The promise of long-acting injectable formulations of HIV medications to maintain viral load suppression is closer to reality, according to Constance A. Benson, MD, Professor of Medicine and Global Public Health at University of California San Diego. She shared her assessment during a session at the 2020 Ryan White HIV/AIDS Program Clinical Conference, held online earlier this month for over 600 physicians, nurse practitioners, physician assistants, and other key clinical decision makers in HRSA’s Ryan White HIV/AIDS Program-funded clinics and programs.
Dr. Benson and Dr. Roy Gulick of Weill Cornell Medicine presented recent research findings on long-acting injectables for HIV treatment. Both presented data from the ATLAS-2M trial, a phase 3b open label study which compared the investigational, long-acting, injectable, two-drug combination of cabotegravir and rilpivirine administered intramuscularly (IM) every 4 weeks vs every 8 weeks as maintenance HIV therapy. Study participants had achieved viral load suppression either through standard of care daily oral therapy or long-acting cabotegravir/rilpivarine administered IM every 4 weeks. At 48 weeks, the every 8 weeks regimen was non-inferior to the every 4 weeks regimen with rates of virologic suppression (viral load of <50 copies per milliliter) at 94.3% and 93.5%, respectively. The ATLAS trial concluded that long-acting, injectable cabotegravir and rilpivirine, dosed every 8 weeks, is an effective and well-tolerated approach to maintaining viral suppression in people with HIV.
Advances in studies of possible long-acting formulations for HIV prevention were also discussed by Dr. Gulick. Last month at AIDS 2020, researchers presented findings from the NIH-supported HPTN 083, a randomized, double-blind study, which compared the HIV drug cabotegravir injected every 2 months (after an oral lead-in period) to daily oral tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC), brand name Truvada. The study population was men who have sex with men and transgender women. (An ongoing companion study, HPTN 084, is evaluating long-acting injectable cabotegravir for HIV prevention in cisgender women in sub-Saharan Africa.) At three years, there were fewer new HIV infections with cabotegravir (13) vs daily oral TDF/FTC (39). HIV incidence rates/100 patient years were 0.41 and 1.22 for cabotegravir and TDF/FTC, respectively. There were frequent injection site reactions (81% cabotegravir and 31% placebo) but only 2% in the cabotegravir group discontinued treatment. Dr. Gulick shared the researchers’ conclusions that while both methods were highly effective for HIV prevention in the study population, the final data analysis from HPTN 083 indicated that long-acting injectable cabotegravir had a superior protective effect. (View HIV.gov’s recent conversation with NIH’s Dr. Carl Dieffenbach about the HPTN 083 findings.)
Drs. Gulick and Benson noted that there are several other investigational medications that are in the pipeline for possible long-acting injectable therapy. These include lenacapavir, a capsid inhibitor which has oral and injectable (subcutaneous) formulations, including a long-acting formulation and is in early phase trials. A long-acting injectable formulation of VM1500A is in early phase trials for HIV maintenance therapy and is being considered for HIV prevention. It is a novel, potent NNRTI with broad spectrum anti-HIV-1 activity.
There is more to be learned about long-acting injectable HIV medications from ongoing studies and analyses. For example, for some formulations the medication may persist in people well after the last injection of the drug. This has been seen with cabotegravir and with the combination cabotegravir/rilpivirine; the medications were detectable in plasma greater than a year after the last injection. This persistence could increase the risk for drug resistant HIV and could result in long duration of toxicity if severe side effects occurred. Other potential concerns being studied are safety and efficacy in pregnancy, people’s ability to adhere to injections, and whether they can tolerate frequent injection site reactions. In addition, healthcare providers and clinics will need to consider how best to provide these injections, including the staffing and new workflows required.
“Long-acting injectables, if proven effective in clinical trials and approved by the FDA, will add tools to our HIV therapeutic and preventive toolboxes that will increase options for people with or at risk of HIV. For some people with HIV, these tools may increase convenience and confidentiality, improve adherence, and/or help reduce stigma associated with daily pill taking. These novel approaches may help us realize the goals of the Ending the HIV Epidemic (EHE) initiative: helping more people achieve viral suppression and preventing new HIV transmissions,” observed my colleague Harold Phillips, Chief Operating Officer of EHE & Senior HIV Advisor in the HHS Office of Infectious Disease and HIV/AIDS Policy.
The current data on long-acting injectables for HIV prevention and treatment are promising. Researchers will be sharing more findings in the years ahead and we will all be learning more about the potential opportunities these new tools could provide.
See the Ryan White Clinical Conference presentations by:
- Dr. Gulick, the Rochelle Belfer Professor in Medicine at Weill Cornell Medicine, New York
- Dr. Benson, Professor of Medicine and Global Public Health at the University of California San Diego
Get more information about other presentations at the 2020 Ryan White HIV/AIDS Program Clinical Conference