Sulfamethoxazole Levels in HIV-Exposed Uninfected Ugandan Children

Jingo Kasule, Erin E Gabriel, Aggrey Anok, Jillian Neal, Richard T Eastman, Scott Penzak, Kevin Newell, David Serwadda, Patrick E Duffy, Steven J Reynolds, Charlotte V Hobbs, Jingo Kasule, Erin E Gabriel, Aggrey Anok, Jillian Neal, Richard T Eastman, Scott Penzak, Kevin Newell, David Serwadda, Patrick E Duffy, Steven J Reynolds, Charlotte V Hobbs

Abstract

Trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis in HIV-uninfected, exposed (HUE) children variably reduces clinical malaria burden despite antifolate resistance, but data regarding achieved serum levels and adherence are lacking. Serum samples from 70 HUE children aged 3-12 months from Rakai, Uganda, enrolled in an observational study were assayed for random SMX levels using a colorimetric assay. Adherence with TMP-SMX prophylaxis data (yes/no) was also collected. Of 148 visits with concurrent SMX levels available, 56% had self-reported adherence with TMP-SMX therapy. Among these 82 visits, mean (standard deviation) level was 19.78 (19.22) µg/mL, but 33% had SMX levels below half maximal inhibitory concentrations (IC50) for Plasmodium falciparum with some, but not all, of the reported antifolate resistance mutations reported in Uganda. With TMP-SMX prophylaxis, suboptimal adherence is concerning. Sulfamethoxazole levels below IC50s required to overcome malaria parasites with multiple antifolate resistance mutations may be significant. Further study of TMP-SMX in this context is needed.

Trial registration: ClinicalTrials.gov NCT02094508.

Figures

Figure 1.
Figure 1.
Among clinical visits, 56% reported adherence with TMP–SMX therapy (N = 82). Among these visits, the mean drug level was 19.78 (SD 19.22) µg/mL; yet, 33% of concurrent drug levels were below IC50s for Plasmodium falciparum with some, but not all, of the reported antifolate resistance mutations recently reported in these areas. SD = standard deviation. This figure appears in color at www.ajtmh.org.
Figure 2.
Figure 2.
Resistance mutations of antifolates in laboratory-adapted strains share common resistance mutations with field strains reported in Uganda.– This figure appears in color at www.ajtmh.org.

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Source: PubMed

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