SEQUENCE NOTES Absence of Integrase Strand Transfer Inhibitor Associated Resistance in Antiretroviral Therapy Naı ¨ve and Experienced Individuals from Western India Santosh Karade, 1 Sourav Sen, 1 and Vangal Krishnaswamy Sashindran 2 Abstract The Indian national AIDS control program heavily relies on low cost nucleoside reverse transcriptase inhibitor (NRTI) and non-nucleoside reverse transcriptase inhibitor (NNRTI). With global increase in resistance to these, alternative antiretroviral combinations need to be explored. Owing to higher potency, better efficacy and tolerability, recently WHO recommended integrase strand transfer inhibitor (INSTI) based first-line antiretroviral therapy (ART). There is lack of INSTI resistance surveillance data from India. Thus, there is a need to analyze integrase (IN) gene from primarily HIV-1 subtype C infected Indian population, before widespread introduction of INSTI in first-line ART. Plasma samples were collected from INSTI naı ¨ve individuals reporting to ART centre of Pune, India. RNA was extracted and IN gene was amplified by nested polymerase chain reaction (PCR) using prior published primers. PCR product of 867 bp was bi-directionally sequenced and resistance associated mutation were analyzed using Stanford University HIV drug resistance algorithm. A total of 58 HIV-1 sequences from 62 INSTI naı ¨ve individuals were successfully genotyped. Of these 58, 40 were ART naı ¨ve, newly diagnosed and remaining individuals were on NRTI, NNRTI, or protease inhibitors based failing regimen. The commonest subtype identified in the study was C (93%) followed by A1 (3.5%). A total of 191 (66.31%) fully conserved amino acid (aa) positions were observed in IN gene. Overall there was absence of major INSTI resistance mutation, however, E157Q (13.79%) emerged as common polymorphic mutation. Other accessory mutations were L74IM (34.48%), Q95K (1.72%), and T97A (1.72%). To conclude, this first Indian study on primarily HIV-1 subtype C sequences characterized aa variations in IN gene and indicated absence of major INSTI resistance associated mutations. Keywords: antiretroviral therapy, HIV-1 subtype C, integrase resistance, mutation, URF T he recent Indian HIV estimate indicates *2.14 (15.90–28.39) million individuals living with HIV and AIDS by the year 2017. 1 Initiated in April 2004, the Indian national AIDS control program (NACP) adopted public health approach for initiating free antiretroviral therapy (ART) for all eligible people. 2 Currently, TLE or tenofovir disoproxil fu- marate (TDF), lamivudine (3TC), and efavirenz (EFV) based fixed dose combination is preferred first-line regimen for all HIV seropositive individuals irrespective of CD4 cell counts. Since its inception, the program heavily rely on low cost nu- cleos(t)ide reverse transcriptase inhibitors (NRTIs) and non- nucleoside reverse transcriptase inhibitors (NNRTIs), whereas protease inhibitors (PI) are included in second-line regimen. With global increase in the pretreatment resistance, espe- cially to NNRTI analog, 3 alternative antiretroviral combina- tions need to be explored in resource limited settings. Owing to higher genetic barrier, better efficacy, and tolerability, re- cently WHO recommended integrase strand transfer inhibitors (INSTI), namely dolutegravir (DTG) and raltegravir (RTG) based regimen as preferred first-line and alternate first-line regimen respectively. 4 INSTI are presently used as third-line option in Indian settings. INSTI based ART provides additional therapeutic options to achieve durable viral suppression. However, there are limited data available on natural polymor- phisms of integrase (IN) gene of HIV-1 subtype C of Indian origin. Thus, there is a need for genetic analysis of IN gene from primarily subtype C infected Indian patients, before widespread introduction of DTG and RTG based regimen in the program. Between May and October 2018, viral RNA was ex- tracted from 500 lL plasma sample from 62 INSTI naı ¨ve Departments of 1 Microbiology and 2 Medicine, Armed Forces Medical College, Pune, India. AIDS RESEARCH AND HUMAN RETROVIRUSES Volume 35, Number 6, 2019 ª Mary Ann Liebert, Inc. DOI: 10.1089/aid.2018.0272 567 Downloaded by 117.242.28.212 from www.liebertpub.com at 04/15/20. For personal use only.