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Background: Sub-Saharan Africa (SSA) has the highest burden of HIV in the world and a rising prevalence of cardiometabolic disease; however, the interrelationship between HIV, antiretroviral therapy (ART) and cardiometabolic traits is not well described in

Objectives: To describe the incidence and aetiology of septicaemia, and antimicrobial drug resistance in HIV-infected and uninfected individuals, and the impact of antiretroviral therapy (ART) on septicaemia.Methods: Between 1996 and 2007, we followed up a rural population-based cohort of HIV-infected and uninfected participants. The aetiology and incidence of septicaemia, and antimicrobial drug resistances were determined. ART became available in 2004, and its impact on the incidence of septicaemia was examined.Results: The overall septicaemia incidence (per 1000 pyrs) was 32.4 (95% CI 26.2-40.6) but was only 2.6 (95% CI 1.3-6.2) in HIV-negative patients and 67.1 (95% CI 53.4-85.4) in HIV-positive patients not on ART. Among those on ART, the overall incidence was 71.5 (95% CI 47.1-114.3), although it was 121.4 (95%CI 77.9-200.4) in the first year on ART and 37.4 (95%CI 18.9-85.2) in the subsequent period. Septicaemia incidence was significantly associated with lower CD4 counts. The commonest isolates were Streptococcus pneumoniae (SPN, n = 68) and Non-typhi salmonellae (NTS, n = 42). Most SPN isolates were susceptible to ceftriaxone and erythromycin, while resistance to cotrimoxazole and penicillin was common. All NTS isolates were susceptible to ciprofloxacin, but resistance to cotrimoxazole and chloramphenicol was common.Conclusions: Septicaemia incidence was higher in HIV-infected than in HIV-uninfected participants, and it remained high for some time among those who started ART. Starting ART earlier at higher CD4 counts is likely to lead to lower septicaemia incidence. Both SPN and NTS, the commonest isolates, were resistant to most commonly available antimicrobials. Blood culture laboratory surveillance systems to monitor antibiotic susceptibility and inform treatment guidelines are needed in Africa. [ABSTRACT FROM AUTHOR]

Objectives: To assess the prevalence and risk factors of overweight and obesity among type 2 diabetes mellitus (T2DM) patients in Uganda., Design: Retrospective chart review., Setting: This study was conducted in the outpatient's T2DM clinic in St. Francis Hospital-Nsambya, Uganda between March and May 2017., Participants: Type 2 diabetes patients registered in the diabetes clinic between July 2003 and September 2016., Outcome Measures: Overweight and obesity defined as body mass index (kg/m 2 ) of 25.0-29.9 and obesity as 30.0 or higher., Results: Of 1275 T2DM patients, the median age was 54 (IQR: 44-65) years, 770 (60.40%) were females, 887 (69.6%) had hypertension, 385 (28%) had controlled glycaemia, 349 (27%) were obese, while 455 (36%) were overweight. Overweight/obesity were lower among men (OR: 0.45, 95% CI: 0.340 to 0.593, p≤0.001) and among patients aged ≥65 years (OR: 0.52, 95% CI: 0.350 to 0.770, p=0.001); patients who rarely ate fruits and vegetables (OR: 0.66, 95% CI: 0.475 to 0.921, p=0.014) but higher among patients of middle (OR: 1.83, 95% CI: 1.320 to 2.550, p≤0.001) and upper (OR: 2.10, 95% CI: 1.450 to 2.990, p≤0.001) socioeconomic status; on dual therapy (OR: 2.17, 95% CI: 1.024 to 4.604, p=0.043); with peripheral neuropathy (OR: 1.40, 95% CI: 1.039 to 1.834, p=0.026) and hypertension (OR: 1.70, 95% CI: 1.264 to 2.293, p≤0.001)., Conclusions: Overweight and obesity are high among T2DM patients in this population and may contribute significantly to poor outcomes of T2DM. Therefore, strategies to address this problem are urgently needed., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Although the prevalence of type 2 diabetes mellitus is increasing in Uganda, data on loss to follow up (LTFU) of patients in care is scanty. We aimed to estimate proportions of patients LTFU and document associated factors among patients attending a private not for profit urban diabetes clinic in Uganda., Methods: We conducted a descriptive retrospective study between March and May 2017. We reviewed 1818 out-patient medical records of adults diagnosed with type 2 diabetes mellitus registered between July 2003 and September 2016 at St. Francis Hospital - Nsambya Diabetes clinic in Uganda. Data was extracted on: patients' registration dates, demographics, socioeconomic status, smoking, glycaemic control, type of treatment, diabetes mellitus complications and last follow-up clinic visit. LTFU was defined as missing collecting medication for six months or more from the date of last clinic visit, excluding situations of death or referral to another clinic. We used Kaplan-Meier technique to estimate time to defaulting medical care after initial registration, log-rank test to test the significance of observed differences between groups. Cox proportional hazards regression model was used to determine predictors of patients' LTFU rates in hazard ratios (HRs)., Results: Between July 2003 and September 2016, one thousand eight hundred eighteen patients with type 2 diabetes mellitus were followed for 4847.1 person-years. Majority of patients were female 1066/1818 (59%) and 1317/1818 (72%) had poor glycaemic control. Over the 13 years, 1690/1818 (93%) patients were LTFU, giving a LTFU rate of 34.9 patients per 100 person-years (95%CI: 33.2-36.6). LTFU was significantly higher among males, younger patients (< 45 years), smokers, patients on dual therapy, lower socioeconomic status, and those with diabetes complications like neuropathy and nephropathy., Conclusion: We found high proportions of patients LTFU in this diabetes clinic which warrants intervention studies targeting the identified risk factors and strengthening follow up of patients.

Background: 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.

Background: Antiretroviral therapy (ART) use by people living with HIV reduces HIV transmission, morbidity, mortality, and improves quality of life. Good ART adherence is required to achieve these benefits. We investigated how the environmental, social, economic and behavioural experiences of people living with HIV with poor viral suppression could explain their non-adherence to long term ART., Methods: This qualitative cross-sectional study was conducted in Uganda between September 2015 and April 2016. Thirty individuals on ART for 5 years or more (10 on first line and 20 on second line), with poor viral suppression, were randomly selected from a cohort of people living with HIV on ART. In-depth interviews about ART; awareness, adherence counselling, obstacles to daily adherence and regimen switches were conducted. Emerging themes from the interviews transcripts and field notes were identified and thematic content analysis done. Participants' consent, compensation, confidentiality and study ethical approvals were ensured., Results: We found that poor adherence to long term ART was due to: travel for work or social activities, stigma, receiving little or no continuous ART adherence education, alcohol consumption and use of alternative 'HIV cure' medicines. Other reasons included; ART side effects, treatment fatigue, belief that long-term ART or God can 'cure HIV', and food security., Conclusions: Achieving optimal ART benefits requires continuous provision of ART adherence education to individuals on long term ART. This helps them overcome the challenges related to living with HIV: worries of food insecurity, alcohol misuse, economic hardship, and beliefs in HIV cures and use of unproven alternative HIV treatments. People living with HIV who travel require adherence support and larger quantities of ART refills to cover their time away.

This report describes the identification of a genetically confirmed linked heterosexual human immunodeficiency virus (HIV) superinfection (HIV-SI) in a woman with chronic HIV infection who acquired a second strain of the virus from her husband. Serum neutralizing antibody (NAb) responses against their homologous and heterologous viruses, including the superinfecting strain, in the woman and her husband were examined before and after onset of HIV-SI. The woman displayed a moderately potent and broad anti-HIV NAb response prior to superinfection but did not possess NAb activity against the superinfecting strain. This case highlights the unique potential of linked HIV-SI studies to examine natural protection from HIV infection.

Introduction: We investigated factors affecting Virological failure (VF) on first line Antiretroviral Therapy (ART) and evaluated a pragmatic approach to switching to second line ART., Methods: Between 2004 and 2011, we assessed adults taking ART. After 6 months or more on ART, participants with VL >1000 copies/ml or two successive VL > 400 copies/ml (Conventional VF) received intensified adherence counselling and continued on first-line ART for 6 more months, after which participants who still had VL > 1000 copies/ml (Pragmatic VF) were switched to second line ART. VF rates were calculated and predictors of failure were found by fitting logistic regression and Cox proportional hazards models., Results: The 316 participants accrued 1036 person years at risk (pyar), 84 (26.6%) had conventional VF (rate 8.6 per 100 pyar) of whom 28 (33.3%) had pragmatic VF (rate 2.7 per 100 pyar). Independent predictors of conventional VF were; alcohol consumption, (adjusted Hazard Ratio; aHR = 1.71, 95% CI 1.05-2.79, P = 0.03) and ART adherence: per 10% decrease in proportion of adherent visits, (aHR = 1.83, 95% CI 1.50-2.23; P < 0.001). Using reference age group < 30 years, among conventional failures, the adjusted odds ratio (aOR) of pragmatic failure for age group 30-39 years were 0.12, 95% CI 0.03-0.57, P = 0.02 and for age group > 40 years were 0.14, 95%CI 0.03-0.71, P = 0.02. Alcohol consumers had a threefold odds of pragmatic failure than non-alcohol consumers (aOR = 3.14, 95%CI 0.95-10.34, P = 0.06)., Conclusion: A pragmatic VF approach is essential to guide switching to second line ART. Patient tailored ART adherence counselling among young patients and alcohol users is recommended., Competing Interests: The authors declare no competing interest.

Introduction: We investigated the prevalence, predictors of and effect of Antiretroviral Therapy (ART) regimen on cardiometabolic risk among HIV-positive Ugandan adults at enrolment into a prospective cohort to study the Complications of Long-Term ART (CoLTART)., Methods: We collected data on cardiometabolic risk factors including dyslipidemia, hypertension, hyperglycemia, obesity and calculated the mean atherogenic index for Plasma (AIP) and 10 year Framingham risk score (FHS). Exposures were: ART regimen, duration on ART, demographic, socio-economic, behavioral, and life-style factors including smoking, physical activity and diet (including fruit and vegetables consumption)., Results: We enrolled 1024 participants, 65% female, mean age was 44.8 years (SD 8.0) and median duration on ART was 9.4 years (IQR 6.1-9.8). The prevalence of abdominal obesity was 52.6%, BMI≥25 kg/m 2 -26.1%, hypertension-22.6%, high AIP-31.3% and FHS above 10% was 16.6%. The prevalence of low High Density Lipoprotein (HDL) was 37.5%, high Total cholesterol (Tc)-30.2%, high Low Density Lipoprotein (LDL) -23.6%, high Triglycerides (TG)-21.2%, low physical activity-46.4% and alcohol consumption-26.4%. In multivariate linear regression analyses, increasing age was associated with higher mean Tc, HDL, LDL, FHS (P<0.001) and hyperglycemia (p<0.005). In multivariate logistic regression analyses, Protease Inhibitor (PI) containing regimens were significantly associated with higher risks of abnormal: Tc, LDL, TG, AIP, abdominal obesity, hypertension, low HDL and lower risk of a FHS >10% compared to the non PI regimen., Conclusion: ART increases cardiometabolic risk. Integration of routine assessment for cardiometabolic risk factors and preventive interventions into HIV care programs in resource-limited settings is recommended.

Background: Antiretroviral therapy (ART) improves the survival and quality of life of HIV-positive individuals, but the effects of long-term ART use do eventually manifest. The Complications of Long-Term Antiretroviral Therapy cohort study in Uganda (CoLTART) was established to investigate the metabolic and renal complications of long-term ART use among Ugandan adults. We describe the CoLTART study set-up, aims, objectives, study methods, and also report some preliminary cross-sectional study enrolment metabolic and renal complications data analysis results., Methods: HIV-positive ART naïve and experienced adults (18 years and above) in Uganda were enrolled. Data on demographic, dietary, medical, social economic and behaviour was obtained; and biophysical measurements and a clinical examination were undertaken. We measured: fasting glucose and lipid profiles, renal and liver function tests, full blood counts, immunology, virology and HIV drug resistance testing. Plasma samples were stored for future studies., Results: Between July 2013 and October 2014, we enrolled 1095 individuals, of whom 964 (88.0%) were ART experienced (6 months or more), with a median of 9.4 years (IQR 7.0-9.9) on ART. Overall, 968 (88.4%) were aged 35 years and above, 711 (64.9%) were females, 608 (59.6%) were or had ever been on a Tenofovir ART regimen and 236 (23.1%) on a Protease Inhibitor (PI) regimen. There were no differences in renal dysfunction between patients on Tenofovir and Non-Tenofovir containing ART regimens. Patients on PI regimens had higher total cholesterol, lower high density lipoprotein, higher low density lipoprotein, higher triglycerides, and a high atherogenic index for plasma than the non-PI regimen, p = 0.001 or < 0.001. Patients on Non-PI regimens had higher mean diastolic hypertension than patients on PI regimens, p < 0.001., Conclusions: Our finding of no differences in renal dysfunction between patients on Tenofovir and those on Non-Tenofovir containing ART regimens means that Tenofovir based first line ART can safely be initiated even in settings without routine renal function monitoring. However, integration of cardiovascular risk assessment, preventive and curative measures against cardiovascular disease are required. The CoLTART cohort is a good platform to investigate the complications of long-term ART use in Uganda.

Background: HIV care programs in resource-limited settings have hitherto concentrated on antiretroviral therapy (ART) access, but HIV drug resistance is emerging. In a cross-sectional study of HIV-positive adults on ART for ≥6 months enrolled into a prospective cohort in Uganda, plasma HIV RNA was measured and genotyped if ≥1000 copies/ml. Identified Drug resistance mutations (DRMs) were interpreted using the Stanford database, 2009 WHO list of DRMs and the IAS 2014 update on DRMs, and examined and tabulated by ART drug classes., Findings: Between July 2013 and August 2014, 953 individuals were enrolled, 119 (12.5%) had HIV-RNA ≥1000 copies/ml and 110 were successfully genotyped; 74 (67.3%) were on first-line and 36 (32.7%) on second-line ART regimens. The predominant HIV-1 subtypes were D (34.5%), A (33.6%) and Recombinant forms (21.8%). The commonest clinically significant major resistance mutations associated with the highest levels of reduced susceptibility or virological response to the relevant Nucleoside Reverse Transcriptase Inhibitor (NRTI) were; the Non-thymidine analogue mutations (Non-TAMS) M184V-20.7% and K65R-8.0%; and the TAMs M41L and K70R (both 8.0%). The major Non-NRTI (NNRTI) mutations were K103N-19.0%, G190A-7.0% and Y181C-6.0%. A relatively nonpolymorphic accessory mutation A98G-12.0% was also common. Seven of the 36 patients on second line ART had major Protease Inhibitor (PI) associated DRMS including; V82A-7.0%, I54V, M46I and L33I (all 5.0%). Also common were the accessory PI mutations L10I-27%, L10V-12.0% and L10F-5.0% that either reduce PI susceptibility or increase the replication of viruses containing PI-resistance mutations. Of the 7 patients with major PI DRMs, five had high level resistance to ritonavir boosted Lopinavir and Atazanavir, with Darunavir as the only susceptible PI tested., Conclusions: In resource-limited settings, HIV care programs that have previously concentrated on ART access, should now consider availing access to routine HIV viral load monitoring, targeted HIV drug resistance testing and availability of third-line ART regimens.

Background: WHO 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., Methods: In 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., Results: Between 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., Conclusions: We 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.

HIV-associated Kaposi's sarcoma (KS) is a public health challenge in sub-Saharan Africa since both the causative agent, Kaposi's sarcoma associated-herpesvirus (KSHV), and the major risk factor, HIV, are prevalent. In a nested case-control study within a long-standing clinical cohort in rural Uganda, we used stored sera to examine the evolution of antibody titres against the KSHV antigens K8.1 and latency-associated nuclear antigen (LANA) among 30 HIV-infected subjects who subsequently developed HIV-related KS (cases) and among 108 matched HIV/KSHV coinfected controls who did not develop KS. Throughout the 6 years prior to diagnosis, antibody titres to K8.1 and LANA were significantly higher among cases than controls (p < 0.0001), and titres increased prior to diagnosis in the cases. K8.1 titres differed more between KS cases and controls, compared to LANA titres. These differences in titre between cases and controls suggest a role for lytic viral replication in the pathogenesis of HIV-related KS in this setting., (© 2014 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.)

Objectives: Antiretroviral therapy (ART) availability in a population may influence risky sexual behaviour. We examine the potential impact of ART on the HIV epidemic, incorporating evidence for the impact that ART may have on risky sexual behaviour., Methods: A mathematical model, parameterised using site-specific data from Uganda and worldwide literature review, was used to examine the likely impact of ART on HIV epidemiologic trends. We varied assumptions about rates of initiating ART, and changes in sexual partner turnover rates., Results: Modelling suggests that ART will reduce HIV incidence over 20 years, and increase prevalence. Even in the optimistic scenario of ART enrollment beginning after just five months of infection (in HIV stage 2), prevalence is estimated to rise from a baseline of 10.5% and 8.3% among women and men, respectively, to at least 12.1% and 10.2%, respectively. It will rise further if sexual disinhibition occurs or infectiousness while on ART is slightly higher (2% female to male, rather than 0.5%). The conditions required for ART to reduce prevalence over this period are likely too extreme to be achievable. For example, if ART enrolment begins in HIV stage 1 (within the first 5 months of infection), and if risky sexual behaviour does not increase, then 3 of our 11 top fitting results estimate a potential drop in HIV prevalence by 2025. If sexual risk taking rises, it will have a large additional impact on expected HIV prevalence. Prevalence will rise despite incidence falling, because ART extends life expectancy., Conclusions: HIV prevalence will rise. Even small increases in partner turnover rates will lead to an additional substantial increase in HIV prevalence. Policy makers are urged to continue HIV prevention activities, including promoting sex education, and to be prepared for a higher than previously suggested number of HIV infected people in need of treatment., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

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/mm(3)., Objective: To compare mortality among HIV-infected ART naïve individuals with CD4 counts ≥350 cells/mm(3) 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/mm(3) 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/mm(3) than during periods of CD4 ≥500 cells/mm(3) 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/mm(3) (SMR: 223%, 95% CI: 127-393%) and 146% higher among participants with CD4 350-499 cells/mm(3) (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/m(2) and ≥18.5 Kg/m(2): 6.11, 2.30-16.20)., Conclusion: HIV-infected ART naïve individuals with CD4 count ≥350 cells/mm(3) had a higher mortality than the general population. After adjusting for age, the main predictors of mortality were WHO clinical stage and BMI.

Background: The basic reproduction number, [Formula: see text], is one of the many measures of the epidemic potential of an infection in a population. We estimate HIV [Formula: see text] over 18 years in a rural population in Uganda, examine method-specific differences in estimated [Formula: see text], and estimate behavioural changes that would reduce [Formula: see text] below one., Methods: Data on HIV natural history and infectiousness were collated from literature. Data on new sexual partner count were available from a rural clinical cohort in Uganda over 1991-2008. [Formula: see text] was estimated using six methods. Behavioural changes required to reduce [Formula: see text] below one were calculated., Results: Reported number of new partners per year was 0 to 16 (women) and 0 to 80 (men). When proportionate sexual mixing was assumed, the different methods yielded comparable [Formula: see text] estimates. Assuming totally assortative mixing led to increased [Formula: see text] estimates in the high sexual activity class while all estimates in the low-activity class were below one. Using the "effective" partner change rate introduced by Anderson and colleagues resulted in [Formula: see text] estimates all above one except in the lowest sexual activity class. [Formula: see text] could be reduced below one if: (a) medium risk individuals reduce their partner acquisition rate by 70% and higher risk individuals reduce their partner acquisition rate by 93%, or (b) higher risk individuals reduce the partner acquisition rate by 95%., Conclusions: The estimated [Formula: see text] depended strongly on the method used. Ignoring variation in sexual activity leads to an underestimation of [Formula: see text]. Relying on behaviour change alone to eradicate HIV may require unrealistically large reductions in risk behaviour, even though for a small proportion of the population. To control HIV, complementary prevention strategies such as male circumcision and HIV treatment services need rapid scale up.

Background: Sub-Saharan Africa (SSA) has the highest burden of HIV in the world and a rising prevalence of cardiometabolic disease; however, the interrelationship between HIV, antiretroviral therapy (ART) and cardiometabolic traits is not well described in SSA populations., Methods: We conducted a systematic review and meta-analysis through MEDLINE and EMBASE (up to January 2012), as well as direct author contact. Eligible studies provided summary or individual-level data on one or more of the following traits in HIV+ and HIV-, or ART+ and ART- subgroups in SSA: body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TGs) and fasting blood glucose (FBG) or glycated hemoglobin (HbA1c). Information was synthesized under a random-effects model and the primary outcomes were the standardized mean differences (SMD) of the specified traits between subgroups of participants., Results: Data were obtained from 49 published and 3 unpublished studies which reported on 29 755 individuals. HIV infection was associated with higher TGs [SMD, 0.26; 95% confidence interval (CI), 0.08 to 0.44] and lower HDL (SMD, -0.59; 95% CI, -0.86 to -0.31), BMI (SMD, -0.32; 95% CI, -0.45 to -0.18), SBP (SMD, -0.40; 95% CI, -0.55 to -0.25) and DBP (SMD, -0.34; 95% CI, -0.51 to -0.17). Among HIV+ individuals, ART use was associated with higher LDL (SMD, 0.43; 95% CI, 0.14 to 0.72) and HDL (SMD, 0.39; 95% CI, 0.11 to 0.66), and lower HbA1c (SMD, -0.34; 95% CI, -0.62 to -0.06). Fully adjusted estimates from analyses of individual participant data were consistent with meta-analysis of summary estimates for most traits., Conclusions: Broadly consistent with results from populations of European descent, these results suggest differences in cardiometabolic traits between HIV-infected and uninfected individuals in SSA, which might be modified by ART use. In a region with the highest burden of HIV, it will be important to clarify these findings to reliably assess the need for monitoring and managing cardiometabolic risk in HIV-infected populations in SSA.

Non-consensual sex is associated with HIV infection in Africa, but there is little longitudinal data on this association. We describe reported non-consensual sex among women over two decades in southwest Uganda, including associations with incident HIV infection. Between 1990 and 2008, individuals in a population cohort who recently seroconverted to HIV were enrolled into a clinical cohort, along with randomly selected HIV-negative controls. Participants were invited to the study clinic every 3 months, and females asked about recent experiences of sex against their will. Associations of non-consensual sex with HIV status were analyzed prospectively using conditional logistic regression, adjusting for age and year of interview, allowing for within-woman correlation. 476 women aged 14-81 enrolled and attended 10,475 visits over 19 years. The results show high levels of repeated non-consensual sex, often long after HIV infection. There was more reporting among women living with HIV compared to HIV-negative women (22 vs 9 %; OR = 2.29, 95 %CI 1.03-5.09), with the strongest associations among married participants. HIV programmes should address repeated sexual coercion before and subsequent to HIV infection.

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.

Background: In HIV-infected persons, good adherence to antiretroviral therapy (ART) is essential for successful treatment outcomes. Patients' worries before starting ART may affect their ART adherence and treatment outcomes., Methods: Between 2004 and 2009, HIV-infected individuals in a prospective cohort study in rural Uganda were assessed for ART eligibility. A counsellor explained the ART eligibility criteria, adherence and side effects, and recorded the patients' worries related to ART. Every quarter, patients who initiated ART had clinical, immunological (CD4 cell counts) and virological (viral loads) assessments, and data were collected on ART adherence using patients' self-reports and pill counts. We describe the patients' worries and examine their association with ART adherence, and immunological and virological outcomes., Results: We assessed 421 patients, 271 (64%) were females, 318 (76%) were aged 30 years and above and 315 (75%) were eligible for ART. 277 (66%) reported any worry, and the proportions were similar by sex, age group and ART eligibility status. The baseline median CD4 counts and viral loads were similar among patients with any worry and those with no worry. The commonest worries were: fear of HIV serostatus disclosure; among 69 (16%) participants, lack of food when appetite improved after starting ART; 50 (12%), concurrent use of other medications; 33 (8%), adherence to ART; 28 (7%) and problems concerning condom use; 27 (6%). After 24 months or more on ART, patients who reported any worry had made more scheduled ART refill visits than patients who reported no worry (p<0.01), but the annual CD4 cell increases were similar (p=0.12). After one year on ART, patients who reported any worry had greater virological suppression than patients who reported no worry (p<0.05)., Conclusions: Despite the lack of significant associations of worries with unfavourable ART outcomes, physicians and counsellors should assist patients in overcoming their worries that can cause stress and discomfort. Food supplements may be desirable for some patients initiating ART.

The high diversity of HIV-1 has been shown to affect disease progression, transmission, and response to antiretroviral therapy and may influence HIV vaccine design. We describe the distribution trends of HIV-1 subtypes over a 7-year period among incident cases in a rural clinical cohort in Southwest Uganda and identify transmission clusters. Viral RNA was extracted from cryopreserved plasma samples from 94 participants who seroconverted and enrolled between 2004 and 2010. Partial gag (p24) and env (gp41) genes were directly sequenced to identify subtypes and transmission clusters with more than 95% bootstrap values. Direct sequencing of the partial pol gene and use of individual participant sexual life histories were also used to confirm these transmission clusters. The overall gag/env subtype distribution was A 28% (n=26), C 1% (n=1), and D 45% (n=42) and 27% (n=25) were intergene unique recombinant forms. The proportions of subtype A, D, or recombinants showed no significant increasing or decreasing trend over this time period (p=0.51). Phylogenetic analysis of the three genes confirmed 13 transmission clusters of which seven clusters were confirmed sexual partners using individual participants' sexual life histories. Subtype D has remained the predominant subtype in this population. From 2004 to 2010, there was no change in the proportions of these subtypes. Phylogenetic analysis and participants' sexual life histories revealed several transmission clusters. The high proportion of transmission clusters observed suggests continued high-risk sexual behavior and mixing in some individuals and possibly super transmitters in this presumed low-risk cohort, but also indicates that many transmissions occur in early HIV infection. This calls for early and targeted effective prevention and treatment intervention in this population.

To investigate the prevalence of transmitted drug resistance (TDR) among individuals with recent HIV-1 infection between February 2004 and January 2010 in a rural clinical cohort, samples from 72 participants were analyzed. Results from the 72 participants showed no protease inhibitor and nucleoside reverse transcriptase inhibitor-associated mutations. One participant (1.4%, 95% CI: 0.04-7.5%) had two nonnucleoside reverse transcriptase inhibitor mutations (G190E and P225H). HIV-1 subtype frequencies were A 22 (30.6%), D 38 (52.8%), and C 1 (1.4%); 11 (15.3%) were A/D unique recombinant forms. Seven years after the scale up of antiretroviral therapy (ART) in a rural clinical cohort in Uganda, the prevalence of TDR among recently HIV-1-infected individuals was low at 1.4%. Since our findings from an HIV study cohort may not be generalizable to the general population, routine TDR surveys in specific populations may be necessary to inform policy on the magnitude and prevention strategies of TDR.

Objectives: To investigate antiretroviral therapy (ART) uptake after its introduction in 2004 in a longitudinal population-based cohort and its nested clinical cohort in rural Uganda., Methods: A HIV serosurvey of all adults aged ≥ 15 years is conducted annually. Two intervals were selected for analysis. Interval 1 (November 2004-October 2006) provided 2 years of follow-up to prospectively evaluate access to HIV services. Interval 2 (November 2007-October 2008) was used to evaluate current coverage of services. Logistic regression was used to identify sociodemographic factors associated with ART screening within 2 years of diagnosis. ART coverage was assessed using Weibull survival models to estimate the numbers needing ART., Results: In Interval 1, 636 HIV-positive adults were resident and 295 (46.4%) knew their status. Of those, 248 (84.1%) were screened for ART within 2 years of diagnosis. After adjusting for age, those who were widowed, separated or never married were more likely to be screened than those who were married. In Interval 2, 575 HIV-positive adults were residents, 322 (56.0%) knew their status, 255 (44.3%) had been screened for ART and 189 (32.9%) had started ART. Estimated ART coverage was 66%., Conclusions: In this cohort, ART access and uptake is very high once people are diagnosed. Owing to intensive screening in the study clinic, nearly all participants who were eligible initiated ART. However, this is unlikely to reflect coverage in the general population, intensified efforts are needed to promote HIV testing, and ART screening and uptake are needed among those found to be HIV-positive., (© 2012 Blackwell Publishing Ltd.)

Objective: To investigate trends in all-cause adult mortality after the roll-out of an antiretroviral therapy (ART) programme in rural Uganda., Methods: Longitudinal population-based cohort study of approximately 20,000 residents in rural Uganda. Mortality in adults aged 15-59 years was determined for the 5-year period (1999-2003) before introduction of ART in January 2004 and for the 5-year period afterwards. Poisson regression was used to estimate mortality rate ratios (RRs) for the period before ART, 1 year after ART introduction (from January 2004 to January 2005) and more than 1 year after ART introduction. Trends in mortality were analysed by HIV status, age and sex., Results: Before ART became available, the mortality rate (deaths per 1000 person-years) was 4.0 (95% CI = 3.3-4.8) among HIV-negative individuals and 116.4 (95% CI = 101.9-133.0) among HIV-positive individuals. During the period January 2004-end November 2009, 279 individuals accessed ART. In the year after ART was introduced, the mortality rate (deaths per 1000 person-years) among HIV-negative individuals did not change significantly (adjusted RR = 0.95, 95% CI = 0.61-1.47), but among HIV-positive individuals dropped by 25% to 87.4 (adjusted RR = 0.75, 95% CI = 0.53-1.06). In the period 2005-2009, the mortality rate (deaths per 1000 person-years) among HIV-positive individuals fell further to 39.9 (adjusted RR = 0.33, 95% CI = 0.26-0.43). The effect was greatest among individuals aged 30-44 years, and trends were similar in men and women., Conclusion: The substantially reduced mortality rate among HIV-positive individuals after ART roll-out lends further support to the intensification of efforts to ensure universal access to ART., (© 2012 Blackwell Publishing Ltd.)

Objectives: Before antiretroviral therapy (ART) introduction, pregnancy was associated with a sustained drop in CD4 cell count in HIV-infected women. We examined the effects of pregnancy on immunological and virological ART outcomes., Methods: Between January 2004 and March 2009, we studied HIV-infected women receiving ART in a prospective open cohort study in rural Uganda. We used random effects regression models to compare the CD4 counts of women who became pregnant and those who did not, and among the pregnant women before and after pregnancy. CD4 count and proportions with detectable viral load (≥400 copies/ml) were compared between the two groups using the Mann-Whitney rank sum test and logistic regression respectively., Results: Of 88 women aged 20-40 years receiving ART, 23 became pregnant. At ART initiation, there were no significant differences between those who became pregnant and those who did not in clinical, immunological and virological parameters. Among women who became pregnant, CD4 cell count increased before pregnancy (average 75.9 cells/mm(3) per year), declined during pregnancy (average 106.0) but rose again in the first year after delivery (average 88.6). Among women who did not become pregnant, the average CD4 cell count rise per year for the first 3 years was 88.5. There was no significant difference in the proportions of women with detectable viral load at last clinic visit among those who became pregnant (8.7%) and those who did not (16.1%), P = 0.499., Conclusion: Pregnancy had no lasting effect on the immunological and virological outcomes of HIV-infected women on ART., (© 2011 Blackwell Publishing Ltd.)

Background: Verbal autopsy is important for detecting causes of death including HIV in areas with inadequate vital registration systems. Before antiretroviral therapy (ART) introduction, a verbal autopsy study in rural Uganda found that half of adult deaths assessed were in HIV-positive individuals. We used verbal autopsy to compare the proportion of HIV-positive adult deaths in the periods before and after ART introduction., Methods: Between 2006 and 2008, all adult (≥ 13 years) deaths in a prospective population-based cohort study were identified by monthly death registration, and HIV serostatus was determined through annual serosurveys. A clinical officer interviewed a relative of the deceased using a verbal autopsy questionnaire. Two clinicians independently reviewed the questionnaires and classified the deaths as HIV-positive or not. A third clinician was the tie-breaker in case of nonagreement. The performance of the verbal autopsy tool was assessed using HIV serostatus as the gold standard of comparison. We compared the proportions of HIV-positive deaths as assessed by verbal autopsy in the early 1990s and the 2006-2008 periods., Results: Of 333 deaths among 12,641 adults of known HIV serostatus, 264 (79.3%) were assessed by verbal autopsy, of whom 59 (22.3%) were HIV-seropositive and 68 (25.8%) were classified as HIV-positive by verbal autopsy. Verbal autopsy had a specificity of 90.2% and positive predictive value of 70.6% for identifying deaths among HIV-infected individuals, with substantial interobserver agreement (80.3%; kappa statistic = 0.69). The HIV-attributable mortality fraction estimated by verbal autopsy decreased from 47.0% (pre-ART period) to 25.8% (ART period), p < 0.001., Conclusions: In resource-limited settings, verbal autopsy can provide a good estimate of the prevalence of HIV infection among adult deaths. In this rural population, the proportion of deaths identified by verbal autopsy as HIV-positive declined between the early 1990s and the 2006-2008 period. Verbal autopsy findings can inform policy on HIV health care needs.

Objective: To assess evidence for sexual behavior change in response to antiretroviral therapy (ART) among members of a Ugandan clinical cohort. Secondarily, to examine factors associated with both sexual behavior and ART independently, that may help to assess the impact that ART is likely to have on the HIV epidemic., Design: Retrospective analysis of data from an open cohort., Methods: ART roll-out began in the cohort in 2004. Using 3-monthly data from 2002 to 2009, we conducted regression and descriptive analyses to examine associations between timing of ART initiation and sexual behavior among HIV-infected, and timing of ART availability and sexual behavior among HIV-uninfected. We also examined partner turnover rates, and the proportion of HIV-infected on ART - two important factors for modeling the potential impact of ART on the HIV epidemic., Results: Risky sexual behavior among HIV-infected people rose on several indicators after ART initiation, but not to levels higher than two or more years before initiation. Some evidence suggests that the availability of ART may impact risky behavior among HIV-uninfected people, although this was inconsistent across different reported behavior variables., Conclusion: The HIV-uninfected is larger than the HIV-infected population. If risky behavior among this population increases due to the feeling of safety that ART provides, this will affect the impact of ART on the HIV epidemic. Policy makers are urged to intensify messages associating sexual behavior and HIV and to target both HIV-infected and uninfected people.

We report on the frequency of multiple infections, generation of recombinants and consequences on disease progression in 35 HIV-1 infected individuals from 7 monogamous and 6 polygamous partnerships within a Rural Clinical Cohort in Uganda. The env-C2V3, gag-p24 and pol-IN genes were sequenced. Single genome amplified half genome sequences were used to map recombination breakpoints. Three participants were dually infected with subtypes A and D, one case with subtype A and A/D recombinant and the fifth with 2 phylogenetically distinct A/D recombinants. Occurrence of A/D recombination was observed in two multiple infected individuals. Rate of late stage WHO events using Cox regression was 3 times greater amongst multiple infected compared to singly infected individuals (hazard ratio 3.35; 95% CI 1.09, 10.3; p=0.049). We have shown that polygamous relationships involving subtype discordant partnerships was a major contributor of multiple infections with generation of inter subtype recombinants in our cohort., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Objectives: To determine the prevalence and incidence of anaemia in HIV-positive and negative individuals; to identify risk factors for anaemia, prior to the introduction of HAART; and to determine the validity of the clinical diagnosis of anaemia., Methods: Between 1990 and 2003, we followed a rural population based cohort of HIV-infected and uninfected participants. Prevalence and incidence of anaemia were determined clinically and by laboratory measurements. The sensitivity, specificity and predictive values of clinical diagnosis were calculated., Results: The prevalence of anaemia at enrolment was 18.9% among HIV-positive and 12.9% among HIV-negative participants (P = 0.065). Incidence of anaemia increased with HIV disease progression, from 103 per 1000 person-years of observation among those with CD4 counts >500 to 289 per 1000 person-years of observation among those with CD4 counts <200. Compared to laboratory diagnosis, the clinical diagnosis of anaemia had a sensitivity of 17.8%, specificity of 96.8%, a positive predictive value of 50.6% and a negative predictive value of 86.4%. Being female, low CD4 cell counts, HIV-positive, wasting syndrome, WHO stage 3 or 4, malaria, fever, pneumonia and oral candidiasis were associated with prevalent anaemia., Conclusions: Anaemia prevalence and incidence were higher among HIV-positive than negative participants. Compared to laboratory diagnosis, clinical detection of anaemia had a low sensitivity. Clinicians working in settings with limited laboratory support must be conscious of the risk of anaemia when managing HIV/AIDS patients, particularly when using antiretroviral drugs which by themselves may cause anaemia as a side effect. We recommend that haemoglobin should be measured before starting ART and monthly for the first three months.

Objective: To provide estimates of survival and progression to different HIV disease endpoints after HIV infection among adults in a rural Ugandan setting., Design: A prospective population-based cohort study., Methods: Eligible individuals at least 15 years of age with documented HIV seroconversion were recruited from a general population cohort in rural Uganda, along with a randomly selected proportion of HIV-prevalent and HIV-negative individuals. All participants were followed up every 3 months, and CD4 cell counts taken every 6 months in HIV-positive participants. Life tables and Kaplan-Meier functions were used to estimate survival patterns for all endpoints [death, time to World Health Organization (WHO) stage 2, 3, AIDS and CD4 cell count < 200 cells/mul]. Analysis of follow-up time was truncated when antiretroviral therapy (ART) became available in the area in January 2004., Results: We recruited 240 HIV incident cases, 108 prevalent cases and 257 HIV-negative controls. Crude mortality rates were 70.0 per 1000 person-years in HIV-positive, and 12.1 per 1000 person-years in HIV-negative individuals. The median time from seroconversion to death was 9.0 years (N = 240) and 6.2 years to a CD4 cell count less than 200 cells/mul or WHO stage 4 (N = 229). The median time from ART eligibility (CD4 cell count < 200 cells/mul, < 350 cells/mul and WHO stage 3, or WHO stage 4) to death was 34.7 months. Older age at seroconversion was a risk factor for faster progression to death and ART eligibility., Conclusion: HIV progression in this African cohort is similar to that reported in industrialized countries before the widespread introduction of ART.

Objective: To investigate the effect of pregnancy on HIV disease progression and survival among HIV-infected women in rural Uganda, prior to the introduction of anti-retroviral therapy (ART)., Methods: From a clinical cohort established in 1990, we selected records from HIV-infected women of reproductive age. We conducted two analyses: (1) all HIV-infected cases contributing to analysis of CD4 decline, using a linear regression model with random intercepts and slopes; (b) incident cases with known date of seroconversion contributed to analyses of median time to CD4 <200 cells/microl, AIDS and death., Results: A total of 139 women were included in the analysis of CD4 decline. Women who subsequently became pregnant had higher CD4 counts at enrolment and had a slower CD4 decline than those who did not become pregnant. In women who became pregnant, CD4 decline was faster after pregnancy than before (P < 0.0001). The survival analyses showed no significant differences between women who became pregnant and those who did not with respect to median time to CD4 count <200, AIDS or death., Conclusions: The initial comparative immunological advantage possessed by fertile women before they become pregnant is subsequently lost as a result of their pregnancy. Women should be informed about the potential negative effect of pregnancy on their immunological status and should be offered contraception. In resource-limited settings, women determined to become pregnant should be given priority for ART if eligible.

Thirty-six incident HIV cases were matched for age, sex and time period with 36 controls to examine associations with recent injections. A significant association between HIV incidence and a history of injections was detected that was not reduced after adjusting for available sexual behaviour variables. This association could either be the result of injections causing HIV infection or, more likely, injections for seroconversion illnesses or other consequences of unsafe sex.

Objectives: To estimate the association between HIV disease progression and the incidence of recognized pregnancy; to estimate the risk of subsequent fetal loss., Methods: A total of 191 women (92 HIV seropositive and 99 HIV seronegative at enrolment) aged 15-49 years in an HIV clinical cohort were invited to attend routine clinic visits every 3 months. Information on HIV progression collected at the visit was related to whether there was a pregnancy beginning in the following 3 months. Visits were excluded where the woman was already pregnant, lactating, using modern contraceptives or if there was inadequate follow-up., Results: There were 2524 eligible visits and 216 recognized pregnancies. The reported frequency of sexual intercourse diminished with advancing HIV disease. The adjusted odds ratio (OR) for pregnancy when the woman was in WHO stage 1 compared with HIV seronegatives was 0.58 [95% confidence interval (CI), 0.36-0.93]; stage 2, 0.47 (95% CI, 0.25-0.91); stage 3, 0.43 (95% CI, 0.25-0.74); and stage 4, (AIDS) 0.14 (95% CI, 0.02-1.09). The findings were similar for CD4 cell count, time from seroconversion and time before AIDS. There was an increase in fetal loss from the early stages of HIV infection (adjusted OR for stage 1, 5.38; 95% CI, 1.57-18.44), there were very few recognized pregnancies in the advanced stages., Conclusions: Fertility is reduced from the earliest asymptomatic stage of HIV infection resulting from both a reduced incidence of recognized pregnancy and increased fetal loss. The greatest reduction in fertility was observed following progression to AIDS when there was a very low incidence of recognized pregnancies.