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

TitleDrug susceptibility and resistance mutations after first-line failure in resource limited settings.
Publication TypeJournal Article
Year of Publication2014
AuthorsWallis CL, Aga E, Ribaudo H, Saravanan S, Norton M, Stevens W, Kumarasamy N, Bartlett J, Katzenstein D
Corporate AuthorsA5230 team
JournalClin Infect Dis
Volume59
Issue5
Pagination706-15
Date Published2014 Sep 1
ISSN1537-6591
KeywordsAdult, Anti-HIV Agents, CD4 Lymphocyte Count, Drug Resistance, Viral, Female, Health Resources, HIV Infections, HIV-1, Humans, India, Lopinavir, Malawi, Male, Middle Aged, Mutation Rate, Pilot Projects, Pyridazines, Reverse Transcriptase Inhibitors, Ritonavir, South Africa, Tanzania, Thailand, Treatment Failure, Young Adult
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.

DOI10.1093/cid/ciu314
Alternate JournalClin. Infect. Dis.
PubMed ID24795328
PubMed Central IDPMC4148601
Grant ListAI068634 / AI / NIAID NIH HHS / United States
U01069484 / / PHS HHS / United States
U01AI068636 / AI / NIAID NIH HHS / United States
U01AI069432 / AI / NIAID NIH HHS / United States
U01AI069518 / AI / NIAID NIH HHS / United States
U01AI38858 / AI / NIAID NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI069399 / AI / NIAID NIH HHS / United States
UM1 AI069432 / AI / NIAID NIH HHS / United States
UM1 AI106701 / AI / NIAID NIH HHS / United States