Dawn breaks in Africa: New hope for HIV patients

Dawn breaks on the shores of Africa

HIV remains an ongoing epidemic – incurable, but highly preventable. Individuals at risk of contracting the virus, such as those with HIV-positive partners, are typically given Pre-exposure Prophylaxis (PrEP) in the form of a daily pill. Although PrEP is efficacious and significantly lowers the risk of contracting HIV, factors such as stigma, accessibility, and misconceptions around the likelihood of disease contraction, prevent people from adhering to this preventative regime. The search for a more accessible form of HIV prevention is therefore ongoing.

The structure of HIV is quite simple. It contains a single strand of RNA that encodes all its necessary functions, along with enzymes critical to its survival, packaged in a protein lattice known as a capsid. The virus docks onto human immune cells with receptors present on its capsid. Next, viral enzymes convert the single strand of RNA into double-stranded DNA that integrates with the immune cell’s DNA. The virus is now able to hijack the cell’s replication machinery, forcing the cell to mistakenly produce more viruses instead of more immune cells. Once enough new HIV molecules have been created, the HIV kills the immune cell and spreads to new targets.

Traditionally, the focus for HIV treatment and prevention thus far has been on inhibiting the activity of the viral enzymes. However, a small molecule inhibitor, Lenacapavir, has been developed to interfere with the HIV-1 capsid protein. Lenacapavir, sold as Sunlenca and manufactured by Gilead Sciences, is administered as an oral pill for the treatment of HIV in patients who have already tried several treatment options. Research teams from South Africa and Uganda have engineered this molecule to improve its solubility, making it possible to inject Lenacapavir rather than ingesting it. The injectable version of Lenacapavir stays in the human system for longer than the oral version, prompting researchers to test its feasibility as an HIV vaccine administered twice yearly.

PURPOSE 1, a clinical trial conducted in South Africa and Uganda, tested the safety and efficacy of Lenacapavir in a cohort of over 5,000 cis-gender women and girls. Against the backdrop of 3.5 HIV infections per 100 people, the use of Lenacapavir as PrEP resulted in zero HIV infections. That’s right – it was 100% effective. The research further demonstrated that Lenacapavir results in rigidity of the protein capsid, rendering it unable to slip through the immune cell nucleus and preventing the virus from replicating. Even if the HIV manages to replicate, Lenacapavir interferes with the production of structurally sound capsids, preventing the formation of new, well-functioning HIV molecules.

This astounding finding led to the commencement of PURPOSE 2, in which Lenacapavir was tested on a more diverse cohort of cis-gender, gay, and bisexual men, as well as transgender and non-binary people across 88 sites. The PURPOSE 2 results showed that injectable Lenacapavir was 96% effective, with only 2 incidents of HIV infection in 2,179 participants. It is important to note that the two participants who contracted HIV did so before receiving their second injection of Lenacapavir. This suggests that complete protection may only be achieved after the second injection. However, further research is necessary to confirm this.

This research won Science’s “Breakthrough of the Year 2024” Award and given the estimated 1.3 million cases of HIV infections globally, its significance becomes evident. What a proudly African moment.