Shots: 

• Recently at IDWeek 2024, ViiV Healthcare presented data from two real-world studies on Apretude, a long-acting injectable (LAI) for HIV pre-exposure prophylaxis. 

• Dr. Harmony Garges, Chief Medical Officer at ViiV, shared insights from the presentations. The Opera cohort study found Apretude to be 99.7% effective in preventing HIV among participants. Additionally, the Trio Health cohort study reported zero HIV diagnoses during the follow-up period. 

• Dr. Garges also highlighted ViiV’s innovative pipeline, which focuses on developing next-generation integrase strand transfer inhibitors (INSTIs). 

Saurabh: Based on the recently presented new data across their HIV portfolio by ViiV Healthcare, can you please talk about the study design and results of Apretude of two studies (OPERA and Trio)?  

Harmony: First, I want to say that we’re proud to be the innovator and industry leader in long-acting injectables (LAIs) and we’re the only company to have LAIs approved for HIV treatment and prevention. And at IDWeek 2024, we presented data from two real-world studies—one from the OPERA cohort and the other from the Trio cohort—for Apretude, which is our LAI for HIV pre-exposure prophylaxis or PrEP. Because it’s widely known that medicines often perform better in randomized clinical trials than they do in the real world, findings like these become important because they add more evidence to the fact that Apretude is a highly effective option for preventing HIV.  

Here are the details. The OPERA study found Apretude, as used in the real world, was effective in preventing HIV in 99.7% of participating individuals. It also gives us insights into injection timing, adherence, and effectiveness among individuals in the U.S. All of that is important to clinicians when deciding with their patients about what’s best choice for them. Also, it’s important to know that the study included a large, diverse cohort of 764 individuals, 29% of whom are Black and 29% Hispanic. Eighty-five percent of individuals taking Apretude completed initiation of the regimen. In other words, they completed their first two initiation injections in 60 or fewer days apart from each other and a majority (69%) of these complete initiators received all of their injections on time. We saw some injection delays among those who had completed initiation, but most delays were short and within three days of the target injection date. Two cases of HIV infection (0.3%) were observed. One occurred in a person who discontinued Apretude and one in a person who had inconsistent HIV testing. 

The Trio Health cohort gives us additional real-world data for Apretude showing there were zero HIV diagnoses identified during follow-up time of the study. The study observed a diverse population of 474 cis- and transgender male and female individuals receiving Apretude in the U.S. In addition to zero HIV diagnosis observed, 83% of participants continued receiving Apretude injections, and these were administered on time for most participants. Out of the 396 participants who continued injections, only a third (33%) experienced delays with a median of one delayed injection and a median delay time of 12 days. And finally, we saw that adherence to Apretude was high, and only 3% of participants missed getting an injection. 

In the end, both studies reinforce findings from the efficacy data from the pivotal trials, all together giving us confidence that Apretude is an effective option for preventing HIV in diverse populations. 

Saurabh: Give us some more details (MOA, ROA, formulations, etc.) about Apretude.   

Harmony: Apretude is an integrase strand transfer inhibitor or INSTI. INSTIs inhibit HIV replication by preventing the HIV viral DNA from integrating into the DNA of human immune cells which are also known as T-cells. That step is essential in how HIV replicates and is also responsible for establishing HIV as a chronic infection. 

Apretude is an injection that’s given intramuscularly in the buttocks as few as six times per year.  It’s started with a single injection that’s given one month apart for two consecutive months. After the second initiation injection, a single injection given every two months.  

Saurabh: Highlight the study design evaluating Apretude in patients with HIV pre-exposure prophylaxis (PrEP).   

Harmony: Apretude was approved by the U.S. FDA in December of 2021 and the evidence supporting that approval came from two large, diverse clinical trials evaluating its safety and efficacy. These trials, HIV Prevention Trials Network (HPTN) 083 and HPTN 084, were conducted several years ago and were among the most diverse, comprehensive HIV prevention trials ever done. For more context, these trials enrolled some of the largest numbers of transgender women and Black men who have sex with men. In both clinical trials, in these diverse populations, Apretude demonstrated superior efficacy compared to a daily oral PrEP regimen. 

Another thing to remember is that both trials were stopped early because Apretude demonstrated superior efficacy versus the comparator PrEP medicine. In the HPTN 083 trial, Apretude injections reduced the HIV risk in cisgender men and transgender women by 69% compared to daily oral pills. The HPTN 084 trial demonstrated a 90% overall reduction in HIV risk compared to daily pills among cisgender women. 

Saurabh: What are the next steps for ViiV Healthcare in terms of regulatory approvals and market availability?  

Harmony: Apretude, the first and only approved LAI for PrEP, has received regulatory approval in 21 countries, including the U.S. The critical evidence in the OPERA and Trio studies reinforce Apretude’s impact, demonstrating positive results in real world effectiveness and adherence that add to a growing body of evidence in the communities that stand to benefit most from HIV PrEP. By bridging the gap between clinical trials and real-world practice, we're empowering healthcare providers and people who can benefit from HIV prevention to make informed decisions that optimize their care today. 

Saurabh: What can we expect next from ViiV’s portfolio of HIV drugs?  

Harmony: Your readers should know that ViiV Healthcare has one of the most innovative pipelines in the industry. Our innovative approach aims to deliver a new generation of longer acting medicines, based on our experiences and leadership in creating long-acting therapies, for people seeking options to treat or prevent HIV.  

I mentioned earlier that Apretude is an integrase inhibitor or INSTI. INSTIs have come to be known as the gold standard, trusted by healthcare professionals worldwide for their potency, durability, long-term tolerability and high barrier to resistance. Our pipeline is centered on what we call INSTI at the Core, where we’re continuing to develop next generation INSTIs and match them with other compounds that can include capsid inhibitors and broadly neutralizing antibodies. It’s our intention that creating new generations of ultra-long-acting HIV regimens will further reduce the number of required clinic visits, provide expanded choice for treatment and prevention, and offer the assurance of long-term efficacy to healthcare professionals and those they serve.  

You can learn more about our clinical development pipeline here. 

Image Source: Canva 

About the Author: 

Harmony Garges 

Dr Harmony Garges is Chief Medical Officer at ViiV Healthcare. She is responsible for Regulatory, Safety and Medical Affairs. In 2005, Harmony joined the Infectious Diseases group at GSK and spent several years working on global development programmes, as project physician leader for Fosamprenavir, Valtrex and Altabax, leading to three successful NDA/MAA files for new or expanded indications. Harmony provided medical leadership and strategy for the development of various other anti-infectives through phases I to III, including the FTIH dolutegravir trial. 

She then joined Global Clinical Safety & Pharmacovigilance, where she provided safety strategy and governance for several large global clinical development programmes in Pharma, and as Global VP of the Mature Products Safety Group, with accountability for the safety of over 500 marketed products across the Pharma and Consumer Healthcare (CH) portfolio. Harmony spent three years as the Chief Medical Officer for GSK's Consumer Healthcare business, where she was accountable for all aspects of product safety and medical governance for the global portfolio and led the medical organisation though the complex JV integration with Novartis. 

Harmony graduated with high honours from Colgate University with a degree in Chemistry. She obtained her MD degree and completed her paediatrics residency at Duke University. Following a year as Chief Resident, she completed Paediatric Infectious Diseases and Medical Microbiology fellowships at Duke, along with her MPH in Epidemiology from the University of North Carolina at Chapel Hill. 

Harmony is board-certified in General Paediatrics, Medical Microbiology and Paediatrics Infectious Diseases. Harmony is Adjunct Faculty at Duke, where she continues to provide patient care in the Duke Pediatric HIV/ clinic. 

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