BACKGROUNDTwo drugs under consideration for inclusion in antiretroviral therapy (ART) regimens for human immunodeiciency virus (HIV) infection are dolutegravir (DTG) and tenofovir alafenamide fumarate (TAF). There are limited data on their use in low-and middle-income countries. METHODSWe conducted a 96-week, phase 3, investigator-led, open-label, randomized trial in South Africa, in which we compared a triple-therapy combination of emtricitabine (FTC) and DTG plus either of two tenofovir prodrugs -TAF (TAF-based group) or tenofovir disoproxil fumarate (TDF) (TDF-based group) -against the local standard-of-care regimen of TDF-FTC-efavirenz (standard-care group). Inclusion criteria included an age of 12 years or older, no receipt of ART in the previous 6 months, a creatinine clearance of more than 60 ml per minute (>80 ml per minute in patients younger than 19 years of age), and an HIV type 1 (HIV-1) RNA level of 500 copies or more per milliliter. The primary end point was the percentage of patients with a 48week HIV-1 RNA level of less than 50 copies per milliliter (as determined with the Snapshot algorithm from the Food and Drug Administration; noninferiority margin, −10 percentage points). We report the primary (48-week) efficacy and safety data. RESULTSA total of 1053 patients underwent randomization from February 2017 through May 2018. More than 99% of the patients were black, and 59% were female. The mean age was 32 years, and the mean CD4 count was 337 cells per cubic millimeter. At week 48, the percentage of patients with an HIV-1 RNA level of less than 50 copies per milliliter was 84% in the TAF-based group, 85% in the TDF-based group, and 79% in the standard-care group, findings that indicate that the DTG-containing regimens were noninferior to the standard-care regimen. The number of patients who discontinued the trial regimen was higher in the standard-care group than in the other two groups. In the per-protocol population, the standard-care regimen had equivalent potency to the other two regimens. The TAF-based regimen had less effect on bone density and renal function than the other regimens. Weight increase (both lean and fat mass) was greatest in the TAF-based group and among female patients (mean increase, 6.4 kg in the TAF-based group, 3.2 kg in the TDF-based group, and 1.7 kg in the standard-care group). No resistance to integrase inhibitors was identified in patients receiving the DTG-containing regimens. CONCLUSIONSTreatment with DTG combined with either of two tenofovir prodrugs (TAF and TDF) showed noninferior efficacy to treatment with the standard-care regimen. There was significantly more weight gain with the DTG-containing regimens, especially in combination with TAF, than with the standard-care regimen. (ADVANCE ClinicalTrials.gov number, NCT03122262.

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Outcomes of HIV-infected children have improved dramatically over the past decade, but are undermined by patient loss to follow-up (LTFU). We assessed patterns of LTFU among HIV-infected children receiving antiretroviral treatment (ART) at a large inner-city HIV clinic in Johannesburg, South Africa between 2005 and 2014.Demographic and clinical data were extracted from clinic records of children under 12 years. Differences between characteristics of children retained in care and LTFU were assessed using Wilcoxon rank sum tests or Pearson χ2 tests. Cox proportional hazard models then identified characteristics associated with LTFU.Of 135 children, the median age at ART initiation was 21.5 months (IQR: 6.3–47.7) with a median follow-up time of 3.3 years (IQR: 1.4–5.0). The incidence rate of LTFU was 10.8 per 100 person-years (95% CI: 8.2–14.4); cumulatively 36% of children were LTFU. Almost a third (n = 39) of children missed a clinic visit, but then returned to care; 77% of these were eventually LTFU. In total, 18% of children had elevated viral loads after 6 or more months of ART. Older age at ART initiation (18–59 months: aHR 1.6, 95% CI: 3.9–14.2) and ever missing a clinic visit (aHR 7.4 95% CI: 3.9–14.2) were independent predictors of LTFU.High rates of LTFU were observed in this primary care clinic. Risks for LTFU included older age (>18 months old) and missed clinic visits. Identifying children who miss scheduled visits and developing strategies directed at retaining them in care is critical to improving long-term pediatric HIV outcomes.

Participants randomised to first-line tenofovir alafenamide (TAF)/emtricitabine (FTC)+dolutegravir (DTG), tenofovir disoproxil fumarate (TDF)/FTC+DTG or TDF/FTC/efavirenz (EFV) for 192 weeks were then switched to TDF/lamivudine (3TC)/DTG for 52 weeks. Participants switching either TAF/FTC+DTG or TDF/FTC/EFV to TDF/3TC/DTG showed statistically significant reductions in weight, low density lipoprotein, triglycerides, glucose and glycated haemoglobin.

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