Cardiometabolic risk among HIV-POSITIVE Ugandan adults: prevalence, predictors and effect of long-term antiretroviral therapy.

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/m2 -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 (P10% 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

The effect of antiretroviral therapy provision on all-cause, AIDS and non-AIDS mortality at the population level--a comparative analysis of data from four settings in Southern and East Africa.

OBJECTIVE: To provide a broad and up-to-date picture of the effect of antiretroviral therapy (ART) provision on population-level mortality in Southern and East Africa. METHODS: Data on all-cause, AIDS and non-AIDS mortality among 15-59 year olds were analysed from demographic surveillance sites (DSS) in Karonga (Malawi), Kisesa (Tanzania), Masaka (Uganda) and the Africa Centre (South Africa), using Poisson regression. Trends over time from up to 5 years prior to ART roll-out, to 4-6 years afterwards, are presented, overall and by age and sex. For Masaka and Kisesa, trends are analysed separately for HIV-negative and HIV-positive individuals. For Karonga and the Africa Centre, trends in AIDS and non-AIDS mortality are analysed using verbal autopsy data. RESULTS: For all-cause mortality, overall rate ratios (RRs) comparing the period 2-6 years following ART roll-out with the pre-ART period were 0.58 (5.9 vs. 10.2 deaths per 1000 person-years) in Karonga, 0.79 (7.2 vs. 9.1 deaths per 1000 person-years) in Kisesa, 0.61 (6.7 compared with 11.0 deaths per 1000 person-years) in Masaka and 0.79 (14.8 compared with 18.6 deaths per 1000 person-years) in the Africa Centre DSS. The mortality decline was seen only in HIV-positive individuals/AIDS mortality, with no decline in HIV-negative individuals/non-AIDS mortality. Less difference was seen in Kisesa where ART uptake was lower. CONCLUSIONS: Falls in all-cause mortality are consistent with ART uptake. The largest falls occurred where ART provision has been decentralised or available locally, suggesting that this is important

COHORT PROFILE: The Complications of Long-Term Antiretroviral Therapy study in Uganda (CoLTART), a prospective clinical cohort.

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

Human Immunodeficiency Virus Incidence Among Women at High-Risk of Human Immunodeficiency Virus Infection Attending a Dedicated Clinic in Kampala, Uganda: 2008-2017.

Background: High attrition and irregular testing for human immunodeficiency virus (HIV) in cohort studies for high-risk populations can bias incidence estimates. We compare incidence trends for high-risk women attending a dedicated HIV prevention and treatment clinic, using common methods for assigning when seroconversion occurs and whether seroconversion occurs among those with attrition. Methods: Between April 2008 and May 2009, women were enrolled into cohort 1 and from January 2013 into cohort 2, then scheduled for follow-up once every 3 months. Incidence trends based on assuming a midpoint in the seroconversion interval were compared with those of assigning a random-point. We also compared estimates based on the random-point with and without multiple imputation (MI) of serostatuses for participants with attrition. Results: By May 2017, 3084 HIV-negative women had been enrolled with 18,364 clinic visits. Before attrition, 27.6% (6990 of 25,354) were missed visits. By August 2017, 65.8% (426 of 647) of those enrolled in cohort 1 and 49.0% (1194 of 2437) in cohort 2 were defined with attrition. Among women with 1 or more follow-up visit, 93 of 605 in cohort 1 and 77 of 1601 in cohort 2 seroconverted. Periods with longer seroconversion intervals appeared to have noticeable differences in incidences when comparing the midpoint and random-point values. The MI for attrition is likely to have overestimated incidence after escalated attrition of participants. Based on random-point without MI for attrition, incidence at end of observation was 3.8/100 person-years in cohort 1 and 1.8/100 in cohort 2. Conclusions: The random-point approach attenuated variation in incidence observed using midpoint. The high incidence after years of ongoing prevention efforts in this vulnerable population should be investigated to further reduce incidence

Atherogenic Risk Assessment among Persons Living in Rural Uganda

Background. Hypertension and dyslipidemia are independent risk factors for coronary heart disease and commonly coexist. Cardiovascular risk can be reliably predicted using lipid ratios such as the atherogenic index, a useful prognostic parameter for guiding timely interventions. Objective. We assessed the cardiovascular risk profile based on the atherogenic index of residents within a rural Ugandan cohort. Methods. In 2011, a population based survey was conducted among 7507 participants. Sociodemographic characteristics, physical measurements (blood pressure, weight, height, and waist and hip circumference), and blood sampling for non fasting lipid profile were collected for each participant. Atherogenic risk profile, defined as logarithm base ten of (triglyceride divided by high density lipoprotein cholesterol), was categorised as low risk (0.24). Results. Fifty-five percent of participants were female and the mean age was 49.9 years (SD± 20.2). Forty-two percent of participants had high and intermediate atherogenic risk. Persons with hypertension, untreated HIV infection, abnormal glycaemia, and obesity and living in less urbanised villages were more at risk. Conclusion. A significant proportion of persons in this rural population are at risk of atherosclerosis. Key identified populations at risk should be considered for future intervention against cardiovascular related morbidity and mortality. The study however used parameters from unfasted samples that may have a bearing on observed results

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

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

Adult life expectancy trends in the era of antiretroviral treatment in rural Uganda (1991-2012).

OBJECTIVE: To estimate the impact of antiretroviral therapy (ART) on population-wide adult life expectancy. STUDY DESIGN: A population-based open cohort study with repeated HIV status measurements and registration of vital events in Southwestern Uganda (1991-2012). METHODS: Nonparametric survival analysis techniques are used for estimating trends in the adult life expectancy of the general population (aged 15 and above), the adult life expectancy by HIV status, and the adult life expectancy deficit. The life expectancy deficit is estimated as the difference between overall life expectancy and life expectancy of the HIV-negative population. All estimates are disaggregated by sex. RESULTS: Between 1991-1993 and 2009-2012, population-wide adult life expectancy increased from 39.3 [95% confidence interval (CI): 35.9-42.8] to 56.1 years (95% CI: 54.0-58.5) in women, and from 38.6 (95% CI: 35.4-42.1) to 51.4 years (95% CI: 49.2-53.7) in men. Most of the adult life expectancy gains coincide with the introduction of ART in 2004; as evidenced by an increase in the adult life expectancy of people living with HIV between 2000-2002 and 2009-2012 of 22.9 and 20.0 years for women and men, respectively. Over the whole period of observation, the adult life expectancy deficit associated with HIV decreased from 16.1 (95% CI: 12.7-19.8) to 6.0 years (95% CI: 4.1-7.8) among women, and from 16.0 (95% CI: 12.1-19.9) to 2.8 years (95% CI: 1.2-4.6) among men. CONCLUSION: Population-wide life expectancy increased substantially, largely driven by reductions in HIV-related mortality. Women have gained more adult life years than men since the introduction of ART, but the burden of HIV in terms of the life years lost is still larger for women than it is for men

The general population cohort in rural south-western Uganda: a platform for communicable and non-communicable disease studies.

The General Population Cohort (GPC) was set up in 1989 to examine trends in HIV prevalence and incidence, and their determinants in rural south-western Uganda. Recently, the research questions have included the epidemiology and genetics of communicable and non-communicable diseases (NCDs) to address the limited data on the burden and risk factors for NCDs in sub-Saharan Africa. The cohort comprises all residents (52% aged ≥13years, men and women in equal proportions) within one-half of a rural sub-county, residing in scattered houses, and largely farmers of three major ethnic groups. Data collected through annual surveys include; mapping for spatial analysis and participant location; census for individual socio-demographic and household socioeconomic status assessment; and a medical survey for health, lifestyle and biophysical and blood measurements to ascertain disease outcomes and risk factors for selected participants. This cohort offers a rich platform to investigate the interplay between communicable diseases and NCDs. There is robust infrastructure for data management, sample processing and storage, and diverse expertise in epidemiology, social and basic sciences. For any data access enquiries you may contact the director, MRC/UVRI, Uganda Research Unit on AIDS by email to [email protected] or the corresponding author

Thirty years of change in HIV incidence among adults in the Kyamulibwa General Population Cohort in rural southwest Uganda, 1989-2021

Objectives To document the changes in HIV incidence over thirty years in Kalungu district, Uganda. Methods Since 1989, residents aged ≥15 years old have been tested for HIV, and data were collected on HIV risk factors annually and later, biennially in the Kyamulibwa open cohort. In the 2019-2021 survey, people living with HIV self-reported on knowledge of their HIV status, antiretroviral therapy (ART) use, and their most recent viral load data were obtained from health facilities. The HIV seroconversion dates were randomly imputed between the last negative and first positive test dates using a uniform distribution. Results Among 20,959 residents who were HIV-negative, 669 seroconverted within 176,659 person-years. Data showed a downward trend in age-adjusted HIV incidence over 30 years (

Missed Study Visits and Subsequent HIV Incidence Among Women in a Predominantly Sex Worker Cohort Attending a Dedicated Clinic Service in Kampala, Uganda.

BACKGROUND: There is limited evidence on the relationship between sustained exposure of female sex workers (FSWs) to targeted HIV programmes and HIV incidence. We investigate the relationship between the number of missed study visits (MSVs) within each episode of 2 consecutively attended visits (MSVs) and subsequent HIV risk in a predominantly FSW cohort. METHODS: Women at high risk of HIV are invited to attend an ongoing dedicated clinic offering a combination HIV prevention intervention in Kampala, Uganda. Study visits are scheduled once every 3 months. The analysis included HIV-seronegative women with ≥1 follow-up visit from enrollment (between April 2008 and May 2017) to August 2017. Cox regression models were fitted adjusted for characteristics on sociodemographic, reproductive, behavioral, and sexually transmitted infections (through clinical examination and serological testing for syphilis). FINDINGS: Among 2206 participants, HIV incidence was 3.1/100 (170/5540) person-years [95% confidence interval (CI): 2.6 to 3.5]. Incidence increased from 2.6/100 person-years (95% CI: 2.1 to 3.2) in episodes without a MSV to 3.0/100 (95% CI: 2.2 to 4.1) for 1-2 MSVs and 4.3/100 (95% CI: 3.3 to 5.6) for ≥3 MSVs. Relative to episodes without a MSV, the hazard ratios (adjusted for confounding variables) were 1.40 (95% CI: 0.93 to 2.12) for 1-2 MSVs and 2.00 (95% CI: 1.35 to 2.95) for ≥3 MSVs (P-trend = 0.001). CONCLUSION: Missing study visits was associated with increased subsequent HIV risk. Although several factors may underlie this association, the finding suggests effectiveness of targeted combination HIV prevention. But exposure to targeted interventions needs to be monitored, facilitated, and sustained in FSWs