title: High frequency of rapid immunological progression in African infants infected in the era of perinatal HIV prophylaxis.
abstract: OBJECTIVE
  To determine the natural history of HIV infection following peripartum single-dose nevirapine (sd-NVP) prophylaxis in a resource-limited country, and to assess implications for antiretroviral therapy (ART) roll-out programmes.
  
  
  METHODS
  Infants of HIV-infected mothers in KwaZulu-Natal, South Africa, were tested on days 1 and 28 to detect intrauterine (IU) and intrapartum (IP) infection. Infant follow-up included monthly viral load and CD4 cell measurement. ART was initiated at infant CD4 cell% < or = 20%.
  
  
  RESULTS
  In 740 infants born to 719 HIV-infected women, mother-to-child transmission (MTCT) was 10.3% (69% IU, 31% IP). Median viral load was higher in mothers of infants infected IP than IU (279 000 versus 86 600 copies/ml; P = 0.039) and lower in mothers of uninfected infants (median 26 750 copies/ml; P < 0.001). Peak viraemia was higher in infants infected IP than IU (5 160 000 versus 984 000 copies/ml; P < 0.001). Median viral load at birth in IU-infected infants (155 000 copies/ml) fell 1.4 log to 6510 copies/ml by day 5 and was beneath the detection limit using dried blood spot analysis in 38% of infants. CD4 cell% declined rapidly, to < or = 20% in 70% and < or = 25% in 85% [current World Health Organization (WHO) criteria for initiating ART] of infants by 6 months.
  
  
  CONCLUSIONS
  MTCT was reduced by sd-NVP through an effect on IP transmission. Where MTCT occurred despite NVP, two-thirds of transmissions arose IU; IP-infected babies were born to mothers with very high viral load. Disease progression was particularly rapid, 85% infants meeting WHO criteria for ART within 6 months. These findings argue for more effective MTCT-prevention programmes in resource-limited countries.
authors.affiliation: HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Wendy
authors.initials: W
authors.lastname: Mphatswe
authors.forename: Natasha
authors.initials: N
authors.lastname: Blanckenberg
authors.forename: Gareth
authors.initials: G
authors.lastname: Tudor-Williams
authors.forename: Andrew
authors.initials: A
authors.lastname: Prendergast
authors.forename: Christina
authors.initials: C
authors.lastname: Thobakgale
authors.forename: Nompumelelo
authors.initials: N
authors.lastname: Mkhwanazi
authors.forename: Noel
authors.initials: N
authors.lastname: McCarthy
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.forename: Photini
authors.initials: P
authors.lastname: Kiepiela
authors.forename: Philip
authors.initials: P
authors.lastname: Goulder
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage*; D018791:CD4 Lymphocyte Count; D018450:Disease Progression; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000453:epidemiology / Q000276:immunology* / Q000517:prevention & control; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D009017:Morbidity; D009035:Mothers; D019829:Nevirapine / Q000008:administration & dosage*; D018743:Perinatal Care / Q000379:methods; D013019:South Africa / Q000453:epidemiology; D019562:Viral Load; D014766:Viremia / Q000276:immunology
chemical_list: D019380:Anti-HIV Agents; D019829:Nevirapine