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.

Trial registration: ClinicalTrials.gov NCT00978068.

Figures

Figure 1. Study Flow Chart

LPV/r, lopinavir/ritonavir; NNRTI, non-nucleoside-reverse-transcriptase-inhibitor.

Figure 2. Time to Virologic Failure, ART-naïve

Time to virologic failure, the first of 2 successive HIV RNA levels > 400 copies/ml in Kaplan-Meier modeling. LPV/r, ritonavir-boosted lopinavir; NNRTI, non-nucleoside-reverse-transcriptase-inhibitor

Figure 3. Change in CD4 measures over time, ART-naive

a) CD4 Number b) CD4 Percentage CD4 count and percentage by duration of time receiving ART during the study. Values are means with standard deviation error bars. Data were included from subjects on per-protocol basis with some patients missing scheduled visits at each time point, as shown below.

Figure 3. Change in CD4 measures over time, ART-naive

a) CD4 Number b) CD4 Percentage CD4 count and percentage by duration of time receiving ART during the study. Values are means with standard deviation error bars. Data were included from subjects on per-protocol basis with some patients missing scheduled visits at each time point, as shown below.