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Clin Infect Dis. 2014 Sep 1;59(5):706-15. doi: 10.1093/cid/ciu314. Epub 2014 May 1.

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

Author information

1
Lancet Laboratories, Johannesburg, South Africa.
2
Statistical Data Analysis Center, Harvard School of Public Health, Boston, Massachusetts.
3
YRG Centre for AIDS Research and Education, Chennai, India.
4
Medical Affairs Therapeutic Area, Virology and Nanotechnology, Global Pharmaceutical Research and Development, AbbVie, Chicago, Illinois.
5
University of Witwatersrand, Johannesburg, South Africa.
6
Duke Global Health Institute, Duke University, Durham, North Carolina Kilimanjaro Christian Medical Centre, Moshi, Tanzania.
7
Division of Infectious Diseases, Stanford University, Palo Alto, California.

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.

KEYWORDS:

HIV-1 drug resistance; first-line failure; nonsubtype B; resource limited setting

PMID:
24795328
PMCID:
PMC4148601
DOI:
10.1093/cid/ciu314
[Indexed for MEDLINE]
Free PMC Article

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