Moderate prevalence of HIV-1 transmitted drug resistance mutations in southern Brazil

Abstract Background Despite the advances in therapy, the occurrence of drug-resistant human immunodeficiency virus type 1 (HIV-1) is a major obstacle to successful treatment. This study aimed to characterize the genetic diversity and to determine the prevalence of transmitted drug resistance mutations (TDRM) between individuals recently or chronically diagnosed with HIV-1 from Paraná, Brazil. Methods A total of 260 HIV-1 positive antiretroviral therapy-naïve patients were recruited to participate on the study, of which 39 were recently diagnosed. HIV-1 genotyping was performed using sequencing reaction followed by phylogenetic analyses to determine the HIV-1 subtype. TDRM were defined using the Calibrated Population Resistance Tool program. Results The HIV-1 subtypes frequency found in the studied population were 54.0% of subtype B, 26.7% subtype C, 6.7% subtype F1 and 12.7% recombinant forms. The overall prevalence of TDRM was 6.7%, including 13.3% for recently diagnosed subjects and 5.9% for the chronic group. Conclusions The prevalence of resistance mutations found in this study is considered moderate, thus to perform genotyping tests before the initiation of antiretroviral therapy may be important to define the first line therapy and contribute for the improvement of regional prevention strategies for epidemic control

Correction: In Vitro Activity of Rifampicin and Verapamil Combination in Multidrug-Resistant Mycobacterium tuberculosis.

The aim of the present study was to evaluate the effect of the combination of rifampicin (RIF) and verapamil (VP) against the Mycobacterium tuberculosis H37Rv reference strain and six multidrug-resistant (MDR) M. tuberculosis clinical isolates by determining Time-Kill Curves and the ability to efflux drug by fluorometry. The RIF+VP combination showed synergism in one MDR clinical isolate. For the other five MDR clinical isolates, the drug combination showed no interaction. The MDR clinical isolate had lower ethidium bromide (EtBr) accumulation when exposed to the RIF+VP combination, compared with RIF and VP exposure alone. The other MDR clinical isolates showed no significant difference in EtBr accumulation. These results suggest greater efflux action in one of the MDR clinical isolates compared with the M. tuberculosis H37Rv reference strain. The other five MDR isolates may have additional mechanisms of drug resistance to RIF. The use of the RIF+VP combination made one MDR bacillus more susceptible to RIF probably by inhibiting efflux pumps, and this combination therapy, in some cases, may contribute to a reduction of resistance to RIF in M. tuberculosis

Time-kill curve of the <i>Mycobacterium tuberculosis</i> H₃₇Rv reference strain and multidrug-resistant clinical isolates 71A, 18, 19, 109, 3614, and 64A exposed to rifampicin (RIF), verapamil (VP), and RIF+VP combination for 7 days at 35–37°C.

<p>Time-kill curve of the <i>Mycobacterium tuberculosis</i> H₃₇Rv reference strain and multidrug-resistant clinical isolates 71A, 18, 19, 109, 3614, and 64A exposed to rifampicin (RIF), verapamil (VP), and RIF+VP combination for 7 days at 35–37°C.</p

Molecular characterization, drug susceptibility profile, minimum inhibitory concentration, and drug interaction in the <i>M. tuberculosis</i> H₃₇Rv reference strain and multidrug-resistant clinical isolates.

<p>R, resistant; NP, not performed; INH, isoniazid; RIF, rifampicin; EMB, ethambutol; PZA, pirazinamid; FICI, fractional inhibitory concentration index; REDCA; Resazurin Drugs Combination Microtiter Assay. VP, verapamil; EtBr, ethidium bromide. Numbers in bold represent synergism.</p><p>Molecular characterization, drug susceptibility profile, minimum inhibitory concentration, and drug interaction in the <i>M. tuberculosis</i> H₃₇Rv reference strain and multidrug-resistant clinical isolates.</p