5 New HIV Drugs in the Pipeline

More than 36 million people worldwide are living with HIV, according to the World Health Organization (WHO). Therefore, inexpensive, effective, and long-lasting medications are essential if the scientific community wants to successfully treat them.

Problems with adherence that plagued many individuals could be alleviated with the addition of new longer-acting HIV medications. These long-acting medications may also reduce costly laboratory tests to monitor their efficacy, and bring down drug costs—a major factor in middle- and low-income countries where HIV is most prevalent.

“With several highly potent agents in the pipeline and a healthy proliferation of many promising technologies for long-acting delivery, the prospects for very long-acting ARVs [anti-retrovirals] for treatment and prevention have never been brighter,” said Matthew Barnhart MD, MPH, medical officer for the US Agency for International Development (USAID) and associate editor of Global Health: Science and Practice in a recent editorial.

Dr. Barnhart outlined and described 5 types of drug developments that put HIV treatment on the threshold of a breakthrough:

1- or 2-Month Injectables

A combination of two antiretrovirals (AVRs), ViiV's cabotegravir (an integrase inhibitor) and Janssen's rilpivirine (a non-nucleoside reverse transcriptase inhibitor) is in phase 3 trials. The combination is a monthly or every-other-month maintenance medication for people who have achieved non-detectable viral loads on standard ARV oral protocols. Investigators are also looking at cabotegravir alone as an every-other-month injection for HIV prevention.

New AVRs

These include the capsid inhibitor GS-CA1, a new class of AVRs, and new nucleoside/tide reverse transcriptase inhibitors (NRTIs). Two of these NRTIs, EFdA (GS-9131) and TAF (tenofovir alafenamide fumarate), have the advantage of long half-lives that allow them to become “effectively trapped within cells, thereby amplifying their levels and potency,” Dr. Barnhart explained in his editorial. TAF, already approved as an oral medication, is being investigated as a drug that can be released from a long-lasting implant. Gilead’s GS-CA1 is in the pre-clinical stage, Merck’s EFdA is in phase 1, and Gilead’s TAF as an implant is in phase 1.

Broadly Neutralizing Antibodies (bnAbs)

Two large trials are investigating bnAbs called VRC01 as a medication for HIV prevention. It could be impractical, however, because VRC01 would have to be given intravenously. Combinations of other antibodies show potential for 6-month duration and administration by subcutaneous injection, according to the editorial.

Biodegradable and Refillable Implants

Long-acting AVRs could have a duration of up to a year in an implant, but Dr. Barnhart questioned how practical it would be to require annual removal and replacement of the implant. He instead proposed biodegradable or refillable implants, which would require new implant designs.

Implants under development release AVRs through a membrane so that the reservoir gradually empties after the outer coating biodegrades and consequently avoids the potential problem of the device dumping medication when it wears out. A refillable implant has been conceived using refillable nanochannels that would release more than one type of AVR at potentially high doses, the editorial said.

Improved Injection Techniques

Easier-to-use subcutaneous injection devices that allow self-administration or administration by low-level community health workers have already been developed for use with other drugs. Another option would be micro-needle patches—these could be used with new drugs that only need low doses and volumes that could be used quarterly. Their implementation hinges on the ability to manage the cost of manufacturing the injection devices.

Dr. Barnhart stressed that cost is a major consideration when designing treatments for use in middle-to-low income countries. In the past, there have been large gaps between the time new ARV agents were introduced in affluent countries and when they became available in low- and middle-income nations.

To narrow that gap, requirements for products in resource-limited settings may need to be more stringent, according to Dr. Barnhart. For example, the cost of manufacturing, safety during pregnancy, and compatibility with tuberculosis medications need to be considered before new drugs and treatment systems can be useful in the less affluent nations.

“If the current promise is fulfilled, long-acting AVRs can be the keystone in finally controlling the HIV epidemic, and many of the technological and scientific advances made in the process will have application to combating other global healthy scourges, multiplying the long-term impact of these efforts,” Dr. Barnhart concluded.

Disclosure: Dr. Barnhart stated that the opinions expressed in the editorial are his own and not those of USAID.