Treating malaria in HIV-coinfected individuals should consider potential drug-drug interactions. Artemether-lumefantrine is the most widely recommended treatment for uncomplicated malaria globally. Lumefantrine is metabolized by CYP3A4, an enzyme that commonly used antiretrovirals often induce or inhibit. A population pharmacokinetic meta-analysis was conducted using individual participant data from 10 studies with 6,100 lumefantrine concentrations from 793 nonpregnant adult participants (41% HIV-malaria-coinfected, 36% malaria-infected, 20% HIV-infected, and 3% healthy volunteers). Lumefantrine exposure increased 3.4-fold with coadministration of lopinavir-ritonavir-based antiretroviral therapy (ART), while it decreased by 47% with efavirenz-based ART and by 59% in the patients with rifampin-based antituberculosis treatment. Nevirapine- or dolutegravir-based ART and malaria or HIV infection were not associated with significant effects. Monte Carlo simulations showed that those on concomitant efavirenz or rifampin have 49% and 80% probability of day 7 concentrations <200 ng/ml, respectively, a threshold associated with an increased risk of treatment failure. The risk of achieving subtherapeutic concentrations increases with larger body weight. An extended 5-day and 6-day artemether-lumefantrine regimen is predicted to overcome these drug-drug interactions with efavirenz and rifampin, respectively.
e Management of coinfection with malaria and HIV is a major challenge to public health in developing countries, and yet potential drug-drug interactions between antimalarial and antiviral regimens have not been adequately investigated in people with both infections. Each of the constituent components of artemether-lumefantrine, the first-line regimen for malaria treatment in Nigeria, and nevirapine, a major component of highly active antiretroviral therapy, are drugs metabolized by the cytochrome P450 3A4 isoenzyme system, which is also known to be induced by nevirapine. We examined potential interactions between lumefantrine and nevirapine in 68 HIV-positive adults, all of whom were diagnosed with asymptomatic Plasmodium falciparum infections by microscopy. Post hoc PCR analysis confirmed the presence of P. falciparum in only a minority of participants. Day 7 capillary blood levels of lumefantrine were significantly higher in HIV-positive participants than in 99 HIV-negative controls (P ؍ 0.0011). Associations between day 7 levels of lumefantrine and risk of persistent parasitemia could not be evaluated due to inadequate power. Further investigations of the impact of nevirapine on in vivo malaria treatment outcomes in HIV-infected patients are thus needed.
In Nigeria, mass distribution of Long Lasting Insecticide Treated Nets (LLINs), community awareness programs, increased availability of Artemisinin-based combination therapies (ACTs) and Biolarviciding have been part of strategies employed, with the aim of contributing to the realization of the sixth Millennium Development Goal-Combating Malaria. This study investigates malaria prevalence among adult subjects presenting for routine medical examination at the Lulu Briggs Health Centre, University of Port Harcourt. Blood samples of 354 willing subjects were tested for parasitemia using double microscopy and standard Rapid Diagnostic (RDT) Test Kits. Axillary temperature, genotype, blood group and packed cell volume of the subjects were also determined. Questionnaire was used to obtain information regarding their demographics, previous use of antimalarials, and malaria prevention strategies they have adopted. The results obtained on the prevalence of malaria were as follows; RDT, 7.4%, double microscopy 11.0%. Among the parasite-positive samples, 32 (82.1%) were of AA, 6 (15.4%) AS, and 1 (2.5%) SS genotype, while on the other hand, 23 (59%) were of O + , 10 (25%) of A + , 3 (8%) of AB + , and 3(8%) of the B + blood groups. The decline in malaria prevalence rate when compared to other studies, suggests that malaria control measures are having a degree of success and that individuals are making conscious effort to reduce mosquito bites. Also, the study reaffirms that microscopy still remains the gold standard in malaria diagnosis, even though RDTs are invaluable when immediate result is desired and where a laboratory is not in sight.
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