title: Correlation ofrpoBMutations with Minimal Inhibitory Concentration of Rifampin and Rifabutin inMycobacterium tuberculosisin an HIV/AIDS Endemic Setting, South Africa.
abstract: Treatment of tuberculosis (TB) and HIV co-infections is often complicated by drug-to-drug interactions between anti-mycobacterial and anti-retroviral agents. Rifabutin (RFB) is an alternative to rifampin (RIF) for TB regimens and is recommended for HIV patients concurrently receiving protease inhibitors because of reduced induction of CYP3A4. This study sought to determine the proportion of RFB susceptible isolates among RIF-resistant strains in a high HIV prevalence setting in South Africa. In addition, the study explored the association betweenrpoBmutations and minimum inhibitory concentrations (MIC) of RIF and RFB. A total of 189 multidrug resistant (MDR)Mycobacterium tuberculosisisolates from the Centre for Tuberculosis repository were analyzed. The MICs were determined using a MYCOTB Sensititre plate method and therpoBgene was sequenced. Of the 189 MDR isolates, 138 (73%) showed resistance to both RIF and RFB, while 51 (27%) isolates were resistant to RIF but retained susceptibility to RFB. The S531L was the most frequentrpoBpoint mutation in 105/189 (56%) isolates, followed by H526Y in 27/189 (14%) isolates. Resistance to both RIF and RFB was found predominantly in association with mutations S531L (91/105, 87%), H526Y (20/27, 74%), and H526D (15/19, 79%), while D516V (15/17, 88%), and L533P (3/4, 75%) were found in RIF-resistant, RFB-susceptible isolates. This study has shown that up to 27% of MDR-TB patients in South Africa may benefit from a treatment regimen that includes RFB.
authors.affiliation: Department of Medical Microbiology, Faculty of Health Sciences, University of the Free State Bloemfontein, South Africa.
authors.forename: Ivy
authors.initials: I
authors.lastname: Rukasha
authors.affiliation: Department of Medical Microbiology, Faculty of Health Sciences, University of the Free StateBloemfontein, South Africa; Centre for Tuberculosis, National Institute for Communicable DiseasesSandringham, South Africa.
authors.forename: Halima M
authors.initials: HM
authors.lastname: Said
authors.affiliation: Centre for Tuberculosis, National Institute for Communicable Diseases Sandringham, South Africa.
authors.forename: Shaheed V
authors.initials: SV
authors.lastname: Omar
authors.affiliation: Centre for Tuberculosis, National Institute for Communicable DiseasesSandringham, South Africa; Department of Medical Microbiology, Faculty of Health Sciences, University of the WitwatersrandJohannesburg, South Africa.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Koornhof
authors.affiliation: Centre for Tuberculosis, National Institute for Communicable DiseasesSandringham, South Africa; Department of Medical Microbiology, Faculty of Health Sciences, University of the WitwatersrandJohannesburg, South Africa.
authors.forename: Andries W
authors.initials: AW
authors.lastname: Dreyer
authors.affiliation: Centre for Evidence-based Health Care, Faculty of Medicine and Health Sciences, Stellenbosch University Cape Town, South Africa.
authors.forename: Alfred
authors.initials: A
authors.lastname: Musekiwa
authors.affiliation: Medical Research Council, Respiratory and Meningeal Pathogens Research Unit, School of Pathology, University of the Witwatersrand Johannesburg, South Africa.
authors.forename: Harry
authors.initials: H
authors.lastname: Moultrie
authors.affiliation: Department of Medical Microbiology, Faculty of Health Sciences, University of the Free State Bloemfontein, South Africa.
authors.forename: Anwar A
authors.initials: AA
authors.lastname: Hoosen
authors.affiliation: The Bill and Melinda Gates Foundation, Seattle WA, USA.
authors.forename: Gilla
authors.initials: G
authors.lastname: Kaplan
authors.affiliation: Public Health Research Institute, New Jersey Medical School, The State University of New Jersey, Rutgers University, Newark NJ, USA.
authors.forename: Dorothy
authors.initials: D
authors.lastname: Fallows
authors.affiliation: Centre for Tuberculosis, National Institute for Communicable DiseasesSandringham, South Africa; Department of Medical Microbiology, Faculty of Health Sciences, University of PretoriaPretoria, South Africa.
authors.forename: Nazir
authors.initials: N
authors.lastname: Ismail
keywords: HIV/AIDS; Mycobacterium tuberculosis; South Africa; minimum inhibitory concentration; point mutation; rifabutin; rifampicin; rpoB