Poor CD4 recovery and risk of subsequent progression to AIDS or death despite viral suppression in a South African cohort

Introduction: The prognostic role of CD4 response in the first six months of treatment in patients achieving early viral suppression during HIV treatment is unclear. Methods: This 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. Results: A 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. Conclusions: Patients 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.