Background Malaria/HIV co-infection (MHC) is a public health challenge which may present with worse health outcomes due to interactions. Coadministration of artemether lumefantrine (ALU) and antiretroviral therapy may have potential drug-drug interactions that can affect the course of treatment for both diseases. Generic ALU medications are used in Ghana for malaria treatment after RDT or microscopy diagnosis. ALU is metabolized by the enzymes CYP2B6, CYP3A4/5, CYP2A6 and UGTs which can be affected by pharmacogenetics. A better understanding of the effects of MHC on ALU drugs could help prompt treatment, and control of malarial parasites among HIV-infected patients. This study evaluated effects of MHC on ALU drugs used in antimalarial treatment and pharmacogenetic influences on their efficacy. Methods To compare metabolite profiles and treatment outcome in patients on generic ALU for uncomplicated malaria and MHC, this study has recruited about 218 participants. However, we currently have complete preliminary metabolite and genomic data on 52 participants. Blood was taken for microscopy, genotyping using iPLEX Gold microarray and PCR-RFLP, and metabolite analysis using LC-MS/MS. Results Median parasite density was 2119.42/uL, 760.10/uL, 0/uL and 0/uL on days 1,2,3 and 7 for malaria-only participants and 7322.52/uL, 3928.60/uL, 0/uL and 0/uL for MHC participants. Plasma concentrations of dihydroartemisinin (DHA) ranged from 3.30–35.85ng/ml. Desbutyl-lumefantrine (DBL) concentrations ranged from 7.8ng/ml-40.44ng/ml on days 3 and 7. Decreased concentrations of lumefantrine, DBL and DHA were observed across CYP2B6 *1/*1, CYP2B6 *1/*18/*1/*6, CYP3A5 *1/* and CYP3A5 *1/*3/*1/*6/1*/*7 carriers for MHC participants. However, MHC carriers of non-functional haplotypes CYP2B6*6/*6 or *6/*18 or *18/*18 showed increase in lumefantrine, DBL, artemether and DHA concentrations. Conclusion Pharmacogenetic variations affected ALU plasma concentrations although blood parasites were eliminated by day 3 in malaria monoinfected and MHC participants. This however shows there is potential drug-drug interactions between ALU-ART components which can influence the progression of either disease.

ABSTRACT Rifabutin, used to treat HIV-infected tuberculosis, shows highly variable drug exposure, complicating dosing. Effects of SLCO1B1 polymorphisms on rifabutin pharmacokinetics were investigated in 35 African HIV-infected tuberculosis patients after multiple doses. Nonlinear mixed-effects modeling found that influential covariates for the pharmacokinetics were weight, sex, and a 30% increased bioavailability among heterozygous carriers of SLCO1B1 rs1104581 (previously associated with low rifampin concentrations). Larger studies are needed to understand the complex interactions of host genetics in HIV-infected tuberculosis patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT00640887.)

Seventy-eight crude organic fractions from nineteen species of marine algae collected from the coast of South Africa were screened for activity against a chloroquine sensitive strain of Plasmodium falciparum (D10), Staphylococcus aureus, Klebsiella pneumoniae, Mycobacterium aurum and Candida albicans. Fifteen crude fractions showed good antiplasmodical activity (IC50 < 10 mu g/mL). The dichloromethane fraction from Sargassum heterophyllum (Turner) C. Agardh (Sargassaceae) was the most active with an IC50 value of 2.8 mu g/mL. Eleven extracts showed MIC values <= 1 mg/mL against at least one of S. aureus, K. pneumoniae, M. aurum and C. albicans. The broadest spectrum of antimicrobial activity was exhibited by the aqueous-HP20 fraction of Polysiphonia incompta Harvey (Rhodomelaceae). This study shows that marine algae not only produce antimicrobial compounds but also may be a source of antimalarial lead compounds.