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IntroductionThe prognostic role of CD4 response in the first six months of treatment in patients achieving early viral suppression during HIV treatment is unclear.MethodsThis was a cohort study of HIV-positive adults initiating antiretroviral therapy (ART) between April 2004 and August 2007 who achieved viral suppression (<400 copies/ml) by six months on treatment in South Africa. Immunological response at six months was defined as: (1) absolute CD4 reached (<200 vs. ≥200 cells/ml); (2) absolute CD4 reached (0–49, 50–200 and ≥200 cells/ml); and (3) CD4 increase from ART initiation (<0, 0–49, 50–199 and ≥200 cells/ml). We used Cox regression models to determine the relationship between each definition and both new AIDS-defining condition and death.ResultsA total of 4129 patients were eligible for analysis; 212 (5.1%) of those patients experienced a new AIDS-defining condition and 154 (3.7%) died. Smaller CD4 gains by six months were associated with higher hazards of progression to AIDS (CD4<50 vs. ≥200 cells/ml; adjusted hazard ratio (aHR): 2.6; 95% CI: 1.2–2.1) and death (aHR: 2.8; 95% CI: 1.4–5.7). A decrease in CD4 count since ART initiation through six months (aHR: 2.4; 95% CI: 1.2–4.9) and smaller CD4 count gains (0–49 cells/ml; aHR: 2.0; 95% CI: 1.2–3.4 and 50–199 cells/ml; aHR: 1.5; 95% CI: 0.9–2.2) were also associated with greater risk of progression to AIDS compared to an increase of ≥200 cells/ml. When we examined mortality differences by gender among this virally suppressed cohort, a higher proportion of males died compared to females, 4.7% versus 3.2%, p=0.01. However, in multivariable analysis, we did not observe any significant differences: aHR: 1.39; 95% CI: 0.98–1.95.ConclusionsPatients on ART with poor CD4 recovery early in treatment are at greater risk of progression to new AIDS diagnosis or death despite viral suppression. Approaches to managing this sub-group of patients need further investigation.

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Background: Optimizing initial antiretroviral therapy (ART) regimens is critical in improving the durability of treatment efficacy and patient prognosis. Reasons for and risk factors relating to the need for ART modifications were evaluated in an outpatient cohort in Mbabane, Swaziland. Methods:We examined routine clinical data for 782 patients initiating first-line ART between 1 March 2006 and 31 March 2008. Treatment modification was defined as either a first time single drug substitution or first time regimen switch. Multivariate piecewise Cox regression models were used to identify risk factors for ART modification.Results: Over a median follow-up period of 21 months, 17.5% of patients modified their regimen. Drug toxicity (incidence rate of 6.3 per 100 person years (95% CI 5.2-7.7)) accounted for 76.6% of the reasons for modification. Drug contra-indications (incidence rate 9.5 per 100 person years (95% CI 6.5-13.9)), namely tuberculosis (13.1%) and pregnancy (6.6%), accounted for 19.7% of modifications. In the adjusted multivariate Cox piecewise regression model, beyond 11 months on ART, a baseline CD4 cell count <200 cells/mm 3 (HR 4.42; 95% CI: 1.62 -12.1), having stavudine (d4T) in the initial regimen (HR 2.64; 95% CI: 1.56 -4.46), baseline weight > 60kg (HR 2.40; 95% CI: 1.43 -4.04) and increase in age (HR 1.03; 95% CI: 1.00 -1.05) increased the risk of modification. Conclusions:Initiating ART earlier, at higher CD4 counts, avoiding drugs with poor safety profiles, such as d4T, and identifying individuals who may require tuberculosis treatment or may become pregnant could reduce modification rates. This would improve regimen tolerability, while preserving future treatment options.