Journal Article

Persistent Minority K103N Mutations among Women Exposed to Single-Dose Nevirapine and Virologic Response to Nonnucleoside Reverse-Transcriptase Inhibitor–Based Therapy

Ashraf Coovadia, Gillian Hunt, Elaine J. Abrams, Gayle Sherman, Tammy Meyers, Gill Barry, Eloise Malan, Belinda Marais, Renate Stehlau, Johanna Ledwaba, Scott M. Hammer, Lynn Morris and Louise Kuhn

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 48, issue 4, pages 462-472
Published in print February 2009 | ISSN: 1058-4838
Published online February 2009 | e-ISSN: 1537-6591 | DOI: https://dx.doi.org/10.1086/596486
Persistent Minority K103N Mutations among Women Exposed to Single-Dose Nevirapine and Virologic Response to Nonnucleoside Reverse-Transcriptase Inhibitor–Based Therapy

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Objective. We investigated whether there are long-lasting effects of exposure to single-dose nevirapine (sdNVP) treatment on virologic response to nonnucleoside reverse-transcriptase inhibitor (NNRTI)–based therapy among human immunodeficiency virus (HIV)–infected women.

Methods. An observational epidemiologic study was conducted in Johannesburg, South Africa. Initial and sustained virologic response to NNRTI-based therapy was compared between 94 HIV-infected women who had received sdNVP 18–36 months earlier and 60 unexposed, HIV-infected women who had been pregnant 12–36 months earlier. Viral load was measured every 4 weeks up to week 24 and then every 12 weeks up to week 78. Time to viral suppression (viral load, <50 copies/mL) and confirmed rebound in the viral load (viral load, >400 copies/mL) were compared. Drug resistance was assessed using K103N allele–specific real-time polymerase chain reaction assay and population sequencing.

Results. Almost all women (97.5% of sdNVP-exposed women and 91.3% of sdNVP-unexposed women; P=.21) achieved viral suppression by week 24, and similar percentages of sdNVP-exposed and -unexposed women (19.4% and 15.1%, respectively) experienced viral rebound within 78 weeks after treatment (P=.57). K103N was detected with the K103N allele–specific real-time polymerase chain reaction assay among sdNVP-exposed and -unexposed women before treatment; detection was strongly predictive of inadequate viral response: 60.9% of women for whom K103N was detected in either viral RNA or DNA did not experience viral suppression or experienced viral rebound, compared with 15.1% of women for whom K103N was not detected (P<.001). After treatment, the M184V mutation occurred less frequently among sdNVP-exposed women than among sdNVP-unexposed women, but the frequency of NNRTI-associated mutations was similar between these groups of women with inadequate virologic response.

Conclusions. Exposure to sdNVP in the prior 18–36 months was not associated with a reduced likelihood of achieving and sustaining viral suppression while receiving NNRTI-based therapy. However, women with minority K103N mutations before treatment had a reduced durability of virologic suppression.

Journal Article.  4703 words.  Illustrated.

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

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