Session 15Oral Abstract Presentations Treatment Strategies Session Day and Time: Wednesday 11:15 am - 12:45 pm Presentation Time: 12:00 Room: Auditorium
67 CPCRA 064: A Randomized Trial Examining Structured Treatment Interruption for Patients Failing Therapy with Multi-drug Resistant HIV J. Lawrence*1, D. Mayers2, K. Huppler Hullsiek3, G. Collins3, D. Abrams1, R. Reisler4, L. Crane5, B. Schmetter6, T. Dionne7, J. Saldanha8, M. Jones1, J. Baxter9, the CPCRA 064 Study Team of the Terry Beirn Community Programs for Clinical Research on AIDS. 1Univ of California at San Francisco; 2Henry Ford Hosp, Detroit, MI; 3Univ of Minnesota, Minneapolis; 4Natl Inst of Hlth, NIAID, Div of AIDS, Bethesda, MD; 5Wayne State Univ, Detroit, MI; 6Social and Sci Sys, Silver Spring, MD; 7Veterans Admin Med Ctr, Washington, DC; 8Denver Publ Hlth Dept, CO; and 9Cooper Hosp /RWJ Med Sch, Camden, NJ
Background: CPCRA 064 is the first prospective randomized clinical endpoint study for patients with Multi-drug Resistant (MDR) HIV to test whether a strategy of using an Structured Treatment Interruption (STI) prior to changing therapy reduces progression of disease (POD) or death compared with immediately changing therapy. Previous studies, focused on short-term virologic responses, have reported conflicting results.
Methods: CPCRA 064 is a multicenter study of HIV-infected patients (pts) on stable antiretroviral (AR) regimens with virologic failure (HIV RNA > 5,000 copies/mL) and MDR virus documented by genotypic testing. Pts were randomized 1:1 to a) 4-month (mo) STI followed by a new regimen or b) immediate change to a new regimen. Baseline genotypic and phenotypic resistance tests were provided to help optimize new regimens. Active drugs were defined by genotypic or phenotypic susceptibility. USPHS OI prophylaxis guidelines were stressed. The primary endpoint was POD or death. Secondary endpoints included changes in CD4 cell count, HIV RNA levels, and quality of life (QOL [SF-12]). All analyses were intent-to-treat, using proportional hazard and longitudinal regression models.
Results: The study closed to accrual 6/28/02 as recommended by the DSMB based on data from 270 participants. Mean baseline CD4 = 180 cells/mm3, HIV RNA = 5.0 log10 copies/mL, and prior # of Ars = 10.6. Forty-eight percent (48%) had broad 3-class resistance and 56% had prior POD. Median follow-up was 11.3 mos. Mean # of drugs in the new regimen was 3.6 (2.7 active) in the STI arm and 3.8 (2.8 active) in the no-STI arm. There were 22 primary endpoints (POD or death) in the STI group and 12 in the no-STI group (hazard ratio = 2.57, 95% CI = 1.2, 5.5, p = 0.01). There were 8 deaths in each arm. POD events in the STI arm included 7 esophageal candidiasis (EC), 4 PCP, 3 cryptosporidiosis, 2 lymphomas, and 1 CMV. POD events in the no-STI arm included 1 EC, 1 cryptosporidiosis, 1 CMV, 1 MAC, and 1 HSV. Mean difference in CD4 favored the no-STI arm by 85 cells/mm3 (p < 0.001) for mos 1-4 (STI phase), 47 cells (p < 0.001) for mos 5-8, and 31 cells (p = 0.11) for mos 12-20. Mean HIV RNA log10 difference was 1.2 higher in the STI arm for mos 1-4 (p < 0.001), 0.02 higher for mos 5-8 (NS) and 0.12 lower for mos 12-20 (NS). QOL measures were similar for each arm.
Conclusions: In treatment experienced pts failing therapy with MDR virus, STIs as used in this study do not appear to confer clinical, immunologic, virologic, or QOL benefits.