MEXICO CITY – Merck Sharp & Dohme's MK-8591, a nucleoside reverse transcriptase translocation inhibitor (NRTTI), impressed in both treatment and prevention studies at the 2019 International AIDS Society (IAS) Conference on HIV Science.
In a first-in-human trial delivering the drug via an implant, the authors showed that drug levels remained adequate for pre-exposure prophylaxis (PrEP) for three months, and mathematical modeling suggested that drug levels would remain high enough to offer protection for a year.
Michael Robertson, executive director of clinical research in infectious diseases at Merck, pointed out that the study so far is small – 16 patients, which includes four placebo patients – and that the implanted device is a prototype, and not the one the company ultimately plans to use.
But if the numbers hold up, long-acting implantable PrEP could greatly increase PrEP uptake.
In principle, PrEP has been available since the approval of Truvada for PrEP purposes in 2012.
However, current PrEP needs to be taken as a once-daily pill, and adherence among women in particular needs to be strict, as the drug is less effective in women.
Such adherence can be problematic for some of the groups that are at highest risk of contracting HIV. Some individuals whose living arrangements lack privacy are also concerned about being perceived as either HIV-positive – since the same medications are used for treatment and PrEP – or promiscuous if their pills are discovered.
An implantable PrEP option would be especially useful for one key group that is collectively at high risk for contracting HIV, namely transgender women.
Asa Radix, executive director of the Callen-Lorde Community Health Center, which serves transgender individuals, gave a Monday plenary speech on "Lost in Translation: PrEP implementation and transgender people."
Transgender individuals have 40 times the risk of the general population of becoming infected with HIV, Radix said. But PrEP uptake and adherence remain very low. Radix enumerated reasons why current PrEP options, as well as those in development, largely fail to meet the needs of transgender individuals.
Barriers to care range from the stigma and violence faced by transgender individuals, including discrimination in health care settings – one in four transgender individuals has avoided medical care due to stigmatization by the health care system – to physiological ones.
One issue is that while clinical trials of long-acting PrEP are currently ongoing, the drug in those trials is being delivered via intramuscular injection into the buttocks. Many transgender women have silicone implants in the buttocks and so cannot receive such injections. Implants, which are typically done in the arm, would not be a barrier for transwomen.
Another experimental form of long-acting PrEP, vaginal rings, would be an option only for those who have had gender-confirming vaginoplasty surgery, which is a minority of transwomen.
Treatment, too, shows la isla bonita
On Wednesday, Merck also reported 48-week data from a phase IIb trial of previously untreated patients infected with HIV-1. The trial investigated the efficacy, safety and tolerability of treatment with islatravir initially for 24 weeks in combination with Pifeltro (doravirine Merck & Co. Inc.) plus lamivudine (3TC, 300 mg, Merck & Co. Inc.), followed by further 24 weeks of islatravir plus Pifeltro. That combination led to viral suppression that was similar to that observed in the comparator arm, which was treated with Delstrigo (doravirine 100 mg/3TC 300 mg/tenofovir disoproxil fumarate 300 mg).
Based on the trial results, Merck plans to take the Pifeltro/islatravir combination into phase III.
In the treatment trial, the combination of islatavir and doravirine was administered daily. But the islatravir's implant's longevity also implies that longer-acting antiretroviral treatment (ART) for infected individuals is a possibility.
Such longer-acting treatment would be a boon for infected individuals as well.
At a preconference workshop by the IAS Towards an HIV Cure initiative, Jan van Lunzen, head of translational medical research at Viiv Healthcare Ltd., argued that cure and remission could be thought of as a continuum, and under that conceptualization, sufficiently long viral suppression by ART could be considered a form of cure.
"This is not a revolution, it's an evolution," van Lunzen said.
Robertson was circumspect about the practical barriers to a long-acting islatravir treatment regimen.
A key difference between treatment and prevention, he said, is that "we think you can use a single drug for prophylaxis."
Treatment, however, needs a combination approach – and for an extremely long-acting implant, all drugs would have to be equally long-acting.
Also, "theoretically you could put other drugs" into the implant, he told BioWorld, but "the drugs have to be compatible with each other."
Beyond the question of how, specifically, long-acting treatment regimens will come about, Robertson, who has been working on HIV in one role or another for decades, was enthusiastic about the field's progress in general.
"In the 80s and 90s, it was palliative care," he said of the options for HIV-infected individuals. "That we can even mention cure is an amazing thing."