Douches, Long-Acting Jabs, Implants – All The New HIV Prevention Products Coming Our Way

Shibu Thomas reports from the fifth HIV Research for Prevention Conference (HIVR4P 2024) in Peru.

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Would young gay men in the US prefer using an anal PrEP douche before a date instead of taking a daily pill to prevent HIV? That was the question researchers at a hospital in Philadelphia were exploring as they examined the acceptance of a new HIV prevention tool.

While news of the successful trials of the new long-acting, twice-yearly injectable PrEP lenacapavir dominated the headlines from HIVR4P 2024, the conference showcased cutting-edge research and innovative HIV prevention tools—those ready to hit the market, as well as those in various stages of trials.

From an anal PrEP douche to the first women-controlled HIV prevention product, the dapivirine vaginal ring, here’s a look at the highlights from the HIVR4P conference that concluded in Lima, Peru, on October 10, 2024.

What is the anal PrEP douche?

A daily pill is great, but what if gay men had the choice of an on-demand HIV prevention product in the form of an anal douche. 

A Phase 1 trial conducted in the US looked at providing alternatives to oral or injectable pre-exposure prophylaxis (PrEP) with an on-demand tenofovir anal douche.

Emtricitabine/tenofovir is used to both treat and prevent HIV—it is sold as PrEP under the brand name Truvada. Researchers at Johns Hopkins University conducted Phase 1 of the trial to check the safety, acceptability, and efficacy of tenofovir rectal douches. 

In the trial, 21 HIV-negative cisgender men who have sex with men were given tenofovir rectal douches with variable dosages. The study, published in 2023 in The Journal of Infectious Diseases, found that the tenofovir rectal douches “achieved tissue tenofovir-diphosphate concentrations and colorectal antiviral effects exceeding oral tenofovir and with lower systemic tenofovir.”

Anal PrEP douche is the top choice for HIV prevention

The study revealed that 94 percent of participants indicated they would use the PrEP douche before anal intercourse.

Calling for further research, the study concluded that tenofovir rectal douches could provide a single-dose, on-demand PrEP option for receptive partners.

While this study was conducted with cisgender men with a median age of 38, another study was conducted with men between the ages of 18 and 24 who used a 125-millilitre douche containing 660 mg of tenofovir.

The results of this second study, conducted by the Children’s Hospital of Philadelphia, were presented at the 5th HIV Research for Prevention Conference (HIVR4P 2024), which took place in Lima, Peru from October 7 to 10, 2024.

Around 80 percent of participants said they would prefer to use the anal tenofovir douche over daily oral PrEP. The remaining 20 percent said they valued both products equally. Lead researcher Renata Arrington-Sanders from the Children’s Hospital of Philadelphia stated that rectal tenofovir douches would “fill a critical gap in PrEP product availability.”

Research on anal PrEP douches is still in its early stages, and it may take years before they are available for purchase at the local pharmacy.

What is the vaginal ring?

The Dapivirine Vaginal Ring (DVR) is touted as the “world’s first women-controlled” HIV prevention tool.

The silicone ring is inserted inside the vagina and releases the anti-retroviral drug dapivirine over 28 days, functioning as a long-acting HIV prevention product for women. The ring must be replaced every month for continued protection.

The WHO endorsed DVR in 2021, and 11 African countries approved the monthly ring. At the HIVR4P conference, new research showed that a three-month dapivirine vaginal ring was “pharmacokinetically superior” to the monthly ring. Jeremy Nuttall from the Population Council’s Center for Biomedical Research hoped that this long-acting three-month ring would increase its acceptability among women.

Another study showed that while 66% of participants chose oral PrEP, only 30% chose the monthly DVR.

Two in one: HIV prevention and contraception

Globally, women and girls accounted for 46 percent of all new HIV infections according to the UNAIDS Global Report 2023. In sub-Saharan Africa, 63% of all new HIV infections were among women and girls.

Women have long expressed a preference for a long-acting product that simultaneously protects against HIV acquisition and unwanted pregnancies. At the conference, researchers from CONRAD presented early results on a new product—a long-acting silica-based hydrogel injection that can deliver medication for both HIV prevention and contraception under the skin for up to three months.

The biodegradable “silica-based hydrogel injectable platform,” comprises two compartments that are loaded with long-acting cabotegravir (for HIV prevention) and levonorgestrel (for contraception). The drugs are released over three months and provided protection against HIV and/or unwanted pregnancies. 

In tests on rats, this treatment showed no safety issues and maintained effective drug levels. Additional tests are being conducted in non-human primates.

A sub-study on long-acting cabotegravir injections also looked at “pharmacologic interactions” with hormonal contraceptives. The study presented at the conference by researchers from Johns Hopkins University School of Medicine found no interactions between cabotegravir and popular contraceptive hormones like etonogestrel, norethindrone, or medroxyprogesterone acetate (MPA).

Subdermal implants

Researchers at Houston Methodist Hospital have developed a new type of implant that could deliver ultra-long-acting antiretrovirals for HIV prevention. This implant, made of titanium and a special silicone, can be refilled through the skin with a simple injection, making it easier to use than traditional methods.

Tests on monkeys showed that this implant safely released medication for up to 29 months and completely protected against rectal and vaginal simian HIV exposures. 

The implants can deliver different HIV drugs and can also be combined with contraceptives. This innovative approach could lead to an affordable and beneficial way to provide long-lasting protection against HIV in the future. 

Long-acting HIV PrEP injections

Long-acting Cabotegravir injections every two months is currently the only approved long-acting HIV PrEP. In 2022, WHO recommended long-acting cabotegravir injections for HIV prevention, following successful trials and approval from the US Food and Drug Administration in 2021. 

Zambia was one of the first countries to roll out long-acting Cabotegravir injections for HIV prevention in February 2024. Lloyd Mulenga from the Zambia Ministry of Health revealed to media persons that over 90 per cent of those eligible for their second injections had turned up (compared to 40 percent of those returning for their oral PrEP medication). “These are early figures, but it is still exciting,” said Mulenga. 

Gilead Sciences’ lenacapavir, a biannual injection for PrEP, that showed a 96% reduction in HIV infections, was hailed as a “breakthrough” at the conference. Gilead said it will commence regulatory filings for lenacapavir for PrEP by late 2024. 

At the HIVR4P 2024 conference, the word on everyone’s lips was “choice.” As the world eagerly awaits a vaccine or the elusive “cure” for HIV, the focus was on expanding the options for those at risk, and to  empower individuals to take control of their sexual health.

The growing array of HIV prevention tools underline that expanding access to these innovative prevention methods will be crucial in the fight against HIV. 

Shibu Thomas was awarded a Journalism Fellowship by the International AIDS Society to attend the 5th HIV Research for Prevention Conference (HIVR4P 2024) in Peru in October 2024.