Background: In the Prevention of Malaria and HIV disease in Tororo pediatrics trial, HIV-infected Ugandan children randomized to receive lopinavir/ritonavir (LPV/r)-based antiretroviral therapy (ART) experienced a lower incidence of malaria compared with children receiving nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART. Here we present the results of the noninferiority analysis of virologic efficacy and comparison of immunologic outcomes.
Methods: ART-naive or -experienced (HIV RNA <400 copies/mL) children aged 2 months to 6 years received either LPV/r or NNRTI-based ART. The proportion of children with virologic suppression (HIV RNA <400 copies/mL) at 48 weeks was compared using a prespecified noninferiority margin of −11% in per-protocol analysis. Time to virologic failure by 96 weeks, change in CD4 counts and percentages, and incidence of adverse event rates were also compared.
Results: Of 185 children enrolled, 91 initiated LPV/r and 92 initiated NNRTI-based ART. At baseline, the median age was 3.1 years (range, 0.4–5.9), and 131 (71%) children were ART-naive. The proportion of children with virologic suppression at 48 weeks was 80% (67/84) in the LPV/r arm vs. 76% (59/78) in the NNRTI arm, a difference of 4% (95% confidence interval: −9% to +17%). Time to virologic failure, CD4 changes, and the incidence of Division of AIDS grade III/IV adverse events were similar between arms.
Conclusions: LPV/r-based ART was not associated with worse virologic efficacy, immunologic efficacy, or adverse event rates compared with NNRTI-based ART. Considering these results and the reduction in malaria incidence associated with LPV/r previously reported for this trial, wider use of LPV/r to treat HIV-infected African children in similar malaria-endemic settings could be considered.
*Department of Pediatrics, University of California, San Francisco, CA;
†Infectious Diseases Research Collaboration, Kampala, Uganda;
‡Department of Medicine, University of California, San Francisco, San Francisco, CA; and
Departments of §Medicine;
‖Pediatrics and Child Health, Makerere University College of Health Sciences, Kampala, Uganda.
Correspondence to: Theodore D. Ruel, MD, Division of Infectious Disease, Department of Pediatrics, UCSF-Benioff Children's Hospital, University of California, San Francisco, 500 Parnassus Avenue, San Francisco, CA 94143-0136, (e-mail: firstname.lastname@example.org).
Supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (P01HD059454 and T.D.R.: K23HD60459) at the National Institutes of Health. Lopinavir/ritonavir was donated by AbbVie.
Presented in part at the 18th (March 2, 2011, Boston, MA) and 20th (March 5, 2013, Atlanta, GA) Conferences on Retrovirus and Opportunistic Infections.
T.D.R. and J.A. contributed significantly to the design of the study, acquisition and interpretation of data, and drafted/edited the article. A.K., G.I., and F.M. contributed significantly to the acquisition of data and edited the article. G.D., P.J.R., D.H., and M.K. contributed significantly to the design of the study, acquisition and interpretation of data, and edited the article. All authors approved the final version.
The authors have no conflicts of interest to disclose.
Clinical Trial Registration: Prevention of Malaria and HIV disease in Tororo (PROMOTE) pediatrics trial registration: NCT00978068.
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Received July 25, 2013
Accepted November 10, 2013