Artemether-lumefantrine efficacy among adults on antiretroviral therapy in Malawi.

Autor: Nyangulu W; Dignitas International, Zomba, Malawi.; Public Health and Nutrition Research Group, Kamuzu University of Health Sciences, Mangochi, Malawi., Mungwira RG; Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi., Divala TH; Dignitas International, Zomba, Malawi., Nampota-Nkomba N; Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi., Nyirenda OM; Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi., Buchwald AG; Center for Vaccine Development and Global Health, University of Maryland School of Medicine, 685 W. Baltimore St., Baltimore, MD, 21201, USA., Miller J; Center for Vaccine Development and Global Health, University of Maryland School of Medicine, 685 W. Baltimore St., Baltimore, MD, 21201, USA., Earland DE; Center for Vaccine Development and Global Health, University of Maryland School of Medicine, 685 W. Baltimore St., Baltimore, MD, 21201, USA., Adams M; Center for Vaccine Development and Global Health, University of Maryland School of Medicine, 685 W. Baltimore St., Baltimore, MD, 21201, USA., Plowe CV; Center for Vaccine Development and Global Health, University of Maryland School of Medicine, 685 W. Baltimore St., Baltimore, MD, 21201, USA., Taylor TE; Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi.; Michigan State University, East Lansing, USA., Mallewa JE; Department of Medicine, Kamuzu University of Health Sciences, Blantyre, Malawi., van Oosterhout JJ; Dignitas International, Zomba, Malawi.; Partners in Hope, Lilongwe Malawi and David Geffen School of Medicine, University of California, Los Angeles, USA., Parikh S; Yale School of Public Health, New Haven, USA., Laurens MB; Center for Vaccine Development and Global Health, University of Maryland School of Medicine, 685 W. Baltimore St., Baltimore, MD, 21201, USA., Laufer MK; Center for Vaccine Development and Global Health, University of Maryland School of Medicine, 685 W. Baltimore St., Baltimore, MD, 21201, USA. mlaufer@som.umaryland.edu.
Jazyk: angličtina
Zdroj: Malaria journal [Malar J] 2023 Jan 27; Vol. 22 (1), pp. 32. Date of Electronic Publication: 2023 Jan 27.
DOI: 10.1186/s12936-023-04466-w
Abstrakt: Background: When people with human immunodeficiency virus (HIV) infection (PWH) develop malaria, they are at risk of poor anti-malarial treatment efficacy resulting from impairment in the immune response and/or drug-drug interactions that alter anti-malarial metabolism. The therapeutic efficacy of artemether-lumefantrine was evaluated in a cohort of PWH on antiretroviral therapy (ART) and included measurement of day 7 lumefantrine levels in a subset to evaluate for associations between lumefantrine exposure and treatment response.
Methods: Adults living with HIV (≥ 18 years), on ART for ≥ 6 months with undetectable HIV RNA viral load and CD4 count ≥ 250/mm 3 were randomized to daily trimethoprim-sulfamethoxazole (TS), weekly chloroquine (CQ) or no prophylaxis. After diagnosis of uncomplicated Plasmodium falciparum malaria, a therapeutic efficacy monitoring was conducted with PCR-correction according to WHO guidelines. The plasma lumefantrine levels on day 7 in 100 episodes of uncomplicated malaria was measured. A frailty proportional hazards model with random effects models to account for clustering examined the relationship between participant characteristics and malaria treatment failure within 28 days. Pearson's Chi-squared test was used to compare lumefantrine concentrations among patients with treatment failure and adequate clinical and parasitological response (ACPR).
Results: 411 malaria episodes were observed among 186 participants over 5 years. The unadjusted ACPR rate was 81% (95% CI 77-86). However, after PCR correction to exclude new infections, ACPR rate was 94% (95% CI 92-97). Increasing age and living in Ndirande were associated with decreased hazard of treatment failure. In this population of adults with HIV on ART, 54% (51/94) had levels below a previously defined optimal day 7 lumefantrine level of 200 ng/ml. This occurred more commonly among participants who were receiving an efavirenz-based ART compared to other ART regimens (OR 5.09 [95% CI 1.52-7.9]). Participants who experienced treatment failure had lower day 7 median lumefantrine levels (91 ng/ml [95% CI 48-231]) than participants who experienced ACPR (190 ng/ml [95% CI 101-378], p-value < 0.008).
Conclusion: Recurrent malaria infections are frequent in this population of PWH on ART. The PCR-adjusted efficacy of AL meets the WHO criteria for acceptable treatment efficacy. Nevertheless, lumefantrine levels tend to be low in this population, particularly in those on efavirenz-based regimens, with lower concentrations associated with more frequent malaria infections following treatment. These results highlight the importance of understanding drug-drug interactions when diseases commonly co-occur.
(© 2023. The Author(s).)
Databáze: MEDLINE
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