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/μL; 18%(n= 149) had a poor CD4+ recovery (< 50 cells/μL) 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/μL; 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.