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. 2012;7(3):e32144.
doi: 10.1371/journal.pone.0032144. Epub 2012 Mar 13.

Virologic failure of protease inhibitor-based second-line antiretroviral therapy without resistance in a large HIV treatment program in South Africa

Julie H Levison  1 , Catherine Orrell, Sébastien Gallien, Daniel R Kuritzkes, Naishin Fu, Elena Losina, Kenneth A Freedberg, Robin Wood
Affiliations

Virologic failure of protease inhibitor-based second-line antiretroviral therapy without resistance in a large HIV treatment program in South Africa

Julie H Levison et al. PLoS One. 2012.

Abstract

Background: We investigated the prevalence of wild-type virus (no major drug resistance) and drug resistance mutations at second-line antiretroviral treatment (ART) failure in a large HIV treatment program in South Africa.

Methodology/ principal findings: HIV-infected patients ≥ 15 years of age who had failed protease inhibitor (PI)-based second-line ART (2 consecutive HIV RNA tests >1000 copies/ml on lopinavir/ritonavir, didanosine, and zidovudine) were identified retrospectively. Patients with virologic failure were continued on second-line ART. Genotypic testing for drug resistance was performed on frozen plasma samples obtained closest to and after the date of laboratory confirmed second-line ART failure. Of 322 HIV-infected patients on second-line ART, 43 were adults with confirmed virologic failure, and 33 had available plasma for viral sequencing. HIV-1 RNA subtype C predominated (n = 32, 97%). Mean duration on ART (SD) prior to initiation of second-line ART was 23 (17) months, and time from second-line ART initiation to failure was 10 (9) months. Plasma samples were obtained 7(9) months from confirmed failure. At second-line failure, 22 patients (67%) had wild-type virus. There was no major resistance to PIs found. Eleven of 33 patients had a second plasma sample taken 8 (5.5) months after the first. Median HIV-1 RNA and the genotypic resistance profile were unchanged.

Conclusions/ significance: Most patients who failed second-line ART had wild-type virus. We did not observe evolution of resistance despite continuation of PI-based ART after failure. Interventions that successfully improve adherence could allow patients to continue to benefit from second-line ART therapy even after initial failure.

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Conflict of interest statement

Competing Interests: The authors have read the journal's policy and have the following competing interest: DRK is a consultant to and has received honoraria or research support from Abbott, Boehringer Ingelheim, Gilead, GlaxoSmithKline, Merck and ViiV. This does not alter the authors' adherence to all the PloS ONE policies on sharing data and materials. All other authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Study flow diagram.
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