CROI 2024 Highlights: Conference on Retroviruses and Opportunistic Infections

By: Ranier Simons, ADAP Blog Guest Contributor

The fight against HIV and other viruses like HCV and SARS-CoV-2 is a worldwide team effort. That is why the Conference on Retroviruses and Opportunistic Infections (CROI) convened from March 3rd through March 6th, 2024 in Denver, Colorado. Since 1993, CROI has brought together scientists, clinical scientists, and epidemiologists to present original groundbreaking research and collaborate to advance the treatment and prevention of HIV and other viral infections and opportunistic diseases.[8] CROI is one the first places research showing the effectiveness of triple-drug therapy for HIV was shared. It was also one of the first places where the results of the SMART study were shared, which proved that early treatment of HIV provides the best outcomes.[8] This year, 4,000 attendees gathered at CROI. Participants presented a multitude of novel and emerging therapies and studies. What follows are just a few notable highlights.

Photo Source: CROI

Long-Acting Injectables Blaze Forward

GSK’s long-acting injectable, cabotegravir, has already shifted the antiretroviral therapy (ART) paradigm. Coupled with rilpivirine, it is one-half of Cabenuva, the first complete ART injectable approved by the U.S. Food & Drug Administration (FDA). Cabenuva allows people who live with HIV (PLWH) to change from taking daily pills to the Cabenuva injection monthly or every two months. Studies have proven it is effective for those who have medication adherence challenges. It also presents an option for PLWH who wish to make medication management a less intrusive part of their lives.

ViiV Healthcare, the HIV-focused subsidiary of GSK, presented data from a clinical trial for a revolutionary new ultra-long-acting cabotegravir at CROI.[7] The new formulation has a higher concentration and double the half-life, potentially allowing it to be dosed every four months instead of every two.[7] Further clinical trials will be conducted to explore the use of the new formulation of cabotegravir as PrEP and as a treatment for PLWH. GSK’s goal is to have the first long-acting injectable for HIV prevention on the market by 2026 and for HIV treatment by 2027. The company also aims for an annual long-acting injectable by the first part of the 2030s.

DoxyPEP for STIs

DoxyPEP stands for doxycycline post-exposure prophylaxis. It is the practice of taking 200mg of oral doxycycline within 24 to 72 hours of condomless sex. Clinical trials have shown that DoxyPEP is effective in reducing the incidence of bacterial STIs such as syphilis and chlamydia. Results of Doxy PEP clinical studies of reducing STIs have been so promising that the CDC proposed guidelines for DoxyPEP usage in October 2022. However, those guidelines are not finalized.[1] 

Infectious disease professionals at CROI presented new data regarding DoxyPEP usage out in the real world among populations of people, mainly cisgender MSM and transgender women. Previous data was from clinical trials in contrast with new data that examined the results of DoxyPEP uptake in over 3,700 clients of sexual health clinics across San Francisco. Usage resulted in a 58% reduction in bacterial STI cases overall, a 67% reduction in chlamydia, and a 78% reduction in syphilis cases.[2] The real-world data indicated that when offered, there was a demand for DoxyPEP, and people consistently integrated it into their sexual health routine. As the Centers for Disease Control & Prevention (CDC) finalizes formal guidelines, DoxyPEP may potentially be solidified as another viable form of population wide STI prophylaxis.

Weekly Oral Antiretroviral Therapy

Long-acting injectable HIV therapy is not an optimal treatment modality for everyone. Nevertheless, other options for medication adherence that do not involve a daily regimen are needed for optimal health outcomes. At CROI, Gilead Sciences and Merck presented data from a clinical trial for a possible weekly oral antiretroviral therapy (ART) solution.

The solution is a weekly dosage of Gilead’s Sunlenca (lenacapavir), and an experimental drug named islatravir from Merck. [3,4] The phase 2 trial compared 104 patients taking daily Biktarvy (bictegravir 50mg/emtricitabine 200mg/tenofovir alafenamide 25mg tablets) with a group taking the weekly oral lenacapavir with islatravir. Data indicated that 94.2% of subjects taking the lenacapavir/islatravir combination maintained their viral suppression compared to 92.3% of the Biktarvy group.[3,4] The study will continue for another 48 weeks as open-label. This means that the study is no longer randomized. Both the medical professionals and the subjects know precisely what they are being given. There is no placebo. Studies move forward to open-label from randomized controlled studies once a high level of efficacy is proven and high benchmarks of defined endpoints are reached. 

Protecting Pregnant Women from HIV Infection

Research has shown there are physiological changes in the female body that cause a threefold increase in the risk of contracting HIV while pregnant.[5] This is especially troubling for countries where HIV is at an endemic level. Medications for HIV treatment and prevention are powerful, and it is crucial to find safe pharmaceuticals that will not harm the mother or the developing fetus.

At CROI, data from a multi-country (South Africa, Uganda, and Zimbabwe) clinical study presented safe options. A monthly flexible vaginal ring containing dapivirine as well as oral daily tenofovir disoproxil fumarate/emtricitabine PrEP (Truvada) were shown to be safe for use for pregnant women. The dapivirine vaginal ring is established in some African countries to be used as HIV prevention for cisgender women who are not pregnant. Truvada has already been proven to be safe for pregnant HIV-positive mothers to use.

The study was a randomized trial where pregnant women aged 18-40 used the dapivirine ring or received the oral PrEP up until delivery or for 41 weeks and six days, depending on which came first.[6] Only 1% experienced stillbirth or miscarriage, 95% of the women’s pregnancies went to term, and 4% of the births were premature.[6] Most importantly, none of the women contracted HIV. The results indicate that both the ring and Truvada are safe for pregnant mothers and their unborn fetuses to protect them from infection.

CROI continues to be a catalyst for pushing HIV and other infectious disease research forward. Scientific communities meet there, spurring the most qualified and passionate minds to collaborate and innovate. Whenever a cure for HIV is found, it would not be surprising if someone at a future session of CROI first presents it.

[1] DiMarco DE, Urban MA, Fine SM, et al. Doxycycline Post-Exposure Prophylaxis to Prevent Bacterial Sexually Transmitted Infections [Internet]. Baltimore (MD): Johns Hopkins University; 2023 Sep. Available from: https://www.ncbi.nlm.nih.gov/books/NBK597440/

[2] Carstens, A. (2024, March 6). DoxyPEP aces first real-world test. Retrieved from https://www.thebodypro.com/article/croi-2024-doxypep-real-world-clinical-data

[3] Clinical Trials Arena. (2024, March 7). Gilead-Merck’s combination therapy maintains HIV suppression in trial. Retrieved from https://www.clinicaltrialsarena.com/news/gilead-merck-hiv-trial/?cf-view

[4] Taylor, P. (2024, March 7). Gilead and MSD say weekly oral therapy controls HIV. Retrieved from https://pharmaphorum.com/news/gilead-and-msd-say-weekly-oral-therapy-controls-hiv

[5] Salzman, S. (2018, March 9).New study shows women's HIV risk triples during pregnancy, quadruples postpartum. Retrieved from https://www.thebodypro.com/article/new-study-shows-womens-hiv-risk-triples-during-pre

[6] HIV.gov. (2024, March 5). Vaginal ring and oral Pre-Exposure Prophylaxis found safe for HIV prevention throughout pregnancy. Retrieved from https://www.hiv.gov/blog/vaginal-ring-and-oral-pre-exposure-prophylaxis-found-safe-for-hiv-prevention-throughout-pregnancy

[7] Reuters. (2024, March 5). GSK's new HIV drug formula could support longer dosing intervals. Retrieved from https://www.reuters.com/business/healthcare-pharmaceuticals/gsks-new-hiv-drug-formula-could-support-longer-dosing-intervals-2024-03-04/

[8] CROI Foundation. (2024). General information about CROI. Retrieved from https://www.croiconference.org/about/

Disclaimer: Guest blogs do not necessarily reflect the views of the ADAP Advocacy Association, but rather they provide a neutral platform whereby the author serves to promote open, honest discussion about public health-related issues and updates. 

Is Long-Lasting, Injectable Medication the Future of HIV Therapy?

By: Sarah Hooper,  intern, ADAP Advocacy Association, and rising senior at East Carolina University

Long-lasting medication to treat patients living with HIV/AIDS has been a goal of the medical field since the early days of the epidemic. Currently, most HIV therapies include daily medication involving multiple pills, which has proven to be expensive for the average patient, as well as potentially challenging for medication adherence. That could be changing, because an investigational, long-acting, injectable, 2-drug regimen of cabotegravir (ViiV Healthcare) and rilpivirine (Janssen) for the treatment of HIV is showing promise.

At the 2020 Conference on Retroviruses and Opportunistic Infections, ViiV Healthcare announced results from its 96-week global phase III FLAIR study. The results demonstrated the injectable therapy "continued to provide non-inferior efficacy and comparable safety to the daily, oral, three-drug regimen of Triumeq (abacavir/dolutegravir/lamivudine-ABC/DTG/3TC)." Also, compared to their previous, oral treatment, patients who participated in the study expressed a high level of treatment satisfaction at week 48, as well as week 96 (ViiV Healthcare).

Photo Source: Christian Today

"Our focus on creating innovative treatment options for people living with HIV is further supported by these long-term findings of a long-acting injectable HIV treatment regimen. The efficacy and safety data of cabotegravir and rilpivirine at 96 weeks, as well as a high level of treatment satisfaction for the long-acting regimen, further encourage us as we work to bring this treatment option to people living with HIV," said Kimberly Smith, M.D., Head of Research & Development at ViiV Healthcare.

"Seeing the longer-term data is really exciting. It confirms that the long-acting, two-drug regimen of cabotegravir and rilpivirine has maintained its efficacy and has the potential to be a generally well-tolerated alternative to the standard-of-care, daily, oral pill. For some people living with HIV, reducing their dosing schedules from 365 days per year to 12 may be a realistic option in the future," said Chloe Orkin, M.D., Consultant Physician and Clinical Professor at Queen Mary University of London (ViiV Healthcare).

The use of cabotegravir has implications broader than HIV therapy, too. Injectable cabotegravir is also being evaluated for pre-exposure prophylaxis (PrEP). Whereas the aforementioned news of cabotegravir’s (in combination with and rilpivirine) initial effectiveness in treating patients is new to celebrate, questions still remain as it relates to its use in HIV prevention - one being its effectiveness in women living with HIV.

As it relates to PrEP, Molly Walker wrote in MedPage Today on May 19 that she worries this drug will be approved for only one HIV positive population.

"While results for the long-acting HIV prevention medication cabotegravir are promising in men who have sex with men (MSM), there is still no data on this drug in women, begging the question of whether this will be another HIV prevention option that ends up being approved for only one population," said Walker (MedPage Today).

Mitchell Warren is executive director of AVAC: Global Advocacy for HIV Prevention. He described the experience with another drug, F/TAF as 'completely dropping the ball early on in the process'. According to Walker, the experience with cabotegravir is not similar to F/TAF.

Thousands of women are getting cabotegravir injections and the same data safety monitoring board oversees both studies," he noted, adding HPTN 083 data has not been fully analyzed and yet to be peer reviewed. "It's still a long way from submission to the FDA and other regulators," said Warren.

Unlike F/TAF trials, the test trials for cabotegravir is almost 'fully enrolled' among women, which is promising. Warren also noted that if cabotegravir is effective in HIV positive women or at-risk women, it could be good news to those who still carry the social stigma of taking multiple pills a day.

"While PrEP has been "normalized" in the gay community, he added, the idea of carrying "a large pill bottle" still imparts a great deal of stigma for at-risk women," Warren said.

Warren emphasized that having more options with HIV medications is helpful to those around the world, citing that many women are comfortable getting injections every 3 months for contraception.

Cabotegravir is still in the testing stages, but the initial results of effectiveness in trail patients has been positive. The hope is that this new drug will be effective for both men and women, while also lessening the social stigma of taking large dosages of pills to treat and prevent HIV.

References:

• ViiV Healthcare (2020, March 9). ViiV Healthcare presents positive long-term data from phase III study demonstrating efficacy and safety of cabotegravir and rilpivirine, its investigational, long-acting injectable treatment regimen in adults living with HIV-1. Retrieved from https://viivhealthcare.com/en-gb/media/press-releases/2020/march/viiv-healthcare-presents-positive-long-term-data-from-phase-iii-/#:~:text=Cabotegravir%20is%20being%20developed%20by,prior%20to%20long%2Dacting%20injection
• Walker, Molly (2020, May 19). HIV Injectable Tx May Work in Men -- But What About Women? MedPage Today. Retrieved from https://www.medpagetoday.com/hivaids/hivaids/86580.

Disclaimer: Guest blogs do not necessarily reflect the views of the ADAP Advocacy Association, but rather they provide a neutral platform whereby the author serves to promote open, honest discussion about public health-related issues and updates.