Forty years after it first appeared, there is finally a realistic prospect of eradicating HIV using the combination of prevention and scientific advances. Research into a cure is making great strides, and we may have a vaccine in a few years too. As with other areas of medicine, investment will be a key driver for change.

 

The alert was raised on the 5th of June 1981. A rare form of pneumonia that was ravaging a gay district in San Francisco became the subject of an official communication from the Centers for Disease Control and Prevention (CDC). The human immunodeficiency virus was finally isolated two years later by two French researchers from the Institut Pasteur: Luc Montagnier and Françoise Barré-Sinoussi. Transmitted sexually, through blood, or breast milk from mother to her child, HIV causes a serious viral infection that gradually destroys the immune system. HIV causes AIDS, the Acquired Immune Deficiency Syndrome, which is the final stage of the disease. AIDS patients often acquire life-threatening secondary opportunistic diseases, such as candidiasis, tuberculosis, cerebral toxoplasmosis and Kaposi’s sarcoma.

According to UNAIDS, in 2020 there were the total 37.7 million people who tested positive for HIV at some point in their life. Two-thirds of them lived in sub-Saharan Africa, which was home to most of those who died from AIDS last year globally (680,000 people died). The human toll is not insignificant, but it has halved over the past decade. Since the start of the epidemic, 36.3 million people died from AIDS-related illnesses.

 

A priority area for investment

The Joint United Nations Programme on HIV and AIDS (UNAIDS) has set an ambitious goal of eradicating HIV by 2030. It hopes to achieve this by helping bring about a significant improvement in both HIV testing and in access to treatment, This would cover not only poorer countries but also their Western peers with the highest HIV infection rates.

As is often the case, investment will be one of the main drivers of change. Statistical modelling predicts that an annual investment of USD 29 billion is needed in low and middle income countries between now and 2025. Correctly invested, this money is expected to result in a very significant drop in the numbers of deaths and new infections.

However, UNAIDS has fallen behind on its programme targets whilst also having to contend with the Covid-19 pandemic. Closures and health restrictions have resulted in significant delays in diagnosis and treatment. People infected with HIV are more vulnerable from COVID-19 and have a risk of death twice as high as that of the general population. In many poorer countries, HIV positive people do not have access to COVID vaccines, especially in Africa.

 

A wide range of therapies

Thanks to advances in antiretroviral combination therapy, it has become possible for HIV positive people to lead a normal life, with their life-threatening disease. Several therapeutic options now make it possible to slow down its spread, but also prevent its appearance. Triple combination therapies have revolutionised care and are now the standard treatment for seropositive individuals. A combination of three antiretroviral molecules is used to block the replication of the virus and contain the viral load of patients, thus limiting their contagiousness. Treatments are also increasingly effective and cause fewer and fewer side effects. According to UNAIDS, 27.5 million people had access to such therapy last year, or nearly three-quarters of the target population. 

Where there is a risk of possible transmission, post-exposure prophylaxis started within 48 hours after exposure and taken diligently for 28 days can prevent the virus from taking hold. Conversely, pre-exposure prophylaxis prevents any infection. Composed of two antiretrovirals, it is intended for seronegative populations at high risk, such as injecting drug users or members of the LGBT community. If it is administered before and after contact, its clinical efficacy is estimated at 99%.

 

Productive pharmaceutical research

A radical pharmaceutical development could soon remove the major constraint of having to take daily medication. Recently approved in the United States and Europe, a long-acting injectable dual therapy can now be prescribed to patients stabilised on daily oral therapy. As it involves a bimonthly treatment, it should significantly improve the quality of life of patients. The EMA (European Medicines Agency) is currently reviewing another injectable medication that could soon be approved for use in patients whose treatment has failed due to multi-drug resistance. Taken every six months, it would be used in combination with one or more antiretrovirals. Pharmaceutical research is fairly active in this area and is not merely limited to just these two therapeutic innovations. Prolonged-release tablets, auto-injectors, subcutaneous implants are some of the concrete solutions currently in the pipeline.

In addition, a vaccine for HIV could also become a reality in the coming years, notably thanks to messenger RNA technology. A long-awaited clinical trial was also recently launched. Phase I is scheduled to last two years, i.e. until April 20231.

 

Promising leads

Scripps Research and International AIDS Vaccine Initiative have a head start. At the end of the first clinical phase, their vaccine candidate reported a 97% efficacy. Based on the stimulation of specific immune cells, the technique could even be used against other viruses. Less advanced but no less promising, a range of different research projects are ongoing. They include encouraging research into a vaccine consisting of antibodies genetically modified using molecular scissors2. Based on compelling evidence in mice, it could prevent HIV infection. Drug research is also making great strides. Researchers at the University of Utah have developed an injectable drug capable of preventing and curing people with HIV3. Successfully tested on primates, human testing is due to start in the near future.

HIV/AIDS: key figures

  • 37.7 million people are living with HIV
  • 1.5 million new infections have been reported
  • 680,000 people have died of an AIDS-related illness 
  • 27.5 million people have access to triple antiretroviral therapy
  • 16% of people living with HIV are unaware of their HIV status
  • 66% of people living with HIV have an undetectable viral load

Source: UNAIDS - Figures as of 31 December 2020

 

Confirmed case of a second person cured of HIV

The news caused a stir in the international scientific community. A British patient is now considered as the second case of functional remission from HIV infection. After receiving a stem cell transplant at the end of 2017, Adam Castillejo was able to stop taking his antiretroviral treatment and has not relapsed. Confirmed thirty months later in The Lancet*, this great victory over the disease was nevertheless tarnished by the death of the famous “Berlin patient”. Declared cured by his doctors ten years ago after a double bone marrow transplant which had allowed him to become seronegative, the American Timothy Ray Brown succumbed to cancer unrelated to his previous HIV infection. He died on 30 September 2020 at the age of 54.

*“Evidence for HIV-1 cure after CCR5Δ32/Δ32 allogeneic haemopoietic stem-cell transplantation 30 months post analytical treatment interruption: a case report”, The Lancet HIV (March 2020).

 


1 “A Phase 1 Study to Evaluate the Safety and Immunogenicity of eOD-GT8 60mer mRNA Vaccine (mRNA-1644) and Core-g28v2 60mer mRNA Vaccine (mRNA-1644v2-Core) », ClinicalTrials.gov (August 2021).

2 « Vaccine elicitation of HIV broadly neutralizing antibodies from engineered B cells », Nature Communications (November 2020).

3 “Dual CD4-based CAR T cells with distinct costimulatory domains mitigate HIV pathogenesis in vivo”, Nature Medicine (August 2020).