title: 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.
abstract: BACKGROUND
  Single-dose nevirapine (SD NVP) at birth plus NVP prophylaxis for the infant up to 6 weeks of age is superior to SD NVP 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.
authors.affiliation: School of Medicine, Johns Hopkins University, Baltimore, Maryland 21205, USA.
authors.forename: Jessica D
authors.initials: JD
authors.lastname: Church
authors.forename: Saad B
authors.initials: SB
authors.lastname: Omer
authors.forename: Laura A
authors.initials: LA
authors.lastname: Guay
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Jessica
authors.initials: J
authors.lastname: Lidstrom
authors.forename: Philippa
authors.initials: P
authors.lastname: Musoke
authors.forename: Francis
authors.initials: F
authors.lastname: Mmiro
authors.forename: J Brooks
authors.initials: JB
authors.lastname: Jackson
authors.forename: Susan H
authors.initials: SH
authors.lastname: Eshleman
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D006678:HIV / Q000235:genetics; D015658:HIV Infections / Q000517:prevention & control / Q000635:transmission*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D009154:Mutation; D019829:Nevirapine / Q000627:therapeutic use*; D010641:Phenotype
chemical_list: D019380:Anti-HIV Agents; D019829:Nevirapine