Effect of baseline CD4 cell counts on the clinical significance of short-term immunologic response to antiretroviral therapy in individuals with virologic suppression.

Abstract

Achieving virologic suppression is a clear therapeutic goal for patients receiving combination antiretroviral therapy (cART). However, the effects of immunologic responses, whether measured as CD4 count changes from baseline or CD4 counts at follow-up, in patients with virologic suppression, have not been clearly established. Treatment-naive individuals aged > or =16 years, who initiated cART between 1998 and 2005 in participating cohorts of the ART Cohort Collaboration and achieved viral load < or =400 copies per milliliter 6 months after cART initiation, were included. We used Cox models to examine associations of CD4 change from baseline to 6 months, and absolute CD4 counts at 6 months, with subsequent rates of mortality and AIDS. Analyses were stratified by baseline CD4 count. Among 23,679 eligible participants, the median increase in CD4 count at 6 months, and the implications of these increases for subsequent mortality and AIDS, varied with baseline CD4 count. Mortality hazard ratios for increases of 0-50 cells per microliter, compared with >100 cells per microliter, were 1.87 (95% confidence interval: 1.28 to 2.73), 1.60 (1.13 to 2.28), 0.98 (0.58 to 1.65) and 1.24 (0.70 to 2.18) in participants with baseline CD4 cell count <50, 50-199, 200-349 and > or =350 cells per microliter, respectively. In contrast, hazard ratios for mortality or AIDS associated with absolute CD4 cell counts at 6 months were similar across all but the highest baseline CD4 cell count strata. It is not possible to derive thresholds for change in CD4 count that define an adequate immunologic response in individuals receiving cART. Absolute CD4 counts at 6 months are a more useful measure of immunologic response and subsequent prognosis.