New HIV PrEP Options Emerging, but Gold Standard Remains

Ingrid Hein

October 17, 2016

New pre-exposure prophylaxis (PrEP) drugs that offer protection against HIV infection, including bimonthly injections, are in the works, but they will not be available before 2020, and they are not without their shortcomings, experts said at the Controlling the HIV Epidemic With Antiretrovirals Summit 2016 in Geneva.

The combination of emtricitabine and tenofovir disoproxil fumarate (Truvada, Gilead Sciences) remains the only drug approved for PrEP, and uptake should be encouraged to slow the spread of HIV, said Karen Hoover, MD, from the division of HIV/AIDS prevention at the Centers for Disease Control and Prevention (CDC).

"It has been overwhelmingly effective in clinical trials and demonstration projects," she told Medscape Medical News. If it's taken every day, protection against HIV infection is "nearly perfect." Even when it is taken only four times a week, "we've seen that it has greater than 90% efficacy."

Although rare, the combination is not without adverse effects, including a mild decrease in kidney function and a small decrease in bone mineral density. When patients stop taking the drug, though, both kidney function and bone mineral density return to normal. However, Dr Hoover pointed out, "the importance of these side effects is still unknown in adolescents and young people."

 
One size does not fit all.
 

Although the combination is relatively safe, the daily dosing regimen can cause problems with adherence, especially for young people. "It would be nice to have another choice. One size does not fit all," she pointed out. "Some people would do well with an injectable option."

In fact, several second-generation PrEP drugs are in development and several clinical trials are underway, Dr Hoover reported.

Next-Generation PrEP

Cabotegravir, a long-acting injectable from ViiV Healthcare, showed promise in the phase 2a ÉCLAIR study, as reported by Medscape Medical News.

The dosing regimen for cabotegravir — an injection once every 2 months — virtually eliminates problems related to adherence with oral drugs.

"Injectable PrEP might help those who have trouble taking a daily pill, but it's not a panacea," Dr Hoover acknowledged.

In a clinical trial that will soon begin recruiting participants, patients will take an oral version of cabotegravir to see if any toxicity issues arise before starting the injections. It usually takes several days of oral daily doses before the patient is fully protected against HIV.

And when a patient stops getting the injections, other problems can arise, she reported.

"This long-acting version stays in the body for weeks, maybe even a year. If a person has insufficient protection with low but inadequate treatment, they can become resistant. So if they stop, they need to take oral medication if their risk of becoming infected is ongoing," she explained.

Another drug that has shown promise is tenofovir alafenamide in combination with emtricitibine, according to Dr Hoover. This prodrug delivers tenofovir diphosphate, the active agent, more efficiently to cells that might become infected with HIV.

Because tenofovir alafenamide is potent, a patient can take a 25 mg dose instead of a 300 mg dose of Truvada, she explained. "That means a lot less renal toxicity and fewer side effects. I look forward to seeing the phase 3 trial results."

VRC01, a broadly neutralizing human monoclonal antibody to HIV, is a new type of drug being studied as both PrEP and treatment. The antibody was found to be safe in phase 1 studies with intravenous and subcutaneous dosing, and there is hope that phase 2 research could lead to a vaccine.

Still, said Dr Hoover, none of these trials will be completed until 2020, and time will then be required for regulatory approval and marketing.

At best, it will be 4 or 5 years before they are available. "We have a safe and effective drug — that's Truvada. What we need now is to do a better job of implementing PrEP," she said.

A Matter of Supply and Demand

In the United States, a better response to both supply and demand is needed for PrEP, said Dr Hoover.

"On the demand side, we need to really help patients understand what it is, how it works, and whether it would be appropriate for them. We need to help them find doctors they can talk to about PrEP," she explained.

In some communities in the United States, awareness of PrEP is still relatively low. One recent study showed that only 40.5% of 622 young black men who have sex with men and who live on the south side of Chicago reported knowing about PrEP, and only 12.1% knew someone who had used PrEP (JAMA Intern Med. 2016;176:136-138).

On the supply side, physicians who provide PrEP care need better support, said Dr Hoover.

A clinical hotline, supported by the CDC and other organizations, offers up-to-date clinical consultation to help healthcare providers learn about PrEP.

"We get all kinds of clinicians calling, from primary care to subspecialists in various fields," said Ronald Goldschmidt, MD, director of the Clinician Consultation Center at the University of California, San Francisco.

Physicians call for many reasons, including to double-check that a patient is a good candidate for PrEP, to determine whether it is appropriate to give, and to find out what the dosing should be.

"Most of the time, we tell them that if there's any ongoing risk of contracting HIV — especially if the person has risky sex with multiple partners or is an injection drug user — the benefits of PrEP are certainly something the physician should offer," said Dr Goldschmidt.

"There is also certain testing that has to be done before and during PrEP therapy. Sometimes physicians just want to make sure they have the testing protocols correct," he told Medscape Medical News.

"Often it's a question about whether to use PEP [postexposure prophylaxis] or PrEP," he added. PEP is used to treat patients who have been exposed to the virus in the previous few hours or days. PrEP, in contrast, takes a month to become effective.

"PrEP is never an emergency; PEP is," Dr Goldschmidt explained. "However, we answer quite promptly for PREP calls."

Dr Hoover and Dr Goldschmidt have disclosed no relevant financial relationships.

Controlling the HIV Epidemic With Antiretrovirals Summit 2016. Presented October 14, 2016.

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