1 (HIV-1) viral load (cVL) for predictingdiseaseoutcomes, with discrepant results. We reviewedthe disparatemethodologicalapproachestakenand evaluated the prognostic utility of cVL in a resource-limited setting. Using data on the Infectious Diseases Institute (Makerere University, Kampala,Uganda) cohort, who initiated antiretroviral therapy in2004–2005and were followed upfor9years,wecalculatedpatients’ time-updatedcVLbysummingtheareaundertheirviralloadcurvesoneithera linearscale (cVL1) ora logarithmicscale(cVL2). Using Coxproportional hazards models, we evaluated bothmetrics as predictors of incident opportunistic infections and mortality. Among 489 patients analyzed, neither cVL measure wasastatisticallysignificantpredictorofopportunisticinfectionrisk.Incontrast,cVL2 (butnotcVL1)wasastatistically significantpredictorofmortality,witheachlog10 increasecorrespondingtoa1.63-fold(95%confidenceinterval:1.02, 2.60)elevationinmortalityriskwhencVL2 wasaccumulatedfrombaseline.However,whethercVLispredictiveornot hingesondifficultchoicessurroundingthecVLmetricandstatisticalmodelemployed.Previousstudiesmayhavesuffered fromconfounding bias due to their focus oncVL1, which strongly correlates with other variables. Further methodological development is needed to illuminate whether the inconsistent predictive utility of cVL arises from causal relationships or from statistical artifacts.

Cox proportional hazards models; HIV; human immunodeficiency virus; Martingale residuals; mortality; opportunistic infections; viral load; viremia copy-years

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Alvarez2016,

title = {Which HIV patients should be screened for osteoporosis: an international perspective },

author = {Alvarez, Elena ; Belloso, Waldo H. ; Boyd, Mark A. ; Inkaya, Ahmet Ç. ; Hsieh, Evelyn ; Kambugu, Andrew; Kaminski, Greg ; Martinez, Esteban; Stellbrink, Hans-Jürgen; Walmsley, Sharon; Brown, Todd T.; Mallon, Patrick W.G.},

doi = {https://doi.org/10.1097/COH.0000000000000269},

year  = {2016},

date = {2016-05-01},

journal = {Wolters Kluwer},

volume = {11},

number = {3},

pages = {268-276(9)},

abstract = { Purpose of review



This review provides international insights into the real-world clinical approach to screening for bone mineral density (BMD) and osteoporosis in people living with HIV (PLWH) using opinions from HIV physicians from key regions around the world.



Recent findings



Although a significant proportion of PLWH are aged over 50, the relative importance of low BMD to clinical care differs significantly between countries and regions, based on factors such as the population at risk, access to adequate screening resources, and physicians’ knowledge. Generally, management of osteoporosis in PLWH follows similar principals as for the general population, with risk factors for fracture combined with measurement of BMD by dual energy X-ray absorptiometry in algorithms such as Fracture Risk Assessment Tool, designed to provide an overall risk estimation. Although in most regions age is considered among the most important factors contributing to low BMD and fractures, considerable country and region-specific factors become apparent, such as malnutrition, inactivity and impact of comorbidities, substance abuse, and increasing use of tenofovir disoproxil fumarate.Summary



These opinions highlight the diversity that still exists in the approach to the long-term management of PLWH and highlight challenges facing development of consensus guidelines that can be effectively implemented worldwide. },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Shenai2016,

title = {Analytical and Clinical Evaluation of the Epistem Genedrive Assay for Detection of Mycobacterium tuberculosis},

author = {Shubhada Shenai and Derek T. Armstrong and Eloise Valli and David L. Dolinger and Lydia Nakiyingi and Reynaldo Dietze and Margareth Pretti Dalcolmo and Mark P. Nicol and Widaad Zemanay and Yuka Manabe and David Jamil Hadad Patricia Marques-Rodrigues and Moises Palaci and Renata L. Peres and Mary Gaeddert and Sandra Armakovitch and Bareng A. S. Nonyane,h Claudia M. Denkinger,c Padmapriya Banada,a Moses L. Joloba,i Jerrold Ellner,g Catharina Boehme and David Alland and Susan E. Dorman and the TB Clinical Diagnostics Research Consortium },

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Analytical-and-Clinical-Evaluation-of-the-Epistem-Genedrive-Assay-for-Detection-of-Mycobacterium-tuberculosis.pdf},

doi = {10.1128/JCM.02847-15},

year  = {2016},

date = {2016-04-25},

journal = {Journal of Microbiology},

volume = {56},

number = {4},

pages = {1051-1057},

abstract = {The Epistem Genedrive assay rapidly detects the Mycobacterium tuberculosis complex from sputum and is currently available for clinical use. However, the analytical and clinical performance of this test has not been fully evaluated. The analytical limit of detection (LOD) of the Genedrive PCR amplification was tested with genomic DNA; the performance of the complete (sample processing plus amplification) system was tested by spiking M. tuberculosis mc26030 cells into distilled water and M. tuberculosis-negative sputum. Specificity was tested using common respiratory pathogens and nontuberculosis mycobacteria. A clinical evaluation enrolled adults with suspected pulmonary tuberculosis, obtained three sputum samples from each participant, and compared the accuracy of the Genedrive to that of the Xpert MTB/RIF assay using M. tuberculosis cultures as the reference standard. The Genedrive assay had an LOD of 1 pg/μl (100 genomic DNA copies/reaction). The LODs of the system were 2.5 × 104 CFU/ml and 2.5 × 105 CFU/ml for cells spiked into water and sputum, respectively. False-positive rpoB probe signals were observed in 3/32 (9.4%) of the negative controls and also in few samples containing Mycobacterium abscessus, Mycobacterium gordonae, or Mycobacterium thermoresistibile. In the clinical study, among 336 analyzed participants, the overall sensitivities for the tuberculosis case detection of Genedrive, Xpert, and smear microscopy were 45.4% (95% confidence interval [CI], 35.2% to 55.8%), 91.8% (95% CI, 84.4% to 96.4%), and 77.3% (95% CI, 67.7% to 85.2%), respectively. The sensitivities of Genedrive and Xpert for the detection of smear-microscopy-negative tuberculosis were 0% (95% CI, 0% to 15.4%) and 68.2% (95% CI, 45.1% to 86.1%), respectively. The Genedrive assay did not meet performance standards recommended by the World Health Organization for a smear microscopy replacement tuberculosis test. Epistem is working on modifications to improve the assay.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kambugu2016,

title = {Neurocognitive Function at the First-Line Failure and on the Second-Line Antiretroviral Therapy in Africa: Analyses From the EARNEST Trial},

author = {Andrew Kambugu and Jennifer Thompson and James Hakim and Dinah Tumukunde and Joep J. van Oosterhout and Raymond Mwebaze and Anne Hoppe and James Abach and Charles Kwobah and Alejandro Arenas-Pinto and Sarah A. Walker and Nicholas I. Paton for the EARNEST Trial Team

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Neurocognitive-Function-at-the-First-Line-Failure-and-on-the-Second-Line-Antiretroviral-Therapy-in-Africa-Analyses-From-the-EARNEST-Trial..pdf},

doi = {10.1097/QAI.0000000000000898.},

year  = {2016},

date = {2016-04-15},

journal = {Journal of Acquired Immune Defficiency Syndrome},

volume = {71},

number = {5},

pages = {506-513},

abstract = {Objective: To assess neurocognitive function at the first-line antiretroviral therapy failure and change on the second-line therapy. Design: Randomized controlled trial was conducted in 5 subSaharan African countries. Methods: Patients failing the first-line therapy according to WHO criteria after .12 months on non-nucleoside reverse transcriptase inhibitors-based regimens were randomized to the second-line therapy (open-label) with lopinavir/ritonavir (400 mg/100 mg twice daily) plus either 2–3 clinician-selectednucleoside reversetranscriptaseinhibitors, raltegravir, or as monotherapy after 12-week induction with raltegravir. Neurocognitive function was tested at baseline, weeks 48 and 96 using color trails tests 1 and 2, and the Grooved Pegboard test. Test results were converted to an average of the 3 individual test z-scores. Results: A total of 1036 patients (90% of those .18 years enrolled at 13 evaluable sites) had valid baseline tests (58% women, median: 38 years, viral load: 65,000 copies per milliliter, CD4 count: 73 cells per cubic millimeter). Mean (SD) baseline z-score was 22.96 (1.74); lower baseline z-scores were independently associated with older age,

lower body weight, higher viral load, lower hemoglobin, less education, fewer weekly working hours, previous central nervous system disease, and taking fluconazole (P , 0.05 in multivariable model). Z-score was increased by mean (SE) of +1.23 (0.04) after 96 weeksonthe second-line therapy (P , 0.001; n =915evaluable), with no evidence of difference between the treatment arms (P = 0.35). Conclusions: Patients in sub-Saharan Africa failing the first-line therapy had low neurocognitive function test scores, but performance improved on the second-line therapy. Regimens with more central nervous system-penetrating drugs did not enhance neurocognitive recovery indicating this need not be a primary consideration in choosing a second-line regimen.

Key Words: neurocognitive function, antiretroviral therapy, failure, second line, Africa, trial

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Charles2016,

title = {Implementation of Tuberculosis Intensive Case Finding, Isoniazid Preventive Therapy, and Infection Control ("Three I's") and HIV-Tuberculosis Service Integration in Lower Income Countries.},

author = {M. Katherine Charles and Mary LouLindegren and C. William Wester and Meridith Blevins and Timothy R. Sterling and Nguyen ThiDung and Jean Claude Dusingize and Divine Avit-Edi and Nicolas Durier and Barbara Castelnuovo and Gertrude Nakigozi and Claudia P.Cortes MarieBallif9,LukasFenner9,10,11,InternationalepidemiologyDatabasestoEvaluateAIDS (IeDEA)Collaboration¶

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Implementation-of-Tuberculosis-Intensive-Case-Finding-Isoniazid-Preventive-Therapy-and-Infection-Control-Three-Is-and-HIV-Tuberculosis-Service-Integration-in-Lower-Income-Countries.pdf},

doi = {10.1371/journal.pone.0153243},

year  = {2016},

date = {2016-04-13},

journal = {PloS One},

volume = {11},

number = {4},

abstract = {Setting World Health Organization advocates for integration of HIV-tuberculosis(TB) services and recommends intensive casefinding (ICF),isoniazid preventive therapy(IPT),and infection control (“ThreeI’s”) for TB prevention and control among personsliving with HIV.

Objective To assess the implementation of the “ThreeI’s” ofTB-control at HIV treatmentsites i nlower incomecountries.

Design Survey conducted between March-July,201 2at 47sitesin26countries:6(13%)Asia Pacific,7(15%),Caribbean,Central and South America,5(10%)Central  Africa,8(17%) East Africa,14(30%)Southern Africa,and7(15%)West Africa

Results ICFusingsymptom-basedscreeningwasperformed at38%ofsites;45%ofsitesused symptom-screening plusadditionaldiagnostics.IPTatenrollmentorARTinitiationwas implemented inonly17%ofsites,with9%ofsitesprovidingIPTtotuberculin-skin-testpositivepatients.Infectioncontrolmeasuresvaried:62%ofsitesseparatedsmear-positive patients,andhealthcareworkersusedmasksat57%ofsites.Only12(26%)sitesintegratedHIV-TBservices.IntegrationwasnotassociatedwithimplementationofTBpreventionmeasuresexceptforIPTprovisionatenrollment(42%integratedvs.9%nonintegrated;p=0.03).

Conclusions ImplementationofTBscreening,IPTprovision,andinfectioncontrolmeasureswaslowand variableacrossregional HIVtreatmentsites,regardless ofintegration status.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Nalintya2016,

title = {Evolution of Cryptococcal Antigen Testing: What Is New?},

author = {Elizabeth Nalintya, Reuben Kiggundu & David Meya },

doi = {https://doi.org/10.1007/s12281-016-0256-3},

year  = {2016},

date = {2016-04-12},

journal = {Current Fungal Infection Reports},

pages = {62-67},

abstract = {Over the last decade, an upsurge in both the frequency and severity of fungal infections due to the HIV/AIDS epidemic and the use of immunosuppressive therapy has occurred. Even diagnostic methods like culture and microscopy, which have low sensitivity and longer turnaround times, are not widely available, leading to delays in timely antifungal therapy and detrimental patient outcomes. The evolution of cryptococcal antigen (CrAg) testing to develop inexpensive and more sensitive methods to detect cryptococcal antigen is significant. These newer tests employ immunoassays as part of point-of-care platforms, which do not require complex laboratory infrastructure, and they have the potential to detect early disease and reduce time to diagnosis of cryptococcal infection. Advocacy for widely available and efficacious life-saving antifungal treatment should be the only remaining challenge.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Mujugira2016,

title = {Seminal HIV-1 RNA Detection in Heterosexual African Men Initiating Antiretroviral Therapy},

author = {Andrew Mujugira and Robert W. Coombs and Renee Heffron and Connie Celum and Allan Ronald and Nelly Mugo and Jared M. Baeten for the Partners PrEP Study Teama },

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Seminal-HIV-1-RNA-Detection-in-Heterosexual-African-Men-Initiating-Antiretroviral-Therapy.pdf},

doi = {10.1093/infdis/jiw131.},

year  = {2016},

date = {2016-04-06},

journal = {Journal of Infectious Diseases},

volume = {214},

number = {2},

pages = {212-215},

abstract = {BACKGROUND:



Intermittent shedding of human immunodeficiency virus type 1 (HIV) in semen occurs despite effective antiretroviral therapy (ART) and suppressed blood HIV-1 RNA levels.

METHODS:



We assessed the frequency, magnitude, and correlates of seminal HIV-1 RNA shedding in HIV-1-infected African men initiating ART.

RESULTS:



Seminal HIV-1 RNA was detected in 24% (37 of 155), 10% (5 of 49), and 11% (8 of 70) of samples collected 0-3, 4-6, and >6 months after ART initiation. When blood HIV-1 levels were suppressed, seminal HIV-1 RNA was detected in 8% (16 of 195), and 82% (13 of 16) had an HIV-1 RNA load of < 1000 copies/mL.

CONCLUSIONS:



Seminal HIV-1 RNA shedding was infrequent and present at low levels in HIV-1-infected African men with suppressed blood HIV-1 RNA.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Mugwanya2016,

title = {Reversibility of Glomerular Renal Function Decline in HIV-Uninfected Men and Women Discontinuing Emtricitabine-Tenofovir Disoproxil Fumarate Pre-Exposure Prophylaxis},

author = {Kenneth K. Mugwanya and Christina Wyatt and Connie Celum and Deborah Donnell and James Kiarie and Allan Ronald and Jared M. Baeten and the Partners PrEP Study Team},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Reversibility-of-Glomerular-Renal-Function-Decline-in-HIV-Uninfected-Men-and-Women-Discontinuing-Emtricitabine-Tenofovir-Disoproxil-Fumarate-Pre-Exposure-Prophylaxis.pdf},

doi = {10.1097/QAI.0000000000000868},

year  = {2016},

date = {2016-04-01},

journal = {Journal of Acquired Immune Defficiency Syndrome},

volume = {71},

number = {4},

pages = {374-380},

abstract = {BACKGROUND:



Tenofovir disoproxil fumarate (TDF) pre-exposure prophylaxis (PrEP) use is associated with a small but statistically significant decline in estimated glomerular filtration rate (eGFR). We investigated the reversibility of eGFR decline among HIV-uninfected adults discontinuing PrEP.

METHODS:



Data were from the Partners PrEP Study, a randomized trial of daily oral TDF and emtricitabine (FTC)-TDF PrEP among African HIV-uninfected men and women with baseline creatinine clearance ≥60 mL/min. Serum creatinine was measured quarterly while on-study medication and at month 1 and 2 after discontinuation. eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration Equation.

RESULTS:



A total of 3924 individuals had a poststudy drug serum creatinine measurement after the scheduled drug discontinuation (1271 for TDF, 1308 for FTC-TDF, and 1345 for placebo); 65% were men, median age was 35 (range 18-64) years. Median time on study drug was 33 (interquartile range 25-36) months overall, and 36 months (interquartile range 30-36) for TDF and FTC-TDF. Mean eGFR at the last on-treatment visit was 129 mL·min·1.73 m for TDF and 128 mL·min·1.73 m for FTC-TDF versus 131 mL·min·1.73 m for placebo (2-3 mL·min·1.73 m mean decline for PrEP versus placebo, P ≤ 0.01), and this difference reversed by 4 weeks after drug discontinuation (mean eGFR at the first postdrug visit: 130 mL·min 1.73 m in all groups). More than 96% of participants had a confirmed >75% eGFR rebound to baseline level by 8 weeks after drug discontinuation, with similar proportions across treatment groups.

CONCLUSIONS:



In this large, placebo-controlled study of TDF-based PrEP, the small reduction in mean eGFR associated with PrEP reversed within weeks after discontinuation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Hamza2016,

title = {Cost Effectiveness of Antivenoms for Snakebite Envenoming in 16 Countries in West Africa},

author = {Muhammad Hamza and Maryam A.Idris and Musa B. Maiyaki and Mohammed Lamorde and Jean Philippe Chippaux and David A. Warrell and Andreas Kuznik and Abdul Razaq and G. Habib},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Cost-EffectivenessofAntivenomsfor-SnakebiteEnvenomingin16Countriesin-WestAfrica.pdf},

year  = {2016},

date = {2016-03-30},

journal = {PloS Neglected Tropical Diseases},

volume = {10},

number = {3},

abstract = {Background



Snakebite poisoning is a significant medical problem in agricultural societies in Sub Saharan Africa. Antivenom (AV) is the standard treatment, and we assessed the cost-effectiveness of making it available in 16 countries in West Africa.

Methods



We determined the cost-effectiveness of AV based on a decision-tree model from a public payer perspective. Specific AVs included in the model were Antivipmyn, FAV Afrique, EchiTab-G and EchiTab-Plus. We derived inputs from the literature which included: type of snakes causing bites (carpet viper (Echis species)/non-carpet viper), AV effectiveness against death, mortality without AV, probability of Early Adverse Reactions (EAR), likelihood of death from EAR, average age at envenomation in years, anticipated remaining life span and likelihood of amputation. Costs incurred by the victims include: costs of confirming and evaluating envenomation, AV acquisition, routine care, AV transportation logistics, hospital admission and related transportation costs, management of AV EAR compared to the alternative of free snakebite care with ineffective or no AV. Incremental Cost Effectiveness Ratios (ICERs) were assessed as the cost per death averted and the cost per Disability-Adjusted-Life-Years (DALY) averted. Probabilistic Sensitivity Analyses (PSA) using Monte Carlo simulations were used to obtain 95% Confidence Intervals of ICERs.

Results



The cost/death averted for the 16 countries of interest ranged from $1,997 in Guinea Bissau to $6,205 for Liberia and Sierra Leone. The cost/DALY averted ranged from $83 (95% Confidence Interval: $36-$240) for Benin Republic to $281 ($159–457) for Sierra-Leone. In all cases, the base-case cost/DALY averted estimate fell below the commonly accepted threshold of one time per capita GDP, suggesting that AV is highly cost-effective for the treatment of snakebite in all 16 WA countries. The findings were consistent even with variations of inputs in 1—way sensitivity analyses. In addition, the PSA showed that in the majority of iterations ranging from 97.3% in Liberia to 100% in Cameroun, Guinea Bissau, Mali, Nigeria and Senegal, our model results yielded an ICER that fell below the threshold of one time per capita GDP, thus, indicating a high degree of confidence in our results.

Conclusions



Therapy for SBE with AV in countries of WA is highly cost-effective at commonly accepted thresholds. Broadening access to effective AVs in rural communities in West Africa is a priority.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Crook2016,

title = {Tuberculosis incidence is high in HIV-infected African children but is reduced by co-trimoxazole and time on antiretroviral therapy},

author = {Angela M. Crook and Anna Turkova and Victor Musiime and Mutsa Bwakura-Dangarembizi and Sabrina Bakeera-Kitaka and Patricia Nahirya-Ntege and Margaret Thomason and Peter Mugyenyi and Philippa Musoke and Adeodata Kekitiinwa and Paula Munderi and Kusum Nathoo and Andrew J. Prendergast and A. Sarah Walker and Diana M. Gibb and And The ARROW Trial Team},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Tuberculosis-incidence-is-high-in-HIV-infected-African-children-but-is-reduced-by-co-trimoxazole-and-time-on-antiretroviral-therapy.pdf},

doi = {10.1186/s12916-016-0593-7},

year  = {2016},

date = {2016-03-23},

journal = {BMC Medicine},

volume = {14},

abstract = {

Background



There are few data on tuberculosis (TB) incidence in HIV-infected children on antiretroviral therapy (ART). Observational studies suggest co-trimoxazole prophylaxis may prevent TB, but there are no randomized data supporting this. The ARROW trial, which enrolled HIV-infected children initiating ART in Uganda and Zimbabwe and included randomized cessation of co-trimoxazole prophylaxis, provided an opportunity to estimate the incidence of TB over time, to explore potential risk factors for TB, and to evaluate the effect of stopping co-trimoxazole prophylaxis.

Methods



Of 1,206 children enrolled in ARROW, there were 969 children with no previous TB history. After 96 weeks on ART, children older than 3 years were randomized to stop or continue co-trimoxazole prophylaxis; 622 were eligible and included in the co-trimoxazole analysis. Endpoints, including TB, were adjudicated blind to randomization by an independent endpoint review committee (ERC). Crude incidence rates of TB were estimated and potential risk factors, including age, sex, center, CD4, weight, height, and initial ART strategy, were explored in multivariable Cox proportional hazards models.

Results



After a median of 4 years follow-up (3,632 child-years), 69 children had an ERC-confirmed TB diagnosis. The overall TB incidence was 1.9/100 child-years (95 % CI, 1.5–2.4), and was highest in the first 12 weeks following ART initiation (8.8/100 child-years (5.2–13.4) versus 1.2/100 child-years (0.8–1.6) after 52 weeks). A higher TB risk was independently associated with younger age (<3 years), female sex, lower pre-ART weight-for-age Z-score, and current CD4 percent; fewer TB diagnoses were observed in children on maintenance triple nucleoside reverse transcriptase inhibitor (NRTI) ART compared to standard non-NRTI + 2NRTI.



Over the median 2 years of follow-up, there were 20 ERC-adjudicated TB cases among 622 children in the co-trimoxazole analysis: 5 in the continue arm and 15 in the stop arm (hazard ratio (stop: continue) = 3.0 (95 % CI, 1.1–8.3), P = 0.028). TB risk was also independently associated with lower current CD4 percent (P <0.001).

Conclusions



TB incidence varies over time following ART initiation, and is particularly high during the first 3 months post-ART, reinforcing the importance of TB screening prior to starting ART and use of isoniazid preventive therapy once active TB is excluded. HIV-infected children continuing co-trimoxazole prophylaxis after 96 weeks of ART were diagnosed with TB less frequently, highlighting a potentially important role of co-trimoxazole in preventing TB.

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kiragga2016b,

title = {Impact of nurse-targeted care on HIV outcomes among immunocompromised persons: a before-after study in Uganda},

author = {Agnes N. Kiragga and Elizabeth Nalintya and Bozena M. Morawski and Joanita Kigozi and Benjamin J. Park and Jonathan E. Kaplan and David R. Boulware and David B. Meya and Yukari C. Manabe

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Impact-of-nurse-targeted-care-on-HIV-outcomes-among-immunocompromised-persons.pdf},

doi = {10.1097/QAI.0000000000001002},

year  = {2016},

date = {2016-03-19},

journal = {Journal of Acquired Immune Defficiency Syndrome},

volume = {72},

number = {2},

pages = {32-36},

abstract = {Introduction—Improving HIV outcomes among severely immunocompromised HIV-infected persons who have increased morbidity and mortality remains an important issue in sub-Saharan Africa. We sought to evaluate the impact of targeted clinic- based nurse care on ART initiation and retention among severely immunocompromised HIV-infected persons.

Methods—The study included ART-naïve patients with CD4<100 cells/μL registered in seven urban clinics in Kampala, Uganda. Data were retrospectively collected on patients enrolled from July to December 2011 (routine care cohort). Between July 2012 and September 2013, one additional nurse per clinic was hired (nurse counselor cohort) to identify new patients, expedite ART initiation and trace those loss-to-follow-up. We compared time to ART initiation and 6month retention in care between cohorts and used a generalized linear model to estimate the relative risk of retention.

Results—The study included 258 patients in the routine care cohort and 593 in the nurse counselor cohort. The proportion of patients who initiated ART increased from 190 (73.6%) in the routine care cohort to 506 (85.3%) in the nurse counselor cohort (p<0.001). At 6 months, 62% of the routine care cohort were retained in care versus 76% in the nurse counselor cohort (p=0.001). A 21% increase in likelihood of retention in the nurse counselor cohort (relative risk 1.21, 95% CI, 1.09–1.34) compared with the routine care cohort was observed 

Conclusion—Implementation of targeted nurse–led care of severely immunocompromised HIVinfected patients in public outpatient health care facilities resulted in decreased time to ART initiation and increased retention},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Scarsi2016b,

title = {Unintended Pregnancies Observed With Combined Use of the Levonorgestrel Contraceptive Implant and Efavirenz-based Antiretroviral Therapy: A Three-Arm Pharmacokinetic Evaluation Over 48 Weeks},

author = {Kimberly K. Scarsi and KristinM.Darin and Shadia Nakalema and David J. Back,5 Pauline Byakika-Kibwika and Laura J. Else and Sujan Dilly Penchala and Allan Buzibye and Susan E. Cohn and Concepta Merry and Mohammed Lamorde },

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Unintended-Pregnancies-Observed-With-Combined-Use-of-the-Levonorgestrel-Contraceptive-Implant-and-Efavirenz-based-Antiretroviral-Therapy-A-Three-Arm-Pharmacokinetic-Evaluation-Over-48-Week.pdf},

doi = {10.1093/cid/civ1001},

year  = {2016},

date = {2016-03-15},

journal = {Clinical Infectious Diseases},

volume = {62},

number = {6},

pages = {673-682},

abstract = {Background. Levonorgestrel subdermal implants are preferred contraceptives with an expected failure rate of <1% over 5 years. We assessed the effect of efavirenz- or nevirapine-based antiretroviral therapy (ART) coadministration on levonorgestrel pharmacokinetics. Methods. This nonrandomized, parallel group, pharmacokinetic evaluation was conducted in three groups of human immunodeficiency virus–infected Ugandan women: ART-naive (n=17), efavirenz-based ART (n=20), and nevirapine-based ART (n=20). Levonorgestrel implants were inserted at baseline in all women. Blood was collected at 1, 4, 12, 24, 36, and 48 weeks. The primary endpoint was week 24 levonorgestrel concentrations, compared between the ART-naive group and each ART group by geometric mean ratio (GMR) with 90% confidence interval (CI). Secondary endpoints included week 48 levonorgestrel concentrations and unintended pregnancies. Results. Week 24 geometric mean levonorgestrel concentrations were 528, 280, and 710 pg/mL in the ART-naive, efavirenz, and nevirapine groups, respectively (efavirenz: ART-naive GMR, 0.53; 90% CI, .50, .55 and nevirapine: ART-naive GMR, 1.35; 90% CI, 1.29,1.43).Week48levonorgestrelconcentrationswere580,247,and664 pg/mLintheART-naive,efavirenz,andnevirapinegroups, respectively (efavirenz: ART-naive GMR, 0.43; 90% CI, .42, .44 and nevirapine: ART-naive GMR, 1.14; 90% CI, 1.14, 1.16). Three pregnancies (3/20, 15%) occurred in the efavirenz group between weeks 36 and 48. No pregnancies occurred in the ART-naive or nevirapine groups. Conclusions. Within 1 year of combined use, levonorgestrel exposure was markedly reduced in participants who received efavirenz-based ART, accompanied by contraceptive failures. In contrast, nevirapine-based ART did not adversely affect levonorgestrel exposure or efficacy. Clinical Trials Registration. NCT01789879. Keywords. contraceptive implant; levonorgestrel; efavirenz; nevirapine; unintended pregnancy.

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Rhein2016,

title = {Efficacy of adjunctive sertraline for the treatment of HIV-associated cryptococcal meningitis: an open-label dose-ranging study},

author = {Joshua Rhein and Bozena M Morawski and Kathy Huppler Hullsiek and Henry W Nabeta and Reuben Kiggundu and Lillian Tugume and Abdu Musubire and Andrew Akampurira and Kyle D Smith and Ali Alhadab and Darlisha A Williams and Mahsa Abassi and Nathan C Bahr and Sruti S Velamakanni and James Fisher and Kirsten Nielsen and David B Meya and David R Boulware on behalf of ASTRO-CM Study Team

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Efficacy-of-Adjunctive-Sertraline-for-the-Treatment-of-HIVAssociated-Cryptococcal-Meningitis-an-open-label-dose-ranging-study.pdf},

doi = {10.1016/S1473-3099(16)00074-8},

year  = {2016},

date = {2016-03-10},

journal = {Lancent Infectious Diseases},

volume = {16},

number = {7},

pages = {809-818},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Nakanjako2016,

title = {Frequency and impact of suboptimal immune recovery on first-line antiretroviral therapy (ART) within the IeDEA-East Africa cohort},

author = {Damalie Nakanjako and Agnes N. Kiraggaa and Beverly S. Musickc and Constantin T. Yiannoutsosc and Kara Wools-Kaloustiane and Lameck Dierof and Patrick Oyarog and Emanuel Luginah and John C. Ssalii, Andrew Kambugua nd Philippa Easterbrooka

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Frequency-and-impact-of-suboptimal-immune-recovery-on-first-line-antiretroviral-therapy-ART-within-the-IeDEA-East-Africa-cohort.pdf},

doi = {10.1097/QAD.0000000000001085},

year  = {2016},

date = {2016-03-08},

journal = {AIDS},

volume = {30},

number = {12},

pages = {1913-22},

abstract = {Objective—To describe patterns of suboptimal immune recovery (SO-IR) and associated HIVrelated-illnesses during the first 5 years following first-line antiretroviral therapy (ART) initiation across seven ART sites in East Africa.

Design—Retrospective analysis of data from seven ART clinical sites (three Uganda, two Kenya and two Tanzania). Methods—SO-IR was described by proportions of ART-treated adults with CD4+ cell counts less than 200, less than 350 and less than 500 cells/μl. Kaplan–Meier survival analysis techniques were used to assess predictors of SO-IR, and incident rates of HIV-related illnesses at CD4+ cell counts less than 200, 200–350, 351–499, and >500 cells/μl, respectively.

Results—Overall 80 843 adults initiated non-nucleoside reverse transcriptase inhibitor-based first-line ART; 65% were women and median CD4+ cell count was 126 [interquartile range (IQR), 52–202] cells/μl. Cumulative probability of SO-IR <200 cells/μl, <350 cells/μl and <500 cells/μl, after 5 years, was 11, 38 and 63%, respectively. Incidence of HIV-related illnesses was higher among those with CD4+ cell counts less than 200 and 200–350 cells/μl, than those who achieved CD4 counts above these thresholds. The most common events, at CD4 <200 cells/μl, were pulmonary tuberculosis [incident rate 15.98 (15.47–16.51)/100 person-years at risk (PYAR), oral candidiasis [incident rate 12.5 (12.03–12.94)] and herpes zoster [incident rate 6.30 (5.99–6.64)] events/100 PYAR. With attainment of a CD4+ cell count level 200–350 cells/μl, there was a substantial reduction in events/100 PYAR – by 91% to 1.45 (1.29–1.63) for TB, by 94% to 0.75 (0.64–0.89) for oral candidiasis, by 84% to 0.99 (0.86–1.14) for Herpes Zoster, and by 78% to 1.22 (1.07–1.39) for chronic diarrhea. The incidence of all events decreased further with CD4 counts above these thresholds.

Conclusion—Around 40% of adults initiated on ART have suboptimal immune recovery with CD4 counts <350 cells/ml after five years. Such patients will require closer monitoring for both HIV-related and non-HIV-related clinical events

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Rhein2016b,

title = {Diagnostic performance of a multiplex PCR assay for meningitis in an HIV-infected population in Uganda.},

author = {Joshua Rhein and Nathan C Bahr and Andrew C Hemmert and Joann L Cloud and Satya Bellamkonda and Cody Oswald and Eric Lo and Henry Nabeta and Reuben Kiggundu and Andrew Akampurira and Abdu Musubire and Darlisha Williams and David B Meya and David R Boulware on behalf of the ASTRO-CM Team},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Diagnostic-Performance-of-a-Multiplex-PCR-assay-for-meningitis-in-an-HIV-infected-population-in-Uganda.pdf},

doi = { 10.1016/j.diagmicrobio.2015.11.017},

year  = {2016},

date = {2016-03-01},

journal = {Diagonostic Microbiology and Infectious Disease},

volume = {84},

number = {3},

pages = {268-273},

abstract = {Meningitis remains a worldwide problem, and rapid diagnosis is essential to optimize survival. We evaluated the utility of a multiplex PCR test in differentiating possible etiologies of meningitis. Cerebrospinal fluid (CSF) from 69 HIV-infected Ugandan adults with meningitis was collected at diagnosis (n=51) and among persons with cryptococcal meningitis during therapeutic lumbar punctures (n=68). Cryopreserved CSF specimens were analyzed with BioFire FilmArray® Meningitis/Encephalitis panel, which targets 17 pathogens. The panel detected Cryptococcus in the CSF of patients diagnosed with a first-episode of cryptococcal meningitis by fungal culture with 100% sensitivity and specificity, and differentiated between fungal relapse and paradoxical immune reconstitution inflammatory syndrome in recurrent episodes. A negative FilmArray result was predictive of CSF sterility on follow-up lumbar punctures for cryptococcal meningitis. EBV was frequently detected in this immunosuppressed population (n=45). Other pathogens detected included: CMV (n=2), VZV (n=2), HHV-6 (n=1), and Streptococcus pneumoniae (n=1). The FilmArray Meningitis/Encephalitis panel offers a promising platform for rapid meningitis diagonosis},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ezeamama2016,

title = {Depressive and Anxiety Symptoms Predict Sustained Quality of Life Deficits in HIV-Positive Ugandan Adults Despite Antiretroviral Therapy : A prospective Therapy},

author = {Amara E Ezeamama and Makhable N. Woodfork and David Guwantudde and Danstan Bagenda and Yukari C Manabe and wafie W Fawzi and Mary C smith Fawzi },

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Depressive-and-Anxiety-Symptoms-Predict-Sustained-Quality-of-Life-Deficits-in-HIV-Positive-Ugandan-Adults-Despite-Antiretroviral-Therapy.pdf},

doi = {10.1097/MD.0000000000002525},

year  = {2016},

date = {2016-03-01},

journal = {Medicine (Baltimore)},

volume = {95},

number = {9},

abstract = {The impact of psychosocial status at onset of antiretroviral therapy on changes in quality of life (QOL) and subjectively rated health (SRH) among adults on highly active antiretroviral therapy (HAART) in resource-limited settings is poorly understood. Therefore, we evaluate the association between stigma, anxiety, depression, and social support and change in QOL and SRH in HIV-infected Ugandan adults during an 18-month period.



Psychosocial indicators were assessed at enrollment using structured questionnaires. QOL and SRH measures were assessed at months 0, 6, 12, and 18 using the Medical Outcomes Survey-HIV. Linear mixed models determined risk estimated differences in QOL and SRH in relation to quartiles of each psychosocial status indicator. Repeated measures generalized estimating equations modeling was implemented to assess differences in likelihood of improved versus nonimproved SRH during follow-up.



QOL scores and SRH improved significantly for all participants over 18 months (P < 0.0001). The gain in QOL increased dose-dependently as baseline depressive symptoms (time∗depression P < 0.001) and anxiety levels (time∗anxiety P < 0.001) declined. Lower social support was associated with worse QOL at baseline (P = 0.0005) but QOL improvement during follow-up was not dependent on baseline level of social support (time∗social support P = 0.8943) or number of stigmatizing experiences (time∗stigma P = 0.8662). Psychosocial determinants did not predict changes in SRH in this study.



High levels of depression and anxiety symptoms at HAART initiation predicts lower gains in QOL for HIV-positive patients for as long as 18 months. Long-term QOL improvements in HIV-infected adults may be enhanced by implementation of psychosocial interventions to reduce depression and anxiety in HIV-infected adults.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Amerson2016,

title = {Accuracy of Clinical Suspicion and Pathologic Diagnosis of Kaposi Sarcoma in East Africa},

author = {Erin Amerson and Carina Martin Woodruff and Amy Forrestel and Megan Wenger and Timothy McCalmont and Philip LeBoit and Toby Maurer and Miriam Laker-Oketta and Winnie Muyindike and Mwebesa Bwana and Nathan BuzibaMMed and Naftali Busakhala and Kara Wools-Kaloustian and Jeffrey Martin},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Accuracy-of-Clinical-Suspicion-and-Pathologic-Diagnosis-of-Kaposi-Sarcoma-in-East-Africa.pdf},

doi = {10.1097/QAI.0000000000000862},

year  = {2016},

date = {2016-03-01},

journal = {Journal of Acquired Immune Defficiency Syndrome},

volume = {71},

number = {3},

pages = {295-301},

abstract = {Background: HIV-associated Kaposi sarcoma (KS) is one of the most common malignancies in sub-Saharan Africa. The diagnosis is often based on clinical suspicion, without histopathologic confirmation. When biopsies are performed, the accuracy of interpretation by local pathologists is poorly understood. We assessed the accuracy of clinical suspicion and pathologic diagnosis of KS in 2 East African countries. Methods: At 2 large HIV care sites in Uganda and Kenya, we evaluated consecutive biopsies performed from October 2008 to January 2013 on HIV-infected adults with clinically suspected KS. Biopsies were interpreted by both local African pathologists and a group of US-based dermatopathologists from a high volume medical center. For the purpose of this analysis, the US-based dermatopathologist interpretation was used as the gold standard. Positive predictive value was used to characterize accuracy of local African clinical suspicion of KS, and concordance, sensitivity, and specificity were used to characterize accuracy of local pathologic diagnosis.

Results: Among 1106 biopsies, the positive predictive value of clinical suspicion of KS was 77% (95% confidence interval: 74% to 79%). When KS was not histopathologically diagnosed, clinically banal conditions were found in 35%, medically significant disorders which required different therapy in 59% and life-threatening diseases in 6%. Concordance between African pathologists and US-based dermatopathologists was 69% (95% confidence interval: 66% to 72%). Sensitivity and specificity of African pathologic diagnoses were 68% and 89%, respectively. Conclusions: Among East African HIV-infected patients, we found suboptimal positive predictive value of clinical suspicion of KS and specific, but not sensitive, histopathologic interpretation. The findings call for abandonment of isolated clinical diagnosis of KS in the region and augmentation of local dermatopathologic services.

Key Words: Kaposi sarcoma, cancer, diagnosis, sub-Saharan Africa, pathology, dermatopathology

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Elul2016,

title = {Untangling the Relationship Between Antiretroviral Therapy Use and Incident Pregnancy: A Marginal Structural Model Analysis Using Data From 47,313 HIV-Positive Women in East Africa.},

author = {Batya Elul and Kara K. Wools-Kaloustian and Yingfeng Wu and Beverly S. Musick and Harriet Nuwagaba-Biribonwoha and Denis Nas and Samuel Ayaya, MMed and Elizabeth Bukusi and Pius Okong and Juliana Otieno and Deo Wabwire and Andrew Kambugu and Constantin T. Yiannoutsos},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Untangling-the-Relationship-Between-Antiretroviral-Therapy-Use-and-Incident-Pregnancy-A-Marginal-Structural-Model-Analysis-Using-Data-From-47313-HIV-Positive-Women-in-East-Africa..pdf},

doi = {10.1097/QAI.0000000000000963},

year  = {2016},

date = {2016-02-19},

journal = {Journal of Acquired Immune Defficiency Syndrome},

volume = {72},

number = {3},

pages = {324-332},

abstract = {Background: Scale-upoftriple-drug antiretroviral therapy (ART) in Africa has transformed the context of childbearing for HIV-positive women and may impact pregnancy incidence in HIV programs. Methods: Using observational data from 47,313 HIV-positive women enrolled at 26 HIV clinics in Kenya and Uganda between 2001 and 2009, we calculated the crude cumulative incidence of pregnancy for the pre-ART and on-ART periods. The causal effect of ART use on incident pregnancy was assessed using inverse probability weighted marginal structural models, and the relationship was further explored in multivariable Cox models. Results: Crude cumulative pregnancy incidence at 1 year after enrollment/ART initiation was 4.0% and 3.9% during the pre-ART

and on-ART periods, respectively. In marginal structural models, ART use was not significantly associated with incident pregnancy [hazard ratio = 1.06; 95% confidence interval (CI): 0.99 to 1.12]. Similarly, in Cox models, there was no significant relationship between ART use and incident pregnancy (cause-specific hazard ratio: 0.98; 95% CI: 0.91 to 1.05), but effect modification was observed. Specifically, women who were pregnant at enrollment and on ART had an increased risk of incident pregnancy compared to those not pregnant at enrollment and not on ART (cause-specific hazard ratio: 1.11; 95% CI: 1.01 to 1.23). Conclusions: In this large cohort, ART initiation was not associated with incident pregnancy in the general population of women enrolling in HIV care but rather only among those pregnant at enrollment. This finding further highlights the importance of scaling up access to lifelong treatment for pregnant women.

Key Words: pregnancy incidence, ART, HIV/AIDS, sub-Saharan Africa

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Freeman2016,

title = {Pitfalls of practicing cancer epidemiology in resource-limited settings: the case of survival and loss to follow-up after a diagnosis of Kaposi's sarcoma in five countries across sub-Saharan Africa},

author = {Esther Freeman and Aggrey Semeere and Megan Wenger and Mwebesa Bwana and F. Chite Asirwa and Naftali Busakhala and Emmanuel Oga and Elima Jedy-Agba and Vivian Kwaghe and Kenneth Iregbu and Antoine Jaquet and Francois Dabis and Habakkuk Azinyui Yumo and Jean Claude Dusingize and David Bangsberg and Kathryn Anastos and Sam Phiri and Julia Bohlius and Matthias Egger and Constantin Yiannoutsos and Kara Wools-Kaloustian and Jeffrey Martin

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Pitfalls-of-practising-cancer-epidemiology-in-resource-limitted-setting.pdf},

doi = {10.1186/s12885-016-2080-0},

year  = {2016},

date = {2016-02-06},

journal = {BMC Cancer},

volume = {16},

number = {1},

abstract = {Background: Survival after diagnosis is a fundamental concern in cancer epidemiology. In resource-rich settings, ambient clinical databases, municipal data and cancer registries make survival estimation in real-world populations relatively straightforward. In resource-poor settings, given the deficiencies in a variety of health-related data systems, it is less clear how well we can determine cancer survival from ambient data. Methods: We addressed this issue in sub-Saharan Africa for Kaposi’s sarcoma (KS), a cancer for which incidence has exploded with the HIV epidemic but for which survival in the region may be changing with the recent advent of antiretroviral therapy (ART). From 33 primary care HIV Clinics in Kenya, Uganda, Malawi, Nigeria and Cameroon participating in the International Epidemiologic Databases to Evaluate AIDS (IeDEA) Consortia in 2009–2012, we identified 1328 adults with newly diagnosed KS. Patients were evaluated from KS diagnosis until death, transfer to another facility or database closure. Results: Nominally, 22 % of patients were estimated to be dead by 2 years, but this estimate was clouded by 45 % cumulative lost to follow-up with unknown vital status by 2 years. After adjustment for site and CD4 count, age <30 years and male sex were independently associated with becoming lost. Conclusions: In this community-based sample of patients diagnosed with KS in sub-Saharan Africa, almost half became lost to follow-up by 2 years. This precluded accurate estimation of survival. Until we either generally strengthen data systems or implement cancer-specific enhancements (e.g., tracking of the lost) in the region, insights from cancer epidemiology will be limited. Keywords: Survival, Mortality, Kaposi’s sarcoma, HIV/AIDS, Cancer, Resource-limited settings, Africa, Loss to follow-up, Cohort

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Mujugira2016b,

title = {Younger Age Predicts Failure to Achieve Viral Suppression and Virologic Rebound Among HIV-1-Infected Persons in Serodiscordant Partnerships},

author = {Andrew Mujugira and Connie Celum and Jordan W. Tappero and Allan Ronald and Nelly Mugo and Jared M. Baeten},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Younger-Age-Predicts-Failure-to-Achieve-Viral-Suppression-and-Virologic-Rebound-Among-HIV-1-Infected-Persons-in-Serodiscordant-Partnerships.pdf},

doi = {10.1089/AID.2015.0296},

year  = {2016},

date = {2016-02-05},

journal = {AIDS Research and Human Retroviruses},

volume = {32},

number = {2},

pages = {148-154},

abstract = {Background: Antiretroviral therapy (ART) markedly reduces the risk of HIV-1 transmission in serodiscordant partnerships. We previously found that younger age and higher CD4 counts were associated with delayed initiation of ART by HIV-1-infected partners in serodiscordant partnerships. Among those initiating ART, we sought to explore whether those same factors were associated with failure to achieve viral suppression. Methods: In a prospective study of HIV-1-infected persons who had a known heterosexual HIV-1-uninfected partner in Kenya and Uganda [Partners Pre-Exposure Prophylaxis (PrEP) Study], we used Cox proportional hazards regression to evaluate correlates of viral nonsuppression (HIV-1 RNA >80 copies/ml). Results: Of 1,035 HIV-1-infected participants initiating ART, 867 (84%) achieved viral suppression: 77% by 6 months and 86% by 12 months. Younger age [adjusted hazard ratio (aHR) 1.05 for every 5 years younger; p=.006], lower pretreatment CD4 count (aHR 1.26; p=.009 for £250 compared with >250 cells/ll), and higher pretreatment HIV-1 RNA quantity (aHR 1.21 per log10; p<.001) independently predicted failure to achieve viral suppression. Following initial viral suppression, 8.8% (76/867) experienced virologic rebound (HIV-1 RNA >200 copies/ml): 6.3% and 11.5% by 6 and 12 months after initial suppression, respectively. Age was the only factor associated with increased risk of virologic rebound (aHR 1.33 for every 5 years younger; p=.005). Conclusions: For HIV-1-infected persons in serodiscordant couples, younger age was associated with delayed ART initiation, failure to achieve viral suppression, and increased risk of virologic rebound. Motivating ART initiation and early adherence is a key to achieving and sustaining viral suppression.

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Meya2016,

title = {The immunopathogenesis of cryptococcal immune reconstitution inflammatory syndrome: understanding a conundrum},

author = {David B Meya and Yukari C Manabe and David R Boulware and Edward N Janoff

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/The-Immunopathogenesis-of-Cryptococcal-Immune-Reconstitution-Inflammatory-Syndrome-Understanding-a-Conundrum.pdf},

doi = {10.1097/QCO.0000000000000224},

year  = {2016},

date = {2016-02-01},

journal = {Current Opinion in Infectious Diseases},

volume = {29},

number = {1},

pages = {10-22},

abstract = {Purpose of Review—Cryptococcal meningitis (CM) causes significant mortality among HIVinfected patients, despite antifungal therapy and use of antiretroviral therapy (ART). In patients with CM, ART is often complicated by immune reconstitution inflammatory syndrome (IRIS), manifesting as unmasking of previously unrecognized subclinical infection (unmasking CM-IRIS) or paradoxical worsening of symptoms in the central nervous system after prior improvement with antifungal therapy (paradoxical CM-IRIS). We review our current understanding of the pathogenesis of this phenomenon, focusing on unifying innate and adaptive immune mechanisms leading to the development of this often fatal syndrome. Recent Findings—We propose that HIV-associated CD4+ T cell depletion, chemokine-driven trafficking of monocytes into cerebrospinal fluid (CSF) in response to CM, and poor localized innate cytokine responses lead to inadequate cryptococcal killing and clearance of the fungus. Subsequent ART-associated recovery of T cell signaling and restored cytokine responses, characterized by Interferon-γ production, triggers an inflammatory response. The inflammatory response triggered by ART is dysregulated due to impaired homeostatic and regulatory mechanisms, culminating in the development of CM-IRIS.

Summary—Despite our incomplete understanding of the immunopathogenesis of CM-IRIS, emerging data exploring innate and adaptive immune responses could be exploited to predict, prevent and manage CM-IRIS and associated morbid consequences},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Camlin2016,

title = {Patient-reported factors associated with reengagement among HIV-infected patients disengaged from care in East Africa.},

author = {Carol S. Camlin and Torsten and Neilands and Thomas A. Odeny and Rita Lyamuya and Alice Nakiwogga-Muwanga and Lameck Diero and Mwebesa Bwana and Paula Braitstein and Geoffrey Somi and Andrew Kambugu and Elizabeth A. Bukusi and David V. Glidden and Kara K. Wools-Kaloustian and Megan Wenger and Elvin H. Geng and East Africa International Epidemiologic Databases to Evaluate AIDS (EA-IeDEA) Consortium},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Patient-reported-factors-associated-with-reengagement-among-HIV-infected-patients-disengaged-from-care-in-East-Africa..pdf},

doi = {10.1097/QAD.0000000000000931},

year  = {2016},

date = {2016-01-28},

journal = {AIDS},

volume = {30},

number = {3},

pages = {495-502},

abstract = {OBJECTIVE:



Engagement in care is key to successful HIV treatment in resource-limited settings; yet little is known about the magnitude and determinants of reengagement among patients out of care. We assessed patient-reported reasons for not returning to clinic, identified latent variables underlying these reasons, and examined their influence on subsequent care reengagement.

DESIGN:



We used data from the East Africa International Epidemiologic Databases to Evaluate AIDS to identify a cohort of patients disengaged from care (>3 months late for last appointment, reporting no HIV care in preceding 3 months) (n = 430) who were interviewed about reasons why they stopped care. Among the 399 patients for whom follow-up data were available, 104 returned to clinic within a median observation time of 273 days (interquartile range: 165-325).

METHODS:



We conducted exploratory and confirmatory factor analyses (EFA, CFA) to identify latent variables underlying patient-reported reasons, then used these factors as predictors of time to clinic return in adjusted Cox regression models.

RESULTS:



EFA and CFA findings suggested a six-factor structure that lent coherence to the range of barriers and motivations underlying care disengagement, including poverty, transport costs, and interference with work responsibilities; health system 'failures,' including poor treatment by providers; fearing disclosure of HIV status; feeling healthy; and treatment fatigue/seeking spiritual alternatives to medicine. Factors related to poverty and poor treatment predicted higher rate of return to clinic, whereas the treatment fatigue factor was suggestive of a reduced rate of return.

CONCLUSION:



Certain barriers to reengagement appear easier to overcome than factors such as treatment fatigue. Further research will be needed to identify the easiest, least expensive interventions to reengage patients lost to HIV care systems. Interpersonal interventions may continue to play an important role in addressing psychological barriers to retention.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Cox2016,

title = {Reply to “A Word of Caution in Considering the Use of the Lipoarabinomannan Lateral Flow Assay on Cerebrospinal Fluid for Detection of Tuberculous Meningitis”},

author = {Janneke A. Cox and Robert Colebunders and Yukari C. Manabeb },

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Reply-to-“A-Word-of-Caution-in-Considering-the-Use-of-the-Lipoarabinomannan-Lateral-Flow-Assay-on-Cerebrospinal-Fluid-for-Detection-of-Tuberculous-Meningitis”.pdf},

doi = { 10.1128/JCM.02823-15 PMCID: PMC4702761},

year  = {2016},

date = {2016-01-25},

journal = {Journal of Clinical Microbiology},

volume = {54},

number = {1},

abstract = {In their letter, Bahrand colleague srepor ttheir in ability to detect lipoarabinomannan (LAM) in the cerebrospinal fluid (CSF) of patients with tuberculous meningitis (TBM) by using a lateral flowassay   (DetermineTBLAM;Alere, Waltham,MA,USA). Several studies have shown LAM positivity in the CSF of patients with TBM by using an enzyme-linked immunosorbent assay for antigen detection (1, 2). The lateral flow assay (LFA) that was used in our study and in the study by Bahr et al. for LAM detection is an immunochromatographic assay that attaches colloidal gold-labeled antibodies to LAM (3, 4). These complexes are captured by immobilized LAM antibodies further along the teststripandform a visual band. A number of test and sample properties determine the accuracy of a lateral flow assay, including the composition of the sample fluid and the concentration of the analyte(5).The use of LAM LFA with CSF is off label. Therefore, the test and sample properties of the LAMLFA with CSF have not been systematically determined. },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Mugwanya2016b,

title = {Safety of oral tenofovir disoproxil fumarate-based pre-exposure prophylaxis for HIV prevention},

author = {Kenneth K. Mugwanya and Jared M. Baeten},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Safety-of-Oral-Tenofovir-Disoproxil-Fumarate-Based-Pre-Exposure-Prophylaxis-for-HIV-Prevention.pdf},

doi = { 10.1517/14740338.2016.1128412},

year  = {2016},

date = {2016-01-23},

journal = {Expert Opinion on Drug safety},

volume = {17},

number = {2},

pages = {265-273.},

abstract = {INTRODUCTION:



Tenofovir disoproxil fumarate (TDF)-based pre-exposure prophylaxis is a novel HIV prevention strategy for individuals at increased sexual risk for HIV infection. For any biomedical prevention intervention, the bar for tolerating adverse effects in healthy persons is high compared to therapeutic interventions.

AREAS COVERED:



We provide a concise summary of the clinical safety of TDF-based pre-exposure prophylaxis with focus on TDF-related effects on tolerability, kidney function, bone density, HIV resistance, sexual and reproductive health. The evidence base for this review is derived from a literature search of both randomized and observational studies evaluating efficacy and safety of TDF-based PrEP, TDF alone or in combination with emtricitabine, identified from PUBMED and EMBASE electronic databases, clinicaltrials.gov and major HIV conferences.

EXPERT OPINION:



TDF-based pre-exposure prophylaxis is a potent intervention against HIV acquisition when taken which is generally safe and well tolerated. The risk of the small, non-progressive, and reversible decline in glomerular filtration rate and bone mineral density as well as the potential selection for drug resistance associated with PrEP are outweighed, at the population level and broadly for individuals, by PrEP's substantial reduction in the risk of HIV infection.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Musinguzi2016,

title = {Does Adherence Change When No One is Looking? Comparing Announced and Unannounced Tenofovir Levels in a PrEP Trial. },

author = {  Nicholas Musinguzi and Timothy Muwonge and Katherine Thomas Jared and M. Baeten David and R. Bangsberg and Jessica E. Haberer},

year  = {2016},

date = {2016-01-18},

journal = {AIDS and Behavior},

volume = {20},

number = {11},

pages = {2639–2643 },

abstract = {Differences between unannounced and announced tenofovir levels as measures of PrEP adherence are not well understood. In an ancillary adherence study involving one urban site (Kampala) and two rural sites (Kabwohe and Tororo) from the Partners PrEP study, 268 specimen pairs from chronologically proximal clinic and home visits were tested for plasma tenofovir levels. Comparing clinic and home specimens, 89 versus 89 % were classified as detectable (>0.31 ng/ml; p = 0.77), 87 versus 86 % as recent dosing (>10 ng/ml; p = 0.80), and 82 versus 80 % as steady-state (>40 ng/ml; p = 0.44). Mean difference between announced and unannounced drug levels, adjusted for specimen collection time was 3.2 ng/ml (p = 0.50) for Kabwohe, 23.2 ng/ml (p = 0.003) for Kampala and −3.3 ng/ml p = 0.69) for Tororo. In the setting of high adherence, plasma tenofovir levels tested at the clinic were categorically similar as levels tested at home; however, differences were seen between urban and rural settings.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Dyal2016,

title = {Reproducibility of CSF quantitative culture methods for estimating rate of clearance in cryptococcal meningitis},

author = {Jonathan Dyal and Andrew Akampurira and Joshua Rhein and Bozena M Morawski and Reuben Kiggundu and Henry W Nabeta and Abdu K Musubire and Nathan C Bahr and Darlisha A Williams and Tihana Bicanic and Robert A Larsen and David B Meya and David R Boulware on behalf of the ASTRO-CM Trial Team},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Reproducibility-of-CSF-Quantitative-Culture-Methods-for-Estimating-Rate-of-Clearance-in-Cryptococcal-Meningitis.pdf},

doi = {10.1093/mmy/myv104},

year  = {2016},

date = {2016-01-14},

journal = {Medical Mycology},

volume = {54},

number = {4},

pages = {361-9},

abstract = {Quantitative cerebrospinal fluid (CSF) cultures provide a measure of disease severity in cryptococcal meningitis. The fungal clearance rate by quantitative cultures has become a primary endpoint for phase II clinical trials. This study determined the inter-assay accuracy of three different quantitative culture methodologies. Among 91 participants with meningitis symptoms in Kampala, Uganda during Aug-Nov 2013, 305 CSF samples were prospectively collected from patients at multiple time points during treatment. Samples were simultaneously cultured by three methods: 1) St. George’s 100mcL input volume of CSF with five 1:10 serial dilutions, 2 AIDS Clinical Trials Group (ACTG) method using 1000, 100, 10mcL input volumes, and two 1:100 dilutions with 100 and 10 mcL input volume per dilution on seven agar plates; and 3) 10mcL calibrated loop of undiluted and 1:100 diluted CSF (loop). Quantitative culture values did not statistically differ between St. George-ACTG methods ( P =0.09) but did for St. George-10mcL loop ( P <0.001). Repeated measures pairwise correlation between any of the methods was high (r≥0.88). For detecting sterility, the ACTG-method had the highest negative predictive value of 97% (91% St. George, 60% loop), but the ACTG-method had occasional (~10%) difficulties in quantification due to colony clumping. For CSF clearance rate, St. George-ACTG methods did not differ overall (mean −0.05±0.07 log10CFU/mL/day; P =0.14) on a group level; however, individual-level clearance varied. The St. George and ACTG quantitative CSF culture methods produced comparable but not identical results. Quantitative cultures can inform treatment management strategies},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ezeamama2016b,

title = {High perceived social standing is associated with better health in HIV-infected Ugandan adults on highly active antiretroviral therapy.},

author = {  A. E. Ezeamama and D. Guwatudde and M. Wang and D. Bagenda K. Brown and R. Kyeyune Emily Smith and H. Wamani and Y. C. Manabe and W. W. Fawzi},

url = {https://link.springer.com/article/10.1007%2Fs10865-015-9710-x},

year  = {2016},

date = {2016-01-05},

journal = {Journal of Behavior Medicine},

volume = {39},

number = {3},

pages = {453-464},

abstract = {Perceived social standing (PSS) was evaluated as a determinant of differences in health outcomes among Ugandan HIV-infected adults from Kampala using cross-sectional study design. PSS was defined using the MacArthur scale of subjective social status translated and adapted for the study setting. Socio-demographic and psychosocial correlates of PSS ranking at enrollment were determined using linear regression models. High versus low PSS was defined based on the median PSS score and evaluated as a determinant of body mass index, hemoglobin, quality of life (QOL) and frailty-related phenotype via linear regression. A log-binomial regression model estimated the relative-risk of good, very good or excellent versus fair or poor self-rated health (SRH) in relation to PSS. Older age, increasing social support and material wealth were correlated with high PSS ranking, whereas female sex, experience of multiple stigmas and multiple depressive symptoms were correlated with low PSS ranking. High PSS participants were on average 1.1 kg/m(2) heavier, had 4.7 % lower frailty scores and 3.6 % higher QOL scores compared to low PSS patients (all p < 0.05); they were also more likely to self-classify as high SRH (RR 1.4, 95 % confidence interval 1.1, 1.7) but had comparable hemoglobin levels (p = 0.634). Low PSS correlated with poor physical and psychosocial wellbeing in HIV-positive Ugandan adults. The assessment of PSS as part of clinical management, combined with efforts to reduce stigma and improve social support, may identify and possibly reduce PSS-associated health inequality in Ugandan adults with HIV.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kiggundu2016b,

title = {Brief Report: Effects of Tenofovir and Amphotericin B Deoxycholate Coadministration on Kidney Function in Patients Treated for Cryptococcal Meningitis},

author = {Reuben Kiggundu and Bozena M Morawski and Nathan C Bahr and Joshua Rhein and Abdu K Musubire and Darlisha A Williams and Mahsa Abassi and Henry W Nabeta and Kathy Huppler Hullsiek and David B Meya and David R Boulware, on behalf of the ASTRO-CM Team

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Brief-Report-Effects-of-Tenofovir-and-Amphotericin-B-Deoxycholate-Coadministration-on-Kidney-Function-in-Patients-Treated-for-Cryptococcal-Meningitis.pdf},

doi = {10.1097/QAI.0000000000000812},

year  = {2016},

date = {2016-01-01},

journal = {Journal of Acquired Immune Defficiency Syndrome},

volume = {71},

number = {1},

pages = {65-69},

abstract = {The effect of tenofovir and amphotericin coadministration on kidney function is poorly characterized. We measured creatinine during induction therapy and at 4 weeks after diagnosis in Ugandans undergoing cryptococcal meningitis therapy and classified as not receiving antiretroviral therapy (ART), receiving nontenofovir ART or receiving tenofovir-based ART. Longitudinal creatinine changes and grade 2-4 creatinine adverse events were evaluated across groups. Creatinine concentrations were similar across ART groups. At 4 weeks after diagnosis, creatinine was 0.25 mg/dL higher than at diagnosis, but similar across groups. Adverse event incidence was also similar across ART groups. Tenofovir and amphotericin coadministration did not increase the risk of kidney dysfunction.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Zirabamuzale2016,

title = {Hepatitis B virus genotypes A and D in Uganda. },

author = {JackieT Zirabamuzale and Christopher K Opio and Freddie Bwanga and Emmanuel Seremba and Betty S Apica and Robert Colebunders and Ponsiano Ocama},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Hepatitis-B-virus-genotypes-A-and-D-in-Uganda.-.pdf},

year  = {2016},

date = {2016-01-01},

journal = {Joornal of Virus Eradication},

volume = {2},

number = {1},

pages = {19-21},

abstract = {Background: The prevalence of hepatitis B virus (HBV) infection in Uganda is 10%. Hepatitis B virus genotypes impact ontreatmentresponse,rateofspontaneousrecoveryandprogressionofchronicHBVinfectionandhepatocellularcarcinoma. There is little information on the HBV genotypic distribution in Uganda. Objectives: To determine HBV genotypes in Uganda. Methods: The MBN clinical laboratory performs HBV viral load and genotype testing in Uganda. It receives hepatitis B surface antigen (HBsAg)-positive samples from all over the country for additional HBV testing. Samples are stored for 6 months before being discarded. Our study used delinked stored samples. PCR-positive samples had DNA extracted and used as template for HBV genome amplification by nested PCR. Reverse hybridisation was performed and genotypes were determined by the line probe assay method (INNO-LiPA). Results: One hundred stored HBsAg-positive plasma samples with detectable viral loads were analysed. Of these, 93 samples showed PCR amplification products and gave genotype-specific probe lines on the INNO-LiPA assay. Of the patients, where gender was recorded, 60.9% were female, and the overall median age (IQR) was 25 (2–60) years.There was a predominance of HBV genotype D (47 patients; 50.5%), followed by genotypeA, (16 patients; 17.2%). One patient (1.1%) had genotype E. In 28% of the samples mixed infections were detected with genotypes A/E (9.7%) and A/D (6.5%) being most common. Genotypes B, C, E and H only occurred as part of mixed infections. Conclusion Hepatitis B genotypes D and A were predominant in our study population.

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Rolfes2015,

title = {Cerebrospinal Fluid Culture Positivity and Clinical Outcomes After Amphotericin-Based Induction Therapy for Cryptococcal Meningitis},

author = {Melissa A. Rolfes and Joshua Rhein and Charlotte Schutz and Kabanda Taseera and Henry W. Nabeta and Kathy Huppler Hullsiek and Andrew Akampuira and Radha Rajasingham and Abdu Musubire and Darlisha A. Williams and Friedrich Thienemann,3 Paul R. Bohjanen,1,2 Conrad Muzoora,4 Graeme Meintjes,3,7 David B. Meya,1,2,8 and David R. Boulware1 },

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Cerebrospinal-Fluid-Culture-Positivity-and-Clinical-Outcomes-After-Amphotericin-Based-Induction-Therapy-for-Cryptococcal-Meningitis.pdf},

doi = {10.1093/ofid/ofv157},

year  = {2015},

date = {2015-12-28},

journal = {Open Forum Infectious Diseases},

volume = {70},

number = {3},

pages = {296-303},

abstract = {BACKGROUND:



Amphotericin-based combination antifungal therapy reduces mortality from human immunodeficiency virus (HIV)-associated cryptococcal meningitis. However, 40%-50% of individuals have positive cerebrospinal fluid (CSF) fungal cultures at completion of 2 weeks of amphotericin induction therapy. Residual CSF culture positivity has historically been associated with poor clinical outcomes. We investigated whether persistent CSF fungemia was associated with detrimental clinical outcomes in a contemporary African cohort.

METHODS:



 Human immunodeficiency virus-infected individuals with cryptococcal meningitis in Uganda and South Africa received amphotericin (0.7-1.0 mg/kg per day) plus fluconazole (800 mg/day) for 2 weeks, followed by "enhanced consolidation" therapy with fluconazole 800 mg/day for at least 3 weeks or until cultures were sterile, and then 400 mg/day for 8 weeks. Participants were randomized to receive antiretroviral therapy (ART) either 1-2 or 5 weeks after diagnosis and observed for 6 months. Survivors were classified as having sterile or nonsterile CSF based on 2-week CSF cultures. Mortality, immune reconstitution inflammatory syndrome (IRIS), and culture-positive relapse were compared in those with sterile or nonsterile CSF using Cox regression.

RESULTS:



 Of 132 participants surviving 2 weeks, 57% had sterile CSF at 2 weeks, 23 died within 5 weeks, and 40 died within 6 months. Culture positivity was not significantly associated with mortality (adjusted 6-month hazard ratio, 1.2; 95% confidence interval, 0.6-2.3; P = .28). Incidence of IRIS or relapse was also not significantly related to culture positivity.

CONCLUSIONS:



 Among patients, all treated with enhanced consolidation antifungal therapy and ART, residual cryptococcal culture positivity was not found to be associated with poor clinical outcomes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{B.2015,

title = {Strengthening the "Viral Failure Pathway": Clinical Decision and Outcomes of Patients With Confirmed Viral Failure in a Large HIV Care Clinic in Uganda.},

author = {Castelnuovo B. and Nsumba M and Musomba R and Kaimal A and Lwanga I and Kambugu A and Parkes-Ratanshi R},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Strengthening-the-...-Clinical-Decision-and-Outcomes-of-Patients-With-Confirmed-Viral-Failure-in-a-Large-HIV-Care-Clinic-in-Uganda.pdf},

doi = {10.1097/QAI.0000000000000820},

year  = {2015},

date = {2015-12-15},

journal = {Journal of Acquired Immune Defficiency Syndrome},

volume = {70},

number = {5},

pages = {174-176},

abstract = {Programmatic research has shown that routine viral load monitoring of patients on antiretroviral treatment (ART), with adherence interventions for patients with detectable viral load, is associated with improved treatment outcomes and earlier switches to second-line therapy.1–3 Starting in 2013, the World Health Organization (WHO) has included prospective viral load measurements as the preferred option to monitor patients on ART.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Geng2015,

title = {Retention in Care and Patient-Reported Reasons for Undocumented Transfer or Stopping Care Among HIV-Infected Patients on Antiretroviral Therapy in Eastern Africa: Application of a Sampling-Based Approach. },

author = {Elvin H. Geng and Thomas A. Odeny and Rita Lyamuya and Alice Nakiwogga-Muwanga and Lameck Diero and Mwebesa Bwana and Paula Braitstein and Geoffrey Somi and Andrew Kambugu and Elizabeth Bukusi and Megan Wenger and Torsten B. Neilands and David V. Glidden and Kara Wools-Kaloustian and Constantin Yiannoutsos and Jeffrey Martin for the East Africa International Epidemiologic Databases to Evaluate AIDS (EA-IeDEA) Consortium },

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Retention-in-Care-and-Patient-Reported-Reasons-for-Undocumented-Transfer-or-Stopping-Care-Among-HIV-Infected-Patients-on-Antiretroviral-Therapy-in-Eastern-Africa.pdf},

doi = {10.1093/cid/civ1004},

year  = {2015},

date = {2015-12-15},

journal = {Clinical Infectious Diseases},

volume = {62},

number = {7},

pages = {933-944},

abstract = {BACKGROUND:



Improving the implementation of the global response to human immunodeficiency virus requires understanding retention after starting antiretroviral therapy (ART), but loss to follow-up undermines assessment of the magnitude of and reasons for stopping care.

METHODS:



We evaluated adults starting ART over 2.5 years in 14 clinics in Uganda, Tanzania, and Kenya. We traced a random sample of patients lost to follow-up and incorporated updated information in weighted competing risks estimates of retention. Reasons for nonreturn were surveyed.

RESULTS:



Among 18 081 patients, 3150 (18%) were lost to follow-up and 579 (18%) were traced. Of 497 (86%) with ascertained vital status, 340 (69%) were alive and, in 278 (82%) cases, updated care status was obtained. Among all patients initiating ART, weighted estimates incorporating tracing outcomes found that 2 years after ART, 69% were in care at their original clinic, 14% transferred (4% official and 10% unofficial), 6% were alive but out of care, 6% died in care (<60 days after last visit), and 6% died out of care (≥ 60 days after last visit). Among lost patients found in care elsewhere, structural barriers (eg, transportation) were most prevalent (65%), followed by clinic-based (eg, waiting times) (33%) and psychosocial (eg, stigma) (27%). Among patients not in care elsewhere, psychosocial barriers were most prevalent (76%), followed by structural (51%) and clinic based (15%).

CONCLUSIONS:



Accounting for outcomes among those lost to follow-up yields a more informative assessment of retention. Structural barriers contribute most to silent transfers, whereas psychological and social barriers tend to result in longer-term care discontinuation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Castelnuovo2015,

title = {Outcomes in a Cohort of Patients Started on Antiretroviral Treatment and Followed up for a Decade in an Urban Clinic in Uganda. },

author = {Barbara Castelnuovo and AgnesKiragga and JosephMusaazi and JosephSempa and Frank Mubiru and Jane Wanyama and Bonnie Wandera and Moses Robert Kamya and Andrew Kambugu },

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Outcomes-in-a-Cohort-of-Patients-Started-on-Antiretroviral-Treatment-and-Followed-up-for-a-Decade-in-an-Urban-Clinic-in-Uganda.-.pdf},

doi = {10.1371/journal.pone.0142722},

year  = {2015},

date = {2015-12-07},

journal = {PloS One},

volume = {10},

number = {12},

abstract = {Background Short-mediumtermstudiesfromsub-SaharanAfricashowthat,despitehighearlymortality, substantiallosstoprogram, andhighratestoxicity,patientsonantiretroviraltreatment have achievedoutcomescomparabletothoseindevelopedsettings.However,thesestudies wereunabletoaccountforlongtermoutcomesofpatientsastheystayedlongeron treatment.

Objectives Weaimtodescribetenyearsoutcomes ofoneofthefirstcohortofHIVpositive patients startedonantiretroviraltreatment(ART)inSub-SaharanAfrica.

Methods Wereport10-yearsoutcomes includingmortality,retention,CD4-countresponse,virologicaloutcomes,ARTregimenschangefrom aprospectivecohortof559patientsinitiating ARTandfollowedupfor10yearsUganda.

Results Of559patients,69.1%werefemale,medianage(IQR) was38(33–44)years,median CD4-count(IQR) 98(21–163)cell/μL;74%werestartedonstavudine,lamivudineandnevirapine,26%onzidovudine,lamivudineandefavirenz.After10years361(65%)patients werestillinthestudy;127(22.7%)haddied;30(5%)werelosttofollow-up;27(5%)transferred;18(3%)withdrewconsent.Theprobabilityofdeathwashighinthefirstyear(0.15, 95%,CI0.12–0.18).ThemedianCD4countincreased from98to589cell/μL(IQR:450– 739cell/μL)withamedianincreaseof357cells/μL(IQR:128–600cells/μL);7.4%never attained initialviralsuppressionandofthose whodid31.7%experiencedviralfailure.Three hundredandtwopatientshadatleastonedrugsubstitutionwhileonfirstlineafteramedian

PLOSONE|DOI:10.1371/journal.pone.0142722 December7,2015 1/11

OPENACCESS

Citation:CastelnuovoB,KiraggaA,MusaaziJ, SempaJ,MubiruF,WanyamaJ,etal.(2015) OutcomesinaCohortofPatientsStartedon AntiretroviralTreatmentandFollowedupfora DecadeinanUrbanClinicinUganda.PLoSONE10 (12):e0142722.doi:10.1371/journal.pone.0142722

Editor:AlanLanday,RushUniversity,UNITED STATES

Received:May14,2015

Accepted:October25,2015

Published:December7,2015

Copyright:©2015Castelnuovoetal.Thisisan openaccessarticledistributedunderthetermsofthe CreativeCommonsAttributionLicense,whichpermits unrestricteduse,distribution,andreproductioninany medium,providedtheoriginalauthorandsourceare credited.

DataAvailabilityStatement:Duetoethical restrictionsregardingpatientdata,dataareavailable uponrequesttothedataaccesscommittee. RequestsforthedatamaybesentRachelMusomba, thecohortstudycommitteesecretary (rmusomba@idi.co.ug).

Funding:Theseauthorshavenosupportorfunding toreport.Thestudywasself-sponsored.

CompetingInterests:Theauthorshavedeclared thatnocompetinginterestsexist.

of40months; 66(11.9%)ofthepatientswereswitchedtoasecondlinePI-basedregimen duetoconfirmedtreatmentfailure.

Conclusions Despitethehighrateofearlymortalityduetoadvanceddiseaseatpresentation theoutcomesfromthiscohortareencouraging,particularlytheremarkableandincremental immune-recoveryandasatisfactoryrateofvirologicsuppression.

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Nöstlingera2015,

title = {Factors influencing social self-disclosure among adolescents living with HIV in Eastern Africa},

author = {Christiana Nöstlingera and Sabrina Bakeera-Kitakac and Jozefien Buyze and Jasna Loosa and Anne Buvé},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Factors-influencing-social-self-disclosure-among-adolescents-living-with-HIV-in-Eastern-AfricaFactors-influencing-social-self-disclosure-among-adolescents-living-with-HIV-in-Eastern-Africa.pdf},

doi = {10.1080/09540121.2015},

year  = {2015},

date = {2015-12-07},

journal = {AIDS Care},

volume = {27},

number = {1},

pages = {36-46},

abstract = {Adolescents living with HIV (ALHIV) face many psychosocial challenges, including HIV disclosure to others. Given the importance of socialization during the adolescent transition process, this study investigated the psychological and social factors influencing self-disclosure of own HIV status to peers. We examined social HIV self-disclosure to peers, and its relationship to perceived HIV-related stigma, self-efficacy to disclose, self-esteem, and social support among a sample of n = 582 ALHIV aged 13-17 years in Kampala, Uganda, and Western Kenya. Data were collected between February and April 2011. Among them, 39% were double orphans. We conducted a secondary data analysis to assess the degree of social disclosure, reactions received, and influencing factors. Interviewer-administered questionnaires assessed medical, socio-demographic, and psychological variables (Rosenberg self-esteem scale; self-efficacy to disclose to peers), HIV-related stigma (10-item stigma scale), and social support (family-life and friends). Descriptive, bivariate, and logistic regression analyses were performed with social self-disclosure to peers with gender as covariates. Almost half of ALHIV had told nobody (except health-care providers) about their HIV status, and about 18% had disclosed to either one of their friends, schoolmates, or a boy- or girlfriend. Logistic regression models revealed that having disclosed to peers was significantly related to being older, being a paternal orphan, contributing to family income, regular visits to the HIV clinic, and greater social support through peers. Low self-efficacy to disclose was negatively associated to the outcome variable. While social self-disclosure was linked to individual factors such as self-efficacy, factors relating to the social context and adolescents' access to psychosocial resources play an important role. ALHIV need safe environments to practice disclosure skills. Interventions should enable them to make optimal use of available psychosocial resources even under constraining conditions such as disruptive family structures},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{etal.al.2015,

title = {Sustainable HIV treatment in Africa through viral-load-informed differentiated care. Nature},

author = {Phillips et al.},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Sustainable-HIV-Treatment-in-Africa-through-Viral-Load-Informed-Differentiated-Care.pdf},

doi = {10.1038/nature16046},

year  = {2015},

date = {2015-12-03},

journal = {Nature},

volume = {528},

number = {7580},

pages = {68-76},

abstract = {There are inefficiencies in current approaches to monitoring patients on antiretroviral therapy in sub-Saharan Africa. Patients typically attend clinics every 1 to 3 months for clinical assessment. The clinic costs are comparable with the costs of the drugs themselves and CD4 counts are measured every 6 months, but patients are rarely switched to second-line therapies. To ensure sustainability of treatment programmes, a transition to more cost-effective delivery of antiretroviral therapy is needed. In contrast to the CD4 count, measurement of the level of HIV RNA in plasma (the viral load) provides a direct measure of the current treatment effect. Viral-load-informed differentiated care is a means of tailoring care so that those with suppressed viral load visit the clinic less frequently and attention is focussed on those with unsuppressed viral load to promote adherence and timely switching to a second-line regimen. The most feasible approach to measuring viral load in many countries is to collect dried blood spot samples for testing in regional laboratories; however, there have been concerns over the sensitivity and specificity of this approach to define treatment failure and the delay in returning results to the clinic. We use modelling to synthesize evidence and evaluate the cost-effectiveness of viral-load-informed differentiated care, accounting for limitations of dried blood sample testing. We find that viral-load-informed differentiated care using dried blood sample testing is cost-effective and is a recommended strategy for patient monitoring, although further empirical evidence as the approach is rolled out would be of value. We also explore the potential benefits of point-of-care viral load tests that may become available in the future.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Boulware2015,

title = {Human Immune Response Varies by the Degree of Relative Cryptococcal Antigen Shedding},

author = {David R. Boulware and Maximilian von Hohenberg and Melissa A. Rolfes and Nathan C. Bahr and Joshua Rhein and Andrew Akampurira and Darlisha A. Williams and Kabanda Taseera and Charlotte Schutz and Tami McDonald and Conrad Muzoora and Graeme Meintjes and David B. Meya and Kirsten Nielsen and Katherine Huppler Hullsiek2; For the Cryptococcal Optimal ART Timing (COAT) Trial Team },

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Human-Immune-Response-Varies-by-the-Degree-of-Relative-Cryptococcal-Antigen-Shedding.pdf},

doi = {10.1093/ofid/ofv194},

year  = {2015},

date = {2015-12-03},

journal = {Open Forum Infectious Diseases},

volume = {3},

number = {1},

abstract = {BACKGROUND:



 Cerebrospinal fluid (CSF) cryptococcal glucuronoxylomannan antigen (CrAg) titers generally correlate with quantitative fungal culture burden; however, correlation is not precise. Some patients have higher CrAg titers with lower fungal burdens and vice versa. We hypothesized that the relative discordancy between CrAg titer and quantitative culture burden reflects the relative degree of CrAg shedding by Cryptococcus neoformans and is associated with human immune responses.

METHODS:



 One hundred ninety human immunodeficiency virus-infected individuals with cryptococcal meningitis were enrolled in Uganda and South Africa. We compared initial CSF CrAg titers relative to their CSF quantitative cultures to determine low (n = 58), intermediate (n = 68), or high (n = 64) CrAg shedders. We compared cytokines measured by Luminex multiplex assay on cryopreserved CSF and 10-week mortality across shedding groups using linear and logistic regression and distribution of genotypes by multilocus sequence typing.

RESULTS:



 The relative degree of CrAg shedding was positively associated with increasing CSF levels of the following: interleukin (IL)-6, IL-7, IL-8, and tumor necrosis factor-α (each P < 0.01), which are all secreted by antigen-presenting cells and negatively associated with vascular endothelial growth factor (P = .01). In addition, IL-5, IL-13, granulocyte colony-stimulating factor, and macrophage chemotactic protein were decreased in low-CrAg shedders compared with intermediate shedders (each P ≤ .01). Type 1 T-helper cells (Th1) cytokine responses and 10-week mortality did not differ between the shedding groups. Cryptococcal genotypes were equally distributed across shedding groups.

CONCLUSIONS:



 Discordancy between CrAg shedding and expected shedding based on quantitative fungal burden is associated with detectable immunologic differences in CSF, primarily among secreted cytokines and chemokines produced by antigen-presenting cells and Th2.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Smith2015,

title = {Increased Antifungal Drug Resistance in Clinical Isolates of Cryptococcus neoformans in Uganda},

author = {Kyle D. Smith and Beatrice Achan and Kathy Huppler Hullsiek and Tami R. McDonald and Laura H. Okagaki and Ali A. Alhadab and Andrew Akampurira and Joshua R. Rhein and David B. Meya and David R. Boulware and Kirsten Nielsen and on behalf of the ASTRO-CM/COAT Team },

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Increased-Antifungal-Drug-Resistance-in-Clinical-Isolates-of-Cryptococcus-neoformans-in-Uganda.pdf},

doi = {10.1128/AAC.01299-15},

year  = {2015},

date = {2015-11-03},

journal = {Antimicrobial Agents and Chemotherapy},

volume = {59},

number = {12},

pages = {7197-7204},

abstract = {Cryptococcal antigen screening is recommended among people living with AIDS when entering HIV care with a CD4 count of <100 cells/μl, and preemptive fluconazole monotherapy treatment is recommended for those with subclinical cryptococcal antigenemia. Yet, knowledge is limited of current antimicrobial resistance in Africa. We examined antifungal drug susceptibility in 198 clinical isolates collected from Kampala, Uganda, between 2010 and 2014 using the CLSI broth microdilution assay. In comparison with two previous studies from 1998 to 1999 that reported an MIC50 of 4 μg/ml and an MIC90 of 8 μg/ml prior to widespread human fluconazole and agricultural azole fungicide usage, we report an upward shift in the fluconazole MIC50 to 8 μg/ml and an MIC90 value of 32 μg/ml, with 31% of isolates with a fluconazole MIC of ≥ 16 μg/ml. We observed an amphotericin B MIC50 of 0.5 μg/ml and an MIC90 of 1 μg/ml, of which 99.5% of isolates (197 of 198 isolates) were still susceptible. No correlation between MIC and clinical outcome was observed in the context of amphotericin B and fluconazole combination induction therapy. We also analyzed Cryptococcus susceptibility to sertraline, with an MIC50 of 4 μg/ml, suggesting that sertraline is a promising oral, low-cost, available, novel medication and a possible alternative to fluconazole. Although the CLSI broth microdilution assay is ideal to standardize results, limit human bias, and increase assay capacity, such assays are often inaccessible in low-income countries. Thus, we also developed and validated an assay that could easily be implemented in a resource-limited setting, with similar susceptibility results (P = 0.52).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bahra2015,

title = {Seroprevalence of histoplasmosis in Kampala, Uganda},

author = {Nathan C Bahra and George A. Sarosi and David B Meya and Paul R Bohjanen and Sarah M Richer and Samantha Swartzentruber and Ryan Halupnick and Deidre Jarrett and L. Joseph Wheat and David R Boulware},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Seroprevalence-of-histoplasmosis-in-Kampala-Uganda.pdf},

doi = { 10.1093/mmy/myv081},

year  = {2015},

date = {2015-11-02},

journal = {Medical Mycology},

volume = {54},

number = {3},

pages = {295-300},

abstract = {Histoplasmosis is endemic to the Midwestern United States, but cases have been reported nearly worldwide. A 1970 study found 3.8% skin test sensitivity to Histoplasma capsulatum in Uganda but no systemic study of histoplasmosis exposure has occurred since the onset of the human immunodeficiency virus (HIV) pandemic. This study investigated the seroprevalence of H. capsulatum and sought previously undetected cases of histoplasmosis in Kampala, Uganda. Serum, cerebrospinal fluid (CSF) and/or urine specimens were obtained from HIV-infected persons with suspected meningitis. Specimens were tested for H. capsulatum IgG and IgM by enzyme immune assay and Histoplasma antigen. 147 of the 257 subjects who were enrolled had cryptococcal meningitis. Overall, 1.3% (2/151) of subjects were serum Histoplasma IgG positive, and zero of 151 were IgM positive. Antigen was not detected in any serum (n = 57), urine (n = 37, or CSF (n = 63) samples. Both subjects with serum Histoplasma IgG positivity had cryptococcal meningitis. Histoplasma capsulatum IgG was detected at low levels in persons with HIV/AIDS in Kampala, Uganda. Histoplasmosis is not widespread in Uganda but microfoci do exist. There appears to be no cross-reactivity between Cryptococcus neoformans and Histoplasma antigen testing, and cryptococcosis appears to be at most, a rare cause of positive Histoplasma IgG.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Musomba2015,

title = {Monitoring Of Critical Laboratory Results To Improve Quality Of Patient Care In A Large Urban Clinic In Uganda},

author = { R Musomba and B Castelnuovo and M Nsumba and I Kaluleand P Rosalind Parkes-Ratanshi},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Monitoring-Of-Critical-Laboratory-Results-To-Improve-Quality-Of-Patient-Care-In-A-Large-Urban-Clinic-In-Uganda.pdf},

doi = {10.1016/j.jval.2015.09},

year  = {2015},

date = {2015-11-02},

journal = {Value in Health},

volume = {18},

number = {7},

abstract = {Objectives



Follow-up of critical laboratory results can present a challenge in resource limited settings due to high patient volumes, overstretched human resources and no systematic communication from the laboratory. An audit conducted in 2013 in a large outpatient HIV-center revealed that <50% of critical results were acted upon within 24 hours. Our objective is to describe the impact of the new developed guidelines on reducing mortality of patients with critical results.

Methods



Results must be immediately communicated by the laboratory to a physician via an “on-call phone”; patients should be contacted and asked to return to the clinic. In addition all critical laboratory results were reviewed and tagged by Quality Management staff. Design: retrospective survey of all files of patients who had in 2014 at least one of the following: Hb <5.5g/dl, creatinine >3.4mg/dl, positive serum Cryptococcus-Antigen (Crag). Clinician’s actions were categorized and described. Turnaround time was determined and incidence of mortality between 2013 and 2014 compared.

Results



During 2014, 5,907 patients had any laboratory test done. Hb <5.5g/dl: 36(0.6%) patients. Action taken: blood transfusion 17/36 (47%), heamatinics14/36(39%) and 2/36(6%) dewormed. Creatinine >3.4mg/dl: 64/3291(1.9%) patients. Action taken: antiretroviral treatment regimen switched 43/64(67%), 2/64(3%) stopped, 12/64(19%) referral to the renal unit. Positive serum-Crag 17/464(3.7%). Action taken: 12/17(71%) started on fluconazole, 5/17(29%) were already on treatment. Turnaround time for Hb and serum crag was <1 day, creatinine 13.3 days. From 2013 and 2014 the mortality decreased in patients with Hb<5.5g/dl from 27.9 to 2.8%, with creatinine>3.4mg/dl from 32.9 to 3.1% and with positive serum-Crag from 36.4 to 23.5%

Conclusions



Critical results monitoring system greatly improves patient turnaround time, and reduces mortality through timely communication and patients follow up. We believe our system could serve as a role model for similar programs in Sub-Saharan Africa to improve quality of care.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Adelline2015,

title = {Exploring Attitudes and Perceptions of Patients and Staff Towards a Fee For Service "After Hours" Clinic Supplementing Free Hiv Services in Uganda: A Qualitative Study},

author = { T Adelline and R Kingand WF Schlech and M Faridah and T Kakaire and P Rosalind Parkes-Ratanshi},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Exploring-attitudes-and-perceptions-of-patients-and-staff-towards-an-after-hours-co-pay-clinic-supplementing-free-HIV-services-in-Kampala-Uganda.pdf},

doi = {10.1186/s12913-017-2524-5},

year  = {2015},

date = {2015-11-02},

journal = {BMC Health Services Research},

volume = {18},

number = {7},

abstract = {BACKGROUND:



There has been a rapid scale up of HIV services and access to anti-retroviral therapy in Africa over the last 10 years as a result of multilateral donor funding mechanisms. However, in order to continue to expand and to sustain these services it is important that "in country" options are explored. This study sought to explore attitudes and perceptions of people living with HIV (PLHIV) and health care staff towards using a fee-based "after hours" clinic (AHC) at the Infectious Diseases Institute (IDI) in Kampala, Uganda.

METHODS:



A cross-sectional study design, using qualitative methods for data collection was used. A purposeful sample of 188 adults including PLHIV accessing care at IDI and IDI staff were selected. We conducted 14 focus group discussions and 55 in-depth interviews. Thematic content analysis was conducted and Nvivo Software Version 10 was used to manage data.

RESULTS:



Findings suggested that some respondents were willing to pay for consultation, brand-name drugs, laboratory tests and other services. Many were willing to recommend the AHC to friends and/or relatives. However, there were concerns expressed of a risk that the co-pay model may lead to reduction in quality or provision of the free service. Respondents agreed that, as a sign of social responsibility, fees for service could help underprivileged patients.

CONCLUSION:



The IDI AHC clinic is perceived as beneficial to PLHIV because it provides access to HIV services at convenient times. Many PLHIV are willing to pay for this enhanced service. Innovations in HIV care delivery such as quality private-public partnerships may help to improve overall coverage and sustain quality HIV services in Uganda in the long term},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Byakwaga2015,

title = {The Kynurenine Pathway of Tryptophan Catabolism and AIDS-Associated Kaposi Sarcoma in Africa},

author = {Helen Byakwaga and Peter W. Hunt and Miriam Laker-Oketta and David V. Glidden and Yong Huang and Bosco M Bwana and A. Rain Mocello and John Bennett and Victoria Walusansa and Sheila C. Dollard and David R. Bangsberg and Edward K. Mbidde and Jeffrey N. Martin},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/The-Kynurenine-Pathway-of-Tryptophan-Catabolism-and-AIDS-associated-Kaposis-Sarcoma-in-Africa.pdf},

doi = {10.1097/QAI.0000000000000747},

year  = {2015},

date = {2015-11-01},

journal = {Journal of Acquired Immune Defficiency Syndrome},

volume = {70},

number = {3},

pages = {296-303},

abstract = {BACKGROUND:



Other than Kaposi sarcoma (KS)-associated herpesvirus and CD4 T-cell lymphopenia, the mechanisms responsible for KS in the context of HIV are poorly understood. One recently explored pathway of HIV pathogenesis involves induction of the enzyme indoleamine 2,3-dioxygenase-1 (IDO), which catabolizes tryptophan into kynurenine and several other immunologically active metabolites that suppress T-cell proliferation. We investigated the role of IDO in the development of KS in HIV disease.

METHODS:



In a case-control study among untreated HIV-infected Ugandans, cases were adults with KS and controls were without KS. IDO activity was assessed by the ratio of plasma kynurenine to tryptophan levels (KT ratio), measured by liquid chromatography-tandem mass spectrometry.

RESULTS:



We studied 631 HIV-infected subjects: 222 KS cases and 409 controls. Non-KS controls had a higher median plasma KT ratio (130, interquartile range: 90 to 190 nM/μM) than KS cases (110, interquartile range: 90 to 150 nM/μM) (P = 0.004). After adjustment for age, sex, CD4 count, and plasma HIV RNA level, subjects with the highest (fourth quartile) plasma KT ratios had a 59% reduction (95% confidence interval: 27% to 77%) in the odds of KS compared with those with the lowest (first quartile) levels. KS was also independently associated with lower CD4 count, higher plasma HIV RNA, and men.

CONCLUSIONS:



Among HIV-infected individuals, greater activity of the kynurenine pathway of tryptophan catabolism, as evidenced by higher levels of plasma KT ratio, was associated with lower occurrence of KS. Some consequences of immune activation in HIV infection might actually suppress certain cancers.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Yang2015,

title = {Hepatocellular Carcinoma Occurs at an Earlier Age in Africans, Particularly in Association With Chronic Hepatitis B},

author = {Yang, Ju Dong; Gyedu, Adam; Afihene, Mary Yeboah; Duduyemi, Babatunde; Micah, Eileen; Kingham, Peter T; Nyirenda, Mulinda; Nkansah, Adwoa Agyei; Bandoh, Salome; Duguru, Mary J; Okeke, Edith N; Kouakou-Lohoues, Marie-Jeanne, Abdo, Abdelmounem; Awuku, Yaw Asante; Ajayi, Akande Oladimeji; Omonisi, Abidemi Emmanuel; Ocama, Ponsiano; Malu, Abraham O; Mustapha, Shettim; Okonkwo, Uchenna; Kooffreh-Ada, Mbang; Debes, Jose D; Onyekwere, Charles; Ekere, Francis; Rufina, Igetei; Roberts, Lewis R and the Africa Network for Gastrointestinal and Liver Diseases},

doi = {doi: 10.1038/ajg.2015.289},

year  = {2015},

date = {2015-11-01},

journal = {American Journal of Gastroenterology},

volume = {110},

number = {11},

pages = {1629-1631},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Byakika‑Kibwika2015,

title = {A situation analysis of inter-professional education and practice for ethics and professionalism training at Makerere University College of Health Sciences},

author = {Pauline Byakika‑Kibwika and Annet Kutesa and Rhona Baingana and Christine Muhumuza and Freddy Eric Kitutu and Catherine Mwesigwa and Rose Nabirye Chalo and Nelson K. Sewankambo

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/A-situation-analysis-of-inter-professional-education-and-practice-for-ethics-and-professionalism-training-at-Makerere-University-College-of-Health-Sciences.pdf},

doi = { 10.1186/s13104-015-1577-y},

year  = {2015},

date = {2015-10-23},

journal = {BMC Researh Notes},

volume = {8},

abstract = {Background: Students at Makerere University College of Health Sciences (MakCHS) are introduced to ethics and pro‑ fessionalism using the inter‑professional education (IPE) model. Ethics and professionalism should be running themes throughout succeeding years of study during which students are expected to develop qualities and skills for future inter‑professional practice (IPP). We performed a situation analysis of IPE and IPP among students and teaching health professionals at MakCHS to guide development of a relevant training curriculum of ethics and professionalism. Methods: A cross sectional study with quantitative and qualitative methods which included questionnaires, focus group discussions and key informant interviews. Results: We interviewed 236 undergraduate students (148, 63 % male) and 32 teaching health professionals (25, 78 % male). Two hundred fifteen (91 %) students indicated they had joint learning activities with students of other professions and 166 (70 %) stated there was benefit in having an IPE model training curriculum. Most students (140, 59 %) strongly agreed that learning with other students will make them more effective members of the health team. Whereas the respondents reported inter professionalism as being well articulated in their course curricula, more than half said IPE is only implemented in the pre‑clinical years of study. They noted that IPE and IPP concepts were not well programmed, health professionals engaged in teaching had poor attitudes towards IPE and IPP, there were limited numbers of skilled health care workers to implement IPP and there was poor communication between students and teaching health professionals. Majority of teaching health professionals noted challenges in implementation of IPE such as poor coordination and large student population and major factors influencing ethics and professionalism in healthcare such as limited government support, low pay for the health care workers, disrespect and lack of apprecia‑ tion of the health workers by the public. Conclusions: Our findings demonstrate that IPE, IPP, ethics and professionalism are not emphasized in the clinical years of study at MakCHS. We recommend increased sensitization on the concepts of IPE and IPP plus enhanced men‑ torship for both students and teaching health professionals. Innovative strategies of implementation of IPE and IPP for training in ethics and professionalism must be introduced. Keywords: Inter‑professional education, Practice, Ethics, Professionalism, Makerere University

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Nakanjako2015,

title = {Global health leadership training in resource-limited settings: a collaborative approach by academic institutions and local health care programs in Uganda},

author = {Damalie Nakanjako and Elizabeth Namagala and Aggrey Semeere and Joanitor Kigozi and Joseph Sempa and John Bosco Ddamulira and Achilles Katamba and Sam Biraro and Sarah Naikoba and Yohana Mashalla and Carey Farquhar and Afya Bora Consortium members and Nelson Sewankambo

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Global-health-leadership-training-in-resource-limited-settings.pdf},

doi = {10.1186/s12960-015-0087-2},

year  = {2015},

date = {2015-10-18},

journal = {Humam Resources for Health},

volume = {13},

abstract = {INTRODUCTION:



Due to a limited health workforce, many health care providers in Africa must take on health leadership roles with minimal formal training in leadership. Hence, the need to equip health care providers with practical skills required to lead high-impact health care programs. In Uganda, the Afya Bora Global Health Leadership Fellowship is implemented through the Makerere University College of Health Sciences (MakCHS) and her partner institutions. Lessons learned from the program, presented in this paper, may guide development of in-service training opportunities to enhance leadership skills of health workers in resource-limited settings.

METHODS:



The Afya Bora Consortium, a consortium of four African and four U.S. academic institutions, offers 1-year global health leadership-training opportunities for nurses and doctors. Applications are received and vetted internationally by members of the consortium institutions in Botswana, Kenya, Tanzania, Uganda, and the USA. Fellows have 3 months of didactic modules and 9 months of mentored field attachment with 80% time dedicated to fellowship activities. Fellows' projects and experiences, documented during weekly mentor-fellow meetings and monthly mentoring team meetings, were compiled and analyzed manually using pre-determined themes to assess the effect of the program on fellows' daily leadership opportunities.

RESULTS:



Between January 2011 and January 2015, 15 Ugandan fellows (nine doctors and six nurses) participated in the program. Each fellow received 8 weeks of didactic modules held at one of the African partner institutions and three online modules to enhance fellows' foundation in leadership, communication, monitoring and evaluation, health informatics, research methodology, grant writing, implementation science, and responsible conduct of research. In addition, fellows embarked on innovative projects that covered a wide spectrum of global health challenges including critical analysis of policy formulation and review processes, bottlenecks in implementation of national HIV early infant diagnosis and prevention of mother-to-child HIV-transmission programs, and use of routine laboratory data about antibiotic resistance to guide updates of essential drug lists.

CONCLUSION:



In-service leadership training was feasible, with ensured protected time for fellows to generate evidence-based solutions to challenges within their work environment. With structured mentorship, collaborative activities at academic institutions and local health care programs equipped health care providers with leadership skills.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{J2015,

title = {1,3-β-D-glucan in cryptococcal meningitis.},

author = {Rhein J and Boulware DR and Bahr NC},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/13-β-D-glucan-in-cryptococcal-meningitis..pdf},

year  = {2015},

date = {2015-10-07},

journal = {Lancent Infectious Diseases},

volume = {15},

number = {10},

pages = {1136-7},

abstract = {We read with interest the updated best practice guidelines for the diagnosis of serious fungal diseases as proposed by the British Society for Medical Mycology.1

Invasive fungal infections remain a substantial worldwide health problem, and we applaud the authors' considerate, well researched, and comprehensive recommendations for the diagnosis of a wide variety of invasive fungal diseases. However, we would like to bring attention to one minor but important inaccuracy alluded to in the guidelines.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}