Preventive HIV Vaccines
1.0 Global Investment in Preventive HIV Vaccines R&D
In 2021, global investment in preventive HIV vaccines R&D decreased US$30 million from the previous year, for a total of US$795 million. The public sector made up 84 percent of overall investment, at US$671 million, with the philanthropic and commercial sectors contributing an estimated 8 percent and 7 percent, respectively.
At US$637 million, the US public sector remained the largest donor of preventive HIV vaccine research globally despite decreased investment by two percent from 2020 levels. Overall European investment in preventive HIV vaccine R&D increased by 47 percent and amounted to US$27.5 million.
Philanthropic contributions decreased from US$93.5 million to US$66 million in 2021 due to year-to-year reduction in BMGF funding. BMGF remains the largest philanthropic funder of HIV vaccine research, accounting for 99 percent of philanthropic funding.
1.1 Developments in the Field of Preventive HIV Vaccine Research
As of June 2023, only one HIV vaccine efficacy trial is underway, known as PrEPVacc. The PrEPVacc trial is simultaneously testing experimental HIV vaccines and oral PrEP, but the trial is not intended to result in licensure of a product. Following disappointing results of the Uhambo/HVTN 702 trial in 2020 and the Imbokodo/HVTN 705 trial in 2021, the Mosaico/HVTN 706 ended in early 2023, after findings showed this vaccine candidate did not significantly reduce the risk of HIV infection.
Results from the Antibody Mediated Prevention (AMP) trials also presented in 2021, showed that the VRC01 antibody did not significantly reduce the overall risk of HIV acquisition in participants who received the antibody compared to those who received the placebo. However, VRC01 did safely and effectively reduce the risk of acquiring HIV from strains of the virus that are classified as “highly-sensitive” to VRC01. The trials suggest a single bNAb, such as VRC01, does not offer sufficient protection against a broad range of HIV, and a combination of bNAbs is likely needed to achieve broad protection.
Several phase 1 trials have subsequently started to explore mRNA-based technology to test new HIV vaccine candidates that might elicit similar antibody responses, and there are additional studies looking at the direct administration of combinations of neutralizing antibodies.
1.2 Funding Allocations for Preventive HIV Vaccine R&D
Funding for HIV vaccine R&D was allocated to the following areas in 2021: basic research (18.9 percent), preclinical (43.6 percent), clinical (36.8 percent) and advocacy and policy (< 1 percent). 2021 allocations are similar compared to those of 2020.
The lack of efficacy in these recent late-phase efficacy trials has prompted researchers to look for trial designs that can quickly ask and answer key questions, inform decisions about which vaccine candidates to advance into larger trials and, hopefully, increase the probability of demonstrating efficacy.
Researchers, funders and vaccine developers are now focusing on experimental medicine vaccine trials (EMVTs; also sometimes referred to as Discovery Medicine trials) to build on current knowledge and help to advance the field. This significant shift upstream in research will likely influence the funding allocations in future years.
2.0 Global Investment in Microbicide R&D
Investment in microbicide R&D totaled US$112.7 million in 2021, a 20 percent decrease from 2020 funding levels. This is the seventh consecutive year of declining microbicide funding and the lowest investment levels reported since 2003. The majority of funding originated from the public sector (99 percent), while philanthropic funding trailed (1 percent).
It is important to note that the apparent decline in microbicide investments may reflect the fact that several donors now consolidate their microbicide and other ARV-based prevention investments now shifting these to the PrEP category, which has seen a significant increase over 2020. The Working Group categorizes all topical HIV prevention as microbicides, but accepts funder categorizations of systemic approaches between PrEP and microbicides where appropriate.
2.1 Developments in the Field of Microbicide Research
A range of microbicide strategies are under investigation, including gels, douches and rings. Developed by the International Partnership for Microbicides (IPM), now part of the Population Council, the dapivirine vaginal ring (DVR) is the first topical HIV prevention method to be submitted for regulatory approval. The World Health Organization (WHO) recommended the ring in January 2021, and several countries have approved or are reviewing the status of the ring. In 2021, the Microbicides Trials Network responsible for the DVR clinical trials ended its status as an independent NIH clinical trials network.
Also in late 2021, the US Agency for International Development launched the Microbicide R&D to Advance HIV Prevention Technologies through Responsive Innovation and excellence Consortium (MATRIX), a $125 million five-year cooperative agreement to support research into microbicide and other HIV prevention and dual prevention options. These investments will be recorded by the Working Group from 2022 onwards.
2.2 Funding Allocations for Microbicide R&D
Allocations for microbicide R&D in 2021 were as follows: basic research (4.5 percent), basic mechanisms of mucosal transmission (1.5 percent), preclinical research (22.6 percent), formulations and modes of delivery (11.6 percent), clinical trials (40.8 percent), behavioral and social science research (2.7 percent), research infrastructure (8.3 percent) and advocacy and policy (6.2 percent). These 2021 allocations as compared to 2020 exhibit a shift toward clinical work away from basic, preclinical and social/behavioral research.
Pre-Exposure Prophylaxis (PrEP)
3.0 Global Investment in PrEP R&D
In 2021, global investment in PrEP R&D amounted to US$269.8 million. This is a more than two-fold increase from 2020 and the highest funding level the Working Group has recorded for PrEP R&D. The impetus behind this surge is the increase in investment from the public sector, rising from US$63 million to US$188 million, and an increase in philanthropic investment from US$20 million to US$56 million. In addition, this increase reflects the shift by some donors to include both microbicides and other next-generation prevention options under the PrEP category.
The Working Group saw an increasing share of policy/advocacy and social/behavioral research in the PrEP space as more products became more widely available, especially focused on African American youth in the Southern United States, and a global focus on men who have sex with men and adolescent girls and young women around PrEP use and access.
3.1 Developments in the Field of PrEP Research
In 2019, F/TAF (brand name Descovy) became the second oral PrEP product to be approved after TDF/FTC (brand name Truvada), but only for men who have sex with men (MSM) and transgender women. An efficacy study of F/TAF among cisgender women is ongoing. Studies reported in 2020 show injectable cabotegravir is safe and effective. In December 2021 the FDA approved injectable cabotegravir as a prevention option, and since then Australia, Botswana, Brazil, Malawi, South Africa and Zimbabwe have followed, while other countries continue their reviews. These approvals represent a significant increase in the number and time to approval for injectable PrEP, especially in low- and middle-income countries when compared to the prior slow pace of oral TDF/FTC approvals.
Also in late 2021, the US Agency for International Development launched the Maximizing Options to Advance Informed Choice for HIV Prevention (MOSAIC), a $85 million five-year cooperative agreement to develop and expedite women’s access to new HIV prevention products. These investments will be recorded by the Working Group from 2022 onwards.
3.2 Funding Allocations for PrEP R&D
In 2021, PrEP R&D was allocated across the following six categories: basic (3 percent), preclinical (3.5 percent), clinical (32.7 percent), implementation science (37.8 percent), behavioral and social science (13.1 percent), research infrastructure (8.6 percent) and advocacy and policy (< 1 percent). These 2021 allocations as compared to 2020 exhibit a shift toward clinical, preclinical, research infrastructure and behavioral/social science work away from implementation science which comprised over 50 percent of research in 2020. This is likely to change in 2022 with a significant number of implementation studies being designed and implemented following the approvals and recommendations of both the dapivirine vaginal ring and injectable cabotegravir.
Other biomedical prevention options
4.0 Global Investment in Treatment as Prevention (TasP) R&D
Funding for TasP increased five-fold totaling US$49 million up from US$9 million in 2020. This increase is fueled by a number of new funders as well as increased investment by Canadian Institute for Health Research (CIHR), the BMGF and the European Commission. Public sector and philanthropic funding increased each to US$31.5 million and US$17.4 million respectively. This increase in TasP investment is also due to efforts of integrating PrEP provision with HIV self-testing and early ART initiation and links to expanded undetectable equals untransmittable (U=U) research.
5.0 Global Investment in Female Condom R&D
Investment in female condom research increased from no reported funding in 2020 to US$0.2 million with a new investment by the UK Medical Research Council.
6.0 Investment in Voluntary Medical Male Circumcision (VMMC)
The 30 percent increase in VMMC observed in 2021 reversed the decline seen in 2020. Overall funding was US$8.6 million. This increase is attributed to a US$7.8 million investment from BMGF.
7.0 Global investment in Prevention of Vertical Transmission (PVT)
Funding for PVT decreased from US$25 million in 2020 to US$14.3 million in 2021, the lowest level recorded by the Working Group. Most PVT research (US$13.1 million) was funded by the public sector, with the US NIH, the European & Developing Countries Clinical Trials Partnership (EDCTP) and CIHR the largest donors. European funding equaled US$7.5 million or 52.7 percent of total PVT funding.