PARIS – A bird in the hand is worth two in the bush. And in that spirit, the newest research on a wide variety of prevention strategies other than vaccination are being presented at the meeting of the International AIDS Society (IAS) this week, despite the conviction that a vaccine will ultimately be necessary to end the HIV pandemic. (See BioWorld, July 25, 2017.)

The ABC of prevention – abstain, be faithful, condomize – was first joined by the D of drugs when Gilead Sciences Inc.'s Truvada (tenofovir/emtricitabine) was approved for pre-exposure prophylaxis (PrEP) by the FDA in 2012. A generic version by Teva Pharmaceutical Industries Ltd. was approved last month. (See BioWorld, June 12, 2017.)

Truvada is a daily oral medication, and whether that is a good thing or a bad one is in the eye of the consumer.

Certainly, there is a market for longer-acting products that need to be taken less frequently. Kenneth Mayer, professor of global health at the Harvard School of Public Health, told the audience at a Sunday satellite session on "The Next Wave of Prevention Options" that surveys conducted by his team indicated that "injectable PrEP and infusible antibodies are most interesting to those who need PrEP," with the infrequent dosing being "a big plus" for injectable as opposed to oral PrEP.

He also noted that less frequent dosing may increase adherence.

"We talk about bio-prevention, but it's really always biobehavioral – pills, rings and injections do not take themselves."

Adherence to any preventive medication schedule is notoriously poor, and in the case of PrEP, it is often used by marginalized populations with high rates of depression, anxiety and substance abuse – all of which make adherence less likely still.

And it's not just the users who have biobehavioral issues – the health care community does, too.

Mayer said it is "not normative for us to recommend medications so that people can stop using condoms." As a result, passivity is something of the norm in the medical community, with "few clinical champions of the approach."

That situation is all the more problematic because studies of female condom uptake in Africa have shown that provider enthusiasm for the method was the only thing that predicted adoption rates by users.

Taking PrEP pills can also be a source of stigma, because the same pills are used for treatment. At the satellite symposium, one of the audience members said that in her home country of Zimbabwe, "as soon as you are found with Truvada, people begin to suspect that you might be HIV-positive."

Some devices are being developed for longer-term use – in fact, the "condomize" in prevention's ABC might be considered a device, and antiretroviral-eluting vaginal rings are being tested in all phases of clinical trials.

At the conference, Leah Johnson, a researcher at medical nonprofit RTI International, described a subcutaneous implant the institute is developing that is long-acting, biodegradable and releases tenofovir alafenamide fumarate (Gilead Sciences Inc.). Intarcia Therapeutics Inc. is working on a similar device. Such devices could deliver drugs for six months to a year.

Both long-acting small molecules and broadly neutralizing antibodies are being tested for their ability to protect against HIV when given prophylactically at longer intervals.

When drugs are given at longer intervals, one of the critical questions is how long the dosing interval can be to reliably keep drugs at therapeutic levels. At an oral abstract session, Raphael Landovitz, co-director of the center for HIV identification, prevention and treatment services at the University of California, Los Angeles, reported results suggesting that for cabotegravir (Viiv Healthcare Ltd.), that interval is six weeks.

Previous studies had shown that injecting 800 mg of cabotegravir every 12 weeks did not reliably keep the drug at effective levels in study participants, and so in the phase IIa HPTN-077 trial, Landovitz and his team directly compared drug levels with injection schedules of 800 mg every 12 weeks and 600 mg every eight weeks. They found that injecting every eight weeks at a lower dose led to levels of drug that were reliably therapeutic.

Daily oral cabotegravir is also being tested in the HPTN-083 study.

Antibodies are well-suited for HIV prevention is several ways. On average, they have longer half-lives than small molecules. And broadly neutralizing antibodies (bnAbs) are "widely regarded as the approach that will ultimately allow us to take treatment and prevention to the next level," IAS meeting chair Linda-Gail Bekker told reporters at a press conference highlighting new findings on bnAbs in both prevention and treatment.

The first antibody to enter advanced clinical trials is VRC-01. Originally discovered in an elite controller, recombinant VRC-01 is being tested in the antibody-mediated prevention study for its ability to prevent HIV infection. For now, the approach is being tested in high-risk young women in Africa, and in men who have sex with men in North and South America. The study will run until 2021.