Breaking NewsPerspective

Injectable cabotegravir effective as HIV PrEP when given every 2 months

Carlos del Rio

Administered as an injection every 2 months, the investigational drug cabotegravir was 69% more effective at preventing HIV than currently approved pre-exposure prophylaxis, or PrEP, ViiV Healthcare said today.

The finding was part of an interim analysis of data from the HIV Prevention Trials Network (HPTN) 083 study. The data have not been peer reviewed, but ViiV said detailed results will be presented at an upcoming meeting. It plans to use the data for regulatory submissions.

HPTN 083 enrolled approximately 4,600 men who have sex with men and transgender women at more than 40 sites in the United States, Argentina, Brazil, Peru, South Africa, Thailand and Vietnam and randomly assigned them to receive an injection of cabotegravir every 8 weeks or daily oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF). Two-thirds of the study participants were aged younger than 30 years and 12% were transgender women, ViiV said. In the U.S., half of the participants identified as black or African American.

According to ViiV:

  • Among 50 participants who acquired HIV, 12 were randomly assigned long-acting cabotegravir and 38 were randomly assigned to FTC/TD, for an HIV incidence rate of 0.38% (95% CI, 0.2%-0.66%) in the cabotegravir arm and 1.21% (95% CI, 0.86%-1.66%) in the FTC/TDF arm.
  • Despite a high level of adherence to oral FTC/TDF — 87% of tested samples were positive for tenofovir — the study showed that long-acting cabotegravir was 69% (95% CI, 41%-84%) more effective than FTC/TDF in preventing HIV acquisition.

“This is a practice-changing study,” Carlos del Rio, MD, executive associate dean at Emory University School of Medicine, told Healio. Del Rio was a protocol team member and an investigator on the study.

After an independent data and safety monitoring board (DSMB) found that the study data “clearly indicated” cabotegravir was highly effective at preventing HIV, it recommended that the blinded, randomized portion of the phase 2b/3 study be terminated, ViiV said. The company said that participants in the FTC/TDF arm would be offered the chance to receive cabotegravir. Safety was similar in both groups.

Another trial, HPTN 084, is evaluating injectable cabotegravir as HIV PrEP among women who are at an increased risk for HIV. The trial, which started a year after HPTN 083, is being conducted in seven African countries. ViiV said the DSMB also reviewed data from that trial and recommended that it continue as planned.

Cabotegravir is also part of a long-acting injectable HIV treatment regimen that has been approved in Canada but not by the FDA. – by Gerard Gallagher

Disclosure: Del Rio is a protocol team member and an investigator of record on HPTN 083.

Carlos del Rio

Administered as an injection every 2 months, the investigational drug cabotegravir was 69% more effective at preventing HIV than currently approved pre-exposure prophylaxis, or PrEP, ViiV Healthcare said today.

The finding was part of an interim analysis of data from the HIV Prevention Trials Network (HPTN) 083 study. The data have not been peer reviewed, but ViiV said detailed results will be presented at an upcoming meeting. It plans to use the data for regulatory submissions.

HPTN 083 enrolled approximately 4,600 men who have sex with men and transgender women at more than 40 sites in the United States, Argentina, Brazil, Peru, South Africa, Thailand and Vietnam and randomly assigned them to receive an injection of cabotegravir every 8 weeks or daily oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF). Two-thirds of the study participants were aged younger than 30 years and 12% were transgender women, ViiV said. In the U.S., half of the participants identified as black or African American.

According to ViiV:

  • Among 50 participants who acquired HIV, 12 were randomly assigned long-acting cabotegravir and 38 were randomly assigned to FTC/TD, for an HIV incidence rate of 0.38% (95% CI, 0.2%-0.66%) in the cabotegravir arm and 1.21% (95% CI, 0.86%-1.66%) in the FTC/TDF arm.
  • Despite a high level of adherence to oral FTC/TDF — 87% of tested samples were positive for tenofovir — the study showed that long-acting cabotegravir was 69% (95% CI, 41%-84%) more effective than FTC/TDF in preventing HIV acquisition.

“This is a practice-changing study,” Carlos del Rio, MD, executive associate dean at Emory University School of Medicine, told Healio. Del Rio was a protocol team member and an investigator on the study.

After an independent data and safety monitoring board (DSMB) found that the study data “clearly indicated” cabotegravir was highly effective at preventing HIV, it recommended that the blinded, randomized portion of the phase 2b/3 study be terminated, ViiV said. The company said that participants in the FTC/TDF arm would be offered the chance to receive cabotegravir. Safety was similar in both groups.

Another trial, HPTN 084, is evaluating injectable cabotegravir as HIV PrEP among women who are at an increased risk for HIV. The trial, which started a year after HPTN 083, is being conducted in seven African countries. ViiV said the DSMB also reviewed data from that trial and recommended that it continue as planned.

Cabotegravir is also part of a long-acting injectable HIV treatment regimen that has been approved in Canada but not by the FDA. – by Gerard Gallagher

Disclosure: Del Rio is a protocol team member and an investigator of record on HPTN 083.

    Perspective
    Melanie Thompson

    Melanie Thompson

    We are all starved for good news. Today’s announcement about HPTN 083 is welcomed. In the era of COVID-19, the stock market soars on the basis of meager data from pharma press releases, but although we do not have data yet — much less a peer-reviewed publication — the termination of this study by an independent and reputable DSMB lends substantial credibility to the top-line results. As soon as possible, we need details about demographics, study retention, timing of HIV acquisition and viral resistance in those who seroconverted, as well as complete safety data.

    Assuming the data survive scrutiny, implementation issues must be rapidly addressed.

    1. How will PrEP users and clinicians know who is likely to benefit from cabotegravir PrEP? We need more data to know for sure.

    2. How will we build necessary infrastructure — including adequate clinical staff — for bimonthly buttock injections, especially in the era of COVID-19? How will clinics and cabotegravir PrEP recipients deal with visits every 2 rather than 3 months?

     3. How do we track and support visit adherence? Adherence will still be an issue, just not daily. When people miss visits, it is easy to give them an extra month of pills. Will we still do that? What is a safe window for missed visits with cabotegravir?

    4. What will be the effect on PrEP capacity in Federally Qualified Health Centers through the federal Ending the HIV Epidemic initiative? Will there be more federal money for implementation?

    5. What will cabotegravir cost? Will there be a generous patient assistance program from ViiV, and what will be the criteria for participation? What will be the costs to our health systems?

    6. Who will pay? Will insurers insist on prior authorization, and what will be the criteria? Will insurers pay for administration costs? And will we see step therapy if generic TDF/FTC rolls out at a much lower cost?

    Additionally, of course, once again we must ask a familiar question: Will it work in cisgender women? Will the FDA act before HPTN 084 data are available?
    Overall, it is exciting to have another option. Now we must move very rapidly to ensure that it gets to those who will benefit, regardless of ability to pay.

    • Melanie Thompson, MD
    • Principal investigator
      AIDS Research Consortium of Atlanta

    Disclosures: Thompson reports that the AIDS Research Consortium of Atlanta has received clinical trial support from Bristol Myers Squibb, Cepheid, CytoDyn, Gilead Sciences, GlaxoSmithKline, Merck Sharp & Dohme and ViiV Healthcare in the past 24 months. Thompson reports no other funding from any pharmaceutical/biotech company.

    Perspective
    Raghavendra Tirupathi

    Raghavendra Tirupathi

    HPTN 083 is a path-breaking study in HIV prevention. Injectable cabotegravir will be a welcome addition to the PrEP arsenal. It will be the closest pharmaceutical we will have to an HIV vaccine at this time. This agent really could contribute to the goal of ending HIV by 2030. Adherence to daily pill regimens has always been a challenge in some of our at-risk populations, and it is hoped that this option will foster increased adherence in those patients. Intramuscular injections may be a deterrent in some patients, and injection site reactions could lead to discontinuation. There needs to be further evaluation as to why the 12 patients in the cabotegravir group became infected. The next logical question is, Will this service be covered by the payer and will this intervention be available in both resource-rich and resource-limited countries? Despite all the questions about real-world use of this injectable, I am glad to have another option to provide to my high-risk patients.

    • Raghavendra Tirupathi, MD, FACP
    • Infectious Disease News Editorial Board Member
      Medical director, Keystone Infectious Diseases/HIV
      Chair, infection prevention, Summit Health
      Clinical assistant professor of medicine
      Penn State University School of Medicine

    Disclosures: Tirupathi reports no relevant financial disclosures.