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

Published

Journal Article

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.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.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.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 2014

Published In

Volume / Issue

  • 59 / 5

Start / End Page

  • 706 - 715

PubMed ID

  • 24795328

Pubmed Central ID

  • 24795328

Electronic International Standard Serial Number (EISSN)

  • 1537-6591

International Standard Serial Number (ISSN)

  • 1058-4838

Digital Object Identifier (DOI)

  • 10.1093/cid/ciu314

Language

  • eng