A Randomized Study of Antiviral Medication Switch at Lower-Versus Higher-Switch Thresholds: AIDS Clinical Trials Group Study A5115
Year: 2007
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: BACKGROUND: Clinical stability has been observed with continued antiretroviral therapy (ART) in the setting of partial virological suppression. The optimal time to switch treatment in patients with low but detectable HIV-1 RNA is not known. METHODS: Subjects on stable ART with HIV-1 RNA 200-10,000 copies/ml were randomized to an immediate treatment switch, or to a delayed switch when HIV-1 RNA increased to > or = 10,000 copies/ml or CD4+ T-cell count decreased by 20%. The primary outcome measures were immune activation (proportion of CD8+ T-cells expressing CD38 at week 48) and evolution of genotypic drug resistance. RESULTS: The study failed to fully accrue the originally planned 108 subjects. Only 47 subjects were randomized to immediate- or delayed-switch arms. Of the subjects in the delayed-switch arm, 10/23 (43%) met the criteria for ART switch during the study (median follow-up 82 weeks). After 48 weeks of observation, the level of immune activation was comparable in the two arms. New resistance mutations were observed in 3/17 and 8/19 subjects in the immediate- and delayed-switch groups, respectively. The loss of future treatment options, however, was comparable in the delayed- and immediate-switch groups. CONCLUSIONS: Individuals with partial viral suppression tend to remain immunologically stable, however, the accumulation of drug resistance mutations is an ongoing risk. Delayed switch in ART may be a reasonable short-term strategy for individuals with very limited treatment options.
Source: Antiviral Therapy
Institutions: University of Pittsburgh, Harvard University, Rush University Medical Center, Brigham and Women's Hospital, University of Alabama at Birmingham, Social and Scientific Systems (United States), Vanderbilt University, Brown University, The University of Texas Southwestern Medical Center, San Francisco General Hospital, University of California, San Francisco, University of California San Francisco Medical Center, Duke Medical Center
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: G1033683653, G1276011396, G1331000642, G161582775, U.T. SOUTHWESTERN ADULT AIDS CLINICAL TRIALS UNIT, HIV-1 Therapeutics and Drug Resistance, G1840998190, G1939027404, ADULT AIDS CLINICAL TRIALS GROUP, G2239548760, AIDS CLINICAL TRIALS UNIT, G251702431, BIOSYNTHESIS OF MEMBRANE PROTEIN GLYCOLIPID ANCHORS, G2720129059, G273122193, ADULT AIDS CLINICAL TRIALS UNIT, G2941673778, G3206835426, G3285953468, STATISTICAL AND DATA MANAGEMENT CENTER, ADULT THERAPEUTIC CLINICAL TRIALS PROGRAM FOR AIDS, G4122054131, General Clinical Research Center, G4208335746, G5364003616, ADULT ACTG CENTRAL GROUP, ADULT AIDS CLINICAL TRIALS UNIT, ADULT AIDS CLINICAL TRIAL UNIT, G6103943158, G6477019531, COLORADO ADULT AIDS CLINICAL TRIALS UNIT, HAWAII ACTU - ADULT THERAPEUTIC CLINICAL TRIALS PROGRAM, NORTHWESTERN ADULT AIDS CLINICAL TRIALS UNIT, K24 MID-CAREER CLINICAL INVESTIGATOR AWARD, G766489020, AIDS CLINICAL TRIALS UNIT, G7868490553, ADULT AIDS CLINICAL TRIALS UNIT, ADULT THERAPEUTIC CLINICAL TRIALS PROGRAM FOR HIV/AIDS, The University of North Carolina Center for AIDS Research, Center for AIDS Research, Harvard University Center for AIDS Research, MIAMI ADULT AIDS CLINICAL TRIALS GROUP, AACTG, G902161211, G986646304
OpenAlex ID: W83135504