HIV-1 RNA, CD4 T-lymphocytes, and clinical response to highly active antiretroviral therapy

Objective: To determine if HIV-1 RNA and CD4 lymphocyte thresholds for the initiation of highly active antiretroviral therapy (HAART) are associated with clinical response to therapy. Design: Observational cohort study. Setting: Johns Hopkins Hospital HIV Clinic. Patients: HIV-infected adults. Intervention: Patients initiating HAART (n = 530) were compared with concurrent patients who did not receive HAART (n = 484). Main outcome measure: Progression to a new AIDS-defining illness or death. Results: The average duration of follow-up for the cohort was 22 months. HAART resulted in decreased disease progression among persons with fewer than, but not more than, 200 × 10⁶ CD4 lymphocytes/l prior to treatment. Among persons receiving HAART, plasma HIV-1 RNA level prior to therapy was not associated with HIV disease progression within CD4 T-lymphocyte count strata. In a Cox multivariate proportional hazards model that adjusted for age, sex, race, prior opportunistic infection, and CD4 T lymphocytes, ≤ 200 × 10⁶ CD4 lymphocytes/l was the strongest predictor of disease progression. HIV-1 RNA level prior to starting HAART of < 5000 copies/ml, 5001-55 000 copies/ml, or > 55 000 copies/ml was not associated with disease progression on therapy, particularly among persons with > 200 × 10⁶ CD4 lymphocytes/l. There was no sex difference in disease progression on treatment. Conclusions: Our data suggest that current guidelines for initiating HAART should place greater emphasis on CD4 lymphocyte than HIV-1 RNA level for both men and women. Further longitudinal follow-up will be needed to better ascertain whether HAART initiated at > 200 × 10⁶ CD4 lymphocytes/l is effective in slowing disease progression.