Initial response to protease-inhibitor-based antiretroviral therapy among children less than 2 years of age in South Africa: effect of cotreatment for tuberculosis

J Infect Dis. 2010 Apr 15;201(8):1121-31. doi: 10.1086/651454.

Abstract

Background: South African guidelines recommend protease-inhibitor-based antiretroviral therapy (ART) with lopinavir-ritonavir for human immunodeficiency virus (HIV)-infected children <36 months of age. We investigated factors associated with viral suppression and mortality among young children initiating ART.

Methods: Treatment-naive, ART-eligible, HIV-infected children (aged 6-104 weeks) were enrolled in an ART strategies trial in South Africa and initiated protease-inhibitor-based ART. Mortality and the probability of viral suppression (defined as HIV RNA load of <400 copies/mL) by 39 weeks after ART initiation were investigated.

Results: Of 254 children who initiated ART, 99 (39%) were cotreated for tuberculosis during follow-up. The mortality rate was 14%. Factors predicting mortality were lower pre-ART weight-for-age z score and higher HIV RNA load. By 39 weeks, 84% of surviving children achieved viral suppression. Children who were not cotreated for tuberculosis were more likely to achieve viral suppression (94.8%) than were children who were receiving cotreatment at ART initiation (74.2%) or who started tuberculosis cotreatment after ART initiation (51.6%; P < .001). Other factors predicting lower probability of viral suppression were lower pre-ART weight- and length-for-age z score, higher HIV RNA load, and World Health Organization disease stage.

Conclusion: High rates of viral suppression can be achieved among infants and young children who initiate protease-inhibitor-based ART. Cotreatment for tuberculosis reduced viral suppression. How best to treat HIV-infected children who require tuberculosis treatment warrants urgent investigation.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiretroviral Therapy, Highly Active
  • Antitubercular Agents / administration & dosage
  • Antitubercular Agents / therapeutic use*
  • Child, Preschool
  • Drug Therapy, Combination
  • Ethionamide / administration & dosage
  • Ethionamide / therapeutic use
  • Female
  • HIV / drug effects
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • HIV Infections / mortality
  • HIV Protease Inhibitors / administration & dosage
  • HIV Protease Inhibitors / therapeutic use*
  • Humans
  • Infant
  • Isoniazid / administration & dosage
  • Isoniazid / therapeutic use
  • Kaplan-Meier Estimate
  • Lopinavir
  • Male
  • Pyrimidinones / administration & dosage
  • Pyrimidinones / therapeutic use*
  • RNA, Viral / blood
  • Rifampin / administration & dosage
  • Rifampin / therapeutic use
  • Ritonavir / administration & dosage
  • Ritonavir / therapeutic use*
  • South Africa
  • Tuberculosis, Pulmonary / complications
  • Tuberculosis, Pulmonary / drug therapy*
  • Viral Load / drug effects

Substances

  • Antitubercular Agents
  • HIV Protease Inhibitors
  • Pyrimidinones
  • RNA, Viral
  • Lopinavir
  • Ritonavir
  • Ethionamide
  • Isoniazid
  • Rifampin