IntroductionThe 2016 WHO consolidated guidelines on the use of antiretroviral drugs defines HIV virologic failure for low and middle income countries (LMIC) as plasma HIV-RNA ≥ 1000 copies/mL. We evaluated virologic failure and predictors in four African countries.Materials and methodsWe included HIV-infected participants on a WHO recommended antiretroviral therapy (ART) regimen and enrolled in the African Cohort Study between January 2013 and October 2017. Studied outcomes were virologic failure (plasma HIV-RNA ≥ 1000 copies/mL at the most recent visit), viraemia (plasma HIV-RNA ≥ 50 copies/mL at the most recent visit); and persistent viraemia (plasma HIV-RNA ≥ 50 copies/mL at two consecutive visits). Generalized linear models were used to estimate relative risks with their 95% confidence intervals.Results2054 participants were included in this analysis. Viraemia, persistent viraemia and virologic failure were observed in 396 (19.3%), 160 (7.8%) and 184 (9%) participants respectively. Of the participants with persistent viraemia, only 57.5% (92/160) had confirmed virologic failure. In the multivariate analysis, attending clinical care site other than the Uganda sitebeing on 2nd line ART (aRR 1.8, 95% CI 1·28–2·66); other ART combinations not first line and not second line (aRR 3.8, 95% CI 1.18–11.9), a history of fever in the past week (aRR 3.7, 95% CI 1.69–8.05), low CD4 count (aRR 6.9, 95% CI 4.7–10.2) and missing any day of ART (aRR 1·8, 95% CI 1·27–2.57) increased the risk of virologic failure. Being on 2nd line therapy, the site where one receives care and CD4 count < 500 predicted viraemia, persistent viraemia and virologic failure.ConclusionIn conclusion, these findings demonstrate that HIV-infected patients established on ART for more than six months in the African setting frequently experienced viraemia while continuing to be on ART. The findings also show that being on second line, low CD4 count, missing any day of ART and history of fever in the past week remain important predictors of virologic failure that should trigger intensified adherence counselling especially in the absence of reliable or readily available viral load monitoring. Finally, clinical care sites are different calling for further analyses to elucidate on the unique features of these sites.

Background World Health Organization (WHO) guidelines identify human immunodeficiency virus (HIV) viral load <1000 copies/mL as the goal of antiretroviral therapy (ART). However, the clinical implications of viremia below this threshold are unclear in the African context. We examined factors associated with persistent low-level viremia (pLLV) and quantified the risk of subsequent virologic. Methods The African Cohort Study enrolled HIV-infected adults at clinics in Uganda, Kenya, Tanzania, and Nigeria, with assessments every 6 months. We evaluated participants prescribed ART for at least 6 months without virologic failure for pLLV. We used multinomial logistic regression to evaluate associations between prespecified factors of interest and 3 levels of pLLV (<200, 200–499, and 500–999 copies/mL). We used Anderson-Gill extended Cox proportional hazards to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for viremia category associations with time to failure. Results We included 1511 participants with 4382 person-years of follow-up. PLLV <200 copies/mL was observed at 20% of visits while 2% of visits had pLLV 200–499 and 500–999 copies/mL each, with substantial variation by site. Protease inhibitor–containing ART was associated with increased risk of pLLV. Compared to undetectable viral load, pLLV ≥200 copies/mL doubled the risk of developing virologic failure (pLLV 200–499: HR, 1.81 [95% CI, 1.08–3.02]); pLLV 500–999: HR, 2.36 [95% CI, 1.52–3.67]). Conclusions Participants with pLLV ≥200 copies/mL were at increased risk of subsequent virologic failure. Optimized HIV care in this setting should target viral suppression <200 copies/mL.

Background Noninfectious comorbid diseases (NCDs) contribute to morbidity and mortality in human immunodeficiency virus (HIV)–infected populations in resource-rich countries. With antiretroviral therapy (ART) scale-up in Africa, understanding burden NCD informs public health strategy. Methods At enrollment, participants at 11 HIV clinics in Kenya, Uganda, Tanzania, and Nigeria underwent medical history, physical, laboratory, and neuropsychological assessments to identify elevated blood pressure, hypercholesterolemia, dysglycemia, renal insufficiency, and cognitive impairment. Poisson regression models estimated adjusted relative risks (ARRs) and 95% confidence intervals (CIs) for the number of NCDs associated with factors of interest. Logistic regression was used to evaluate each NCD separately among HIV-infected participants. Results Among 2720 participants with complete NCD data, 2159 (79.4%) were HIV-infected. Of those, 1426 (66.0%) were taking ART and 813 (37.7%) had at least 1 NCD. HIV infection was associated with more NCDs, especially with ART (ARR, 1.42; 95% CI, 1.22–1.66). In addition to age, body mass index, and program site, ART usage was associated with more NCDs (ARR, 1.50; 95% CI, 1.27–1.78 for virologically suppressed and ARR, 1.38; 95% CI, 1.13–1.68 for viremic) among HIV-infected participants. In participants taking ART, CD4 nadir below 200 cells/mm3 was associated with more NCDs (ARR, 1.43; 95% CI, 1.06–1.93). ART use was independently associated with hypercholesterolemia and dysglycemia. Program site was significantly associated with all comorbidities except renal insufficiency. Conclusions HIV infection was a risk for NCDs, which were common in HIV-infected participants, geographically variable, and largely consistent with metabolic complications of first-line ART.

Introduction: Dolutegravir (DTG) has become a preferred component of first-line antiretroviral therapy (ART) in many settings but may be associated with excess weight gain. We evaluated changes in weight and body mass index (BMI) after switch to single-tablet tenofovir/lamivudine/dolutegravir (TLD) by people living with HIV (PLWH) in four African countries. Methods: The African Cohort Study (AFRICOS) prospectively follows adults with and without HIV in Kenya, Uganda, Tanzania and Nigeria. Demographics, ART regimen, weight, BMI and waist-to-hip ratio were collected every 6 months. Multivariable Cox proportional hazards modelling was used to estimate hazard ratios and 95% confidence intervals (CIs) for factors associated with developing a BMI ≥25 kg/m 2 . Linear mixed effects models with random effects were used to examine the average change in BMI, weight and waist-to-hip ratio. Results: From 23 January 2013 to 1 December 2020, 2950 PLWH were enrolled in AFRICOS and 1474 transitioned to TLD. In adjusted models, PLWH on TLD had 1.77 times the hazard of developing a high BMI (95% CI: 1.22-2.55) compared to PLWH on non-TLD ART. Examining change in weight among all PLWH on ART, participants on TLD gained an average of 0.68 kg (95% CI: 0.32-1.04) more than PLWH on other regimens after adjusting for duration on ART, sex, age, study site and CD4 nadir. Among participants who switched to TLD, the average change in weight prior to TLD switch was 0.35 kg/year (95% CI: 0.25-0.46) and average change in weight was 1.46 kg/year (95% CI: 1.18-1.75) in the year following transition to TLD after adjustment for confounders. Conclusions: Elevated BMI and weight gain among PLWH on TLD are concerning safety signals. Implications for the development of metabolic comorbidities should be monitored, particularly if annual weight gain persists during continued follow-up after transitioning to TLD.

Background: The vast majority of deaths in the health and Kombewa demographic surveillance system (HDSS) study area are not registered and reported through official systems of vital registration. As a result, few data are available regarding causes of death in this population. Objectives: To describe causes of death among residents of all ages in the Kombewa HDSS, located in rural Western Kenya. Methods: Verbal autopsy (VA) interviews at the site were conducted using the modified 2007 and later 2012 standardized WHO questionnaires. Assignment of causes of death was made using the InterVA-4 model version 4.02. Cox regression model, adjusted for sex, was built to evaluate the influence of age on mortality. Results: There were a total of 5196 deaths recorded between 2011 and 2015 at the site. VA interviews were successfully completed for 3903 of these deaths (75.1%). Mortality rates were highest among neonates HR = 38.54 (<0.001) and among Infants HR = 2.07 (<0.006) in the Kombewa HDSS. Among those deaths in which VA was performed, the top causes of death were HIV/AIDS (12.6%), Malaria (10.3%), Pneumonia (10.1%), Acute abdomen (7.0%), Stroke (5.2%) and TB (4.9%) for the whole population in general. Stroke, acute abdomen heart diseases and Pneumonia were common causes of death (CODs) among the elderly over the age of 65. Conclusions: The analysis established the main CODs among people of all ages within the area served by the Kombewa HDSS. We hope that information generated from this study will help better address preventable deaths in the surveyed community as well as help mitigate negative health impacts in other rural communities throughout the Western Kenya region.