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After failure of first-line antiretroviral therapy (ART) in the public sector, delayed or missed second-line ART switch is linked with poor outcomes in patients with advanced HIV.We investigated delayed or missed second-line ART switch after confirmed virologic failure in the largest private sector HIV cohort in Africa.We included HIV-infected adults with confirmed virologic failure after 6 months of nonnucleoside reverse-transcriptase inhibitor-based ART. We estimated the effect of timing of switch on the hazard of death using inverse probability of treatment weighting of marginal structural models. We adjusted for time-dependent confounding of CD4 count, viral load, and visit frequency.Five thousand seven hundred forty-eight patients (53% female) with confirmed virologic failure met inclusion criteria; the median age was 40 [interquartile range (IQR): 35-47], advanced HIV was present in 48% and the prior duration of nonnucleoside reverse-transcriptase inhibitor-based ART was 1083 days (IQR: 665-1770). Median time to confirmation of virologic failure and to second-line switch was 196 (IQR: 136-316) and 220 days (IQR: 65-542), respectively. Switching to second-line ART after confirmed failure compared with remaining on first-line ART reduced risk of subsequent death [adjusted hazard ratio: 0.47 (95% confidence interval: 0.36 to 0.63)]. Compared with patients who experienced delayed switch, those switched immediately had a lower risk of death, regardless of CD4 cell count.Delayed or missed switch to second-line ART after confirmed first-line ART failure is common in the South African private sector and associated with mortality. Novel interventions to minimize switch delay should be tested and not limited to those with advanced disease at treatment failure.

Both CD4 count and viral load in HIV-infected persons are measured with error. There is no clear guidance on how to deal with this measurement error in the presence of missing data.We used multiple overimputation, a method recently developed in the political sciences, to account for both measurement error and missing data in CD4 count and viral load measurements from four South African cohorts of a Southern African HIV cohort collaboration. Our knowledge about the measurement error of ln CD4 and log10 viral load is part of an imputation model that imputes both missing and mismeasured data. In an illustrative example, we estimate the association of CD4 count and viral load with the hazard of death among patients on highly active antiretroviral therapy by means of a Cox model. Simulation studies evaluate the extent to which multiple overimputation is able to reduce bias in survival analyses.Multiple overimputation emphasizes more strongly the influence of having high baseline CD4 counts compared to both a complete case analysis and multiple imputation (hazard ratio for200 cells/mm vs.25 cells/mm: 0.21 [95% confidence interval: 0.18, 0.24] vs. 0.38 [0.29, 0.48], and 0.29 [0.25, 0.34], respectively). Similar results are obtained when varying assumptions about measurement error, when using p-splines, and when evaluating time-updated CD4 count in a longitudinal analysis. The estimates of the association with viral load are slightly more attenuated when using multiple imputation instead of multiple overimputation. Our simulation studies suggest that multiple overimputation is able to reduce bias and mean squared error in survival analyses.Multiple overimputation, which can be used with existing software, offers a convenient approach to account for both missing and mismeasured data in HIV research.

Initiation criteria and pediatric antiretroviral treatment regimens have changed over the past few years in South Africa. We reported worse early virological outcomes associated with the use of abacavir (ABC)-based regimens at 1 large site: here, we expand this analysis to multiple sites in the IeDEA-Southern Africa collaboration.Data for 9543 antiretroviral treatment-naïve children16 years at treatment initiation started on either stavudine/lamivudine (d4T/3TC) or ABC/3TC with efavirenz (EFV) or ritonavir-boosted lopinavir (LPV/r) treated at 6 clinics in Johannesburg and Cape Town, South Africa, were analyzed with χ tests and logistic regression to evaluate viral suppression at 6 and 12 months.Prevalence of viral suppression at 6 months in 2174 children started on a d4T-based LPV/r regimen was greater (70%) than among 438 children started on an ABC-based LPV/r regimen (54%, P0.0001). Among 3189 children started on a d4T-based EFV regimen, a higher proportion (86%) achieved suppression at 6 months compared with 391 children started on ABC-containing EFV regimens (78%, P0.0001). Relative benefit of d4T versus ABC on 6-month suppression remained in multivariate analysis after adjustment for pretreatment characteristics, cohort and year of program [LPV/r: odds ratio = 0.57 (confidence interval: 0.46-0.72); EFV: odds ratio = 0.46 (confidence interval: 0.32-0.65)].This expanded analysis is consistent with our previous report of worse virological outcomes after ABC was introduced as part of first-line antiretroviral treatment in South Africa. Whether due to the drug itself or coincident with other changes over time, continued monitoring and analyses must clarify causes and prevent suboptimal long-term outcomes.

We studied the immune response after starting antiretroviral treatment (ART) in 15,646 HIV-infected patients with or without tuberculosis (TB) at presentation in 3 ART programs in South Africa between 2003 and 2010. Patients presenting with TB had similar increases in CD4 cells compared with all other patients (adjusted difference 4.9 cells/µL per 6 months, 95% confidence interval: 0.2 to 9.7). Younger age, advanced clinical stage, female sex, and lower CD4 cell count at ART start were all associated with steeper CD4 slopes. In South Africa, HIV-infected patients presenting with TB experience immune recovery after starting ART that is no worse than in other patients.