title: Comparison of nevirapine (NVP) resistance in Ugandan women 7 days vs. 6-8 weeks after single-dose nvp prophylaxis: HIVNET 012.
abstract: We compared nevirapine (NVP) resistance (NVPR) mutations in maternal plasma 7 days vs. 6-8 weeks after single-dose NVP prophylaxis. In the HIVNET 012 trial, Ugandan women received a single dose of NVP in labor for prevention of HIV-1 mother-to-child transmission. NVPR mutations were detected in 70 (25%) of 279 women 6-8 weeks after NVP. Samples collected 7 days after NVP were analyzed from a subset of those 279 women. Genotyping was performed with the ViroSeq HIV-1 Genotyping System. NVPR was analyzed using paired samples from 7 days and 6-8 weeks after NVP. Sixty-five women had genotyping results obtained for samples collected at both 7 days and 6-8 weeks post-NVP. Twenty-one (32%) of those women had NVPR mutations detected in one or both samples. This included three women with NVPR at 7 days only, seven with NVPR at 6-8 weeks only, and 11 with NVPR at both time points. Eight women had >1 NVPR mutation detected 7 days after NVP. Y181C was the most common NVPR mutation detected at 7 days, whereas K103N was the most common NVPR mutation detected at 6-8 weeks. We conclude that NVPR may be detected in women as early as 7 days after single-dose NVP. Complex patterns of NVPR are detected in some women. The Y181C NVPR mutation often fades from detection by 6-8 weeks. In contrast, the K103N mutation emerges more slowly, but often remains detectable 6-8 weeks after NVP.
authors.affiliation: Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA. seshlem@jhmi.edu
authors.forename: S H
authors.initials: SH
authors.lastname: Eshleman
authors.forename: L A
authors.initials: LA
authors.lastname: Guay
authors.forename: A
authors.initials: A
authors.lastname: Mwatha
authors.forename: S P
authors.initials: SP
authors.lastname: Cunningham
authors.forename: E R
authors.initials: ER
authors.lastname: Brown
authors.forename: P
authors.initials: P
authors.lastname: Musoke
authors.forename: F
authors.initials: F
authors.lastname: Mmiro
authors.forename: J B
authors.initials: JB
authors.lastname: Jackson
mesh_terms: D019943:Amino Acid Substitution; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000517:prevention & control / Q000635:transmission / Q000821:virology*; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D008969:Molecular Sequence Data; D009154:Mutation; D019829:Nevirapine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D013997:Time Factors; D014454:Uganda; D014764:Viral Proteins / Q000235:genetics
chemical_list: D019380:Anti-HIV Agents; D014764:Viral Proteins; D019829:Nevirapine; D054303:HIV Reverse Transcriptase; D016333:HIV Protease