The impact of adherence on CD4 cell count responses among HIV-infected patients

Background: There have been concerns that irreversible immune damage may result if highly active antiretroviral therapy (HAART) is initiated after the CD4 cell count declines to below 350 cells/muL; however, the role of antiretroviral adherence on CD4 cell count responses has not been well evaluated. Methods: We evaluated CD4 cell count responses of 1522 antiretroviral-naive patients initiating HAART who were stratified by baseline CD4 cell count (<50, 50-199, and greater than or equal to200 cells/muL) and adherence. Results: Among patients starting HAART with <50 cells/pL, during the fifth 15-week period after the initiation of HAART, absolute CD4 cell counts were 200 cells/muL (interquartile range [IQR]: 130-290) for adherent patients versus 60 cells/pL (IQR: 10-130) for nonadherent patients. Similarly, among patients starting HAART with 50 to 199 cells/pL, during the fifth 15-week period after the initiation of HAART. absolute CD4 cell Counts were 300 cells/muL (IQR: 180-390) versus 125 cells/muL (IQR: 40-210) for nonadherent patients. In Cox regression analyses, adherence was the strongest independent predictor of the time to a gain of :50 cells/pL from baseline (relative hazard [RH] = 2.88: 95% confidence interval [CI]: 2.46-3.37). Among patients with baseline CD4 Cell Counts <200 cells/pL, adherence was the strongest independent predictor of the time to a CD4 cell count >200 cells/muL (RH = 4.85, 95% CI: 3.15-7.47). Conclusions: These data demonstrate that substantial CD4 gains are possible among highly advanced adherent patients and should contribute to the ongoing debate over the optimal time to initiate HAART.