Polymorphisms in CYP2E1, GSTM1 and GSTT1 and anti-tuberculosis drug-induced hepatotoxicity.

Anti-tuberculosis drug-induced hepatitis (ATD- induced hepatitis) has been linked to polymorphisms in genes encoding drug metabolizing enzymes. N-acetyltransferase 2 (NAT2), cytochrome P450 2E1 (CYP2E1) and glutathione S-transferase (loci GSTM1 and GSTT1) are involved in the metabolism of isoniazid, the most toxic drug for the treatment of tuberculosis (TB). This study was designed to determine the frequency and to evaluate whether polymorphisms at CYP2E1, GSTM1 and GSTT1 genes are associated with drug response, as well as to identify clinical risk factors for ATD-induced hepatitis. A total of 245 Brazilian patients undergoing treatment for TB were genotyped using polymerase chain reaction and restriction fragment length polymorphism and sequencing methods. The frequencies of the CYP2E1 polymorphic alleles RsaI, PstI and DraI are 8%, 8.5% and 12%, respectively. GSTM1 and GSTT1 genes are deleted in 42.9% and 12.4% of the population, respectively. Fifteen patients (6.1%) developed hepatotoxicity. Clinical (HIV, female sex and extrapulmonary TB) and genetic characteristics (CYP2E1 without any mutations, having NAT2 slow acetylator profile) are at higher risk of developing ATD-induced hepatitis in this population. Genotyping for GSTM1 and GSTT1 showed no influence on drug response.

HIV behind bars: human immunodeficiency virus cluster analysis and drug resistance in a reference correctional unit from southern Brazil.

People deprived of liberty in prisons are at higher risk of infection by the human immunodeficiency virus (HIV) due to their increased exposure through intravenous drug use, unprotected sexual activity, tattooing in prison and blood exposure in fights and rebellions. Yet, the contribution of intramural HIV transmission to the epidemic is scarcely known, especially in low- and middle-income settings. In this study, we surveyed 1,667 inmates incarcerated at Presídio Central de Porto Alegre, located in southern Brazil, for HIV infection and molecular characterization. The HIV seroprevalence was 6.6% (110/1,667). Further analyses were carried out on 40 HIV-seropositive inmates to assess HIV transmission clusters and drug resistance within the facility with the use of molecular and phylogenetic techniques. The molecular epidemiology of HIV-1 subtypes observed was similar to the one reported for the general population in southern Brazil, with the predominance of HIV-1 subtypes C, B, CRF31_BC and unique BC recombinants. In particular, the high rate (24%) of URF_BC found here may reflect multiple exposures of the population investigated to HIV infection. We failed to find HIV-infected inmates sharing transmission clusters with each other. Importantly, the analysis of HIV-1 pol genomic fragments evidenced high rates of HIV primary and secondary (acquired) drug resistance and an alarming proportion of virologic failure among patients under treatment, unveiling suboptimal access to antiretroviral therapy (ARV), low ARV adherence and dissemination of drug resistant HIV strains in primary infections. Our results call for immediate actions of public authority to implement preventive measures, serological screening and, for HIV-seropositive subjects, clinical and treatment follow-up in order to control HIV infection and limit the spread of drug resistance strains in Brazilian prisons.