Virologic and immunologic outcomes of HIV-infected Ugandan children randomized to lopinavir/ritonavir or nonnucleoside reverse transcriptase inhibitor therapy.

Abstract

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.

• Authors: Theodore D Ruel, Abel Kakuru, Gloria Ikilezi, Florence Mwangwa, Grant Dorsey, Philip J Rosenthal, Edwin Charlebois, Diane Havlir, Moses Kamya, Jane Achan
• Journal: Journal of acquired immune deficiency syndromes (1999) (J Acquir Immune Defic Syndr) Vol. 65 Issue 5 Pg. 535-41 (Apr 15 2014) ISSN: 1944-7884 [Electronic] United States
• PMID: 24326597 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial)

Chemical References

• Anti-HIV Agents
• RNA, Viral
• Reverse Transcriptase Inhibitors
• Lopinavir
• Ritonavir

Topics

• Anti-HIV Agents (adverse effects, therapeutic use)
• CD4 Lymphocyte Count
• Child, Preschool
• Drug-Related Side Effects and Adverse Reactions (epidemiology)
• Female
• HIV Infections (drug therapy, immunology, virology)
• Humans
• Infant
• Lopinavir (adverse effects, therapeutic use)
• Malaria (prevention & control)
• Male
• RNA, Viral (blood)
• Reverse Transcriptase Inhibitors (adverse effects, therapeutic use)
• Ritonavir (adverse effects, therapeutic use)
• Treatment Outcome
• Uganda
• Viral Load