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Distinct Patterns of Emergence and Fading of K103N and Y181C in Women With Subtype A vs. D After Single-Dose Nevirapine: HIVNET 012

Eshleman, Susan H MD, PhD*; Guay, Laura A MD*; Wang, Jing MS; Mwatha, Anthony MS; Brown, Elizabeth R PhD†‡; Musoke, Philippa MBChB§; Mmiro, Francis MBChB§; Jackson, J Brooks MD, MBA*

JAIDS Journal of Acquired Immune Deficiency Syndromes: September 1st, 2005 - Volume 40 - Issue 1 - p 24-29
doi: 10.1097/01.qai.0000174656.71276.d6
Clinical Science

Background: The HIVNET 012 trial in Uganda demonstrated that single-dose nevirapine (NVP) can prevent HIV-1 mother-to-child transmission. NVP resistance (NVPR) mutations were detected in 25% of women 6 to 8 weeks after NVP, with a higher rate of NVPR in women with subtype D than A. This study examined emergence and fading of specific NVPR mutations in women with these subtypes.

Methods: Plasma HIV-1 was analyzed with the ViroSeq genotyping system (Celera Diagnostics, Alameda, CA). Genotypes were obtained from paired samples collected 7 days and 6 to 8 weeks after NVP from 140 women, 83 with subtype A and 57 with subtype D.

Results: The rate of NVPR was similar in women with subtype A vs. D at 7 days but was higher in subtype D than A at 6 to 8 weeks. The higher rate of NVPR in subtype D was explained by at least 2 factors: Y181C faded from detection at a greater rate in women with subtype A (odds ratio = 3.06; 95% CI, 1.04, 8.90) and K103N accumulated at a greater rate in women with subtype D (odds ratio = 1.74; 95% CI, 0.62, 4.87).

Conclusions: HIV-1 subtype influences selection and fading of HIV-1 variants with specific drug resistance mutations after antiretroviral drug exposure.

From *The Johns Hopkins Medical Institutions, Baltimore, MD; †Fred Hutchinson Cancer Research Center, Seattle, WA; ‡University of Washington, Seattle, WA; and §Makerere University, Kampala, Uganda.

Received for publication January 13, 2004; accepted June 10, 2005.

Supported by (1) the HIV Network for Prevention Trials (HIVNET) and sponsored by the US National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Dept. of Health and Human Services (DHHS), through contracts with Family Health International (N01-AI-35173 and Fred Hutchinson Cancer Research Center (N01-AI-45200) and a subcontract with Makerere University (NOI-AI-35173-417); (2) the HIV Prevention Trials Network (HPTN) sponsored by the NIAID, National Institutes of Child Health and Human Development (NICH/HD), National Institute on Drug Abuse, National Institute of Mental Health, and Office of AIDS Research, of the NIH, DHHS (U01-AI-46745 and U01-AI-48054); (3) the Adult AIDS Clinical Trials Groups (NIH, Division of AIDS, NIAID, U01-AI-38858); and (4) R01-HD042965-01.

Reprints: Susan Eshleman, Department of Pathology, The Johns Hopkins Medical Institutions, Ross Bldg. 646, 720 Rutland Ave., Baltimore, MD 21205 (e-mail: seshlem@jhmi.edu).

© 2005 Lippincott Williams & Wilkins, Inc.