Antiretroviral Therapy In Uganda Research Articles

A decade of antiretroviral therapy in Uganda: what are the emerging causes of death?

BackgroundThe roll out of antiretroviral therapy (ART) in Sub-Saharan Africa led to a decrease in mortality. Few studies have documented the causes of deaths among patients on long term antiretroviral therapy in Sub-Saharan Africa. Our objective was to describe the causes of death among patients on long term ART in Sub-Saharan Africa.MethodsWe used data from a prospective cohort of ART naïve patients receiving care and treatment at the Infectious Diseases Institute in Kampala, Uganda. Patients were followed up for 10 years. All deaths were recorded and possible causes established using verbal autopsy. Deaths were grouped as HIV-related (ART toxicities, any opportunistic infections (OIs) and HIV-related malignancies) and non-HIV related deaths while some remained unknown. We used Kaplan Meier survival methods to estimate cumulative incidence and rates of mortality for all causes of death.ResultsOf the 559, (386, 69%) were female, median age 36 years (IQR: 21–44), 89% had WHO clinical stages 3 and 4, and median CD4 count at ART initiation was 98 cells/μL (IQR: 21–163). A total of 127 (22.7%) deaths occurred in 10 years. The HIV related causes of death (n = 70) included the following; Tuberculosis 17 (24.3%), Cryptococcal meningitis 10 (15.7%), Kaposi’s Sarcoma 7(10%), HIV related toxicity 6 (8.6%), HIV related anemia 5(7.1%), Pneumocystis carinii Pneumonia (PCP) 5 (7.1%), HIV related chronic diarrhea 4 (5.7%), Non-Hodgkin Lymphoma 3 (4.3%), Herpes Zoster 2 (2.8%), other 10 (14.3%). The non-HIV related causes of death (n = 20) included non-communicable diseases (diabetes, hypertension, stroke) 6 (30%), malaria 3 (15%), pregnancy-related death 2 (10%), cervical cancer 2 (10%), trauma 1(5%) and others 6 (30%).ConclusionDespite the higher rates of deaths from OIs in the early years of ART initiation, we observed an emergence of non-HIV related causes of morbidity and mortality. It is recommended that HIV programs in resource-limited settings start planning for screening and treatment of non-communicable diseases.

191. Prevalence And Factors Associated With Risky Sexual Behaviour Among Adolescents Living With HIV/AIDS In Mbarara, South-Western Uganda

Scaling up of Highly Active Antiretroviral Therapy in Uganda has improved survival of a cohort of children into adolescence. Adolescence is a turbulent period where experimental sexual behavior may occur. Adolescents living with HIV (ALHIV) with risky sexual behaviour are key players in transmitting HIV. We aimed at establishing the prevalence and factors associated with risky sexual behaviour among ALHIV in Mbarara, Uganda. We conducted a cross-sectional study of adolescents (10-19 years) living with HIV, and attending HIV clinics in Mbarara between March and May 2017. We collected sociology-demographic, behavioral and health service-related data. Risky sexual behaviour was defined as involvement in sexual activity too early, non-condom use, having one or more sexual partners, sex under influence of alcohol or drugs in the past 12 months. Logistic regression models were fitted for factors associated with risky sexual behaviour, using STATA 13∙0 software. We interviewed 346 adolescents, 66% aged 10-14 years, 61% female, 71% living in a rural or semi-urban area, 53% double or single orphan. Overall, ∼10% of ALHIV engaged in risky sexual behavior with higher prevalence in females (15.1%), age category 18-19 years (50%) and among ART naïve (33.3%) (p <0.01). Being an older adolescent (>=15 years) (OR=14.0, 95% C I: 4.55-43.02), being female (OR=4.1, 95% CI:1.12-14.98), staying in households with <5 members (OR=3.0, 95% CI: 1.13-7.31) and ALHIV receiving family planning information from clinic in last 12 months (OR=3.4, 95% CI: 1.42-7.94) were independently associated with risky sexual behaviour. A considerable proportion of ALHIV in Mbarara engage in risky sexual behaviors and could enhance HIV transmission. The greatest risk of risky sexual behaviour at the transition to adulthood and in females. HIV awareness and Sexual Reproductive Health interventions targeting adolescent girls in the late adolescence needs to be prioritized.

Discontinuing cotrimoxazole preventive therapy in HIV-infected adults who are stable on antiretroviral treatment in Uganda (COSTOP): A randomised placebo controlled trial.

BackgroundCotrimoxazole (CTX) preventive therapy (CPT) reduces opportunistic infections and malaria in HIV-infected patients. In Africa, policies on sustained CPT during antiretroviral therapy (ART) differ between countries. We assessed the safety of discontinuing CPT in stable patients on ART in Uganda.MethodsCOSTOP was a double-blind placebo-controlled trial. Patients aged ≥18 years, on CPT, and stable on ART (CD4 counts ≥250 cells/μL); were randomised to daily oral placebo (PLC group) or cotrimoxazole 960 mg/tablet (CTX group). Co-primary outcomes were: (i) time to first cotrimoxazole-preventable infection, with non- inferiority of PLC defined as the upper one-sided 95% confidence limit of the adjusted hazard ratio(aHR) ≤1.25; and (ii) time to first grade 3/4 haematological adverse event.Findings2180 subjects (1091 PLC; 1089 CTX) were enrolled. 932 PLC and 943 CTX completed the trial after 12 months minimum follow up. Ninety-eight participants (59 PLC; 39 CTX) experienced 120 cotrimoxazole- preventable events, mainly bacterial pneumonia (72 events, 4 deaths PLC); (48 events, 2 deaths CTX). The aHR for time to first event was 1.57 (upper one-sided 95% confidence limit 2.21) in per protocol population (similar results in ITT population). 551 participants (318 CTX; 233 PLC) experienced 1043 haematological adverse events (616 CTX; 427 PLC). Time to the first adverse event, mainly neutropenia, was shorter in the CTX group (aHR 0.70 95%CI 0.59–0.82; log-rank χ2 = 18.08; P<0.0001). 362 (276 PLC, 86 CTX) participants experienced at least one episode of confirmed clinical malaria (P<0.0001).InterpretationIn ART stable patients with CD4 counts ≥250 cells/μL, continued CPT significantly reduces risk of severe bacterial infections and protects against malaria, while discontinuing CPT reduces haematological adverse events.

The importance of how research participants think they are perceived: results from an electronic monitoring study of antiretroviral therapy in Uganda

ABSTRACTNovel monitoring technologies in HIV research, such as electronic adherence monitors (EAMs), have changed the nature of researcher-participant interactions. Yet little is known about how EAMs and the resulting interaction between researchers and participants affect research participation and the data gathered. We interviewed participants and research assistants (RAs) in an observational cohort study involving EAMs for HIV antiretroviral therapy (ART) in Uganda. We qualitatively explored interviewees’ views about ethical issues surrounding EAMs and assessed data with conventional and directed content analysis. Participants valued their relationships with RAs and were preoccupied with RAs’ perceptions of them. Participants were pleased when the EAM revealed regular adherence, and annoyed when it revealed non-adherence that contradicted self-reported pill-taking behavior. For many, the desire to maintain a good impression incentivized adherence. But some sought to creatively conceal non-adherence, or refused to use the EAM to avoid revealing non-adherence to RAs. These findings show that participants’ perceptions of the study staff's perceptions of them affected the experience of being monitored, study participation, and ultimately the data gathered in the study. Investigators in monitoring-based research should be aware that social interactions between participants and study staff could affect both the practical and ethical conduct of that research.

Are treatment supporters relevant in long-term Antiretroviral Therapy (ART) adherence? Experiences from a long-term ART cohort in Uganda

ABSTRACTBackground: This study aimed to understand the relevance of treatment supporters in adherence among people living with HIV taking Anti-retroviral therapy (ART) for more than five years in Uganda. Methods: In-depth interviews were conducted with 50 participants (28 women and 22 men) of the Complications of Long-Term ART (CoLTART) cohort with experience of at least five years on ART in Uganda. Participants were stratified by line of ART regimen and viral loads of less or above 1000 copies/ml. Data were analyzed thematically. Results: Many participants felt that a treatment supporter was most useful at the beginning of therapy before individuals get used to the drugs or when they are still weak. However, this did not reflect treatment outcomes, as many individuals without treatment supporters had failed on first line ART regimens and were switched to second line ART. Those who were still on first line had viral loads of ≥1000 copies/ml. There was a preference for female treatment supporters, many of who were persistent in their supportive role. Conclusion: Treatment supporters remain important in adherence to long-term ART. HIV-care providers need to encourage the involvement of a treatment supporter for individuals taking ART long-term.

Late Presentation With HIV in Africa: Phenotypes, Risk, and Risk Stratification in the REALITY Trial.

BackgroundSeverely immunocompromised human immunodeficiency virus (HIV)–infected individuals have high mortality shortly after starting antiretroviral therapy (ART). We investigated predictors of early mortality and “late presenter” phenotypes.MethodsThe Reduction of EArly MortaLITY (REALITY) trial enrolled ART-naive adults and children ≥5 years of age with CD4 counts <100 cells/µL initiating ART in Uganda, Zimbabwe, Malawi, and Kenya. Baseline predictors of mortality through 48 weeks were identified using Cox regression with backwards elimination (exit P > .1).ResultsAmong 1711 included participants, 203 (12%) died. Mortality was independently higher with older age; lower CD4 count, albumin, hemoglobin, and grip strength; presence of World Health Organization stage 3/4 weight loss, fever, or vomiting; and problems with mobility or self-care at baseline (all P < .04). Receiving enhanced antimicrobial prophylaxis independently reduced mortality (P = .02). Of five late-presenter phenotypes, Group 1 (n = 355) had highest mortality (25%; median CD4 count, 28 cells/µL), with high symptom burden, weight loss, poor mobility, and low albumin and hemoglobin. Group 2 (n = 394; 11% mortality; 43 cells/µL) also had weight loss, with high white cell, platelet, and neutrophil counts suggesting underlying inflammation/infection. Group 3 (n = 218; 10% mortality) had low CD4 counts (27 cells/µL), but low symptom burden and maintained fat mass. The remaining groups had 4%–6% mortality.ConclusionsClinical and laboratory features identified groups with highest mortality following ART initiation. A screening tool could identify patients with low CD4 counts for prioritizing same-day ART initiation, enhanced prophylaxis, and intensive follow-up.Clinical Trials RegistrationISRCTN43622374.

The role of children in their HIV-positive parents’ management of antiretroviral therapy in Uganda

Adjustment to life on antiretroviral therapy (ART) and living with HIV as a long-term chronic condition, pose significant medical, social and economic challenges. We investigated children’s role in supporting HIV-positive parents to self-manage life on ART. Between 2010 and 2012, we conducted a qualitative study using semi-structured interviews with 38 HIV-positive parents who had been on ART for over a year. They were randomly selected from people accessing ART from three delivery sites in Wakiso district, Uganda. Data were analysed thematically. Participants reported children between the ages of 1 and 47 years providing support. Children were a source of happiness, self-worth, encouragement, and comfort. Both younger and older children supported parents’ adherence to treatment through reminding them to take the drugs and honour clinic appointments. Older children provided money to buy medication, food and shelter. Parents reported that the encouragement they received after they disclosed to their children enhanced their survival. After HIV disclosure to their children many of their fears about the future were allayed. Thinking about their children’s future brought hope. However, looking after younger children while on ART could be burdensome since some parents could not work to their full capacity due to reduced physical health. Children are an important resource in their parents’ adjustment to living with HIV while taking ART. There is a need for children to be supported by appropriate policy and other social and health development structures.

Retention in care among HIV-infected pregnant and breastfeeding women on lifelong antiretroviral therapy in Uganda: A retrospective cohort study.

BackgroundIn 2013, Uganda updated its prevention of maternal-to-child transmission of HIV program to Option B+, which requires that all HIV-infected pregnant and breastfeeding women be started on lifelong antiretroviral therapy (ART) regardless of CD4 count. We describe retention in care and factors associated with loss to follow-up (LTFU) among women initiated on Option B+ as part of an evaluation of the effectiveness of the national program.MethodsWe conducted a retrospective cohort analysis of data abstracted from records of 2,169 women enrolled on Option B+ between January and March 2013 from a representative sample of 145 health facilities in all 24 districts of the Central region of Uganda. We defined retention as “being alive and receiving ART at the last clinic visit”. We used Kaplan-Meier analysis to estimate retention in care and compared differences between women retained in care and those LTFU using the chi-squared test for dichotomized or categorical variables.ResultsThe median follow-up time was 20.2 months (IQR 4.2–22.5). The proportion of women retained in HIV care at 6, 12 and 18 months post-ART initiation was 74.2%, 66.7% and 62.0%, respectively. Retention at 18 months varied significantly by level of health facility and ranged from 70.0% among those seen at hospitals to 56.6% among those seen at lower level health facilities. LTFU was higher among women aged less than 25 years, 59.3% compared to those aged 25 years and above, 40.7% (p = 0.02); among those attending care at lower level facilities, 44.0% compared to those attending care at hospitals, 34.1% (p = 0.01), and among those who were not tested for CD4 cell count at ART initiation, 69.4% compared to those who were tested, 30.9% (p = 0.002).ConclusionRetention of women who were initiated on Option B+ during the early phases of roll-out was only moderate, and could undermine the effectiveness of the program. Identifying reasons why women drop out and designing targeted interventions for improved retention should be a priority.

Virological response and resistance among HIV-infected children receiving long-term antiretroviral therapy without virological monitoring in Uganda and Zimbabwe: Observational analyses within the randomised ARROW trial.

BackgroundAlthough WHO recommends viral load (VL) monitoring for those on antiretroviral therapy (ART), availability in low-income countries remains limited. We investigated long-term VL and resistance in HIV-infected children managed without real-time VL monitoring.Methods and findingsIn the ARROW factorial trial, 1,206 children initiating ART in Uganda and Zimbabwe between 15 March 2007 and 18 November 2008, aged a median 6 years old, with median CD4% of 12%, were randomised to monitoring with or without 12-weekly CD4 counts and to receive 2 nucleoside reverse transcriptase inhibitors (2NRTI, mainly abacavir+lamivudine) with a non-nucleoside reverse transcriptase inhibitor (NNRTI) or 3 NRTIs as long-term ART. All children had VL assayed retrospectively after a median of 4 years on ART; those with >1,000 copies/ml were genotyped. Three hundred and sixteen children had VL and genotypes assayed longitudinally (at least every 24 weeks). Overall, 67 (6%) switched to second-line ART and 54 (4%) died. In children randomised to WHO-recommended 2NRTI+NNRTI long-term ART, 308/378 (81%) monitored with CD4 counts versus 297/375 (79%) without had VL <1,000 copies/ml at 4 years (difference = +2.3% [95% CI −3.4% to +8.0%]; P = 0.43), with no evidence of differences in intermediate/high-level resistance to 11 drugs. Among children with longitudinal VLs, only 5% of child-time post–week 24 was spent with persistent low-level viraemia (80–5,000 copies/ml) and 10% with VL rebound ≥5,000 copies/ml. No child resuppressed <80 copies/ml after confirmed VL rebound ≥5,000 copies/ml. A median of 1.0 (IQR 0.0,1.5) additional NRTI mutation accumulated over 2 years’ rebound. Nineteen out of 48 (40%) VLs 1,000–5,000 copies/ml were immediately followed by resuppression <1,000 copies/ml, but only 17/155 (11%) VLs ≥5,000 copies/ml resuppressed (P < 0.0001). Main study limitations are that analyses were exploratory and treatment initiation used 2006 criteria, without pre-ART genotypes.ConclusionsIn this study, children receiving first-line ART in sub-Saharan Africa without real-time VL monitoring had good virological and resistance outcomes over 4 years, regardless of CD4 monitoring strategy. Many children with detectable low-level viraemia spontaneously resuppressed, highlighting the importance of confirming virological failure before switching to second-line therapy. Children experiencing rebound ≥5,000 copies/ml were much less likely to resuppress, but NRTI resistance increased only slowly. These results are relevant to the increasing numbers of HIV-infected children receiving first-line ART in sub-Saharan Africa with limited access to virological monitoring.Trial registrationISRCTN Registry, ISRCTN24791884

HIV status disclosure and associated outcomes among pregnant women enrolled in antiretroviral therapy in Uganda: a mixed methods study

BackgroundDisclosure of HIV positive status to sexual partners is promoted by HIV prevention programs including those targeting the prevention of mother-to-child transmission. Among other benefits, disclosure may enhance spousal support and reduce stigma, violence and discrimination. HIV status disclosure and associated outcomes were assessed among a cohort of women, newly initiating lifelong antiretroviral therapy in Uganda between October 2013 and May 2014.MethodsThis was a mixed method study, drawing data from a prospective cohort study of 507 HIV positive pregnant women on lifelong antiretroviral therapy, who were followed for four months to determine disclosure and its outcomes. Women were recruited from three facilities for the cohort study; in addition, fifty-seven women were recruited to participate in qualitative interviews from six facilities. Factors associated with spousal support and negative outcomes were determined using random-effects logistic regression in two separate models, with prevalence ratio as measure of association. In-depth interviews were used to document experiences with disclosure of HIV status.ResultsOverall HIV status disclosure to at least one person was high [(375/507), 83.7%]. Nearly three-quarters [(285/389), 73.3%], had disclosed to their spouse by the fourth month of follow up post-enrolment. Among married women, spousal support was high at the first 330/407 (81.1%) and second follow-up 320/389 (82.2%). The majority of women who reported spousal support for either antenatal care or HIV-related care services had disclosed their HIV status to their spouses (adj.PR = 1.17; 95% CI: 1.02–1.34). However, no significant differences were observed in the proportion of self-reported negative outcomes by HIV status disclosure (adj.PR = 0.89; 95% CI: 0.56–1.42). Qualitative findings highlighted stigma and fear of negative outcomes as the major barriers to disclosure.ConclusionHIV status disclosure to partners by pregnant women on lifelong antiretroviral therapy was associated with increased spousal support, but was impeded by fear of adverse outcomes such as stigma, discrimination and violence. Interventions to reduce negative outcomes could enhance HIV status disclosure.

Factors Associated with Virological Non-suppression among HIV-Positive Patients on Antiretroviral Therapy in Uganda, August 2014\u2013July 2015

BackgroundDespite the growing number of people on antiretroviral therapy (ART), there is limited information about virological non-suppression and its determinants among HIV-positive (HIV+) individuals enrolled in HIV care in many resource-limited settings. We estimated the proportion of virologically non-suppressed patients, and identified the factors associated with virological non-suppression.MethodsWe conducted a descriptive cross-sectional study using routinely collected program data from viral load (VL) samples collected across the country for testing at the Central Public Health Laboratories (CPHL) in Uganda. Data were generated between August 2014 and July 2015. We extracted data on socio-demographic, clinical and VL testing results. We defined virological non-suppression as having ≥1000 copies of viral RNA/ml of blood for plasma or ≥5000 copies of viral RNA/ml of blood for dry blood spots. We used logistic regression to identify factors associated with virological non-suppression.ResultsThe study was composed of 100,678 patients; of these, 94,766(94%) were for routine monitoring, 3492(4%) were suspected treatment failures while 1436(1%) were repeat testers after suspected failure. The overall proportion of non-suppression was 11%. Patients on routine monitoring registered the lowest (10%) proportion of non-suppressed patients. Virological non-suppression was higher among suspected treatment failures (29%) and repeat testers after suspected failure (50%). Repeat testers after suspected failure were six times more likely to have virological non-suppression (ORadj = 6.3, 95%CI = 5.5–7.2) when compared with suspected treatment failures (ORadj = 3.3, 95%CI = 3.0–3.6). The odds of virological non-suppression decreased with increasing age, with children aged 0–4 years (ORadj = 5.3, 95%CI = 4.6–6.1) and young adolescents (ORadj = 4.1, 95%CI = 3.7–4.6) registering the highest odds. Poor adherence (ORadj = 3.4, 95%CI = 2.9–3.9) and having active TB (ORadj = 1.9, 95%CI = 1.6–2.4) increased the odds of virological non-suppression. However, being on second/third line regimens (ORadj = 0.86, 95%CI = 0.78–0.95) protected patients against virological non-suppression.ConclusionYoung age, poor adherence and having active TB increased the odds of virological non-suppression while second/third line ART regimens were protective against non-suppression. We recommend close follow up and intensified targeted adherence support for repeat testers after suspected failure, children and adolescents.

D-Dimer Levels and Traditional Risk Factors Are Associated With Incident Hypertension Among HIV-Infected Individuals Initiating Antiretroviral Therapy in Uganda.

We sought to describe blood pressure (BP) changes after antiretroviral therapy (ART) initiation and evaluate the association of markers of inflammation with incident hypertension in a cohort of HIV-infected individuals in Uganda. We used mixed effects linear regression to model changes in systolic BP over time among a cohort of HIV-infected individuals initiating ART in Uganda. After exclusion of participants with preexisting hypertension, we identified participants with normal BP throughout follow-up (controls) and those with elevated BP on ≥3 consecutive visits (cases). Before ART initiation, participants had testing for interleukin 6, kynurenine/tryptophan ratio, lipopolysaccharide, soluble CD14, soluble CD163, and D-dimer and those with viral suppression at 6 months during ART had repeat tests. We fit logistic regression models to estimate associations between biomarkers and risk of incident hypertension. In the entire cohort, systolic BP increased by 9.6 mm Hg/yr (95% CI: 7.3 to 11.8) in the first 6 months of ART, then plateaued. Traditional factors: male gender (adjusted odds ratio (AOR) 2.76, 95% CI: 1.34 to 5.68), age (AOR 1.09, 95% CI: 1.04 to 1.13), overweight (AOR 4.48, 95% CI: 1.83 to 10.97), and a CD4 count <100 cells (AOR 3.08, 95% CI: 1.07 to 8.89) were associated with incident hypertension. After adjusting for these, D-dimer levels at month 6 were inversely associated with incident hypertension (AOR 0.61, 95% CI: 0.37 to 0.99). Although not significant, similar associations were seen with sCD14 and kynurenine/tryptophan ratio. BP increases early after ART initiation in Ugandans. Traditional risk factors, rather than immune activation, were associated with incident hypertension in this population.

Depression at Treatment Initiation Predicts HIV Antiretroviral Adherence in Uganda.

We examined the relationship between depression (symptom type, diagnostic severity, and change over time) and adherence to HIV antiretroviral therapy (ART) with data from 3 longitudinal studies (N = 1021) of patients starting ART in Uganda. The Patient Health Questionnaire was used to assess depressive symptoms (total score; somatic and cognitive subscales) and categorize severity level. At baseline, 9% had major depression and 30% had minor depression; 82% were adherent (reported no missed ART doses in the past 7 days) at month 6 and 85% at month 12. Controlling for demographic and medical covariates, multivariate random-effects logistic regression models revealed that change in depression was not related to adherence; however, baseline total depression symptoms and cognitive symptoms in particular as well as major and minor depression were significant predictors of adherence. These findings highlight the need for early identification and aggressive treatment of depression to optimize ART adherence.

Trends in one-year cumulative incidence of death between 2005 and 2013 among patients initiating antiretroviral therapy in Uganda

Recent ecological data demonstrate improving outcomes for HIV-infected people in sub-Saharan Africa. Recently, Uganda has experienced a resurgence in HIV incidence and prevalence, but trends in HIV-related deaths have not been well described. Data were collected through the Uganda AIDS Rural Treatment Outcomes (UARTO) Study, an observational longitudinal cohort of Ugandan adults initiating antiretroviral therapy (ART) between 2005 and 2013. We calculated cumulative incidence of death within one year of ART initiation, and fit Poisson models with robust variance estimators to estimate the effect enrollment period on one-year risk of death and loss to follow-up. Of 760 persons in UARTO who started ART, 30 deaths occurred within one year of ART initiation (cumulative incidence 3.9%, 95% confidence interval [CI] 2.7-5.6%). Risk of death was highest for those starting ART in 2005 (13.0%, 95% CI 6.0-24.0%), decreased in 2006-2007 to 4% (95% CI 2.0-6.0%), and did not change thereafter ( P = 0.61). These results were robust to adjustment for age, sex, CD4 cell count, viral load, asset wealth, baseline depression, and body mass index. Here, we demonstrate that one-year cumulative incidence of death was high just after free ART rollout, decreased the following year, and remained low thereafter. Once established, ART programs in President's Emergency Fund for AIDS Relief-supported countries can maintain high quality care.

The effect of Tenofovir on renal function among Ugandan adults on long-term antiretroviral therapy: a cross-sectional enrolment analysis.

BackgroundWHO recommends using Tenofovir containing first line antiretroviral therapy (ART), however, Tenofovir has been reported to be associated with renal impairment and dysfunction. We compared renal function among individuals on Tenofovir and those on non-Tenofovir containing ART.MethodsIn a cross-sectional study of HIV-Positive adults on ART, at enrolment into a prospective cohort to study the long-term complications of ART in Uganda, information on biophysical measurements, medical history, clinical examination and renal function tests (RFTs) was collected. Fractional Tubular phosphate reabsorption and estimated glomerular filtration rate (eGFR) were calculated. Mean values of RFTs and proportions with abnormal RFTs were compared between non-Tenofovir containing (Non-TDF) and Tenofovir containing (TDF-ART) ART regimen groups using a general linear regression model. Durations of TDF exposure were also compared.ResultsBetween July 2013 and October 2014, we enrolled 953 individuals on ART for 6 or more months, median duration on ART was 9.3 years, 385 (40.4 %) were on non-TDF and 568 (59.6 %) on TDF-ART regimens. The proportion of participants with Proteinuria (>30 mg/dl) was higher among the TDF-ART group than the non-TDF ART group. However, in multivariable analysis, there were no significant differences in the adjusted mean differences of eGFR, serum urea, serum creatinine, fractional tubular reabsorption of phosphate and serum phosphates when patients on TDF-ART were compared with those on non-TDF containing ART. There were no differences in renal function even when different durations on Tenofovir were compared.ConclusionsWe found no differences in renal function among patients on Tenofovir and non-Tenofovir containing ART for almost a decade. Tenofovir based first line ART can therefore safely be initiated even in settings without routine renal function monitoring.

Forecast analysis of any opportunistic infection among HIV positive individuals on antiretroviral therapy in Uganda.

BackgroundPredicting future prevalence of any opportunistic infection (OI) among persons infected with the human immunodeficiency virus (HIV) on highly active antiretroviral therapy (HAART) in resource poor settings is important for proper planning, advocacy and resource allocation. We conducted a study to forecast 5-years prevalence of any OI among HIV-infected individuals on HAART in Uganda.MethodsMonthly observational data collected over a 10-years period (2004–2013) by the AIDS support organization (TASO) in Uganda were used to forecast 5-years annual prevalence of any OI covering the period 2014–2018. The OIs considered include 14 AIDS-defining OIs, two non-AIDS defining OIs (malaria & geohelminths) and HIV-associated Kaposi’s sarcoma. Box-Jenkins autoregressive integrated moving average (ARIMA) forecasting methodology was used.ResultsBetween 2004 and 2013, a total of 36,133 HIV patients were enrolled on HAART of which two thirds (66 %) were female. Mean annual prevalence for any OI in 2004 was 57.6 % and in 2013 was 27.5 % (X2trend = 122, b = −0.0283, p <0.0001). ARIMA (1, 1, 1) model was the most parsimonious and best fit for the data. The forecasted mean annual prevalence of any OI was 26.1 % (95 % CI 21.1–31.0 %) in 2014 and 15.3 % (95 % CI 10.4–20.3 %) in 2018.ConclusionsWhile the prevalence of any OI among HIV positive individuals on HAART in Uganda is expected to decrease overall, it’s unlikely that OIs will be completely eliminated in the foreseeable future. There is therefore need for continued efforts in prevention and control of opportunistic infections in all HIV/AIDS care programmes in these settings.Electronic supplementary materialThe online version of this article (doi:10.1186/s12889-016-3455-5) contains supplementary material, which is available to authorized users.

The Framing and Fashioning of Therapeutic Citizenship Among People Living With HIV Taking Antiretroviral Therapy in Uganda.

In this article, we examine how people living with HIV (PLWH) were able to reconceptualize or “reframe” their understanding of HIV and enhance their capacity to self-manage the condition. Two in-depth interviews were held with 38 PLWH (20 women, 18 men) selected from three government and nongovernment antiretroviral therapy (ART) delivery sites in Wakiso District, and the narratives analyzed. ART providers played an important role in shaping participants’ HIV self-management processes. Health workers helped PLWH realize that they could control their condition, provided useful concepts and language for emotional coping, and gave advice about practical self-management tasks, although this could not always be put into practice. ART providers in this setting were spaces for the development of a collective identity and a particular form of therapeutic citizenship that encouraged self-management, including adherence to ART. Positive framing institutions are important for many PLWH in resource-limited settings and the success of ART programs.

Tuberculosis incidence is high in HIV-infected African children but is reduced by co-trimoxazole and time on antiretroviral therapy.

BackgroundThere 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.MethodsOf 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.ResultsAfter 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).ConclusionsTB 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-016-0593-7) contains supplementary material, which is available to authorized users.

Finding Meaning: HIV Self-Management and Wellbeing among People Taking Antiretroviral Therapy in Uganda.

The health of people living with HIV (PLWH) and the sustained success of antiretroviral therapy (ART) programmes depends on PLWH’s motivation and ability to self-manage the condition over the long term, including adherence to drugs on a daily basis. PLWH’s self-management of HIV and their wellbeing are likely to be interrelated. Successful self-management sustains wellbeing, and wellbeing is likely to motivate continued self-management. Detailed research is lacking on PLWH’s self-management processes on ART in resource-limited settings. This paper presents findings from a study of PLWH’s self-management and wellbeing in Wakiso District, Uganda. Thirty-eight PLWH (20 women, 18 men) were purposefully selected at ART facilities run by the government and by The AIDS Support Organisation in and around Entebbe. Two in-depth interviews were completed with each participant over three or four visits. Many were struggling economically, however the recovery of health and hope on ART had enhanced wellbeing and motivated self-management. The majority were managing their condition well across three broad domains of self-management. First, they had mobilised resources, notably through good relationships with health workers. Advice and counselling had helped them to reconceptualise their condition and situation more positively and see hope for the future, motivating their work to self-manage. Many had also developed a new network of support through contacts they had developed at the ART clinic. Second, they had acquired knowledge and skills to manage their health, a useful framework to manage their condition and to live their life. Third, participants were psychologically adjusting to their condition and their new ‘self’: they saw HIV as a normal disease, were coping with stigma and had regained self-esteem, and were finding meaning in life. Our study demonstrates the centrality of social relationships and other non-medical aspects of wellbeing for self-management which ART programmes might explore further and encourage.

Immune Activation and Risk of Hypertension in HIV-Infected Adults Initiating Antiretroviral Therapy in Uganda: A Nested Case-Control Study

Immune Activation and Risk of Hypertension in HIV-Infected Adults Initiating Antiretroviral Therapy in Uganda: A Nested Case-Control Study