Durability and predictors of success of highly active antiretroviral therapy for ambulatory HIV-infected patients
OBJECTIVE: To evaluate the durability and correlates of the effectiveness of highly active antiretroviral therapy (HAART) in terms of AIDS-related mortality and morbidity, HIV viremia, and CD4 cell count. DESIGN AND SETTING: The HIV Outpatient Study (HOPS), a prospective observational cohort from eight clinics in the USA that has been running since 1994. PARTICIPANTS: Mortality and opportunistic infection (OI) rates were calculated for 1769 HOPS patients with CD4 cell count ever < 100 x 106/l. Data from 1022 HAART recipients with CD4 cell count ever < 500 x 106/l were analyzed. MAIN OUTCOME MEASURES: Mortality and AIDS-related OI rates. Treatment success was defined as a reduction in plasma HIV RNA copies/ml of 1.0 log10 or more, or to an undetectable level, with a stable or rising CD4 cell count. Durable success was a successful response lasting at least 12 consecutive months. RESULTS: HAART use remained high; mortality and OIs low. Patients received a mean of 1.8 HAART regimens. Median time on first HAART (n = 1022) was 11.8 months; second HAART (n = 424) 7.4 months; and third HAART (n = 213) 7.2 months. Treatment success was most likely for pre-HAART treatment naive patients; durably successful first HAART most often contained one protease inhibitor, particularly indinavir or nelfinavir (P = 0.006, adjusted for prior antiretroviral therapy). Durable success was most likely with first (49.0%) than with second (29.6%, P = 0.013) or third or more HAART regimens (14.9%, P < 0.0001). Time to success with first HAART was shorter for durable than non-durable responders (3.6 versus 5.3 months, respectively; unadjusted P = 0.002). CONCLUSIONS: Durable response to HAART was associated with being pre-HAART therapy naive, prompt response to HAART, and single protease inhibitor-based initial HAART (indinavir or nelfinavir). Sequential HAART regimens were of progressively shorter duration, demonstrated less viral suppression and CD4 cell count benefit, yet low morbidity and mortality rates were sustained
Palella Jr, F. J., Chmiel, J. S., Moorman, A. C., & Holmberg, S. (2002). Durability and predictors of success of highly active antiretroviral therapy for ambulatory HIV-infected patients. AIDS, 16(12), 1617-1626.