As 2020 draws to a close, we asked David Alain Wohl, M.D., a professor of medicine in the Division of Infectious Diseases at the University of North Carolina and a highly respected HIV clinician-researcher, to take stock of the year's most momentous research developments and other critical events. In this exclusive series of articles, Wohl calls attention to 10 such developments that have tremendous short-term implications for our day-to-day efforts to improve HIV prevention, treatment, patient care, and policy in the U.S., and analyzes each development with his trademark wit and clinical savvy.
“Looking for something we can rely on. There's got to be something better out there,” Tina Turner sings in her 1980s pop hit “We Don’t Need Another Hero.” That song jumps into my head when I think about new HIV therapies, but in my mind, it’s framed as a question: Do we need another hero?
For those with few antiretroviral options, who are downing multiple pills to keep multidrug-resistant virus from replicating, the answer would be yes: We do need another antiretroviral hero.
Fortunately, the number of people living with HIV who are heavily treatment experienced and have few remaining antiretroviral options is fairly small. Among over 27,000 HIV-positive people in the U.S. who were treatment experienced and in care at one of the HIV clinics contributing to the U.S. Centers of AIDS Research Network of Integrated Clinical Systems (CNICS) cohort from 2000 to 2017, just 916 had limited treatment options (LTO)—a status defined as having two or fewer available antiretroviral classes, as well as two or fewer active drugs per class as determined by resistance testing. After 2007, the proportion of people with LTO fell; it has since remained less than 1% of the cohort’s antiretroviral experienced patients.
Still, for that 1%, things can be rough. Many are straddled with antiretroviral regimens that include pharmacological boosters, inconvenient dosing, and side effects. Some may even still fail to achieve virologic suppression. Therefore, U.S. Food and Drug Administration (FDA) approval of fostemsavir (brand name: Rukobia), an HIV attachment inhibitor, in July is welcome news to these patients and their providers.
The drug is a prodrug of temsavir, which binds to the HIV envelope glycoprotein gp120, thereby blocking viral attachment regardless of HIV tropism. A nice video of the mechanism of action of fostemsavir and the clinical trial that led to its approval can be found on the New England Journal of Medicine website.
That trial, the BRIGHTE study, has been previously presented, but was published this year. It demonstrated that, in combination with at least one other antiretroviral predicted to have activity against HIV, fostemsavir was able to suppress viral load to less than 40 copies/mL at 48 weeks in over 50% of patients who entered the study on failing regimens and with no viable combination therapy options.
For a small group that had no active agents at all with predicted activity against HIV, the fostemsavir in combination with best-guess therapy led to 38% becoming undetectable at 48 weeks. In both groups, CD4 cell count increased nicely.
The Bottom Line on Fostemsavir for Heavily HIV Treatment-Experienced Patients
A new drug to treat HIV infection—one with a novel mechanism of action that is well-tolerated—should be big news. Certainly, for those who can most directly benefit from fostemsavir, namely those with viral resistance on regimens that are unable to achieve viral suppression, the drug can be life-saving. This is a 1% we can all root for.
Potential companion agents for fostemsavir include the newer agents in existing classes, such as integrase inhibitors (e.g., dolutegravir or bictegravir) and non-nucleoside reverse transcriptase inhibitors (e.g., doravirine or rilpivirine), as well as ibalizumab, an infused anti-CD4 monoclonal antibody that also inhibits HIV cell entry, but via CD4 binding rather than gp120 binding.
Although it was approved as part of a salvage regimen, fostemsavir may also offer options to those on cumbersome HIV treatment regimens for other reasons. To be sure, fostemsavir has drawbacks: It is taken orally twice a day (albeit with or without food), and it has some interactions with other drugs (e.g., anticonvulsants), which can lead to reduced levels of the antiretroviral. However, a swap from a ritonavir- or cobicistat-boosted agent could be imagined—and beneficial.
Most people living with HIV will never need fostemsavir. But for those who do, the drug can be a life-saver—and that is pretty epic.