Induction of M. tuberculosis (MTB) drug resistance (DR) mutations in HIV-infected hosts and pathways of further spread of the evolutionary successful drug-resistant MTB clonal lines

<b>Introduction:</b> DR and HIV are the major challenges for worldwide eradication of tuberculosis (TB). <b>Aims:</b> To determine MTB DR mutations, prevalent in HIV⁺ and HIV^- individuals; to identify MTB clonal lines evolutionary successful with respect to DR mutations. <b>Methods:</b> MTB cultures were isolated from symptomatic patients (93 HIV⁺ and 267 HIV^-) before the onset of TB treatment and subjected to biochip hybridisation. <b>Results:</b> Latter DR mutations were statistically significant prevalent in HIV⁺ as compared to HIV^- individuals: -S531L rpoB (rifampicin resistance), -M306V embB (etambutol resistance), -‘S531L rpoB + S315T(1) katG’ (isoniazid resistance), -‘S531L rpoB + S315T(1) katG + M306V embB’. The prevalence in HIV^- individuals of S315T(1) katG not combined with S531L rpoB was statistically significant. The prevalence in HIV+ patients of the MDR marker ‘S531L rpoB + S315T(1) katG’ was demonstrated for all genotypes; its proportion amounted to 100% in B0/W148 genotype. Two distinct evolutionary successful MDR clonal lines originating in Chelyabinsk were discovered: 1) Beijing genotype with the marker ‘S531L rpoB + S315T(1) katG + M306V embB’; spread to Kemerovo, Leningrad, Stavropol, and Nizhnii Novgorod regions; 8 out of 19 (42%) cultures were XDR; 2) B0/W148 genotype with the marker ‘S531L rpoB + S315T(1) katG + N296H embB’, spread to Kemerovo, Leningrad, Nizhnii Novgorod, and Moscow regions; 2 out of 12 (17%) cultures were XDR. <b>Conclusion:</b> MTB passage through HIV⁺ patients induces new MDR (and potentially XDR) clonal lines, which retain tropism to HIV⁺ patients even after passage through HIV^- individuals.