What's Hot in HIV Clinical Science

Melanie Thompson, M.D., at IDWeek 2018
Kenyon Farrow

As 2018 comes to a close, it's worth reflecting on all the successes (and many failures) in HIV clinical research. Notably, several novel drugs were approved in 2018, bolstering physicians' armamentarium of medicines that can reduce pill burden and effectively treat drug-resistant HIV. Yet, 2018 also brought us new, discouraging data about stark discrepancies in access to care. Now more than ever, black men and other minorities are diagnosed with HIV and die of AIDS-related complications at a disproportionately high rate.

New therapies have done nothing to bring us closer to achieving the UNAIDS goal of global HIV eradication by 2030, explained Melanie Thompson, M.D., AIDS Research Consortium of Atlanta, during her Oct. 3 round up of HIV clinical research at IDWeek 2018 in San Francisco. The fact that people living with HIV can now expect to live long and healthy lives is a monumental medical achievement, said Thompson, but ultimately that achievement is merely a consolation prize along the long, slow journey toward global AIDS eradication.

Below, we summarize Thompson's take on some of the highs (and lows) of the past year's HIV clinical science research.

"We Are Not on Track to End AIDS"

Speaking to attendees of IDWeek 2018, Thompson summarized a key take-away from the International AIDS Conference held in Amsterdam three months ago. Her synthesis: "We are not on track to end AIDS."

She pointed to a July 2018 Lancet paper published by the International AIDS Society, which noted that the "HIV pandemic is not on track to end" due to the "weakening of global resolve." Thompson worried aloud whether global decreases in HIV funding could spur a resurgence of the epidemic, and flagged alarming disparities of HIV care within populations. For example, Thompson cited a recent study in San Francisco finding that black men living with HIV have the highest mortality rates by far. Meanwhile, Thompson presented data from Atlanta showing that 80% of newly diagnosed patients are black.

What's Hot in HIV Prevention

This past year was a breakout moment for the Prevention Access Campaign, which advocates for the scientifically backed concept that people on treatment cannot transmit HIV to their sexual partners (dubbed "undetectable equals untransmittable" or U=U). While U=U has been a well-established scientific concept for several years, recent data from the PARTNER 2 study and the Prevenir study have further bolstered evidence that treatment does work as prevention, even among serodiscordant couples who don't use condoms.

Published literature aside, 2018 was a year for those living with HIV to internalize what U=U actually means to them. Speaking to the IDWeek audience, Thompson shared a story about her friend, writer and activist Mark S. King, who described how his relationship with HIV had changed since U=U. Previously, he had "internalized being a viral threat," but U=U provided the scientific rationale he needed to feel "the threat had been lifted."

Prevention Works, If Prescribed

Data published this past year once again makes it clear that doctors are not prescribing pre-exposure prophylaxis (PrEP) to enough people at-risk of HIV. A seminal Centers for Disease Control and Prevention (CDC) study found that only 8% of people indicated for PrEP were prescribed the once-daily pill. What's worse, said Thompson, white men "are basically the only people who get PrEP." She pointed out that, per the CDC study, only 1% of blacks and 3% of Latinx Americans at risk received a prescription.

In fact, this study looked at a PrEP-to-need ratio -- meaning it compared the portion of at-risk people in a population relative to the number of people actually prescribed PrEP. Perhaps unsurprisingly, "the South lags behind," Thompson told the crowd, reminding them that the South is currently the epicenter of the HIV epidemic.

Elsewhere in the HIV prevention world, a 2018 Lancet paper found that needle exchange prevention services would have prevented HIV infections in the deadly Scott County, Indiana, outbreak. Said Thompson: "Syringe services programs work. They need to be legal, and we need to use them."

What's Hot in Antiretroviral Research

With a wave of new drug approvals in 2018, physicians and patients now have an assortment of new drugs and drug combinations to choose from. Notably, the U.S. Food and Drug Administration (FDA) approved ibalizumab (Trogarzo) in March 2018, bringing a much-needed treatment for patients with multidrug resistant HIV. In August 2018, the FDA also approved a new NNRTI, doravirine (Pifeltro), which is formulated as a stand-alone drug and in combination with lamivudine and tenofovir disoproxil fumarate (Delstrigo).

The FDA also green lighted a slew of new drug combos, including bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy), lamivudine/tenofovir disoproxil fumarate (Cimduo), efavirenz/lamivudine/tenofovir disoproxil fumarate (Symfi Lo), and cobicistat/darunavir/emtricitabine/tenofovir alafenamide (Symtuza).

Thompson noted, "2018 is also the year of the generics," but she questioned whether they would translate into tangible cost savings for patients. She also alluded to a drug candidate called "MK-8591" that is being explored in a variety of different contexts due it its long half life, including as a drug eluting implant.

New Drugs, New Problems

Along with new drugs come new side effects -- especially when these drugs move from the clinic into the real world. Sure enough, in March 2018, the FDA warned of neural tube birth defects among women being treated with dolutegravir (Tivicay). That warning emanated from a study in Botswana and published in NEJM that found a statistically significant elevated birth defect rate among children born to women who were on dolutegravir relative to other antiretrovirals.

Meanwhile, Thompson summarized the 2018 AIDS cure research in a single phrase: "Unfortunately, there's not a lot of progress toward cure." She added: "That means we need to fix the care continuum we have. Instead of blaming people with HIV, we need to be removing the structural barriers [to treatment], and rapid start of HIV antiretrovirals is one way to do that."

She pointed to a recent paper in Open Forum Infectious Diseases in which authors found that offering patients treatment immediately upon diagnosis reduced the time it took for them to start on antiretroviral therapy from 21 days to seven days. "We need to be thinking about how to do this in our clinics," she said.

What Will It Take to End AIDS?

For Thompson, it's not enough simply to tout the new science supporting novel antiretroviral therapies. As she stood in front of thousands of attendees at IDWeek 2018, she urged them to act. She pointed to a modeling study co-authored by Eli Rosenberg and presented at the 2018 U.S. Conference on AIDS that showed that, if we do nothing, there could be as many as 55,000 new infections annually in the U.S. by 2020.

But, she added, the model went on to show that if 95-95-95 targets were implemented, the number of new infections would drop to 19,000 per year. And, if PrEP were prescribed appropriately on top of that, the number would further drop to 14,000.

"I am here to tell you that all of this hot clinical science we have talked about alone is not going to end AIDS," she said. "I am ending this by asking you all to activate your inner activist. If you don't know how to be an advocate, we can teach you."