Detection of Drug Resistance Mutations in the Reverse Transcriptase Gene of HIV-1-Infected North Indian Population Failing First-Line Antiretroviral Therapy "A Follow-Up Cohort Study".

We aim to characterize the drug resistance mutations in reverse transcriptase gene of HIV-1 subtype C-infected North Indian population in those who are failing first-line antiretroviral therapy (ART) and if these mutations are associated with mortality. We also attempted the assessment of switch over to second-line antiretroviral therapy in these patients. Based on the immunological marker CD4 count (<350 cubic/mm), 192 HIV/AIDS patients were selected and viral load was estimated in those who were enrolled from December 2009 to November 2016. Based on viral load, genotyping was carried out in 57 HIV-1 isolates (VL ≥1,000 copies/mL) by sequencing and drug resistance mutations were examined through the Stanford HIV Drug Resistance Database, USA. Among them, 21 (36.84%) first-line ART failure patients were shifted to second-line ART. These patients were followed for a period wide ranging from 10 months to 11 years. Drug resistance mutation M184V (ATG to GTA) (63.15%) associated with lamivudine and abacavir and K103N (AAG or AAA to AAU) (36.84%) associated with efavirenz and nevirapine were predominantly identified in first-line ART failure patients. During follow-up, it was observed that 3 out of 21 who were in second-line ART died, whereas 9 out of 36 died who were in the first-line ART. No mutation could be associated with mortality although TAM-2 mutations were absent in patients who died. This study indorses the need for a facility for viral load estimation and resistance monitoring in each treatment failure patient and availability of appropriate antiretroviral therapies.

Infection free "resisters" among household contacts of adult pulmonary tuberculosis.

Despite substantial exposure to infectious pulmonary tuberculosis (TB) cases, some household contacts (HHC) never acquire latent TB infection (LTBI). Characterizing these "resisters" can inform who to study immunologically for the development of TB vaccines. We enrolled HHCs of culture-confirmed adult pulmonary TB in India who underwent LTBI testing using tuberculin skin test (TST) and QuantiFERON TB Gold Test-in-tube (QFT-GIT) at baseline and, if negative by both (<5mm TST and <0.35IU/mL QFT-GIT), underwent follow-up testing at 4-6 and/or 12 months. We defined persons with persistently negative LTBI tests at both baseline and followup as pLTBI- and resisters as those who had a high exposure to TB using a published score and remained pLTBI-. We calculated the proportion of resisters overall and resisters with complete absence of response to LTBI tests (0mm TST and/or QFT-GIT <0.01 IU/ml). Using random effects Poisson regression, we assessed factors associated with pLTBI-. Of 799 HHCs in 355 households, 67 (8%) were pLTBI- at 12 months; 52 (6.5%) pLTBI- in 39 households were resisters. Complete absence of response to LTBI tests was found in 27 (53%) resisters. No epidemiological characteristics were associated with the pLTBI- phenotype. LTBI free resisters among HHC exist but are uncommon and are without distinguishing epidemiologic characteristics. Assessing the genetic and immunologic features of such resister individuals is likely to elucidate mechanisms of protective immunity to TB.