Medium-to-long term sustainability of a health systems intervention to improve service readiness and quality of non-communicable disease (NCD) patient care and experience at primary care settings in Uganda.

BACKGROUND: With the double burden of rising chronic non-communicable diseases (NCDs) and persistent infectious diseases facing sub-Saharan Africa, integrated health service delivery strategies among resource-poor countries are needed. Our study explored the post-trial sustainability of a health system intervention to improve NCD care, introduced during a cluster randomised trial between 2013 and 2016 in Uganda, focusing on hypertension (HT) and type-2 diabetes mellitus (DM) services. In 2020, 19 of 38 primary care health facilities (HFs) that constituted the trial's original intervention arm until 2016 and 3 of 6 referral HFs that also received the intervention then, were evaluated on i) their facility performance (FPS) through health worker knowledge, and service availability and readiness (SAR), and ii) the quality-of-patient-care-and-experience (QoCE) received. METHODS: Cross-sectional data from the original trial (2016) and our study (2020) were compared. FPS included a clinical knowledge test with 222 health workers: 131 (2016) and 91 (2020) and a five-element SAR assessment of all 22 HFs. QoCE assessment was performed among 420 patients: 88 (2016) and 332 (2020). Using a pair-matched approach, FPS and QoCE summary scores were compared. Linear and random effects Tobit regression models were also analysed. RESULTS: The mean aggregate facility performance (FPS) in 2020 was lower than in 2016: 70.2 (95%CI = 66.0-74.5) vs. 74.8 (95%CI = 71.3-78.3) respectively, with no significant difference (p = 0.18). Mean scores declined in 4 of 5 SAR elements. Overall FPS was negatively affected by rural or urban HF location relative to peri-urban HFs (p < 0.01). FPS was not independently predicted but patient club functionality showed weak association (p = 0.09). QoCE declined slightly to 8.7 (95%CI = 8.4-91) in 2020 vs 9.5 (95%CI = 9.1-9.9) in 2016 (p = 0.02) while the proportion of patients receiving adequate quality care also declined slightly to 88.2% from 98.5% respectively, with no statistical difference (p = 0.20). Only the parent district weakly predicted QoCE (p = 0.05). CONCLUSIONS: Four years after the end of research-related support, overall facility performance had declined as expected because of the interrupted supplies and a decline in regular supervision. However, both service availability and readiness and quality of HT/DM care were surprisingly well preserved. Sustainability of an NCD intervention in similar settings may remain achievable despite the funding instability following a trial's end but organisational measures to prepare for the post-trial phase should be taken early on in the intervention process.

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.

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.

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.

Pilot study of antibodies against varicella zoster virus and human immunodeficiency virus in relation to the risk of developing stroke, nested within a rural cohort in Uganda.

OBJECTIVE: The risk of stroke rises after episodes of herpes zoster and chickenpox, which are caused by varicella zoster virus (VZV). We conducted a pilot case-control study of stroke, nested within a long-standing cohort in Uganda (the General Population Cohort), to examine antibodies against VZV prior to diagnosis. METHODS: We used stored sera to examine the evolution of IgG and IgM antibodies against VZV among 31 clinically confirmed cases of stroke and 132 matched controls. For each participant, three samples of sera were identified: one each, taken at or near the time of (pseudo)diagnosis, between 5 and 10 years prior to diagnosis and at 15 years prior to diagnosis. RESULTS: All participants had detectable antibodies against VZV, but there were no significant differences between cases and controls in the 15 years prior to diagnosis. As a secondary finding, 16% (5/31) of cases and 6% (8/132) of controls had HIV (OR 3.0; 95% CI 0.8-10.1; P = 0.06). CONCLUSIONS: This is the first prospective study to examine a biological measure of exposure to VZV prior to diagnosis of stroke and although we identified no significant association, in this small pilot, with limited characterisation of cases, we cannot exclude the possibility that the virus is causal for a subset. The impact of HIV on risk of stroke has not been well characterised and warrants further study.

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 (P <0.001) even though HIV prevalence steadily increased with ART availability from 2004. Comparing 1990-1992 and 1996-1998, HIV incidence declined by 43% (0.79 to 0.45/100 person-years, P = 0.002). Between 1999 and 2011, the incidence remained stable at 0.49/100 person-years (95% confidence interval: 0.41-0.58) in men but slowly increased in women (average age-adjusted hazard ratio = 1.13 per 3 years, 95% confidence interval: 1.03-1.24; trend P-value = 0.02). After 2011, however, the incidence trends reversed and continued to decline in men and women and in all age groups. CONCLUSION: Facilitating HIV testing and timely ART initiation, and supporting ART adherence must be emphasized alongside sustainable prevention measures.

Access to, and uptake of, antiretroviral therapy in a developing country with high HIV prevalence: a population-based cohort study in rural Uganda, 2004-2008.

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.

The impact of antiretroviral treatment on mortality trends of HIV-positive adults in rural Uganda: a longitudinal population-based study, 1999-2009.

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.

Using age-specific mortality of HIV infected persons to predict anti-retroviral treatment need: a comparative analysis of data from five African population-based cohort studies.

OBJECTIVES: To present a simple method for estimating population-level anti-retroviral therapy (ART) need that does not rely on knowledge of past HIV incidence. METHODS: A new approach to estimating ART need is developed based on calculating age-specific proportions of HIV-infected adults expected to die within a fixed number of years in the absence of treatment. Mortality data for HIV-infected adults in the pre-treatment era from five African HIV cohort studies were combined to construct a life table, starting at age 15, smoothed with a Weibull model. Assuming that ART should be made available to anyone expected to die within 3 years, conditional 3-year survival probabilities were computed to represent proportions needing ART. The build-up of ART need in a successful programme continuously recruiting infected adults into treatment as they age to within 3 years of expected death was represented by annually extending the conditional survival range. RESULTS: The Weibull model: survival probability in the infected state from age 15 = exp(-0.0073 × (age - 15)(1.69)) fitted the pooled age-specific mortality data very closely. Initial treatment need for infected persons increased rapidly with age, from 15% at age 20-24 to 32% at age 40-44 and 42% at age 60-64. Overall need in the treatment of naïve population was 24%, doubling within 5 years in a programme continually recruiting patients entering the high-risk period for dying. CONCLUSION: A reasonable projection of treatment need in an ART naive population can be made based on the age and gender profile of HIV-infected people.

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.

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.

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 (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.

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 nonfasting 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 (<0.1), intermediate risk (0.1-0.24), and high 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.

From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults.

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.

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.

Mortality trends in the era of antiretroviral therapy: evidence from the Network for Analysing Longitudinal Population based HIV/AIDS data on Africa (ALPHA).

BACKGROUND: The rollout of antiretroviral therapy (ART) is one of the largest public health interventions in Eastern and Southern Africa of recent years. Its impact is well described in clinical cohort studies, but population-based evidence is rare. METHODS: We use data from seven demographic surveillance sites that also conduct community-based HIV testing and collect information on the uptake of HIV services. We present crude death rates of adults (aged 15-64) for the period 2000-2011 by sex, HIV status, and treatment status. Parametric survival models are used to estimate age-adjusted trends in the mortality rates of people living with HIV (PLHIV) before and after the introduction of ART. RESULTS: The pooled ALPHA Network dataset contains 2.4 million person-years of follow-up time, and 39114 deaths (6893 to PLHIV). The mortality rates of PLHIV have been relatively static before the availability of ART. Mortality declined rapidly thereafter, with typical declines between 10 and 20% per annum. Compared with the pre-ART era, the total decline in mortality rates of PLHIV exceeds 58% in all study sites with available data, and amounts to 84% for women in Masaka (Uganda). Mortality declines have been larger for women than for men; a result that is statistically significant in five sites. Apart from the early phase of treatment scale up, when the mortality of PLHIV on ART was often very high, mortality declines have been observed in PLHIV both on and off ART. CONCLUSION: The expansion of treatment has had a large and pervasive effect on adult mortality. Mortality declines have been more pronounced for women, a factor that is often attributed to women's greater engagement with HIV services. Improvements in the timing of ART initiation have contributed to mortality reductions in PLHIV on ART, but also among those who have not (yet) started treatment because they are increasingly selected for early stage disease.

Trends in child mortality: a prospective, population-based cohort study in a rural population in south-west Uganda.

BACKGROUND: Although there has been substantial global progress in decreasing child mortality over the past two decades, progress in sub-Saharan Africa has largely lagged behind. The temporal trends in child mortality and associated risk factors were investigated in a cohort of children in rural Uganda. METHODS: Information on children's vital status, delivery, breastfeeding, vaccination history, maternal vital and HIV status, and children's HIV status for 1993-2007 was retrieved from the Medical Research Council/Uganda Virus Research Institute's (MRC/UVRI) Annual Population Census and Survey in Uganda. Regression models were employed to assess the association of these factors with child mortality. RESULTS: From 1993 to 2007, the death rate (/1000 person-years) in children <13 years of age decreased significantly from 16 to six. Apart from neonates, age-specific death rates fell in all age-groups. A reduction since 1999 in the risk of child mortality was associated with vaccination, birth in a health facility, exclusive breastfeeding for 6 months, 2-3 years since the previous sibling's birth, maternal vital status, and negative mother and child HIV serostatus. Although HIV seropositive children had a 26-fold increased risk of death before 13 years of age, HIV prevalence in children was about 1% and so had a small overall impact on child mortality. CONCLUSION: These findings are consistent with those of repeated national cross-sectional surveys. Meeting the Millennium Development Goals for child survival in sub-Saharan Africa depends on faster progress in implementing measures to improve birth-spacing, safe delivery in health facilities, infant feeding practices and vaccination coverage.

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 mrc@mrcuganda.org or the corresponding author.

Extraspousal partnerships in a community in rural Uganda with high HIV prevalence: a cross-sectional population-based study using linked spousal data.

BACKGROUND: The role of concurrent sexual partnerships in the HIV epidemic in sub-Saharan Africa is not well understood. Although most infections in Africa occur among married individuals, transmission may occur from both spousal and extraspousal partnerships. This article explores extraspousal partnerships as a form of concurrency, examining the association with HIV status, demographic characteristics, and sexual behaviors in a population-based cohort in rural Uganda. METHODS: Prevalence of extraspousal partnerships was estimated using cross-sectional data from 2008, and adjusted odds ratios (aOR) were estimated for factors associated with the prevalence of extraspousal partnerships using logistic regression. Among men who were not in polygynous marriages, we used linked spousal data to investigate the association between extraspousal partnerships and wives' serostatus. RESULTS: Extraspousal partnerships in the past year were reported by 17% of married men and 2% of married women. Among both men and women, extraspousal partnerships were associated with not knowing their partners' HIV status (men: aOR = 1.74; 95% CI: 1.13 to 2.67; women: aOR = 1.76; 95% CI: 1.13 to 2.75), and extraspousal partnerships were also associated with increased condom use for men. There was no evidence that men reporting extraspousal partnerships were at increased risk of HIV (aOR = 0.98; 95% CI: 0.48 to 2.01), or that a woman's risk of HIV was associated with her husband reporting extraspousal partnerships (aOR = 0.68; 95% CI: 0.29 to 1.57). CONCLUSIONS: For both men and women, extraspousal partnerships were associated with not knowing their partners' HIV status. There was no evidence of an association of extraspousal partnerships with HIV serostatus in this cross-sectional analysis.