Sexual & Reproductive Health
HIV continues to be a major public health issue, with almost 40 million people living with the virus as of 2020, the majority in LMICs.
The virus attacks and destroys CD4 cells in the human immune system; without treatment, infected individuals become increasingly susceptible to other diseases, and eventually develop acquired immune deficiency syndrome (AIDS). People with AIDS often die from opportunistic infections like tuberculosis or cryptococcal meningitis, or cancers like Kaposi’s sarcoma.
There is currently no vaccine against HIV, due to the challenge posed by the virus’ genetic elasticity. All Phase III candidates so far have failed to demonstrate efficacy, with the most recent Phase III trial (Mosaico) discontinued in January 2023 after disappointing interim results. Passive immunisation with biologics such as monoclonal antibodies (mAbs) remain promising, with WHO and IAVI publishing preferred product characteristics to guide R&D. AMP mAb trials demonstrated proof of concept, though revealed that one monoclonal antibody alone is insufficient. Microbicides – preventive tools designed to block transmission of HIV through the vaginal or rectal mucosa – have shown promise as a complementary tool, with the dapivirine vaginal ring included in WHO’s prequalification list in 2020. Current methods for early diagnosis are often not adapted to, or suitable for, developing countries, especially for early infant diagnosis. However, there is progress towards robust, point-of-care diagnostics, culminating in the recent WHO prequalification of several promising candidates.
The most advanced HIV vaccine candidate, Ad26.Mos4.HIV, was discontinued in early 2023 after failing to meet interim endpoints, marking the end of purely non-neutralising approaches to vaccination. Focus shifted towards immunogen design directed at antigens eliciting bNAbs response in combination with approaches that elicit cellular/innate response, such as T-cell-based vaccines. Using the human cytomegalovirus vector platform, Vir Biotechnology dosed the first participants in a Phase I trial in South Africa and the US, investigating their novel T-cell VIR-1388 vaccine. Another leading vaccine strategy, germline targeting, uses engineered proteins to raise B-cells with the genetic properties necessary for producing bNAbs. The nanoparticle-based engineered construct eOD-GT8 60-mer, from Fred Hutchinson Cancer Research Center, Scripps Research and IAVI, successfully induced robust CD4 T-cell responses in nearly all participants in a Phase I trial. For the PEPFAR program, the US FDA approved taste-masked dispersible and immediate-release single tablet fixed-dose formulations of abacavir/dolutegravir/lamivudine for children, the second child-friendly drug specifically approved for LMICs behind DNDi’s ‘4-in-1’. United Biopharma’s UB421, a CD4 attachment inhibitor-based monoclonal antibody, began Phase III trials.