Analysis of nevirapine (NVP) resistance in Ugandan infants who were HIV infected despite receiving single-dose (SD) NVP versus SD NVP plus daily NVP up to 6 weeks of age to prevent HIV vertical transmission

Jessica D. Church, Saad B. Omer, Laura A. Guay, Wei Huang, Jessica Lidstrom, Philippa Musoke, Francis Mmiro, J. Brooks Jackson, Susan H. Eshleman

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46 Scopus citations

Abstract

Background. Single-dose nevirapine (SD NVP) at birth plus NVP prophylaxis for the infant up to 6 weeks of age is superior to SDNVP alone for prevention of vertical transmission of human immunodeficiency virus (HIV) through breastfeeding. We analyzed NVP resistance in HIV-infected Ugandan infants who received either SD NVP or extended NVP prophylaxis. Methods. We tested plasma HIV by using a genotyping assay (ViroSeq; Celera Diagnostics), a phenotypic resistance assay (PhenoSense; Monogram Biosciences), and sensitive point mutation assay (LigAmp, for K103N, Y181C, and G190A). Results. When infants were 6 weeks old, ViroSeq detected NVP resistance in a higher proportion of infants in the extended NVP arm than in the SD NVP arm (21 of 25 [84%] vs. 12 of 24 [50%]; P = .01). Similar results were obtained with LigAmp and PhenoSense. In both study arms, infants who were HIV infected at birth frequently had NVP resistance detected. In contrast, infants in the extended NVP arm who were HIV infected after birth were more likely to have resistance detected at 6 weeks, compared with infants in the SD NVP arm. The use of extended NVP prophylaxis was also associated with detection of NVP resistance by ViroSeq at 6 months (7 of 7 [100%] infants in the extended NVP arm had resistance detected, compared with 1 of 6 [16.7%] infants in the SD NVP arm; P = .005). Conclusions. The use of extended NVP prophylaxis was associated with increased selection for and persistence of NVP resistance in HIV-infected Ugandan infants.

Original languageEnglish (US)
Pages (from-to)1075-1082
Number of pages8
JournalJournal of Infectious Diseases
Volume198
Issue number7
DOIs
StatePublished - Oct 1 2008

Bibliographical note

Funding Information:
Financial support: HIV Prevention Trials Network, sponsored by the National Institutes of Allergy and Infectious Diseases (NIAID), National Institute of Child Health and Human Development (NICHD), National Institute on Drug Abuse, National Institute of Mental Health, and Office of AIDS Research, of the National Institutes of Health, Department of Health and Human Services (grant 5U01AI46745 to J.B.J., 5U01AI48054 to L.A.G., and 1U01AI068613 to S.H.E.); International Maternal Pediatric and Adolescent AIDS Clinical Trials Group (grant 1U01AI068632 to J.B.J., NIAID, NICHD; 3R01AI34235 to J.B.J., NIAID; and 5U01AI038576-07 to A.J.R., NIAID). a Deceased Reprints and correspondence: Susan Eshleman, MD, PhD, Dept. of Pathology, The Johns Hopkins Medical Institutions, Ross Bldg. 646, 720 Rutland Ave., Baltimore, MD 21205 (seshlem@jhmi.edu).

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