Pontiano Kaleebu

High HIV incidence and socio-behavioral risk patterns in fishing communities on the shores of Lake Victoria, Uganda.

Background: We report on HIV acquisition and its associated risk factors in 5 fishing communities on the shores of Lake Victoria in Uganda. A cohort of 1000 HIV-uninfected at-risk volunteers aged 13 to 49 years were recruited in 2009 and followed up for 18 months. Methods: At enrollment and semiannual visits, socio-demographic and risk behavior data were collected through a structured questionnaire and blood samples tested for HIV and syphilis. Detailed life histories were collected from 78 volunteers using in-depth interviews. Results: Of the 1000 volunteers enrolled, 919 (91.9%) were followed up, with 762 (76.2%) reaching the study end points (either seroconverted or completed 4 visits). There were 59 incident cases in 1205.6 person-years at risk (PYAR), resulting in an incidence rate of 4.9 (95% CI = 3.8 to 6.3) per 100 PYAR. The highest HIV incidence rates were among those working in bars (9.8/100 PYAR [4.7–20.6]), protestants (8.6/100 PYAR [5.8–12.7]), those aged 13 to 24 years (7.5/100 PYAR [5.2–11.0]), and new immigrants (6.6/100 PYAR [4.9–8.9]). HIV infection was independently associated with being young (adjusted hazard ratio (aHR) = 2.5 [95% CI = 1.3–4.9]), reporting genital sores/discharge recently (aHR = 2.8 [1.6–5.0]), regular alcohol consumption (aHR = 3.3 [1.6–6.1]), use of marijuana (aHR = 2.9 [1.0–8.0]), cigarette smoking (aHR = 3.6 [1.4–9.3]), and religion (compared with Catholics, Protestants had aHR = 2.7 [1.4–5.3] and Muslims had aHR = 2.3 [1.1–4.8]). Conclusions: These fishing communities experienced high HIV infection, which was mainly explained by high-risk behavior. There is an urgent need to target HIV prevention and research efforts to this vulnerable and neglected group.

Transmitted Antiretroviral Drug Resistance Surveillance among Newly HIV Type 1-Diagnosed Women Attending an Antenatal Clinic in Entebbe, Uganda

To evaluate transmitted HIV-1 drug resistance and study the natural polymorphism in pol of HIV-1 strains of newly diagnosed women attending an antenatal clinic in Uganda we sequenced the protease and reverse transcriptase genes for 46 HIV-1 strains from the threshold surveillance. Of the 46 sequences analyzed, 48.0% were subtype A1 (n 22), 39.0% subtype D (n 18), 2.0% subtype A2 (n 1), 2.0% subtype C (n 1), and 9.0% intersubtype recombinant A1/D (n 4). Overall, many minor mutations were identified in the protease sequences. None of the strains had major associated mutations to any RTI drug or drug class interest after genotyping 37 samples of our cohort. The HIV drug resistance prevalence estimate in Entebbe following the HIVDR-TS methodology is less than 5% as set out by WHO guidelines.

Schistosoma mansoni and HIV acquisition in fishing communities of Lake Victoria, Uganda: a nested case–control study

It has been suggested that Schistosoma mansoni, which is endemic in African fishing communities, might increase susceptibility to human immunodeficiency virus (HIV) acquisition. If confirmed, this would be of great public health importance in these high HIV‐risk communities. This study was undertaken to determine whether S. mansoni infection is a risk factor for HIV infection among the fishing communities of Lake Victoria, Uganda. We conducted a matched case–control study, nested within a prospective HIV incidence cohort, including 50 HIV seroconverters (cases) and 150 controls during 2009‐2011.

Mortality and its predictors among antiretroviral therapy naïve HIV-infected individuals with CD4 cell count ≥350 cells/mm3 compared to the general population: data from a population-based prospective HIV cohort in Uganda

Background Evidence exists that even at high CD4 counts, mortality among HIV-infected antiretroviral therapy (ART) naïve individuals is higher than that in the general population. However, many developing countries still initiate ART at CD4 ≤350 cells/mm3. Objective To compare mortality among HIV-infected ART naïve individuals with CD4 counts ≥350 cells/mm3 with mortality in the general Ugandan population and to investigate risk factors for death. Design Population-based prospective HIV cohort. Methods The study population consisted of HIV-infected people in rural southwest Uganda. Patients were reviewed at the study clinic every 3 months. CD4 cell count was measured every 6 months. Rate ratios were estimated using Poisson regression. Indirect methods were used to calculate standardised mortality ratios (SMRs). Results A total of 374 participants with CD4 ≥350 cells/mm3 were followed for 1,328 person-years (PY) over which 27 deaths occurred. Mortality rates (MRs) (per 1,000 PY) were 20.34 (95% CI: 13.95-29.66) among all participants and 16.43 (10.48-25.75) among participants aged 15-49 years. Mortality was higher in periods during which participants had CD4 350-499 cells/mm3 than during periods of CD4 ≥500 cells/mm3 although the difference was not statistically significant [adjusted rate ratio (aRR)=1.52; 95% CI: 0.71-3.25]. Compared to the general Ugandan population aged 15-49 years, MRs were 123% higher among participants with CD4 ≥500 cells/mm3 (SMR: 223%, 95% CI: 127-393%) and 146% higher among participants with CD4 350-499 cells/mm3 (246%, 117%-516). After adjusting for current age, mortality was associated with increasing WHO clinical stage (aRR comparing stage 3 or 4 and stage 1: 10.18, 95% CI: 3.82-27.15) and decreasing body mass index (BMI) (aRR comparing categories ≤17.4 Kg/m2 and ≥18.5 Kg/m2: 6.11, 2.30-16.20). Conclusion HIV-infected ART naïve individuals with CD4 count ≥350 cells/mm3 had a higher mortality than the general population. After adjusting for age, the main predictors of mortality were WHO clinical stage and BMI.Background Evidence exists that even at high CD4 counts, mortality among HIV-infected antiretroviral therapy (ART) naïve individuals is higher than that in the general population. However, many developing countries still initiate ART at CD4 ≤350 cells/mm3. Objective To compare mortality among HIV-infected ART naïve individuals with CD4 counts ≥350 cells/mm3 with mortality in the general Ugandan population and to investigate risk factors for death. Design Population-based prospective HIV cohort. Methods The study population consisted of HIV-infected people in rural southwest Uganda. Patients were reviewed at the study clinic every 3 months. CD4 cell count was measured every 6 months. Rate ratios were estimated using Poisson regression. Indirect methods were used to calculate standardised mortality ratios (SMRs). Results A total of 374 participants with CD4 ≥350 cells/mm3 were followed for 1,328 person-years (PY) over which 27 deaths occurred. Mortality rates (MRs) (per 1,000 PY) were 20.34 (95% CI: 13.95–29.66) among all participants and 16.43 (10.48–25.75) among participants aged 15–49 years. Mortality was higher in periods during which participants had CD4 350–499 cells/mm3 than during periods of CD4 ≥500 cells/mm3 although the difference was not statistically significant [adjusted rate ratio (aRR)=1.52; 95% CI: 0.71–3.25]. Compared to the general Ugandan population aged 15–49 years, MRs were 123% higher among participants with CD4 ≥500 cells/mm3 (SMR: 223%, 95% CI: 127–393%) and 146% higher among participants with CD4 350–499 cells/mm3 (246%, 117%–516). After adjusting for current age, mortality was associated with increasing WHO clinical stage (aRR comparing stage 3 or 4 and stage 1: 10.18, 95% CI: 3.82–27.15) and decreasing body mass index (BMI) (aRR comparing categories ≤17.4 Kg/m2 and ≥18.5 Kg/m2: 6.11, 2.30–16.20). Conclusion HIV-infected ART naïve individuals with CD4 count ≥350 cells/mm3 had a higher mortality than the general population. After adjusting for age, the main predictors of mortality were WHO clinical stage and BMI.

Effect of HIV-1 Subtypes on Disease Progression in Rural Uganda: A Prospective Clinical Cohort Study

Objective We examined the association of HIV-1 subtypes with disease progression based on three viral gene regions. Design A prospective HIV-1 clinical cohort study in rural Uganda. Methods Partial gag, env and pol genes were sequenced. Cox proportional hazard regression modelling was used to estimate adjusted hazard ratios (aHRs) of progression to: CD4≤250, AIDS onset and death, adjusted for sex, age and CD4 count at enrolment. Results Between 1990 and 2010, 292 incident cases were subtyped: 25% had subtype A, 45% had D, 26% had A/D recombinants, 1% had C and 4% were other recombinant forms. Of the 278 incident cases included in the disease progression analysis, 62% progressed to CD4≤250, 32% to AIDS, and 34% died with a higher proportion being among subtype D cases. The proportions of individuals progressing to the three endpoints were significantly higher among individuals infected with subtype D. Throughout the study period, individuals infected with subtype D progressed faster to CD4≤250, adjusted HR (aHR), (95% CI) = 1.72 (1.16–2.54), but this was mainly due to events in the period before antiretroviral therapy (ART) introduction, when individuals infected with subtype D significantly progressed faster to CD4≤250 than subtype A cases; aHR (95% CI) = 1.78 (1.01–3.14). Conclusions In this population, HIV-1 subtype D was the most prevalent and was associated with faster HIV-1 disease progression than subtype A. Further studies are needed to examine the effect of HIV-1 subtypes on disease progression in the ART period and their effect on the virological and immunological ART outcomes.

Lack of Effectiveness of Antiretroviral Therapy in Preventing HIV Infection in Serodiscordant Couples in Uganda: An Observational Study.

Background We examined the real-world effectiveness of ART as an HIV prevention tool among HIV serodiscordant couples in a programmatic setting in a low-income country. Methods We enrolled individuals from HIV serodiscordant couples aged ≥18 years of age in Jinja, Uganda from June 2009 – June 2011. In one group of couples the HIV positive partner was receiving ART as they met clinical eligibility criteria (a CD4 cell count ≤250 cells/ μL or WHO Stage III/IV disease). In the second group the infected partner was not yet ART-eligible. We measured HIV incidence by testing the uninfected partner every three months. We conducted genetic linkage studies to determine the source of new infections in seroconverting participants. Results A total of 586 couples were enrolled of which 249 (42%) of the HIV positive participants were receiving ART at enrollment, and an additional 99 (17%) initiated ART during the study. The median duration of follow-up was 1.5 years. We found 9 new infections among partners of participants who had been receiving ART for at least three months and 8 new infections in partners of participants who had not received ART or received it for less than three months, for incidence rates of 2.09 per 100 person-years (PYRs) and 2.30 per 100 PYRs, respectively. The incidence rate ratio for ART-use was 0.91 (95% confidence interval 0.31-2.70; p=0.999). The hazard ratio for HIV seroconversion associated with ART-use by the positive partner was 1.07 (95% CI 0.41-2.80). A total of 5/7 (71%) of the transmissions on ART and 6/7 (86%) of those not on ART were genetically linked. Conclusion Overall HIV incidence was low in comparison to previous studies of serodiscordant couples. However, ART-use was not associated with a reduced risk of HIV transmission in this study.

Transmitted Antiretroviral Drug Resistance Among Drug-Naive Female Sex Workers With Recent Infection in Kampala, Uganda

During 2006-2007, transmitted human immunodeficiency virus (HIV) drug resistance (TDR) among drug-naive women with newly diagnosed HIV infection and likely to be recently infected when attending antenatal clinics in Entebbe was found to be <5% with use of the World Health Organization (WHO) survey method. Using the same method, we attempted to classify TDR among women who seroconverted during 2008-2010 and who were identified from a cohort of recently infected sex workers in Kampala, Uganda. TDR mutations were identified using the 2009 WHO TDR mutations list. The WHO survey method could not be used to classify TDR because the necessary sample size was not reached during the survey period. However, a point prevalence estimate of 2.6% (95% confidence interval, 0.07%-13.8%) nonnucleoside reverse-transcriptase inhibitor TDR was determined.

Capacity for science in sub-Saharan Africa

During the past decade there has been an increase in funding for research capacity building in Africa. Two major European programmes are at a turning point: the Wellcome Trust’s African Institutions Initiative is about to end, while their new initiative, DELTAS Africa, will be launched later this year. The European Union’s Seventh Framework Programme (FP7) is ending, superseded by Horizon 2020, with the transition of some research areas that are important to Africa into the expanded second phase of the European and Developing Countries Clinical Trials Partnership. This is an opportune moment for refl ection on the value of capacity building for Africa, and on the mutual interdependence of excellence in science and provision of research capacity. Important progress has been made in capacity building for epidemiological research and for research ethics in Africa, and these underpinnings are crucial for excellent science. But research in Africa involving basic science also has many important needs and opportunities, and this area has been relatively neglected. HIV, tuberculosis, malaria, and helminth infections still present a huge health burden in Africa, and few eff ective vaccines are yet available for these diseases. Improved diagnostics and treatments are also needed. At the same time, urbanisation and development are resulting in changes in lifestyle and an emerging burden of non-communicable diseases (NCDs): there are opportunities in Africa, now, to understand the relation between infectious exposures and NCDs in ways that are no longer possible in resource-rich nations. And interest in the genetics of African populations is burgeoning, with greater diversity and a lower degree of linkage disequilibrium as compared with other populations likely to off er unprecedented insights into the genetic basis of susceptibility to common diseases. The only sustainable, and socially equitable, way to address these opportunities is to support the development of African scientists to participate in balanced partnerships, and to lead, in these globally important fi elds. For health research funders, value for money must mean scientifi c results that achieve advances in understanding of relevant biology, in progress on product development, or in strategies for disease prevention and management. The typical indicators of progress in capacity building (ie, equipment purchased, administrative systems upgraded, and PhD students completing) might be less compelling, but are no less crucial to the advancement of human knowledge. We have worked during the past decade on Wellcome Trust funded programmes for capacity building and on European Union programmes designed to conduct scientifi c research. We illustrate here how both contribute to the desired capacity for, and achievement of, scientifi c progress. In 2008, Makerere University College of Health Sciences in Uganda had no laboratory capacity for immunology research. However, the Uganda Virus Research Institute (UVRI) had substantial capacity in immunology and infection research. We combined strengths in the Makerere University–UVRI research training programme on Infection and Immunity (MUII) to foster mutual support in the development of infection and immunity research in Uganda. Among our activities, we established a laboratory for immunology research at the College of Health Sciences, and equipped it with basic requirements for serological and cellular immunology research. The eff ect, in terms of capacity building indicators, includes the emergence of an immunology interest group at Makerere, a new Masters degree course in immunology and clinical microbiology, ten Masters projects, ten PhD projects, and six postdoctoral projects in progress or completed to date. A shift system has been needed to control use of the laboratory, and expansion plans are in progress.

Virological Response and Antiretroviral Drug Resistance Emerging during Antiretroviral Therapy at Three Treatment Centers in Uganda.

Background With the scale-up of antiretroviral therapy (ART), monitoring programme performance is needed to maximize ART efficacy and limit HIV drug resistance (HIVDR). Methods We implemented a WHO HIVDR prospective survey protocol at three treatment centers between 2012 and 2013. Data were abstracted from patient records at ART start (T1) and after 12 months (T2). Genotyping was performed in the HIV pol region at the two time points. Results Of the 425 patients enrolled, at T2, 20 (4.7%) had died, 66 (15.5%) were lost to follow-up, 313 (73.6%) were still on first-line, 8 (1.9%) had switched to second-line, 17 (4.0%) had transferred out and 1 (0.2%) had stopped treatment. At T2, 272 out of 321 on first and second line (84.7%) suppressed below 1000 copies/ml and the HIV DR prevention rate was 70.1%, just within the WHO threshold of ≥70%. The proportion of participants with potential HIVDR was 20.9%, which is higher than the 18.8% based on pooled analyses from African studies. Of the 35 patients with mutations at T2, 80% had M184V/I, 65.7% Y181C, and 48.6% (54.8% excluding those not on Tenofovir) had K65R mutations. 22.9% had Thymidine Analogue Mutations (TAMs). Factors significantly associated with HIVDR prevention at T2 were: baseline viral load (VL) <100,000 copies/ml [Adjusted odds ratio (AOR) 3.13, 95% confidence interval (CI): 1.36–7.19] and facility. Independent baseline predictors for HIVDR mutations at T2 were: CD4 count <250 cells/μl (AOR 2.80, 95% CI: 1.08–7.29) and viral load ≥100,000 copies/ml (AOR 2.48, 95% CI: 1.00–6.14). Conclusion Strengthening defaulter tracing, intensified follow-up for patients with low CD4 counts and/or high VL at ART initiation together with early treatment initiation above 250 CD4 cells/ul and adequate patient counselling would improve ART efficacy and HIVDR prevention. The high rate of K65R and TAMs could compromise second line regimens including NRTIs.

Heterogeneity of HIV incidence: a comparative analysis between fishing communities and in a neighbouring rural general population, Uganda, and implications for HIV control

Objectives To describe HIV heterogeneity in rural Uganda using incidence data collected between January 2012 and December 2014 among fishing cohort (FC) and in an adjacent rural general population cohort (GPC). Methods In the FC, eligible HIV high-risk adults aged 18+ years were enrolled, followed and HIV tested every 3 months. Demographic and sexual behaviour data were also collected. The GPC, approximately 47 km away from the FC, was followed through annual surveys, and sociodemographic and behavioural data collected. A subset of GPC with comparable risk profiles to the FC was selected. We presented sociodemographic and risk profiles and also computed stratified HIV incidence. Cox regression was used to assess factors associated with HIV incidence. Results Overall HIV incidence was higher in the FC than in the ‘high-risk’ GPC, 6.04 and 0.56 per 100 person years at risk, respectively, with a rate ratio (RR) of 10.83 (95% CI 6.11 to 19.76). This was higher among those aged 18–24 years, unmarried and those with more than two sex partners in the past year, RR of 15.44, 22.99 and 19.29, respectively. In the FC, factors associated with high incidence in multivariate analysis were duration in the community and unprotected sex. The factors in the GPC were ethnicity, marital status and duration in the community. Conclusions We have observed a substantial heterogeneity in HIV incidence. The high incidence in fishing communities is contributing greatly to the overall HIV burden in Uganda, and thus urgent combination prevention efforts are needed towards national goal to reduce HIV epidemic.