Study calls for tailored treatments for regional HIV variations

In the absence of a vaccine, injectable antibodies are currently being tested as a way to prevent HIV infection. A vaccine triggers the body’s immune mechanism to produce antibodies — proteins that recognise and neutralise disease-causing organisms such as viruses or bacteria.

Since a vaccine against HIV is still not available, scientists have been testing the efficacy of injecting lab-engineered antibodies that have been found to prevent HIV infection.

There are several variants, or clades, of HIV in circulation. The most widely-circulating variant, HIV-1 Clade C, accounts for nearly half of all infections across the world. This is also the most common variant circulating in Africa and India.

HIV mutates very quickly after infecting a person, sometimes creating millions of slightly different versions of itself. Most antibodies are unable to fight against, or neutralise, all of them. Scientists, however, have been able to identify and isolate some rare antibodies that can neutralise a large number of these slightly different variants. For this reason, these antibodies are called broadly-neutralising antibodies, or bnAbs.

Because these were found to be ‘broadly neutralising’, scientists were working on the assumption that they would be equally effective everywhere and against every HIV variant.

The new Indian study, however, has shown that the geographical origin of the virus affected the effectiveness of these bnAbs. This multi-centre study, supported by DBT/Wellcome Trust India Alliance-funded Team Science Grant, has provided the first thorough evidence that HIV-1 clade C strains circulating in India differ genetically and in antibody response from those found in Africa.

“This study has provided vital insights into the potential of broadly neutralizing antibodies to transform HIV prevention and treatment,” said Dr Jayanta Bhattacharya, Dean, BRIC-Translational Health Science and Technology Institute (THSTI) at Faridabad and corresponding author of the study. It provides compelling evidence for the urgent development of monoclonal antibody products (which specifically target one antigen) and initiate early clinical trials in India, the study’s authors said.

The researchers studied HIV across nine regions in the country. Their findings showed the monitoring of circulating HIV helps assess how well leading bnAbs work against HIV-1 subtype C strains found in India and South Africa, which account for most of the global burden.

“Data from this study provides critical insights for developing region-specific HIV prevention strategies, either by designing vaccines that can trigger strong antibody responses or by using passive immunisation for individuals at high risk,” Bhattacharya told The Indian Express.

BRIC-THSTI, an autonomous institute under the Department of Biotechnology, Ministry of Science and Technology, through various partnerships, has been driving the development of therapeutic monoclonal antibodies as vital public health products. The institute is also working with a large network of collaborators from different institutions in India and Africa, and the International AIDS Vaccine Initiative.

Bhattacharya told The Indian Express that despite no preventive HIV vaccine, promising progress had been made that suggest that significant reduction in infection rates among high-risk groups and key populations can be achieved through the use of broadly neutralizing monoclonal antibodies administered along with antiretroviral therapy. He said that antiretroviral therapy (ART), in which patients are administered drugs that stop the replication of the virus in their bodies, had been successful in the treatment of HIV and slowed down the spread of the initial pandemic.
“However, rising global resistance to available antiretrovirals necessitates the expansion of available therapeutics and has reinvigorated efforts to design effective vaccines,” he said.

This study also identified pre-treatment drug resistance in up to 11 per cent of participants and according to the authors this finding highlighted a growing concern in HIV management.
“During our study we were able to screen (by deep sequencing) about 140 drug-naive HIV positive individuals that showed about 11 per cent pre-treatment antiretroviral drug resistance,” he said, adding that their research strongly suggested that bnAb combinations, when used with current antiretroviral therapy (ART), can effectively combat these drug-resistant HIV strains and improve prevention and treatment outcomes.

“This aligns with proofs-of-concept from trials like the Phase 2B Antibody Mediated Prevention Trial which showcased bnAb combinations as a powerful alternative for HIV prevention, particularly in vulnerable populations,” Dr Bhattacharya added.

He also observed that this study highlights that monoclonal antibodies are a high-value area for development and investment.

“There is a need and sizable market for innovative therapeutic agents that can address drug-resistant HIV,” Dr Bhattacharya said. Study authors have called for prioritization of locally relevant bnAbs.
“Identifying and selecting bnAbs appropriate for comprehensive neutralization of circulating Indian strains will be crucial,” study authors said.

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