Survival differences and artemisinin resistance in severe malaria among HIV coinfected patients: data from Mozambique

Abstract Background Malaria remains a significant cause of morbidity and mortality, especially in sub-Saharan Africa, where rates of HIV coinfection are high. This study aimed to determine whether Plasmodium falciparum malaria treatment outcomes and rates of antimalarial resistance markers differ according to HIV serostatus in Mozambique. Methodology We conducted an observational study of non-pregnant adults, with and without HIV coinfection, admitted to the Hospital Central de Maputo for treatment of severe malaria. Plasmodium falciparum DNA was extracted from whole blood and sequenced to identify single-nucleotide polymorphisms. Statistical analyses to compare clinical outcomes and rates of nonsynonymous mutations in genes associated with drug resistance were performed in R version 4.2. Results We recruited 149 study participants aged between 18-62 years, 72 (48.3%) were female, and 59 (39.6%) were infected with HIV. Comparing clinical outcomes, we found a significant difference in anemia (hemoglobin <5 mg/dl: P-value = 0.01248) but no other predefined clinical characteristics including fever, renal dysfunction, or pulmonary edema in those with and without HIV coinfection. We found significantly higher in hospital mortality in those with HIV coinfection (P-value = 0.03416, and at 30 days post discharge P-value = 0.007526). Mortality correlated inversely with CD4 count. Overall mortality at the end of the study was 20.1%. We did not find a significant increase in the number of nonsynonymous mutations in known antimalarial resistance associated genes pfmdr1, pfcrt, pfdhfr, pfdhps, in patients who reported taking antimalarials prior to admission or in those with HIV coinfection. However, we did find an increase in rates of K189T pfkelch mutations (21.2% vs 2.7%, p = 0.022) in HIV infected patients. We found no increase in rates of nonsynonymous mutations in pfdhfr in HIV infected patients taking TMP-SMX prophylaxis: pfdhfr-pfdhps quintuple mutations were found in almost 100% of the parasite population. Conclusions We find a higher mortality rate in patients with malaria-HIV coinfection, further emphasizing the importance of effective treatment for this vulnerable population. We also provide an important baseline for the rate of resistance-conferring mutations in a population at risk of harboring resistant parasites in Mozambique, highlighting the need for continued surveillance.