title: Outcome of artemether-lumefantrine treatment for uncomplicated malaria in HIV-infected adult patients on anti-retroviral therapy.
abstract: BACKGROUND
  Malaria and HIV infections are both highly prevalent in sub-Saharan Africa, with HIV-infected patients being at higher risks of acquiring malaria. The majority of antiretroviral (ART) and anti-malarial drugs are metabolized by the CYP450 system, creating a chance of drug-drug interaction upon co-administration. Limited data are available on the effectiveness of the artemether-lumefantrine combination (AL) when co-administered with non-nucleoside reverse transcriptase inhibitors (NNRTIs). The aim of this study was to compare anti-malarial treatment responses between HIV-1 infected patients on either nevirapine- or efavirenz-based treatment and those not yet on ART (control-arm) with uncomplicated falciparum malaria, treated with AL.
  
  
  METHODS
  This was a prospective, non-randomized, open-label study conducted in Bagamoyo district, with three arms of HIV-infected adults: efavirenz-based treatment arm (EFV-arm) n = 66, nevirapine-based treatment arm (NVP-arm) n = 128, and control-arm n = 75, with uncomplicated malaria. All patients were treated with AL and followed up for 28 days. The primary outcome measure was an adequate clinical and parasitological response (ACPR) after treatment with AL by day 28.
  
  
  RESULTS
  Day 28 ACPR was 97.6%, 82.5% and 94.5% for the NVP-arm, EFV-arm and control-arm, respectively. No early treatment or late parasitological failure was reported. The cumulative risk of recurrent parasitaemia was >19-fold higher in the EFV-arm than in the control-arm (Hazard ratio [HR], 19.11 [95% confidence interval {CI}, 10.5-34.5]; P < 0.01). The cumulative risk of recurrent parasitaemia in the NVP-arm was not significantly higher than in the control-arm ([HR], 2.44 [95% {CI}, 0.79-7.6]; P = 0.53). The median (IQR) day 7 plasma concentrations of lumefantrine for the three arms were: 1,125 ng/m (638.8-1913), 300.4 ng/ml (220.8-343.1) and 970 ng/ml (562.1-1729) for the NVP-arm, the EFV-arm and the control-arm, respectively (P < 0.001). In all three arms, the reported adverse events were mostly mild.
  
  
  CONCLUSIONS
  After 28 days of follow-up, AL was statistically safe and effective in the treatment of uncomplicated malaria in the NVP-arm. The results of this study also provide an indication of the possible impact of EFV on the performance of AL and the likelihood of it affecting uncomplicated falciparum malaria treatment outcome.
authors.forename: Betty A
authors.initials: BA
authors.lastname: Maganda
authors.affiliation: Unit of Pharmacology and Therapeutics, School of Pharmacy, Muhimbili University of Health and Allied Sciences, P,O, BOX 65013, Dar es Salaam, Tanzania. Minziobejayesu@gmail.com.
authors.forename: Omary M S
authors.initials: OM
authors.lastname: Minzi
authors.forename: Appolinary A R
authors.initials: AA
authors.lastname: Kamuhabwa
authors.forename: Billy
authors.initials: B
authors.lastname: Ngasala
authors.forename: Philip G
authors.initials: PG
authors.lastname: Sasi
mesh_terms: D000328:Adult; D017954:Africa South of the Sahara; D000368:Aged; D000480:Alkynes; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D000962:Antimalarials / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D048588:Benzoxazines / Q000627:therapeutic use; D003521:Cyclopropanes; D004338:Drug Combinations; D004347:Drug Interactions; D004983:Ethanolamines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D005449:Fluorenes / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D008288:Malaria / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D019829:Nevirapine / Q000627:therapeutic use; D011446:Prospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000480:Alkynes; D044966:Anti-Retroviral Agents; D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D048588:Benzoxazines; D003521:Cyclopropanes; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; D019829:Nevirapine; C098320:efavirenz