title: Early virological suppression with three-class antiretroviral therapy in HIV-infected African infants.
abstract: OBJECTIVE
  Infants infected with HIV-1 perinatally despite single-dose nevirapine progress rapidly. Data on treatment outcome in sub-Saharan African infants exposed to single-dose nevirapine are urgently required. This feasibility study addresses efficacy of infant antiretroviral therapy in this setting.
  
  
  METHODS
  HIV-infected infants in Durban, South Africa, received randomized immediate or deferred (when CD4 cell count reached <20%) four-drug antiretroviral therapy (zidovudine/lamivudine/nelfinavir/nevirapine). Genotyping for non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance was undertaken pre-antiretroviral therapy. Monthly follow-up to 1-year post-antiretroviral therapy included viral load, CD4 cell count and verbal/measured adherence monitoring.
  
  
  RESULTS
  All 63 infants were exposed to single-dose nevirapine. Twenty-one out of 51 (39%) infants with baseline genotyping results had NNRTI resistance (most frequently Y181C; 20%). Forty-three infants were randomized to immediate antiretroviral therapy (ART): three withdrew pre-antiretroviral therapy; 36 out of 40 completed 1-year of ART. Twenty infants received deferred ART: 17 reached CD4 cell counts less than 20% (median d99) and 13 out of 17 started antiretroviral therapy in year 1. Verbal and measured adherence was 99% and 95%, respectively. One-year post-ART, 49 out of 49 (100%) infants had a viral load less than 400 copies/ml; 46 out of 49 (94%) had viral load less than 50 copies/ml. Ten infants (20%) required second-line ART due to virological failure or tuberculosis treatment, therefore 39 out of 49 (80%) achieved viral load less than 400 copies/ml by intention-to-treat. Time to viral load less than 50 copies/ml correlated with maternal CD4 cell count (r = -0.42; P = 0.005) and infant pre-ART viral load (r = 0.64; P < 0.001). NNRTI mutations had no significant effect on virological suppression. Infants starting immediate compared with deferred ART had fewer illness episodes (P = 0.003), but no significant difference in virological suppression.
  
  
  CONCLUSIONS
  Excellent adherence and virological suppression are achievable in infants, despite high-frequency NNRTI mutations and rapid disease progression. Infants remain relatively neglected in roll-out programmes and ART provision must be expanded.
authors.affiliation: Department of Paediatrics, University of Oxford, Oxford, UK. andy.prendergast@gmail.com
authors.forename: Andrew
authors.initials: A
authors.lastname: Prendergast
authors.forename: Wendy
authors.initials: W
authors.lastname: Mphatswe
authors.forename: Gareth
authors.initials: G
authors.lastname: Tudor-Williams
authors.forename: Mpho
authors.initials: M
authors.lastname: Rakgotho
authors.forename: Visva
authors.initials: V
authors.lastname: Pillay
authors.forename: Christina
authors.initials: C
authors.lastname: Thobakgale
authors.forename: Noel
authors.initials: N
authors.lastname: McCarthy
authors.forename: Lynn
authors.initials: L
authors.lastname: Morris
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.forename: Philip
authors.initials: P
authors.lastname: Goulder
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral / Q000235:genetics; D005240:Feasibility Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000635:transmission / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D009154:Mutation; D019829:Nevirapine / Q000627:therapeutic use; D010349:Patient Compliance; D010865:Pilot Projects; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious; D012959:Socioeconomic Factors; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D019829:Nevirapine