AIDS RESEARCH AND HUMAN RETROVIRUSES Volume 23, Number 12, 2007, pp. 1515–1520 © Mary Ann Liebert, Inc. DOI: 10.1089/aid.2007.0025 Persistence of Genotypic Resistance to Nelfinavir among Women Exposed to Prophylactic Antiretroviral Therapy during Pregnancy FABIANA M. KAKEHASI, UNAÍ TUPINAMBÁS, SILVIA CLETO, AGDEMIR ALEIXO, ELISA LIN, VICTOR H. MELO, REGINA A.L.P. AGUIAR, and JORGE A. PINTO ABSTRACT We assessed the development of drug resistance in women exposed to antiretroviral therapy (ART) for pre- vention of mother-to-child transmission (PMTCT) after 24 weeks postpartum in a prospective cohort of HIV- 1-infected women. HIV-1-infected women, who received prophylactic ART during pregnancy, had genotypic resistance testing performed at the start (T1) of and 24 weeks after ART interruption (T2). The women had CD4 counts  250 cells/ml and no AIDS defining conditions. Of the 30 eligible women, the median age was 27 years [25–75% interquartile range (IQR): 21–32] and the median gestational age of ART initiation was 22 weeks (IQR: 19–27): 19 (63.3%) received zidovudine (ZDV) plus lamivudine (3TC) plus nelfinavir (NFV). At entry, most women (96.7%) were asymptomatic (CDC93 A1/A2), with a median CD4 count of 446 (IQR: 353–686) and median viral load (VL) of 8560 copies/ml (IQR: 3,252–19,515). No HIV-1 vertical transmission was observed. HIV subtype B was the most prevalent (70%). The development of new mutations associated with ART resistance was analyzed at T2. NFV resistance was observed in 4 out of 17 (23.5%) patients ex- posed to this drug: two major mutations D30N (1/17) and L90M (1/17) and minor mutations (N88S, 2/17). Mutations on positions 44, 69, and 118 (1/28) were present on reverse transcriptase (RT) analysis. No new nonnucleoside reverse transcriptase inhibitor (NNRTI)-associated mutation was observed. In this cohort, ART regimens were very efficient at blocking HIV vertical transmission. However, the high rate of NFV-resistant mutations observed in the postpartum period indicates the need for discussion of ART choices during preg- nancy and the potential impact on future therapeutic options for these women. Women previously exposed to ART for PMTCT who will start HIV treatment should have genotypic resistance testing performed. 1515 INTRODUCTION S IGNIFICANT DECLINES in HIV-1 mother-to-child transmission (MTCT) rates have been observed with the use of anti- retroviral (ART) regimens in women and their infants. Since 1994, when the use of zidovudine (ZDV) was shown to reduce the risk of MTCT by two-thirds, 1 several other antiretroviral trials with different schemas have been studied and also achieved substantial reductions in perinatal HIV-1 transmis- sion. 2–8 Universal, free of charge access to antiretroviral agents have been provided for treatment and prevention of MTCT (PMTCT) in Brazil since 1995. The currently recommended regimens for women starting treatment during pregnancy are ZDV plus lamivudine (3TC) with either nevirapine (NVP) or nelfinavir (NFV). Women who do not need treatment for their own health discontinue ART after delivery. 9 The risk for emergence of virologic resistance may increase with the use of ART for PMTCT, impacting future treatment options for women and children. Thymidine analogue-associ- ated mutations (TAM) conferring resistance to ZDV can occur in 0–24% when ZDV is used as monotherapy or as part of an- tiretroviral therapy during pregnancy. 10–16 Resistance to 3TC can develop rapidly due to a single point mutation at the re- verse transcriptase (RT) 184 position at rates as high as 39%. 17,18 In addition, despite efficient reduction in vertical transmission, a single dose of NVP was associated with the emergence of resistant mutations in 15–65% of exposed women. 19–24 Published data on the maternal use of highly ac- Maternal and Pediatric AIDS Group, School of Medicine, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.