Drug Susceptibility and Resistance Mutations After First-Line Failure in Resource Limited Settings
Year: 2014
Type: article
Abstract: BACKGROUND: The development of drug resistance to nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) has been associated with baseline human immunodeficiency virus (HIV)-1 RNA level (VL), CD4 cell counts (CD4), subtype, and treatment failure duration. This study describes drug resistance and levels of susceptibility after first-line virologic failure in individuals from Thailand, South Africa, India, Malawi, Tanzania. METHODS: CD4 and VL were captured at AIDs Clinical Trial Group (ACTG) A5230 study entry, a study of lopinavir/ritonavir (LPV/r) monotherapy after first-line virologic failure on an NNRTI regimen. HIV drug-resistance mutation associations with subtype, site, study entry VL, and CD4 were evaluated using Fisher exact and Kruskall-Wallis tests. RESULTS: Of the 207 individuals who were screened for A5230, sequence data were available for 148 individuals. Subtypes observed: subtype C (n = 97, 66%) AE (n = 27, 18%), A1 (n = 12, 8%), and D (n = 10, 7%). Of the 148 individuals, 93% (n = 138) and 96% (n = 142) had at least 1 reverse transcriptase (RT) mutation associated with NRTI and NNRTI resistance, respectively. The number of NRTI mutations was significantly associated with a higher study screening VL and lower study screening CD4 (P < .001). Differences in drug-resistance patterns in both NRTI and NNRTI were observed by site. CONCLUSIONS: The degree of NNRTI and NRTI resistance after first-line virologic failure was associated with higher VL at study entry. Thirty-two percent of individuals remained fully susceptible to etravirine and rilpivirine, protease inhibitor resistance was rare. Some level of susceptibility to NRTI remained; however, VL monitoring and earlier virologic failure detection may result in lower NRTI resistance.
Source: Clinical Infectious Diseases
DOI: 10.1093/cid/ciu314
Authors: C. L. Wallis, E. Aga, H. Ribaudo, S. Saravanan, M. Norton, W. Stevens, N. Kumarasamy, J. Bartlett, D. Katzenstein, on behalf of the A5230 team
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: Bill and Melinda Gates Foundation, Gilead Sciences, Clinton Foundation, ACT Government, Chiang Mai University, National Institutes of Health, U.S. Public Health Service, National Institute of Mental Health, National Institute of Allergy and Infectious Diseases, National Institute of Dental and Craniofacial Research
Awards: G1819583291, G1883683914, G188409452, G2737559749, G374818150, G4553935269, ADULT ACTG CENTRAL GROUP, UCSD Department of Medicine HIV/AIDS Clinical Trials Unit, G599975273, G650174051, G7105083719, G857487509, G9000014264, G9000072212, G9000292181, Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections, AIDS Clinical Trial Group Laboratory Center, Statistical and Data Management Center (SDMC), Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections (ACTG), Thailand HIV/AIDS and Infectious Disease Clinical Trials Unit (THAI CTU), Center for AIDS Research
OpenAlex ID: W1967176501