Immune and viral surveillance of HIV-1C reservoirs in an Indian cohort
Indian HIV-1 subtype C, infecting 2.6 million individuals, demonstrates unique geospatial diversity reflecting distinct evolution and host-pathogen interactions that may instruct the development of region-specific therapeutic strategies. An Indian PLHIV cohort was profiled for immune dysfunction, proviral load, broadly neutralizing antibody sensitivity, and drug resistance mutations in putative CD4<sup>+</sup> T cell reservoirs. We demonstrate therapy state specific immune dysfunction, including in ART responding individuals, coincident but not correlated with stable proviral load, apparently enriched in CD4<sup>+</sup> T memory subsets. Reservoir derived full length <i>envs</i> displayed distinct neutralization profiles against best-in-class broadly neutralizing antibodies, highlighting the need for a combinatorial approach to target potential breakthrough viruses. Surveillance of the archival repertoire demonstrated the occurrence of drug resistance conferring mutations (>10%) across therapy states, including instances of primary and acquired resistance to recently introduced integrase strand transfer inhibitors. Our data, underlines the need for incorporating reservoir diversity in intervention and management strategies.
Authors
- Nandini Kasarpalkar (ORCID: https://orcid.org/0000-0001-6625-8897)
- Satyajit Musale
- Jyoti Sutar (ORCID: https://orcid.org/0000-0002-5869-2156)
- Tushar Pandey (ORCID: https://orcid.org/0000-0002-0829-0263)
- Sushma Gaikwad
- Snehal Kaginkar (ORCID: https://orcid.org/0000-0001-7200-2951)
- Jayanthi Shastri (ORCID: https://orcid.org/0000-0001-7360-564X)
- Sharad Bhagat (ORCID: https://orcid.org/0000-0002-4680-1706)
- Jayanta Bhattacharya (ORCID: https://orcid.org/0000-0001-8644-2915)
- Shilpa Velhal
- Vikrant M. Bhor (ORCID: https://orcid.org/0000-0001-9897-4505)
- Varsha Padwal
- Ranajoy Mullick (ORCID: https://orcid.org/0009-0002-9481-9027)
- Neha Sehgal (ORCID: https://orcid.org/0000-0002-2812-1977)
- Pratik Devadiga (ORCID: https://orcid.org/0000-0003-3256-0814)
- Sayantani Ghosh
- Pranay Gurav (ORCID: https://orcid.org/0000-0003-0475-446X)
- Kavita Joshi (ORCID: https://orcid.org/0000-0002-0915-9961)
- Nayana Ingole (ORCID: https://orcid.org/0000-0002-5279-3765)
- Vainav Patel (ORCID: https://orcid.org/0000-0001-6661-3238)
- Priyanka Jayal
- Shilpa Bhowmick (ORCID: https://orcid.org/0000-0002-9586-3989)
- Sapna Yadav (ORCID: https://orcid.org/0000-0001-6038-880X)
- Priya Patil
- Amit Kumar Singh (ORCID: https://orcid.org/0000-0002-1913-1129)
- Nandan Mohite
- Sameen Khan
- Ritam Chatterjee
- Vidya Nagar
- Gita Nataraj
- Sachee Agrawal (ORCID: https://orcid.org/0009-0008-4240-8086)
- Namrata Neman
- Varsha Kalsulkar
Institutions
- International AIDS Vaccine Initiative (US)
- National Institute for Research in Reproductive Health (IN)
- Grant Medical College and Sir Jamshedjee Jeejeebhoy Group of Hospitals (IN)
- Narsee Monjee Institute of Management Studies (IN)
- Translational Health Science and Technology Institute (IN)
- Topiwala National Medical College & BYL Nair Charitable Hospital (IN)
- Shree Guru Gobind Singh Tricentenary University (IN)
- Guavus (India) (IN)
- King Edward Memorial Hospital Research Centre (IN)
Publication Details
- Journal
- iScience
- Published
- 2025-11-28
- DOI
- https://doi.org/10.1016/j.isci.2025.114278
- Primary Topic
- HIV Research and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00