title: Greater suppression of nevirapine resistance with 21- vs 7-day antiretroviral regimens after intrapartum single-dose nevirapine for prevention of mother-to-child transmission of HIV.
abstract: BACKGROUND
  Nevirapine (NVP) resistance emerges in up to 70% of women exposed to single-dose (sd) NVP for prevention of mother-to-child transmission of human immunodeficiency virus (HIV).
  
  
  METHODS
  HIV-infected pregnant women were randomized to receive sdNVP and either zidovudine/lamivudine (3TC), tenofovir/emtricitabine (FTC), or lopinavir/ritonavir for either 7 or 21 days. The primary endpoint was the emergence of new NVP resistance mutations as detected by standard population genotype at 2 and 6 weeks after treatment. Low-frequency NVP- or 3TC/FTC-resistant mutants at codons 103, 181, and 184 were sought using allele-specific polymerase chain reaction (ASP).
  
  
  RESULTS
  Among 484 women randomized, 422 (87%) received study treatment. Four hundred twelve (98%) women had primary endpoint results available; of these, 5 (1.2%) had new NVP resistance detected by population genotype: 4 of 215 in the 7-day arms (1.9%; K103N in 4 women with Y181C, Y188C, or G190A in 3 of 4) and 1 of 197 (0.5%; V108I) in the 21-day arms (P = .37). Among women with ASP results, new NVP resistance mutations emerged significantly more often in the 7-day arms (13/74 [18%]) than in the 21-day arms (3/66 [5%], P = .019). 3TC/FTC-resistant mutants (M184V/I) emerged infrequently (7/134 [5%]), and their occurrence did not differ by arm.
  
  
  CONCLUSIONS
  Three short-term antiretroviral strategies, begun simultaneously with the administration of sdNVP, resulted in a low rate (1.2%) of new NVP-resistance mutations when assessed at 2 and 6 weeks following completion of study treatment by standard genotype. ASP revealed that 21-day regimens were significantly better than 7-day regimens at preventing the emergence of minor NVP resistance variants. Clinical Trials Registration.NCT00099632.
authors.affiliation: Department of Medicine, University of Pittsburgh, PA, USA. mcmahond@pitt.edu
authors.forename: Deborah K
authors.initials: DK
authors.lastname: McMahon
authors.forename: Lu
authors.initials: L
authors.lastname: Zheng
authors.forename: Jane
authors.initials: J
authors.lastname: Hitti
authors.forename: Ellen S
authors.initials: ES
authors.lastname: Chan
authors.forename: Elias K
authors.initials: EK
authors.lastname: Halvas
authors.forename: Feiyu
authors.initials: F
authors.lastname: Hong
authors.forename: Joseph
authors.initials: J
authors.lastname: Kabanda
authors.forename: Frank
authors.initials: F
authors.lastname: Taulo
authors.forename: Nagalingeswaran
authors.initials: N
authors.lastname: Kumarasamy
authors.forename: Jerry
authors.initials: J
authors.lastname: Bonhomme
authors.forename: Carole L
authors.initials: CL
authors.lastname: Wallis
authors.forename: Karin L
authors.initials: KL
authors.lastname: Klingman
authors.forename: Michael D
authors.initials: MD
authors.lastname: Hughes
authors.forename: John W
authors.initials: JW
authors.lastname: Mellors
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D024882:Drug Resistance, Viral; D005260:Female; D006678:HIV / Q000187:drug effects / Q000302:isolation & purification; D015658:HIV Infections / Q000188:drug therapy* / Q000517:prevention & control / Q000821:virology; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D019829:Nevirapine / Q000008:administration & dosage*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy* / Q000821:virology; D011446:Prospective Studies; D013997:Time Factors; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D019829:Nevirapine