Early virological suppression with three-class antiretroviral therapy in HIV-infected African infants

AIDS. 2008 Jul 11;22(11):1333-43. doi: 10.1097/QAD.0b013e32830437df.

Abstract

Objectives: 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.

Conclusion: 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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / therapeutic use
  • Antiretroviral Therapy, Highly Active / methods
  • CD4 Lymphocyte Count
  • Drug Administration Schedule
  • Drug Resistance, Viral / genetics
  • Feasibility Studies
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV Infections / transmission
  • HIV Infections / virology
  • HIV-1* / drug effects
  • HIV-1* / genetics
  • Humans
  • Infant, Newborn
  • Infectious Disease Transmission, Vertical
  • Male
  • Mutation
  • Nevirapine / therapeutic use
  • Patient Compliance
  • Pilot Projects
  • Pregnancy
  • Pregnancy Complications, Infectious
  • Socioeconomic Factors
  • Treatment Outcome
  • Viral Load

Substances

  • Anti-HIV Agents
  • Nevirapine