title: Persistence of genotypic resistance to nelfinavir among women exposed to prophylactic antiretroviral therapy during pregnancy.
abstract: We assessed the development of drug resistance in women exposed to antiretroviral therapy (ART) for prevention 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 exposed 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 pregnancy 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.
authors.affiliation: Maternal and Pediatric AIDS Group, School of Medicine, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Fabiana M
authors.initials: FM
authors.lastname: Kakehasi
authors.forename: Unaí
authors.initials: U
authors.lastname: Tupinambás
authors.forename: Silvia
authors.initials: S
authors.lastname: Cleto
authors.forename: Agdemir
authors.initials: A
authors.lastname: Aleixo
authors.forename: Elisa
authors.initials: E
authors.lastname: Lin
authors.forename: Victor H
authors.initials: VH
authors.lastname: Melo
authors.forename: Regina A L P
authors.initials: RA
authors.lastname: Aguiar
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Pinto
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000517:prevention & control / Q000635:transmission / Q000821:virology; D016333:HIV Protease / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D019259:Lamivudine / Q000627:therapeutic use; D009154:Mutation; D019888:Nelfinavir / Q000494:pharmacology / Q000627:therapeutic use*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D019562:Viral Load; D015215:Zidovudine / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D054303:HIV Reverse Transcriptase; D016333:HIV Protease; D019888:Nelfinavir