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Women exposed to single-dose nevirapine in successive pregnancies: effectiveness and nonnucleoside reverse transcriptase inhibitor resistance

Martinson, Neil Aa,b; Morris, Lynnc; Johnson, Jeffreyd; Gray, Glenda Eb; Pillay, Visvac; Ledwaba, Johannac; Dhlamini, Pulengb; Cohen, Sarahc; Puren, Adrianc; Steyn, Janb; Heneine, Walidd; McIntyre, James Ab

doi: 10.1097/QAD.0b013e328323ad49
Clinical Science

Objective: To assess the impact of prior exposure to single-dose nevirapine (sdNVP) on mother-to-child transmission and genotypic resistance in HIV-infected women.

Design: Prospective study of 120 women exposed to the HIVNET 012 sdNVP regimen in two successive pregnancies and 240 antiretroviral (ARV)-naïve, multiparous women who received sdNVP for the first time.

Results: One hundred and eight of 120 and 193 of 240 women returned for a postpartum visit by 6 weeks. HIV-1 was detected in 11.1% (95% confidence interval = 5.9–18.6) of the infants of women previously exposed to sdNVP and 4.2% (95% confidence interval = 1.3–7.0) of those exposed for the first time (P = 0.028). Rates of maternal HIV-1 genotypic resistance at 6 weeks postdelivery were 37.5% and 46.4%, respectively (P = 0.119). Sensitive mutation-specific real-time PCR testing found three of 12 previously exposed women who transmitted HIV-1 to their infants had either K103N or Y181C at baseline compared with one of eight ARV-naïve, transmitting women who had Y181C. None of 40 randomly selected nontransmitting women from either group had detectable NVP resistance mutations prior to sdNVP exposure.

Conclusion: This study shows that effectiveness of sdNVP may be compromised by prior exposure to sdNVP, although the increase in transmission rate after prior exposure could not be explained by the detection of NVP resistance mutations prior to re-exposure as measured both by standard genotyping and highly sensitive allele-specific PCR assays. Furthermore, transmission rates of women with prior exposure were not higher than those reported elsewhere.

aJohns Hopkins University School of Medicine, Baltimore, Maryland, USA

bPerinatal HIV Research Unit, University of the Witwatersrand, South Africa

cNational Institute for Communicable Diseases, Johannesburg, South Africa

dDivision of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

Received 5 June, 2008

Revised 11 November, 2008

Accepted 21 November, 2008

Correspondence to Neil Martinson, Perinatal HIV Research Unit, PO Box 114, Diepkloof, Johannesburg 1864, South Africa. Tel: +27 119899700; fax: +27 119383973; e-mail: neil1.martinson@gmail.com

© 2009 Lippincott Williams & Wilkins, Inc.