By Sharon Atieno

Cabotegravir (CAB-LA),the first injectable form of HIV pre-exposure prophylaxis (PrEP), joins a wide range of HIV prevention tools including male and female condoms, daily oral PrEP, voluntary medical male circumcision (VMMC) and the Dapivirine Vaginal Ring after receiving the US Food and Drug Administration (FDA) approval.

The CAB-LA, branded Apretude, is an injectable antiretroviral given to adults and adolescents who are confirmed to be HIV-negative at two-month intervals to reduce the risk of HIV.

The approval came after two randomized trials that compared Apretude to Truvada, a once daily oral PrEP.

The first trial included HIV-uninfected men and transgender women who have sex with men and have high-risk behavior for HIV infection while the second trial included uninfected cisgender women at risk of acquiring HIV.

Participants who took Apretude started the trial with cabotegravir (oral, 30 mg tablet) and a placebo -without the drug- daily for up to five weeks, followed by Apretude 600mg injection at months one and two, then every two months thereafter and a daily placebo tablet.

Participants who took Truvada started the trial taking oral Truvada and placebo daily for up to five weeks, followed by oral Truvada daily and placebo intramuscular injection at months one and two and every two months thereafter.

In the first trial, 4,566 cisgender men and transgender women who have sex with men received either Apretude or Truvada. It measured the rate of HIV infections among trial participants taking daily cabotegravir followed by Apretude injections every two months compared to daily oral Truvada.

The trial showed participants who took Apretude had 69% less risk of getting infected with HIV when compared to participants who took Truvada.

In the second trial, 3,224 cisgender women received either Apretude or Truvada. It measured the rate of HIV infections in participants who took oral cabotegravir and injections of Apretude compared to those who took Truvada orally.

The trial showed participants who took Apretude had 90% less risk of getting infected with HIV when compared to participants who took Truvada.

Additionally, the side effects were more frequent in participants who received Apretude than those who received Truvada in both trials. They included injection site reactions, headache, pyrexia (fever), fatigue, back pain, myalgia and rash.

According to Mitchell Warren, executive director, AVAC, a global non-profit organization advocating for HIV Prevention, the approval of CAB-LA is a welcome and much-needed boost for HIV prevention.

“With as few as six shots per year, this highly effective form of injectable PrEP can help bend the curve of the HIV epidemic – but only if its approval is accompanied by strategic, effective and equitable rollout that transforms the growing list of HIV prevention options into real and accessible choices for the people who need prevention most,” Warren said in a statement.

“Without global regulatory approvals, clear guidance from WHO, a commitment to equitable access and fair pricing, and resources to deliver innovation, the best science does not prevent or end pandemics.”

Effective global use of CAB-LA for HIV prevention will also require a significant and long-overdue upgrading of global HIV testing capacity, as injectable PrEP can only be used safely if the recipient is HIV-negative and is tested before every dose, the AVAC statement adds.

It will also require advocacy around self-testing and lower age of consent to testing policies, which has been significantly correlated with oral PrEP initiations.

“Transparency and fairness in pricing, advocacy for accelerated global regulatory review and appropriate and feasible testing policies, and supporting access programs and health system upgrades needed to support effective global access to injectable cabotegravir must all be part of the global HIV prevention agenda moving forward,” noted Warren.

Though the FDA action approves CAB-LA for use in the United States only, ViiV Healthcare, the developer of CAB-LA, has submitted applications to multiple regulatory authorities, including Brazil and several in sub-Saharan Africa that hosted the pivotal clinical trials led by the NIH-funded HIV Prevention Trials Network (HPTN).