Beating off STIs with DOXYVAC, doxy-PEP, Apretude, vaginal ring, implant and booty butter

The world can stop HIV and STIs with medication. Medication taken by people living with the virus and medication taken by people not living with the virus. At the 30th anniversary of CROI—the Conference on Retroviruses and Opportunistic Infections, also known as the Retrovirus Conference—several research teams reported on advances in the battle against HIV and sexually transmitted infections. As the DOXYVAC study team noted, “There is no magic bullet. There’s an interest in combined approaches.” Note: All of these reports were presented via a webcast; GO TO

DOXYVAC study: Vaccination fights off gonorrhea

Incidence of gonorrhea was cut by more than half with two shots of a meningococcal B vaccine, reported the ANSW 170 DOXYVAC study team from Paris. The vaccine fights bacteria that’s similar to gonorrhea. Based on early successful results, randomization was stopped and everyone in the study was offered the vaccine.

All study participants were also offered doxycycline (“doxy” for short) for post-exposure prophylaxis (PEP) against STIs. This involved taking 200 mg of doxycycline within 72 hours of condomless sex. (“Prophylaxis” means prevention.)

The DOXYVAC study looked specifically at these two interventions together because the international IPERGAY study had previously reported that doxy-PEP fights off chlamydia and syphilis incidence by about 70%, but had no significant effect against gonorrhea.

The DOXYVAC study enrolled 502 men who have sex with men (MSM) who were already taking pre-exposure prophylaxis (PrEP) against HIV in a larger study.  

The question of drug resistance is always a concern with antibiotics. In a separate presentation from the DoxyPEP study in the U.S., the researchers reported that, “In this subset of doxy-PEP participants with antimicrobial resistance data, we did not find markedly increased doxycycline resistance.” (See more in Briefly.)

Doxy-PEP based on STI

A research team found that for using doxy-PEP, “The most efficient prescribing strategies are based on STI history rather than HIV status or PrEP use.” The group analyzed the electronic health records of more than 10,000 patients at Fenway Health, a Boston clinic focused on LGBT health. More than half the patients were taking PrEP.

While doxy-PEP “is highly efficacious,” said presenter Michael Traeger, PhD, of Harvard Medical School, the team found that “those prescribing strategies giving patients doxy-PEP after they’ve been diagnosed with an STI are slightly more efficient, which means you need to prescribe less doxy-PEP to fewer people to prevent the same number of STIs.”

Long-acting HIV prevention with Apretude for adolescent girls

The HIV Prevention Trials Network (HPTN) reported early research showing safety and tolerability with the use of a long-acting injectable form of PrEP, cabotegravir LA (CAB-LA, brand name Apretude), in adolescent girls. Apretude is administered as one injection every two months.

“There was high interest in the study and we enrolled very quickly,” said presenter Sybil Hosek, PhD. This was all the more remarkable given that the study began just as the global COVID shutdown took hold. “The product was found to be acceptable by the adolescents. Their adherence was exceptional. In fact, 100% of injections that were expected to occur did occur. There was no safety signal, no serious adverse events, no HIV infections and no discontinuation of product due to injection site reactions.

“These studies are critically important when we have a new product because our ultimate goal is simultaneous licensure of new products for adolescents and adults so that there’s no access issues for those in the young age range,” said Dr. Hosek.

HPTN 084-01 was a Phase 2b safety study of CAB-LA among African adolescent cisgender girls under the age of 18. Most participants, some of whom were as young as 12, chose to continue using CAB-LA rather than be switched to Truvada for PrEP, Dr. Hosek said. Fifty-five girls from Uganda, Zimbabwe and South Africa were enrolled, all during the COVID pandemic.

Vaginal ring and PrEP during pregnancy

“Pregnancy represents a high-risk period for HIV acquisition,” noted the MTN-042/DELIVER study team. “The monthly dapivirine vaginal ring (DVR) has been clinically shown to reduce HIV risk with no safety concerns in nonpregnant reproductive-aged cisgender women; however, data during pregnancy are limited.” Taking this issue head-on, the team enrolled more than 300 pregnant individuals and provided them with either the ring or oral PreP.

Cutting to the chase, the team reported that, “In this first study of a long-acting HIV prevention agent in pregnancy, adverse pregnancy outcomes and complications were uncommon when DVR and TDF/FTC [PrEP] were used in the third trimester of pregnancy and were similar to rates observed in the communities where the study is being conducted. These data support plans for subsequent investigation of DVR safety earlier in pregnancy.”

“I would just like to emphasize that studying safety of an investigational product is hard in pregnancy, but it can be done,” said presenter Katherine E. Bunge, MD, of the University of Pittsburgh. “We are doing it and it should be done, because pregnant people deserve better.”

The DELIVER team noted that pregnant people are three times more likely to acquire HIV per sex act than non-pregnant individuals. The study took place in Uganda, Malawi, Zimbabwe and South Africa.

Refillable PrEP implant

How about an implant under the skin to prevent HIV? Early results with monkeys (specifically, rhesus macaques) showed the ability to sustain prevention drug levels needed to prevent simian HIV (SHIV) for nearly two years. There is hope for a refillable implant for people that can last three years.

“In the PrEP efficacy studies with repeated low-dose SHIVSF162P3 challenges, the implants conferred 100% protection against rectal and vaginal infection. The implants were well tolerated with mild local tissue inflammation and no signs of systemic [throughout the body] toxicity,” a research team from the Houston Methodist Research Institute reported. They used islatravir, a long-acting medication under development for the treatment of HIV as well as for PrEP.

Booty butter: rectal PrEP insert

A fast-dissolving rectal insert containing two medications used for preventing HIV showed good results in early research from the Microbicide Trials Network (MTN).

Credit longtime HIV microbicide advocate Jim Pickett for the phrase “booty butter”—it’s been one of his war cries for more than a decade.

“Currently, the only on-demand product option for PrEP is the tenofovir 2-1-1 regimen [two pills followed by two more pills around the time of sex], which really has only been tested in cisgender men,” said presenter Sharon Riddler, MD, of the University of Pittsburgh. “So if proven to be effective, a product that is discreet and provides protection, potentially both vaginally and rectally, would be a real game changer.”

The MTN-039 study reported safety and high localized drug levels with low systemic exposure. The medications used in the insert, which looks like a tiny bullet, were elvitegravir and tenofovir alafenamide (TAF), both of which are currently available as oral drugs for the treatment of HIV.

The 21 HIV-negative study participants all received one insert and then a week later, 19 of them received two inserts. (Two of the participants had already moved away from the study site area by then, in a research trial taking place during the COVID shutdown, with the research team unsure that the study could even be completed.)

Setback: doxy-PEP in women

For all the great news about doxy-PEP over the past several years, one research team found that it didn’t work for cisgender women.

“This was the first trial evaluating doxycycline-PEP for cisgender women,” said presenter Jenell Stewart, DO, MPH, of the University of Minnesota. “Unfortunately, our primary outcome found that it was statistically not significant. We did not see a reduction in STIs among cisgender women, which is in stark contrast to my colleagues’ studies here among cisgender men and transgender women.”

Which shows, again, the need for research. Among the potential differences, “We don’t know the extent to which perfect adherence is needed to prevent STIs in the endocervix or the opening of the uterus,” said Dr. Stewart. She noted that the women reported high rates of adherence.

The research team is also going to look at the effect of any drug resistance in their setting of Kenya. Nearly 500 ciswomen ages 18 to 30 in the study were already taking HIV PrEP. There was a high incidence of STIs at baseline, but no acquisition of HIV.

“It’s very clear that STI prevention is really important, especially with the impact it can have on the uterus,” Dr. Stewart said. “I’m more motivated than ever to continue figuring out why this did not work, and to find interventions that work for cisgender women.”

Stopping HIV in Black folks  with Apretude

Apretude has shown superior efficacy in preventing HIV compared to Truvada for PrEP. Apretude is taken as one injection every two months, while Truvada for PrEP is prescribed as a daily pill.

Apretude was also better at stopping HIV for Black folks specifically, according to research findings reported by the HPTN 083 study team.

“[Apretude] is an extremely powerful HIV prevention tool to increase access to PrEP and address the continued disparities in the United States that we continue to see, and implementation really needs to focus and prioritize addressing these disparities by making access universal and easy,” presenter Hyman Scott, MD, MPH, of the San Francisco Department of Public Health, noted in his conclusions.

Half of the 1,698 individuals in the U.S. part of the international study self-identified as Black or as mixed race including Black. The vast majority of all participants, more than 90%, were men who have sex with men (MSM). About 7% of all individuals were transgender women who have sex with men. Black MSM and trans women bear the brunt of the HIV epidemic in the U.S., the HPTN 083 team pointed out. The study is ongoing.