Regional HIV Variations Challenge Universal Antibody Protection
Groundbreaking research from Indian scientists has revealed that the most promising antibody-based treatments for HIV do not provide equal protection across different geographical regions. The study, published in the Journal of Virology, demonstrates that the effectiveness of broadly neutralizing antibodies (bnAbs) is significantly influenced by the geographic origin of the HIV virus.
This discovery comes at a crucial time when injectable antibodies are being tested as a preventive measure against HIV infection in the absence of an effective vaccine. The research highlights the urgent need to develop region-specific HIV prevention strategies and customize antibody treatments for different populations.
Understanding HIV Variants and Antibody Response
HIV exists in multiple variants or clades circulating globally. HIV-1 Clade C, the most widely circulating variant, accounts for nearly half of all infections worldwide and is the dominant strain found in both Africa and India. The virus's rapid mutation rate creates millions of slightly different versions within an infected person, making it challenging for most antibodies to neutralize all variants.
Scientists had previously identified rare broadly neutralizing antibodies that can target multiple HIV variants. These bnAbs were considered universal solutions that would work equally well against all HIV strains regardless of geographical origin. However, the new study challenges this assumption.
The multi-center research supported by DBT/Wellcome Trust India Alliance provides the first comprehensive evidence that HIV-1 clade C strains circulating in India differ significantly from African strains in their genomic composition and susceptibility to clinically relevant bnAbs.
Customized Approaches for Indian Context
Dr. Jayanta Bhattacharya, Dean of BRIC-Translational Health Science and Technology Institute (THSTI) in Faridabad and corresponding author of the study, emphasized the transformative potential of these findings. "This study has provided vital insights into the potential of broadly neutralizing antibodies to transform HIV prevention and treatment," he told The Indian Express.
The research involved extensive virological and immunological surveillance of HIV across nine regions in India. The findings demonstrate that monitoring circulating HIV strains helps assess how effectively leading bnAbs work against HIV-1 subtype C strains found in India and South Africa - regions that together account for most of the global HIV burden.
BRIC-THSTI, an autonomous institute under the Department of Biotechnology, has been driving the development of therapeutic monoclonal antibodies as vital public health products through partnerships with institutions in India, Africa, and the International AIDS Vaccine Initiative (IAVI).
Drug Resistance and Future Strategies
The study uncovered another critical concern: pre-treatment drug resistance in up to 11% of participants. During the research, scientists screened approximately 140 drug-naive HIV-positive individuals using deep sequencing technology, revealing significant antiretroviral drug resistance before treatment even began.
Dr. Bhattacharya explained that bnAb combinations used with current antiretroviral therapy (ART) can effectively combat these drug-resistant HIV strains and improve prevention and treatment outcomes. This approach aligns with evidence from trials like the Phase 2B Antibody Mediated Prevention Trial, which demonstrated bnAb combinations as powerful alternatives for HIV prevention, particularly in vulnerable populations.
The authors strongly recommend prioritizing locally relevant bnAbs and initiating early-phase clinical trials in India. "Identifying and selecting bnAbs appropriate for comprehensive neutralization of circulating Indian strains will be crucial," the study authors emphasized.
Despite the absence of a preventive HIV vaccine, Dr. Bhattacharya noted promising progress suggesting that significant reduction in infection rates among high-risk groups can be achieved through broadly neutralizing monoclonal antibodies administered alongside antiretroviral therapy.
The research underscores that monoclonal antibodies represent a high-value area for development and investment, with a substantial market for innovative therapeutic agents that can address drug-resistant HIV. This study marks a pivotal step toward developing region-specific HIV prevention strategies through either designed vaccines that trigger strong antibody responses or passive immunization for high-risk individuals.
