Unknown

Dataset Information

0

Parasite Clearance and Artemether Pharmacokinetics Parameters Over the Course of Artemether-Lumefantrine Treatment for Malaria in Human Immunodeficiency Virus (HIV)-Infected and HIV-Uninfected Ugandan Children.


ABSTRACT:

Background

Artemisinins are primarily responsible for initial parasite clearance. Antimalarial pharmacokinetics (PK), human immunodeficiency virus (HIV) infection, and antiretroviral therapy have been shown to impact treatment outcomes, although their impact on early parasite clearance in children has not been well characterized.

Methods

Parasite clearance parameters were generated from twice-daily blood smears in HIV-infected and HIV-uninfected Ugandan children treated with artemether-lumefantrine (AL). Artemether and dihydroartemisinin (DHA) area-under-the-curve from 0-8 hours (AUC0-8hr) after the 1st AL dose was compared with AUC0-8hr after the last (6th) dose in a concurrently enrolled cohort. The association between post-1st dose artemisinin AUC0-8hr and parasite clearance was assessed.

Results

Parasite clearance was longer in HIV-infected versus HIV-uninfected children (median, 3.5 vs 2.8 hours; P = .003). Artemether AUC0-8hr was 3- to 4-fold lower after the 6th dose versus the 1st dose of AL in HIV-infected children on nevirapine- or lopinavir/ritionavir-based regimens and in HIV-uninfected children (P ? .002, 1st vs 6th-dose comparisons). Children on efavirenz exhibited combined post-1st dose artemether/DHA exposure that was significantly lower than those on lopinavir/ritonavir and HIV-uninfected children. Multiple regression analysis supported that the effect of artemether/DHA exposure on parasite clearance was significantly moderated by HIV status.

Conclusions

Parasite clearance rates remain rapid in Uganda and were not found to associate with PK exposure. However, significant decreases in artemisinin PK with repeated dosing in nearly all children, coupled with small, but significant increase in parasite clearance half-life in those with HIV, may have important implications for AL efficacy, particularly because reports of artemisinin resistance are increasing.

SUBMITTER: Kajubi R 

PROVIDER: S-EPMC5170492 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

altmetric image

Publications

Parasite Clearance and Artemether Pharmacokinetics Parameters Over the Course of Artemether-Lumefantrine Treatment for Malaria in Human Immunodeficiency Virus (HIV)-Infected and HIV-Uninfected Ugandan Children.

Kajubi Richard R   Huang Liusheng L   Were Moses M   Kiconco Sylvia S   Li Fangyong F   Marzan Florence F   Gingrich David D   Nyunt Myaing M MM   Ssebuliba Joshua J   Mwebaza Norah N   Aweeka Francesca T FT   Parikh Sunil S  

Open forum infectious diseases 20161001 4


<h4>Background</h4>Artemisinins are primarily responsible for initial parasite clearance. Antimalarial pharmacokinetics (PK), human immunodeficiency virus (HIV) infection, and antiretroviral therapy have been shown to impact treatment outcomes, although their impact on early parasite clearance in children has not been well characterized.<h4>Methods</h4>Parasite clearance parameters were generated from twice-daily blood smears in HIV-infected and HIV-uninfected Ugandan children treated with artem  ...[more]

Similar Datasets

| S-EPMC5034953 | biostudies-literature
| S-EPMC3465101 | biostudies-literature
| S-EPMC4775973 | biostudies-literature
| S-EPMC2789094 | biostudies-literature
| S-EPMC9016418 | biostudies-literature
| S-EPMC4386948 | biostudies-literature
| S-EPMC2714631 | biostudies-literature
| S-EPMC6086194 | biostudies-literature
| S-EPMC3551967 | biostudies-literature
| S-EPMC3720542 | biostudies-literature