Abstract | BACKGROUND: METHODS: We conducted an open-label trial in which HIV-infected children 2 months to 5 years of age who were eligible for ART or were currently receiving NNRTI-based ART were randomly assigned to either lopinavir- ritonavir-based ART or NNRTI-based ART and were followed for 6 months to 2 years. Cases of uncomplicated malaria were treated with artemether-lumefantrine. The primary end point was the incidence of malaria. RESULTS: We enrolled 176 children, of whom 170 received the study regimen: 86 received NNRTI-based ART, and 84 lopinavir- ritonavir-based ART. The incidence of malaria was lower among children receiving the lopinavir- ritonavir-based regimen than among those receiving the NNRTI-based regimen (1.32 vs. 2.25 episodes per person-year; incidence-rate ratio, 0.59; 95% confidence interval [CI], 0.36 to 0.97; P=0.04), as was the risk of a recurrence of malaria after treatment with artemether-lumefantrine (28.1% vs. 54.2%; hazard ratio, 0.41; 95% CI, 0.22 to 0.76; P=0.004). The median lumefantrine level on day 7 after treatment for malaria was significantly higher in the lopinavir- ritonavir group than in the NNRTI group. In the lopinavir- ritonavir group, lumefantrine levels exceeding 300 ng per milliliter on day 7 were associated with a reduction of more than 85% in the 63-day risk of recurrent malaria. A greater number of serious adverse events occurred in the lopinavir- ritonavir group than in the NNRTI group (5.6% vs. 2.3%, P=0.16). Pruritus occurred significantly more frequently in the lopinavir- ritonavir group, and elevated alanine aminotransferase levels significantly more frequently in the NNRTI group. CONCLUSIONS:
Lopinavir- ritonavir-based ART as compared with NNRTI-based ART reduced the incidence of malaria by 41%, with the lower incidence attributable largely to a significant reduction in the recurrence of malaria after treatment with artemether-lumefantrine. Lopinavir- ritonavir-based ART was accompanied by an increase in serious adverse events. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT00978068.).
|
Authors | Jane Achan, Abel Kakuru, Gloria Ikilezi, Theodore Ruel, Tamara D Clark, Christian Nsanzabana, Edwin Charlebois, Francesca Aweeka, Grant Dorsey, Philip J Rosenthal, Diane Havlir, Moses R Kamya |
Journal | The New England journal of medicine
(N Engl J Med)
Vol. 367
Issue 22
Pg. 2110-8
(Nov 29 2012)
ISSN: 1533-4406 [Electronic] United States |
PMID | 23190222
(Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural)
|
Chemical References |
- Anti-Retroviral Agents
- Antimalarials
- Artemether, Lumefantrine Drug Combination
- Artemisinins
- Drug Combinations
- Ethanolamines
- Fluorenes
- HIV Protease Inhibitors
- Reverse Transcriptase Inhibitors
- Lopinavir
- Ritonavir
|
Topics |
- Anti-Retroviral Agents
(therapeutic use)
- Antimalarials
(pharmacokinetics, therapeutic use)
- Artemether, Lumefantrine Drug Combination
- Artemisinins
(pharmacokinetics, therapeutic use)
- Child, Preschool
- Drug Combinations
- Drug Interactions
- Drug Therapy, Combination
- Ethanolamines
(pharmacokinetics, therapeutic use)
- Female
- Fluorenes
(pharmacokinetics, therapeutic use)
- HIV Infections
(drug therapy)
- HIV Protease Inhibitors
(therapeutic use)
- Humans
- Incidence
- Infant
- Kaplan-Meier Estimate
- Lopinavir
(therapeutic use)
- Malaria
(drug therapy, epidemiology, prevention & control)
- Male
- Reverse Transcriptase Inhibitors
(therapeutic use)
- Ritonavir
(therapeutic use)
- Secondary Prevention
- Uganda
|