title: Nevirapine resistance and breast-milk HIV transmission: effects of single and extended-dose nevirapine prophylaxis in subtype C HIV-infected infants.
abstract: BACKGROUND
  Daily nevirapine (NVP) prophylaxis to HIV-exposed infants significantly reduces breast-milk HIV transmission. We assessed NVP-resistance in Indian infants enrolled in the "six-week extended-dose nevirapine" (SWEN) trial who received single-dose NVP (SD-NVP) or SWEN for prevention of breast-milk HIV transmission but who also acquired subtype C HIV infection during the first year of life.
  
  
  RESULTS
  Standard population sequencing and cloning for viral subpopulations present at > or =5% frequency were used to determine HIV genotypes from 94% of the 79 infected Indian infants studied. Timing of infection was defined based on when an infant's blood sample first tested positive for HIV DNA. SWEN-exposed infants diagnosed with HIV by six weeks of age had a significantly higher prevalence of NVP-resistance than those who received SD-NVP, by both standard population sequencing (92% of 12 vs. 38% of 29; p = 0.002) and low frequency clonal analysis (92% of 12 vs. 59% of 29; p = 0.06). Likelihood of infection with NVP-resistant HIV through breast-milk among infants infected after age six weeks was substantial, but prevalence of NVP-resistance did not differ among SWEN or SD-NVP exposed infants by standard population sequencing (15% of 13 vs. 15% of 20; p = 1.00) and clonal analysis (31% of 13 vs. 40% of 20; p = 0.72). Types of NVP-resistance mutations and patterns of persistence at one year of age were similar between the two groups. NVP-resistance mutations did differ by timing of HIV infection; the Y181C variant was predominant among infants diagnosed in the first six weeks of life, compared to Y188C/H during late breast-milk transmission.
  
  
  CONCLUSIONS
  Use of SWEN to prevent breast-milk HIV transmission carries a high likelihood of resistance if infection occurs in the first six weeks of life. Moreover, there was a continued risk of transmission of NVP-resistant HIV through breastfeeding during the first year of life, but did not differ between SD-NVP and SWEN groups. As with SD-NVP, the value of preventing HIV infection in a large number of infants should be considered alongside the high risk of resistance associated with extended NVP prophylaxis.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00061321.
authors.affiliation: Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Anitha
authors.initials: A
authors.lastname: Moorthy
authors.forename: Amita
authors.initials: A
authors.lastname: Gupta
authors.forename: Ramesh
authors.initials: R
authors.lastname: Bhosale
authors.forename: Srikanth
authors.initials: S
authors.lastname: Tripathy
authors.forename: Jayagowri
authors.initials: J
authors.lastname: Sastry
authors.forename: Smita
authors.initials: S
authors.lastname: Kulkarni
authors.forename: Madhuri
authors.initials: M
authors.lastname: Thakar
authors.forename: Renu
authors.initials: R
authors.lastname: Bharadwaj
authors.forename: Anju
authors.initials: A
authors.lastname: Kagal
authors.forename: Arvind V
authors.initials: AV
authors.lastname: Bhore
authors.forename: Sandesh
authors.initials: S
authors.lastname: Patil
authors.forename: Vandana
authors.initials: V
authors.lastname: Kulkarni
authors.forename: Varadharajan
authors.initials: V
authors.lastname: Venkataramani
authors.forename: Usha
authors.initials: U
authors.lastname: Balasubramaniam
authors.forename: Nishi
authors.initials: N
authors.lastname: Suryavanshi
authors.forename: Carrie
authors.initials: C
authors.lastname: Ziemniak
authors.forename: Nikhil
authors.initials: N
authors.lastname: Gupte
authors.forename: Robert
authors.initials: R
authors.lastname: Bollinger
authors.forename: Deborah
authors.initials: D
authors.lastname: Persaud
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D001942:Breast Feeding / Q000009:adverse effects; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D006678:HIV / Q000235:genetics / Q000378:metabolism*; D015658:HIV Infections / Q000517:prevention & control / Q000635:transmission*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D008895:Milk, Human / Q000821:virology*; D019829:Nevirapine / Q000627:therapeutic use*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D019829:Nevirapine