Journal Article

Association between Detection of HIV-1 DNA Resistance Mutations by a Sensitive Assay at Initiation of Antiretroviral Therapy and Virologic Failure

Gonzague Jourdain, Thor Andrew Wagner, Nicole Ngo-Giang-Huong, Wasna Sirirungsi, Virat Klinbuayaem, Federica Fregonese, Issaren Nantasen, Malee Techapornroong, Guttiga Halue, Ampaipith Nilmanat, Pakorn Wittayapraparat, Veeradet Chalermpolprapa, Panita Pathipvanich, Prapap Yuthavisuthi, Lisa M. Frenkel and Marc Lallemant

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 50, issue 10, pages 1397-1404
Published in print May 2010 | ISSN: 1058-4838
Published online May 2010 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/652148
Association between Detection of HIV-1 DNA Resistance Mutations by a Sensitive Assay at Initiation of Antiretroviral Therapy and Virologic Failure

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Background. Antiretroviral therapy (ART) has become more available throughout the developing world during the past 5 years. The World Health Organization recommends nonnucleoside reverse-transcriptase inhibitor–based regimens as initial ART. However, their efficacy may be compromised by resistance mutations selected by single-dose nevirapine (sdNVP) used to prevent mother-to-child transmission of human immunodeficiency virus (HIV)–1. There is no simple and efficient method to detect such mutations at the initiation of ART.

Methods. One hundred eighty-one women who were participating in a clinical trial to prevent mother-to-child transmission and who started NVP-ART after they had received sdNVP or a placebo were included in the study. One hundred copies of each patient's HIV-1 DNA were tested for NVP-resistance point-mutations (K103N, Y181C, and G190A) with a sensitive oligonucleotide ligation assay that was able to detect mutants even at low concentrations (⩾5% of the viral population). Virologic failure was defined as confirmed plasma HIV-1 RNA >50 copies/mL after 6 to 18 months of NVP-ART.

Results. At initiation of NVP-ART, resistance mutations were identified in 38 (26%) of 148 participants given sdNVP (K103N in 19 [13%], Y181C in 8 [5%], G190A in 28 [19%], and ⩾2 mutations in 15 [10%]), at a median 9.3 months after receipt of sdNVP. The risk of virologic failure was 0.62 (95% confidence interval [CI], 0.46–0.77) in women with ⩾1 resistance mutation, compared with a risk of 0.25 (95% CI, 0.17–0.35) in those without detectable resistance mutations (P < .001). Failure was independently associated with resistance, an interval of <6 months between sdNVP and NVP-ART initiation, and a viral load higher than the median at NVP-ART initiation.

Conclusions. Access to simple and inexpensive assays to detect low concentrations of NVP-resistant HIV-1 DNA before the initiation of ART could help improve the outcome of first-line ART.

Journal Article.  4739 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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