Date Published: January 20, 2018
Publisher: The American Society of Tropical Medicine and Hygiene
Author(s): Charlotte V. Hobbs, Erin E. Gabriel, Portia Kamthunzi, Gerald Tegha, Jean Tauzie, Yonghua Li, Tiina Ilmet, Elena Artimovich, Jillian Neal, Ted Hall, Sunil Parikh, Brian Kirmse, Patrick Jean-Philippe, Jingyang Chen, William R. Prescott, Paul Palumbo, Patrick E. Duffy, William Borkowsky.
Laboratory data and prior pediatric reports indicate that HIV protease inhibitor (PI)–based antiretroviral therapy (ARV) kills gametocytes and reduces rates of gametocytemia, but not asymptomatic parasitemia, in a high malaria-transmission area. To determine whether ARV regimen impacts these rates in areas with less-intense malaria transmission, we compared asymptomatic parasitemia and gametocytemia rates in HIV-infected children by ARV regimen in Lilongwe, Malawi, an area of low-to-moderate transmission intensity. HIV PI lopinavir–ritonavir (LPV–rtv) ARV– or non-nucleoside reverse transcriptase inhibitor nevirapine ARV–treated children did not differ in the rates of polymerase chain reaction-detected asymptomatic parasitemia (relative risk [RR] 0.43 95% confidence interval [CI] [0.16, 1.18], P value 0.10) or microscopically detected gametocytemia with LPV–rtv ARV during symptomatic malaria (RR 0.48 95% CI [0.22,1.04] P value 0.06). LPV–rtv ARV was not associated with reduced rates of asymptomatic parasitemia, or gametocytemia on days of symptomatic malaria episodes, in HIV-infected children. Larger studies should evaluate whether ARV impacts transmission.
HIV and malaria occur co-endemically in sub-Saharan Africa.1 Laboratory data show that HIV protease inhibitors (PIs) kill various life cycle stages of malaria parasites.2–6 PIs are second-line World Health Organization (WHO)-recommended antiretroviral therapy (ARV) for children above 3 years old and first-line ARV for those below 3 years.7 Clinical studies have shown that HIV-infected children on PI ARV may have a modest reduction in clinical malaria episodes, and the effect may be partially attributed to pharmacokinetic interactions resulting in an increase in antimalarial drug levels.8–12 In addition, laboratory data4,5 and recent pediatric clinical studies indicate that HIV PI lopinavir–ritonavir (LPV–rtv) ARV, when compared with non-nucleoside reverse transcriptase inhibitor (NNRTI) ARV, is associated with reduced gametocytemia,11,13 but not asymptomatic parasitemia,13 rates in high malaria-transmission areas.
Thirty-one children were enrolled between September 2009 and December 2011 from Kamuzu Central Hospital, Lilongwe, Malawi; demographic information and ARV regimens for these patients was been previously reported.10 Of 31 children, 18 started on the study on LPV–rtv ARV and 13 on NVP ARV. Eight patients who were randomized to start on NVP ARV switched to LPV–rtv ARV because of HIV treatment failure,10 with two subjects switching to LPV–rtv ARV before enrolling in the P1068s. One patient withdrew because of moving too far away from the study site to attend visits. We followed the enrolled children for a total of 20,771 person days on LPV–rtv and 9,911 person days on NVP ARV.
In an area of low-to-moderate transmission, LPV–rtv ARV was not associated with reduced rates of asymptomatic parasitemia, or gametocytemia with or without concurrent symptomatic malaria episodes, in HIV-infected children.