Female sex and increased BMI were associated with severe LA in this large randomized trial of first-line ARV in South Africa. While female sex, increased BMI and d4T are previously described risk factors for the development of clinically significant lactate elevations, the independent risk associated with EFV is a novel observation warranting further investigation.

BackgroundShort-term morbidity and mortality rates for HIV positive soldiers in the South African National Defence Force (SANDF) would inform decisions about deployment and HIV disease management. Risks were determined according to the latest CD4+ cell count and use of antiretroviral therapy (ART) for HIV positive individuals in the SANDF and their dependents.Methods and FindingsA total of 7,114 participants were enrolled and followed for mortality over a median of 4.7 years (IQR: 1.9, 7.1 years). For a planned subset (5,976), progression of disease (POD) and grade 4, potentially life-threatening events were also ascertained. CD4+ count and viral load were measured every 3 to 6 months. Poisson regression was used to compare event rates by latest CD4+ count (<50, 50–99, 100–199, 200–349, 350–499, 500+) with a focus on upper three strata, and to estimate relative risks (RRs) (ART/no ART). Median entry CD4+ was 207 cells/mm3. During follow-up over 70% were prescribed ART. Over follow-up 1,226 participants died; rates ranged from 57.6 (< 50 cells) to 0.8 (500+ cells) per 100 person years (py). Compared to those with latest CD4+ 200–349 (2.2/100py), death rates were significantly lower (p<0.001), as expected, for those with 350–499 (0.9/100py) and with 500+ cells (0.8/100py). The composite outcome of death, POD or grade 4 events occurred in 2,302 participants (4,045 events); rates were similar in higher CD4+ count strata (9.4 for 350–499 and 7.9 for 500+ cells) and lower than those with counts 200–349 cells (13.5) (p<0.001). For those with latest CD4+ 350+ cells, 63% of the composite outcomes (680 of 1,074) were grade 4 events.ConclusionRates of morbidity and mortality are lowest among those with CD4+ count of 350 or higher and rates do not differ for those with counts of 350–499 versus 500+ cells. Grade 4 events are the predominant morbidity for participants with CD4+ counts of 350+ cells.

NNRTI drug resistance mutations (DRM) are increasingly reported in Africans failing their first antiretroviral regimen. The Phidisa II trial randomized treatment-naïve participants to LPV/r or EFV with d4T+3TC or ZDV+ddI. We report the prevalence of DRM in subjects who achieved HIV RNA < 400 copies/mL at 6-months but subsequently had 2 consecutive HIV RNA >1000 copies/mL. Sixty-eight participants fulfilled the inclusion criteria. NNRTI-DRM were found in 17/36 (47.2%) EFV-recipients, and M184V/I mutation in 14/40 (35.0%) 3TC-recipients. No PI mutation was identified in 38 LPV/r-recipients. This is one of the first studies in Africa confirming the paucity of PI-associated DRM despite virologic failure.

Study Objective-To evaluate the effect of prior single dose nevirapine (sd-NVP) use on HIV RNA and CD4+ T-cell responses after 6 months of efavirenz -or lopinavir/ritonavir -based antiretroviral regimens.Design-This is a retrospective analysis of a subset of participants in the Phidisa II trial, a randomized controlled trial enrolled HIV+ participants 14 years or older with no or < 7 day history of antiretroviral use. At screening, subjects were asked about prior nevirapine nevirapine use, a positive response in a woman was used as a surrogate for prior sd-NVP. Virologic and CD4 responses at 6-month were compared between women with or without prior nevirapine exposure, and amongst women who received efavirenz vs. lopinavir/ritonavir. Setting-Six South African Medical Health Services' Phidisa research clinics.Subjects-478 women responded to the question regarding prior nevirapine use.Measurements and Main Results-392 women were nevirapine-naïve (NVP-), 86 had prior nevirapine (NVP+). At 6-month, 396 women (324 NVP-, 70 NVP+) had follow-up HIV-RNA