Some good news for those at risk of HIV-1 infection

ViiV Healthcare, a company focusing on HIV treatments, received positive opinion from EMA for its long acting cabotegravir therapy in July this year [1]. Cabotegravir, a pre-exposure prophylaxis (PrEP), is used with a view to reducing the risk of sexually acquired HIV-1 infection. This is great news for HIV prevention, however it comes a year and half later than its FDA approval [2].

FDA’s approval and EMA’s positive opinion were based on 2 large multinational studies. These pivotal studies (HPTN 083 NCT02720094, HPTN 084 NCT03164564) compared the efficacy of standard oral PrEP (a daily pill containing the drugs tenofovir disoproxil fumarate and emtricitabine, or TDF/FTC) with an injectable formulation of cabotegravir, which was given to participants as an injection into the buttocks every eight weeks. Both pivotal studies were stopped early in 2020 due to high level of efficacy. In both studies, cabotegravir injections every other month reduced the risk of HIV acquisition more than daily PrEP pills. In the HPTN 083 trial, 4566 gay and bisexual men and transgender women participated in seven countries on four continents. Results showed that participants who took cabotegravir had 69% less risk of getting infected with HIV when compared to participants who took TDF/FTC [3]. This is a remarkable finding, given that daily TDF/FTC reduces the risk of HIV by approximately 99% for gay and bisexual men who use it consistently compared to no prophylaxis.

A parallel study, HPTN 084 compared the safety and efficacy of two-monthly injections of cabotegravir versus daily oral PrEP using TDF/FTC in 3,224 sexually active cisgender women between the ages of 18 and 45 years in seven countries in sub-Saharan Africa [3,4]. Women still make up about 49% of new infections [5]. These countries continue to have very high rates of HIV infection, particularly in young women. Injectable cabotegravir was even more effective in this study. Long-acting cabotegravir was 89% more effective than FTC/TDF. There were just four new infections among women randomly assigned to cabotegravir compared with 34 among those assigned to TDF/FT. This is the highest efficacy ever seen in a trial of PrEP for women. Several prior studies have found PrEP pills to be less effective for women than for gay men. The superior efficacy of injectable PrEP for this population appears to be linked to better adherence [6,7].

If a treatment or prevention trial is stopped early, it means the news is either very good or very bad. Cabotegravir’s results were so good, it would be unethical not to offer it. It makes you wonder why EMA didn’t act faster. It was over a year ago on 28th July 2022 when WHO released new guidance for HIV prevention [8]. In this guideline, WHO recommends that long action caboteglavir, may be offered as an additional prevention choice for people at substantial risk of HIV. Despite great progress, an estimated 1.3 million individuals worldwide acquired HIV in 2022. There are still about 100,000 new HIV diagnoses each year in Europe and, if approved, cabotegravir will become the only prevention option for people at risk of HIV acquisition that is administered as few as six times every year.

Long-acting caboteglavir is a step forward to manage adherence or stigma associated with daily oral PrEP tablets and it is likely to reduce AIDS deaths in addition to HIV incidence [9].

References

1 GSK. ViiV Healthcare’s cabotegravir for HIV prevention receives positive CHMP opinion from European Medicines Agency. July 2023

2 US FDA. FDA Approves First Injectable Treatment for HIV Pre-Exposure Prevention. Dec 2021

3 HTPN. HPTN 084 Study Demonstrates Superiority of CAB LA to Oral TDF/FTC for the Prevention of HIV. Nov 2020

4 Marzinke M, et al. Long-acting injectable PrEP in women: laboratory analysis of HIV infections in HPTN 084 IAS 2021 Abstract 18-21 July 2021

5 Cairns G. PrEP and Women. NAM Aidsmap. April 2023

6 Cottrell ML, et al. A Translational Pharmacology Approach to Predicting Outcomes of Preexposure Prophylaxis Against HIV in Men and Women Using Tenofovir Disoproxil Fumarate With or Without Emtricitabine. J Infect Dis. 2016;214(1):55-64.

7 Patterson KB, et al. Penetration of tenofovir and emtricitabine in mucosal tissues: implications for prevention of HIV-1 transmission. Sci Transl Med. 2011;3(112):112re4.

8 WHO Guidelines on long-acting injectable cabotegravir for HIV prevention. 2022

9 Smith J, et al. Predicted effects of the introduction of long-acting injectable cabotegravir pre-exposure prophylaxis in sub-Saharan Africa: a modelling study. Lancet HIV. 2023;10(4):e254-e65.