Artemisinin-based combination therapies are efficacious and safe for treatment of uncomplicated malaria in HIV-infected Ugandan children.
BACKGROUND
Artemisinin-based combination therapies (ACTs) are highly efficacious and safe, but data from human immunodeficiency virus (HIV)-infected children concurrently receiving antiretroviral therapy (ART) and ACTs are limited.


METHODS
We evaluated 28-day outcomes following malaria treatment with artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DP) in 2 cohorts of HIV-infected Ugandan children taking various ART regimens. In one cohort, children <6 years of age were randomized to lopinavir/ritonavir (LPV/r) or nonnucleoside reverse transcriptase inhibitor-based ART and treated with AL for uncomplicated malaria. In another cohort, children <12 months of age were started on nevirapine-based ART if they were eligible, and randomized to AL or DP for the treatment of their first and all subsequent uncomplicated malaria episodes.


RESULTS
There were 773 and 165 treatments for malaria with AL and DP, respectively. Initial response to therapy was excellent, with 99% clearance of parasites and <1% risk of repeat therapy within 3 days. Recurrent parasitemia within 28 days was common following AL treatment. The risk of recurrent parasitemia was significantly lower among children taking LPV/r-based ART compared with children taking nevirapine-based ART following AL treatment (15.3% vs 35.5%, P = .009), and those treated with DP compared with AL (8.6% vs 36.2%, P < .001). Both ACT regimens were safe and well tolerated.


CONCLUSIONS
Treatment of uncomplicated malaria with AL or DP was efficacious and safe in HIV-infected children taking ART. However, there was a high risk of recurrent parasitemia following AL treatment, which was significantly lower in children taking LPV/r-based ART compared with nevirapine-based ART.
Infectious Diseases Research Collaboration.
Abel
A
Kakuru
Infectious Diseases Research Collaboration Department of Pediatrics and Child Health, Makerere University College of Health Sciences, Kampala, Uganda.
Jane
J
Achan
Infectious Diseases Research Collaboration.
Mary K
MK
Muhindo
Infectious Diseases Research Collaboration.
Gloria
G
Ikilezi
Infectious Diseases Research Collaboration.
Emmanuel
E
Arinaitwe
Infectious Diseases Research Collaboration.
Florence
F
Mwangwa
Department of Pediatrics.
Theodore
T
Ruel
Department of Medicine, University of California, San Francisco.
Tamara D
TD
Clark
Department of Medicine, University of California, San Francisco.
Edwin
E
Charlebois
Department of Medicine, University of California, San Francisco.
Philip J
PJ
Rosenthal
Department of Pediatrics.
Diane
D
Havlir
Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda.
Moses R
MR
Kamya
Global AIDS Program, Centers for Disease Control and Prevention, Atlanta, Georgia.
Jordan W
JW
Tappero
Department of Medicine, University of California, San Francisco.
Grant
G
Dorsey
D000962:Antimalarials / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use*; D002675:Child, Preschool; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D061466:Lopinavir / Q000627:therapeutic use; D008288:Malaria / Q000188:drug therapy*; D008297:Male; D019829:Nevirapine / Q000627:therapeutic use; D018512:Parasitemia / Q000188:drug therapy; D011804:Quinolines / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D019438:Ritonavir / Q000627:therapeutic use; D016896:Treatment Outcome; D014454:Uganda; D010879:Piperazines
D000962:Antimalarials; D037621:Artemisinins; D017320:HIV Protease Inhibitors; D061466:Lopinavir; D019829:Nevirapine; D011804:Quinolines; D018894:Reverse Transcriptase Inhibitors; D019438:Ritonavir; C039060:artenimol; C031327:artemisinin; C034759:piperaquine; D010879:Piperazines
ACTs; ART; HIV; children; malaria