P22

Tuberculosis is the primary cause of death among HIV-infected patients, especially in low-income countries. The clinical manifestation of TB in HIV-infected individuals is different from non-HIV patients, and it has been theorized that an altered immune status may lead to poorer control of bacteria proliferation, with larger bacterial loads and higher chances for drug resistance development. Several studies have also shown a decreased antibiotic bioavailability in HIV+ patients contributing to the acquisition of drug resistance due to suboptimal levels of drug circulation. However, evidence associating HIV with increased odds of developing resistance and the mechanisms by which this occurs are still unclear. In this study, we analyzed a cohort of 23 HIV+ and 29 HIV- TB patients from Mozambique by using deep-sequencing to study the dynamics of early drug resistance acquisition. By investigating TB serial samples over the first month of treatment, we detected a significant accumulation of low-frequency mutations in genes related to drug resistance for HIV+ individuals. We also found evidence of reduced genetic variability in epitope sites likely due to the weakened immune system in HIV+ patients versus controls, along with general trends of decreased capability to eliminate the constantly appearing bacterial diversity over treatment early stages. This suggests lower immune and antibiotic selective pressures acting over the bacterial populations of the coinfected group. Our findings give insight into the host-pathogen interacting selective factors that contribute to higher rates of treatment failure in TB-HIV coinfected individuals, and can help to design better treatment regimes for these patients.