title: Minor drug-resistant HIV type-1 variants in breast milk and plasma of HIV type-1-infected Ugandan women after nevirapine single-dose prophylaxis.
abstract: BACKGROUND
  Nevirapine single-dose (NVP-SD) reduces mother-to-child transmission of HIV type-1 (HIV-1), but frequently induces resistance mutations in the HIV-1 genome. Little is known about drug-resistant HIV-1 variants in the breast milk of women who have taken NVP-SD.
  
  
  METHODS
  Blood and breast milk samples of 39 HIV-1-infected Ugandan women were taken 6-12 weeks after NVP-SD intake. Samples were analysed by population sequencing and allele-specific real-time PCR (AS-PCR) with detection limits for NVP-resistant HIV-1 variants (K103N and Y181C) of < 1% of the total viral population.
  
  
  RESULTS
  AS-PCR results for both plasma and breast milk were obtained for 19 women who constituted the final study group (HIV-1 subtype frequencies were A1 n = 11, D n = 5, G n = 2 and C n = 1). A total of 7 (37%) and 10 (53%) women carried NVP-resistant virus in breast milk and plasma, respectively. Overall, 71% (5/7) women with NVP-resistant HIV-1 in breast milk displayed >1 drug-resistant variant. Resistance in breast milk was higher at week 6 (6/13 samples [46%]) compared with week 12 (1/6 samples [17%]). In total, 10 drug-resistant populations harbouring the K103N and/or Y181C mutation were detected in the 19 breast milk samples; 7 (70%) were caused by resistant minorities (< 5% of the total HIV-1 population). In the four women with drug-resistant virus in both plasma and breast milk, the mutation patterns differed between the two compartments.
  
  
  CONCLUSIONS
  Minor populations of drug-resistant HIV-1 were frequently found in breast milk of Ugandan women after exposure to NVP-SD. Further studies need to explore the role of minor drug-resistant variants in the postnatal transmission of (resistant) HIV-1.
authors.affiliation: Institute of Tropical Medicine and International Health, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Pilger
authors.forename: Andrea
authors.initials: A
authors.lastname: Hauser
authors.forename: Claudia
authors.initials: C
authors.lastname: Kuecherer
authors.forename: Kizito
authors.initials: K
authors.lastname: Mugenyi
authors.forename: Rose
authors.initials: R
authors.lastname: Kabasinguzi
authors.forename: Sybille
authors.initials: S
authors.lastname: Somogyi
authors.forename: Gundel
authors.initials: G
authors.lastname: Harms
authors.forename: Andrea
authors.initials: A
authors.lastname: Kunz
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D015331:Cohort Studies; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics / Q000517:prevention & control* / Q000635:transmission / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D008895:Milk, Human / Q000737:chemistry / Q000187:drug effects / Q000821:virology; D009154:Mutation / Q000187:drug effects; D019829:Nevirapine / Q000008:administration & dosage* / Q000627:therapeutic use; D056990:Post-Exposure Prophylaxis; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy / Q000517:prevention & control / Q000821:virology; D014454:Uganda
chemical_list: D019380:Anti-HIV Agents; D019829:Nevirapine