Response to Highly Active Antiretroviral Therapy According to Duration of HIV Infection

Abstract

Objective: To evaluate whether duration of HIV-1 infection influences the response to highly active antiretroviral therapy (HAART). Design: Prospective study of individuals (Italian Seroconversion Study cohort) with well-estimated dates of HIV-1 seroconversion. Methods: This analysis included 277 participants who began HAART (defined as three antiretroviral drugs used in combination). Cox regression models were used to evaluate the association between duration of infection (as categorical variable [≤3, 3-7.5, >7.5 years from seroconversion] or continuous variable) and an immunologic (rise in CD4 count >100 cells/mm3) and a virologic (decline in plasma HIV-RNA to unquantifiable levels) outcome. All analyses were stratified by center of recruitment and adjustment, when used, was for gender, age at inception of HAART, injection drug use, previous antiretroviral therapy, lag-time between positive and negative HIV test result, year of starting HAART, clinical stage, CD4 count, and HIV-RNA at time of HAART. Results: HAART was initiated a median of 6.4 years after seroconversion. There was a median follow-up of 1.6 years after starting HAART to the calendar cut-off (November 1999). One-hundred-eighty-one (65.3%) patients experienced a decline in viral load to below quantifiable levels and 184 (66.4%) experienced a rise in CD4 >100 cells/mm3. In the Cox models, by 1-year increase in duration of infection, we estimated a lower crude hazard of achieving a CD4 count increase >100 cells (relative hazard [RH], 0.96; 95% confidence interval [CI], 0.92-1.01; p = .09), and a lower hazard of reaching an unquantifiable level of plasma HIV-RNA (RH, 0.97; 95%CI, 0.93-1.02; p = .20). After adjustment, these values became 0.99 (95%CI, 0.93-1.04; p = .62) and 0.98 (95%CI, 0.93-1.04; p = .48), respectively. When duration of HIV infection was considered as a categorical variable, the results were consistent with those already described. Conclusions: These results suggest that the duration of HIV infection does not seem to play an important independent role in determining the virologic and immunologic responses to HAART.