Share this article on:

Selection and fading of resistance mutations in women and infants receiving nevirapine to prevent HIV-1 vertical transmission (HIVNET 012)

Eshleman, Susan H.; Mracna, Martin; Guay, Laura A.; Deseyve, Martinaa; Cunningham, Shawn; Mirochnick, Markb; Musoke, Philippac; Fleming, Thomasd; Fowler, Mary Glenne; Mofenson, Lynne M.f; Mmiro, Francisg; Jackson, J. Brooks

Basic Science

Objective: To examine the emergence and fading of NVP resistance (NVPR) mutations in HIV-1-infected Ugandan women and infants who received single dose NVP to prevent HIV-1 vertical transmission.

Design: We examined NVPR in women and infants who received NVP in the HIVNET 012 clinical trial, including 41 out of 48 women with infected infants, 70 randomly-selected women with uninfected infants, and 33 out of 49 infected infants.

Methods: Plasma HIV-1 was analyzed using the Applied Biosystems ViroSeq HIV-1 Genotyping System.

Results: NVPR mutations were detected in 21 out of 111 (19%) women tested 6–8 weeks after delivery. The rate of NVPR was similar among women whose infants were or were not HIV-1 infected. K103N was the most common mutation detected. NVPR mutations faded from detection within 12–24 months in all 11 evaluable women. High baseline viral load and low baseline CD4 cell count were associated with development of NVPR. NVPR mutations were detected in 11 out of 24 (46%) evaluable infants who were infected by 6–8 weeks of age. The most common NVPR mutation detected in infants was Y181C. Those mutations faded from detection by 12 months of age in all seven evaluable infants. Of nine evaluable infants with late HIV-1 infection, only one had evidence of NVPR.

Conclusions: NVPR was detected more frequently in infants than women following NVP prophylaxis, and different patterns of NVPR mutations were detected in women versus infants. NVPR was detected infrequently in infants with late HIV-1 infection. NVP-resistant HIV-1 faded from detection in women and infants over time.

From the Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland, the aFred Hutchinson Cancer Research Center, Seattle, Washington, the bDepartment of Pediatrics, Boston University, Boston, Massachusetts, USA, the cDepartment of Paediatrics, Makerere University, Kampala, Uganda, the dDepartment of Biostatistics, University of Washington, Seattle, Washington, the eDivision of AIDS, NIAID/NIH, Rockville, the fPediatric, Adolescent, and Maternal AIDS Branch, NICHD/NIH, Rockville, Maryland, USA, and the gDepartment of Obstetrics and Gynaecology, Makerere University, Kampala, Uganda.

Received: 9 March 2001;

revised: 8 June 2001; accepted: 13 June 2001.

Sponsorship: Supported by: (i) the Elizabeth Glaser Pediatric AIDS Foundation; (ii) 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), Department 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 JHU/Makerere Univ. (NOI-AI-35173-417); (iii) 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); (iv) the Pediatric and Adult AIDS Clinical Trials Groups (NIH, Division of AIDS, NIAID); and (v) R29 34348 (NIH, Division of CH/HD).

Requests for reprints to: S. Eshleman, Department of Pathology, The Johns Hopkins Medical Institutions, Ross Building 646, 720 Rutland Avenue, Baltimore, Maryland 21205, USA.

Note: The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.

© 2001 Lippincott Williams & Wilkins, Inc.