To compare the number and type of nevirapine (NVP) resistance mutations detected in Ugandan women with subtype A vs. D HIV-1 infection after single-dose NVP prophylaxis.
In the HIVNET 012 trial, a higher rate of NVP resistance (NVPR) was seen in women with subtype D than A after single-dose NVP. In this study, the number and type of NVPR mutations detected 6–8 weeks after NVP were compared in women with subtypes A vs. D.
Plasma samples were available for 282 (92%) of 306 women who received NVP in HIVNET 012. Samples were analyzed with the ViroSeq HIV-1 Genotyping System (Applied Biosystems, Foster City, CA). Subtyping was performed by phylogenetic analysis of pol region sequences.
Results were obtained for 279 women, including 147 with subtype A, 98 with subtype D, 6 with subtype C, and 28 with recombinant HIV-1. NVPR mutations were detected in 70 (25%) of 279 women. NVPR was more common in women with subtype D vs. A (35.7 vs. 19%, P = 0.0035). Complex patterns of NVPR mutations were detected in both subtypes. Among women with NVPR, 43% of women with subtype A and 46% of women with subtype D had ≥2 NVPR mutations. The mean number and pattern of NVPR mutations detected in women with subtypes A and D were similar.
This study confirms a higher rate of NVPR in women with subtype D than A and further defines the pattern of NVPR mutations that emerge 6–8 weeks after single-dose NVP prophylaxis in these subtypes.
From *Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD; †Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, WA; ‡Department of Biostatistics, University of Washington, Seattle; and §Departments of Paediatrics and ¶Obstetrics and Gynaecology, Makerere University, Kampala, Uganda.
Received for publication July 14, 2003; accepted October 28, 2003.
This work was supported by (1) the HIV Network for Prevention Trials (HIVNET) and the US National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Dept. of Health and Human Services (DHHS), through contract N01-AI-35173 with Family Health International, contract N01-AI-45200 with Fred Hutchinson Cancer Research Center, and subcontracts with Johns Hopkins University and 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); and (4) R01-HD-42965-01.
Dr. Jackson and Dr. Guay have received honoraria and travel expenses for invited talks partially sponsored by Boehringer Ingelheim. Dr. Eshleman has received research support from Applied Biosystems (former manufacturer of the ViroSeq kits) and Celera Diagnostics (current manufacturer of the ViroSeq kits). She has also received honoria and travel expenses from Abbott Laboratories (distributor of the ViroSeq kits) for talks related to HIV genotyping.
Reprints: Susan Eshleman, Department of Pathology, The Johns Hopkins Medical Institutions, Ross Bldg. 646, 720 Rutland Ave., Baltimore, MD 21205 (e-mail: email@example.com).