About Cabotegravir (CAB-LA)

What is CAB-LA?

CAB-LA, or long-acting injectable cabotegravir, is an antiretroviral drug developed by ViiV Healthcare and formulated to be administered once every two months as an injectable form of pre-exposure prophylaxis (PrEP). Currently approved in the US and Canada for treatment in combination with another injectable ARV (rilpivirine), CAB-LA is also being developed as an additional HIV prevention option.

CAB-LA inhibits HIV viral DNA from integrating with human DNA. Blocking this integration plays a role in both treatment and prevention. In treatment, CAB-LA, in combination with injectable rilpivirine, is used as a long-acting agent to maintain virologic suppression and has been approved for use among those who have already demonstrated virologic suppression using oral ARVs.

For prevention, two large scale efficacy trials from the NIH-funded HIV Prevention Trials Network (HPTN), HPTN 083 and HPTN 084, and smaller sub-studies, are currently underway. Both efficacy studies have found that CAB-LA is statistically superior to daily oral PrEP in reducing HIV risk in populations who are at high risk of HIV. HPTN 083 is studying CAB-LA among cisgender men who have sex with men (MSM) and transgender women who have sex with men (TGW); HPTN 084 is taking place among cisgender women. Both studies also confirmed that daily oral PrEP is also safe and effective. Each has unique characteristics, and individuals may prefer a particular PrEP method for any number of reasons. Ensuring informed choice is key. Injectable CAB-LA for PrEP is another strategy to help reduce HIV risk. For some people it will be the right one; for others, daily oral PrEP, the Dapivirine Vaginal Ring or another non ARV-based approach will be right.

CAB-LA reduces the risk of acquiring HIV and is a longer-acting option compared to oral PrEP.

While daily oral PrEP is becoming more available and accessible across the world, complex barriers affect adherence to daily pill-taking—from stigma and patriarchy to pill-size and side-effects. A long-acting option that eliminates the need for a daily pill may improve adherence for some.

Data from both studies show CAB-LA to be effective, safe, and well-tolerated in cisgender MSM, TGW, as well as cisgender women. HPTN 083 found a 66 percent reduction in incident HIV infections in study participants taking CAB-LA compared to those taking oral PrEP. HPTN 084 found an 89 percent risk reduction.

Like daily oral PrEP and the Dapivirine Vaginal Ring, CAB-LA does not protect against unintended pregnancies or STIs.

CAB-LA does not protect against other sexually transmitted infections (STIs) or unintended pregnancies. In fact, during the course of the trial, participants in both arms of HPTN 083 had high rates of other sexually transmitted infections, including new diagnoses of syphilis, chlamydia and gonorrhea. This is consistent with STI rates seen among oral PrEP users both inside and outside of clinical trials as well as with findings in HPTN 084. These findings reinforce the need to deliver all PrEP strategies with comprehensive, integrated services that include counseling, basic healthcare, contraception and other sexual and reproductive health services, and linkages to HIV treatment and care as needed.

Potential Implementation Issues for CAB-LA

One concern related to CAB-LA is the potential for acquiring resistant HIV virus while using CAB-LA. Diagnostics currently used for HIV testing may not be sensitive enough to detect acute HIV infection in people receiving CAB-LA. As a result, people who may have recently acquired HIV close to the time of CAB-LA initiation may not be diagnosed as HIV positive before starting CAB-LA injections. More sophisticated diagnostics such as viral load testing could potentially increase the cost of delivering CAB-LA as well as other HIV prevention products. Employing these diagnostics would also require additional training for providers and adaptations to the supply chain system.

There are also concerns about the CAB-LA tail which refers to the time period after CAB-LA injections have stopped, when trace amounts of the drug are still present in someone who formerly received the injections. The small amount of drug present in the bloodstream during the pharmacologic tail may not be enough to protect an individual from acquiring HIV. In fact, this could result in the development of drug resistant HIV following exposure. Both HPTN 083 and 084 are monitoring this closely. Unfortunately, it is not yet clear whether this long pharmacokinetic tail will have a significant impact on drug resistance.

Once CAB-LA moves from clinical trials to open label extensions to implementation more will be known about the specific barriers to access. Several have been cited including the site of administration (in the buttocks), which require a private room, dosing frequency (every two months), which does not align with most injectable contraceptive visits for many cisgender women in low and middle income countries (LMIC) (which is every two to three months) and having consistent access to a health facility to obtain the injection on a regular basis.

More research is needed to understand how CAB-LA functions in pregnant and breastfeeding people and what impact it might have on an unborn child. A number of participants became pregnant during HPTN 084. While no adverse effects were documented in either the mothers or the infants, HPTN 084 was not designed to answer questions about pregnancy nor was it large enough to detect potentially adverse health effects on participants. Therefore, ongoing research is necessary to determine whether CAB-LA is safe for people who are pregnant or breastfeeding. It is anticipated that any regulatory approvals and guidelines for use of CAB-LA will include guidance for people who are pregnant and breastfeeding.

CAB-LA Introduction, Planning and Coordination - Biomedical Prevention Implementation Collaborative (BioPIC)

The Biomedical Prevention Implementation Collaborative (BioPIC) was established to help coordinate product introduction efforts in the HIV prevention field. Translating clinical trial results into real world impact is challenging unless efforts are coordinated and timely. BioPIC draws on prior experiences from the introduction of oral PrEP to inform advanced planning for the introduction of future biomedical HIV prevention products. BioPIC efforts have initially focused on planning for CAB-LA, while also developing a BioPIC Adaptable Framework to provide an overarching framework for product introduction that can be adapted to specific products.

Currently, BioPIC is supporting both global and country decision-makers in developing well-designed, well-funded, and well-timed plans for the introduction of CAB-LA as a prevention option. Funded by the Bill & Melinda Gates Foundation (BMFG), and initially part of AVAC and CHAI’s HIV Prevention Market Manager project, BioPIC developed a comprehensive CAB-LA introduction strategy. This strategy prioritizes ensuring global and national bodies have sufficient evidence and safety assurance, establishing evidence to understand resource needs and the impact of CAB-LA, enabling programs to quickly move from small projects to scale, and identifying methods to support high uptake and continued use.