Pretreatment HIV Drug Resistance and HIV-1 Subtype C Are Independently Associated With Virologic Failure: Results From the Multinational PEARLS (ACTG A5175) Clinical Trial
Year: 2015
Type: article
Abstract: BACKGROUND: Evaluation of pretreatment HIV genotyping is needed globally to guide treatment programs. We examined the association of pretreatment (baseline) drug resistance and subtype with virologic failure in a multinational, randomized clinical trial that evaluated 3 antiretroviral treatment (ART) regimens and included resource-limited setting sites. METHODS: Pol genotyping was performed in a nested case-cohort study including 270 randomly sampled participants (subcohort), and 218 additional participants failing ART (case group). Failure was defined as confirmed viral load (VL) >1000 copies/mL. Cox proportional hazards models estimated resistance-failure association. RESULTS: In the representative subcohort (261/270 participants with genotypes; 44% women; median age, 35 years; median CD4 cell count, 151 cells/µL; median VL, 5.0 log10 copies/mL; 58% non-B subtypes), baseline resistance occurred in 4.2%, evenly distributed among treatment arms and subtypes. In the subcohort and case groups combined (466/488 participants with genotypes), used to examine the association between resistance and treatment failure, baseline resistance occurred in 7.1% (9.4% with failure, 4.3% without). Baseline resistance was significantly associated with shorter time to virologic failure (hazard ratio [HR], 2.03; P = .035), and after adjusting for sex, treatment arm, sex-treatment arm interaction, pretreatment CD4 cell count, baseline VL, and subtype, was still independently associated (HR, 2.1; P = .05). Compared with subtype B, subtype C infection was associated with higher failure risk (HR, 1.57; 95% confidence interval [CI], 1.04-2.35), whereas non-B/C subtype infection was associated with longer time to failure (HR, 0.47; 95% CI, .22-.98). CONCLUSIONS: In this global clinical trial, pretreatment resistance and HIV-1 subtype were independently associated with virologic failure. Pretreatment genotyping should be considered whenever feasible. CLINICAL TRIALS REGISTRATION: NCT00084136.
Source: Clinical Infectious Diseases
DOI: 10.1093/cid/civ102
Authors: Rami Kantor, Laura Smeaton, Saran Vardhanabhuti, Sarah E. Hudelson, Carol L. Wallis, Srikanth Tripathy, Mariza G. Morgado, Shanmugham Saravanan, Pachamuthu Balakrishnan, Marissa Reitsma, Stephen Hart, John W. Mellors, Elias Halvas, Beatriz Grinsztejn, Mina C. Hosseinipour, Johnstone Kumwenda, Alberto La Rosa, Umesh G. Lalloo, Javier R. Lama, Mohammed Rassool, Breno R. Santos, Khuanchai Supparatpinyo, James Hakim, Timothy Flanigan, Nagalingeswaran Kumarasamy, Thomas B. Campbell, Susan H. Eshleman
Institutions: Brown University, Harvard University, Johns Hopkins University, Johns Hopkins Medicine, Lancet Laboratories, National AIDS Research Institute, Instituto Oswaldo Cruz, YR Gaitonde Centre for AIDS Research and Education, Frontier Science & Technology Research Foundation, Inc., University of Pittsburgh, Fundação Oswaldo Cruz, University of Malawi, Asociación Civil Impacta Salud y Educación, University of the Witwatersrand, Helen Joseph Hospital, Grupo Hospitalar Conceição, Chiang Mai University, University of Zimbabwe, University of Colorado Anschutz, University of Colorado Denver
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: G1819583291, HIV-1 Drug Resistance in Different Subtypes, G7105083719, G9000292181, UZ-UCSF CTU, Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections, Providence/Boston Center for AIDS Research (CFAR), The FIOCRUZ Therapeutic and Prevention HIV/AIDS Clinical Trials Unit., The Johns Hopkins University-Blantyre Clinical Trials Unit, AIDS Clinical Trial Group Laboratory Center, Statistical and Data Management Center (SDMC), Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections (ACTG), The University of North Carolina Center for AIDS Research, Pitt-Ohio State Clinical Trials Unit, LC: HIV PREVENTION TRIALS NETWORK, University of North Carolina Global HIV Prevention and Treatment Clinical Trials Unit, Thailand HIV/AIDS and Infectious Disease Clinical Trials Unit (THAI CTU), UCLA AIDS Prevention and Treatment Clinical Trials Unit, Wits HIV Research Group CLINICAL TRIAL UNIT (CTU) reapplication
OpenAlex ID: W2126014281