Vaccines have been developed against diseases such as smallpox, polio or poliomyelitis, tuberculosis, malaria and coronavirus, but there are none against HIV yet.

It took three decades for the World Health Organization to approve a vaccine for malaria while there has been one tuberculosis vaccine in the last 100 years. On the other hand, the world witnessed swift development and rapid deployment of at least 10 vaccines for COVID-19 within two years from the beginning of the pandemic in 2020.

However, it's been nearly four decades since Human Immunodeficiency Virus (HIV) was first discovered as the cause of Acquired Immunodeficiency Syndrome (AIDS) and there is no vaccine against it yet.

Around 38 million people are living with HIV/AIDS across the world and the disease killed more than half a million people in 2020, according to the International AIDS Vaccine Initiative (IAVI). Around 27% of 1.5 million people, who had contracted the disease in 2020, did not have access to treatment and could infect others, showed IAVI data.

On HIV Vaccine Awareness Day, health experts FactChecker spoke to explain how far science has come in developing an HIV vaccine, the hurdles faced and whether there are any recent findings of a potential HIV vaccine. But before that, let's take stock of the disease's prevalence in India.

India Has Highest HIV Burden in Asia

India has the second-highest HIV burden globally, with an estimated 23.19 lakh people living with HIV in 2020, as per the India HIV Estimates Report 2020, published by National AIDS Control Organization (NACO) and Indian Council of Medical Research (ICMR).

Although, nationally, new HIV infections declined by 48% in the last decade in comparison to the global average of 23% (between 2010 and 2019), this rate of decline is far from the envisaged target of 75%, the report said.

While overall HIV prevalence is low in the country, the HIV epidemic continues to be high (more than 1%) in three north-eastern states: Mizoram had the highest estimated adult HIV prevalence of 2.37%, followed by Nagaland (1.44%) and Manipur (1.15%).

Further, Andhra Pradesh (0.66%), Meghalaya (0.53%), Telangana (0.48%) and Karnataka (0.45%) were the other states with an adult prevalence higher than 0.40%. Besides these states, Delhi, Maharashtra, Puducherry, Punjab, Goa and Tamil Nadu had an estimated adult HIV prevalence greater than the national prevalence (0.22%).

When it comes to deaths, there were approximately 51,000 deaths among people living with HIV in 2020, with almost 63% deaths being AIDS-related. Overall, annual AIDS-related mortality declined by 88% since its peak in 2005 and by 82% since 2010, as per the 2020 report.

Hurdles in Making HIV Vaccine

When HIV was discovered and established as the cause of AIDS in 1983-1984, many people were seldom aware of the complexity of the virus. Health experts FactChecker spoke to highlighted how the lack of a protective immune response against HIV remains one of the most compelling hurdles for development of an HIV vaccine.

Dr Jayanta Bhattacharya, Director, Antibody Translational Research Program at IAVI, said another significant challenge is identifying effective immunogens, or substances that produce an immune response, that could mount broad and long-lasting immunity and simultaneously tackle the enormous genetic diversity and variability that HIV displays.

"Unlike COVID-19, HIV is an unstable virus," said Dr Ishwar Gilada, Consultant in HIV, STDs and Infectious Diseases at Mumbai's Unison Medicare & Research Centre and President, AIDS Society of India (ASI). "There are far more variations. There are two types of HIV virus: HIV-1, HIV-2 and some people have HIV-1 & 2 viruses. Further HIV-1 has Type A,B,C,D,E and then Type C has C1, C2 and C3. Indians mostly have HIV C1 type which is also common in Brazil and South Africa."

Doctors and epidemiologists believe HIV is one of the most complicated viruses ever identified. "The retrovirus (a type of virus that has RNA in its genetic material) hijacks the body's own immune response and destroys the very immune system that a vaccine traditionally triggers," said Dr Bhattacharya.

HIV mutates rapidly and imperfectly within a population, as well as within an individual. This means it can become resistant to the immune defences created by vaccines very quickly, just like it can develop drug resistance. "So, scientists will need to create an immune response that neutralises the virus before it starts diversifying," Dr Bhattacharya explained.

Since the virus only affects human beings, there is no adequate model for early testing of candidates in animals. "It is still being investigated if a single universal vaccine can even create immunity against the different subtypes, or clades, of the HIV virus, or if a different vaccine must be developed against each clade," said the IAVI researcher.

How Far has Science Come

Vaccine development is a very tedious procedure and, unlike the COVID scenario, vaccine development generally is never fast-tracked and takes around 8 to 10 years. Currently, more than 20 HIV vaccine clinical trials are ongoing and until now five large-scale Phase 3 vaccine efficacy trials against HIV have been conducted. While the first three of these failed, the fourth trial (Thai RV144 trial) initially reported minimum protection against the acquisition of HIV infection among vaccinated individuals.

The Uhambo trial (also called HVTN 702), which began in 2016 in South Africa and which was trying to improve upon the vaccine trial conducted in Thailand in 2009, was halted in 2020 because, although the vaccine candidate was safe, data showed that the vaccine was not effective against HIV. Similarly, the proof-of-concept study Imbokodo (also called HVTN 705), begun in Sub-Saharan Africa in 2017, while safe, did not show efficacy overall and was, therefore, stopped in 2021.

Both doctors stressed that it is difficult to commit to a timeline for the development of an HIV vaccine given the complex nature of the virus. But lessons from the rapid development and deployment of, and investment in, COVID-19 vaccines can be applied to HIV vaccine research as well.

"The recent publication of the Antibody-Mediated Prevention study has shown that broadly neutralising antibodies (bnAbs) can prevent HIV transmission, if the antibodies are well-matched to viral strains and present at a high enough concentration," said Dr Bhattacharya.

There are two specific COVID vaccine platforms, which can be used for HIV. One is mRNA and the second one is DNA. "Broadly neutralising antibodies (BNAbs) are produced by certain types of B immunity cells. The mRNA vaccine aims to stimulate production of bnAbs that can act against many variants of HIV," said Dr Gilada. So, what this mRNA vaccine will do is instigate our B-cells and try to produce more neutralising antibodies. The neutralising antibodies are produced in people who are HIV-negative and if that person is exposed to HIV, the neutralising antibodies will neutralise HIV and won't allow the HIV negative person to get infected, the Mumba-based doctor explained.

IAVI, along with Scripps Research in La Jolla, USA, has developed IAVI G001, a potential vaccine in its first phase of trial. The trial conducted on humans was designed to assess the safety of the vaccine candidate and test the hypothesis that a certain approach that primes the immune system to develop a specific type of antibody could be successfully utilised. The study found that 97% of the participants who received the vaccine had the immune response researchers were hoping for. "Building on the promising results from IAVI G001, the Phase I clinical trial, IAVI G002, was launched in January 2022, in partnership with Moderna," said Dr Bhattacharya.

The trial is designed to test the hypothesis that sequential vaccination through a messenger RNA platform (mRNA) can induce specific classes of B-cell responses and guide them toward broadly neutralising antibody (bnAb) development. "Given the speed with which mRNA vaccines can be produced, as seen during the COVID-19 pandemic, this platform offers a responsive approach to vaccine design and testing, potentially shaving off years from typical vaccine development timelines," Dr Bhattacharya concluded.