Drug susceptibility and resistance mutations after first-line failure in resource limited settings.

Journal Article (Journal Article;Multicenter Study)

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.

Full Text

Duke Authors

Cited Authors

  • Wallis, CL; Aga, E; Ribaudo, H; Saravanan, S; Norton, M; Stevens, W; Kumarasamy, N; Bartlett, J; Katzenstein, D; A5230 team,

Published Date

  • September 1, 2014

Published In

Volume / Issue

  • 59 / 5

Start / End Page

  • 706 - 715

PubMed ID

  • 24795328

Pubmed Central ID

  • PMC4148601

Electronic International Standard Serial Number (EISSN)

  • 1537-6591

Digital Object Identifier (DOI)

  • 10.1093/cid/ciu314


  • eng

Conference Location

  • United States