Poor initial CD4+recovery with antiretroviral therapy prolongs immune depletion and increases risk for AIDS and non-AIDS diseases

Background: Low CD4+ increases risk for both AIDS- and non-AIDS-related morbidity and mortality. The magnitude of CD4+ recovery early after initial antiretroviral therapy (ART) is important in the ultimate duration of immune depletion. Methods: We examined CD4+ recovery among 850 participants in the Community Program for Clinical Research on AIDS Flexible Initial Retrovirus Suppressive Therapies study with virologic suppression (ie, achieved an HIV RNA level < 400 copies/mL) with 8 months of initial ART and determined subsequent risk for AIDS, non-AIDS diseases (non-AIDS cancers and cardiovascular, end-stage renal, and liver diseases), or death using Cox regression during a median 5-year follow-up. Results: Mean pretreatment CD4+ was 221 cells/mu L; 18% (n = 149) had a poor CD4+ recovery (< 50 cells/mu L) after 8 months of effective ART, resulting in lower CD4+ over 5 years. Older age (hazard ratio 1.34/10 yrs, P = 0.003) and lower screening HIV RNA (hazard ratio 0.65 per log(10) copies/mL higher, P = 0.001), but not screening CD4+, were associated with a poor CD4+ recovery. After 8 months of effective ART, 30 patients experienced the composite outcome of AIDS, non-AIDS, or death among participants with a poor CD4+ recovery (rate = 5.8/100 person-years) and 74 patients among those with an adequate recovery ( >= 50 cells/mu L; rate = 2.7/100 person-years) (adjusted hazard ratio = 2.24, P < 0.001). The risk of this composite outcome associated with a poor CD4+ recovery declined when ART was initiated at higher CD4+ counts (P < 0.01). Conclusions: Impaired immune recovery, despite effective ART, results in longer time spent at low CD4+, thereby increasing risk for a broad category of HIV-related morbidity and mortality conditions.