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. 

Switching from Efavirenz to Dolutegravir Presents Health Challenges for Black Patients

By: Ranier Simons, ADAP Blog Guest Contributor

It is indisputable that the advent of antiretroviral treatment (ART) has saved many lives and improved the health outcomes of people with HIV. Treatment has advanced over the past few decades from toxic regimens like AZT to more tolerable cocktail regimens like Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide). Side effects vary between drugs and even between people who take the same drug. As such, people who stay on ART for extended periods sometimes switch medication regimens due to undesirable side effects that develop from long-term use or acute responses to cocktail components. Infectious disease doctors weigh the pros and cons of medications for patients in an effort to enable the highest benefit with the least harm. This is why medical science constantly studies and evaluates drugs to reach a consensus of therapeutic value versus harm.

Photo Source: Cleveland.com

A recent study addresses the concern of weight gain for some patients of black African ancestry due to ART. The March 2023 issue of eClinical Medicine contains a study examining the effect of switching from efavirenz to dolutegravir in adults living with HIV in Johannesburg, South Africa. The study published in March was a prospective cohort study of adults (16 years or older) of black African ancestry who started ART between January 2010 and December 2020.[1] The study subjects were ART naïve patients who started fixed-dose regimens of tenofovir disoproxil fumarate (tenofovir), efavirenz, and lamivudine or emtricitabine which were established first-line regimens during the study period. The World Health Organization recommended dolutegravir, an integrase strand transfer inhibitor (INSTI), as an alternative to efavirenz in first-line ART in 2016, updating it as the preferred drug in 2018.[2] The change came because dolutegravir was proven more effective at long-term viral suppression, had less resistance, and increased tolerance over efavirenz.[1]

Dolutegravir became available to the clinic of the patients in the study cohort in 2019. There were 794 patients who were switched to dolutegravir and 794 who remained on efavirenz. All of the patients continued with the fixed doses of tenofovir disoproxil fumarate with lamivudine or emtricitabine and were observed for 12 months. The only change was swapping dolutegravir for efavirenz in one group compared to no swap in the other group. Results showed that those switching to dolutegravir had a mean weight change of 2.8kg (SD: 6.7kg), contrasting with 1.5kg (SD: 5.2kg) of those remaining on efavirenz.

Photo Source: AIDS Map

Weight gain is of concern because it could lead to other health issues, such as an increased risk for hypertension and diabetes. Typically some HIV patients experience wasting in some stages of disease progression, and ART results in weight gain as the body’s immune system strengthens.[1] This is desirable, especially since treatment initiation of patients in low and middle-income countries is frequently delayed until advanced disease states. However, weight gain is not good in HIV patients who are already overweight or may become overweight due to the dolutegravir.[1]

The prospective cohort study was done in response to two large clinical trials done in sub-Saharan Africa in 2020. The New Antiretroviral and Monitoring Strategies in HIV-infected Adults in Low-income countries (NAMSAL) trial and The ADVANCE trial displayed notable weight gain in people treated with dolutegravir compared to efavirenz.[3] The prevalence of obesity and ART utilization are both increasing in sub-Saharan Africa.[1] 

It is crucial to continue clinical trials to verify if weight gain is caused by dolutegravir in efavirenz’s absence or if efavirenz somehow holds back weight gain in the absence of dolutegravir. It is also essential to determine if dolutegravir-related weight gain is sustained over time and if it increases other disease risks. Dolutegravir is cost-effective, has high efficacy, and is tolerated better, thus reducing the need to switch patients to more expensive second-line regimens. Since it is presently here to stay, examining how to mitigate its potential for adverse risk increases of other conditions is imperative.

[1] Brennan, A., Nattey, C., Kileel, E., Rosen, S., Maskew, M., Stokes, A., Fox, M., Venter, W. (2023). Change in body weight and risk of hypertension after switching from efavirenz to dolutegravir in adults living with HIV: evidence from routine care in Johannesburg, South Africa. eClinicalMedicine, Vol 57. https://doi.org/10.1016/j.eclinm.2023.101836

[2] Update of recommendations on first- and second-line antiretroviral regimens, World Health Organization, Geneva, Switzerland (2019). Retrieved from https://apps.who.int/iris/bitstream/handle/10665/325892/WHO-CDS-HIV-19.15-eng.pdf

[3] Volny-Anne, A. (2020, July 17). 96 weeks results from two African studies confirm dolutegravir non-inferiority but highlight continued weight gain. Retrieved from https://www.aidsmap.com/news/jul-2020/96-weeks-results-two-african-studies-confirm-dolutegravir-non-inferiority-highlight

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.  

PEPFAR for the Win!

By: Ranier Simons, ADAP Blog Guest Contributor

What happens when a country realizes the importance of global collaboration in the fight against HIV and AIDS? PEPFAR happens. PEPFAR is the acronym for President’s Emergency Plan for AIDS Relief. This year marks the 20th anniversary of the initiative, the largest commitment ever made by a country targeted at fighting a single disease. The George W. Bush Administration brought PEPFAR into existence via H.R. 1298, the United States Leadership Against HIV/AIDS, Tuberculosis, and Malaria Act of 2003.[1] PEPFAR was initially a five-year plan with Congress appropriating $15 billion to combat the HIV/AIDS epidemic globally.[2] Since its inception and three reauthorizations, the U.S. federal government has invested over $110 billion in PEPFAR.[3] 

Photo Source: HIV.gov

H.R 1298 created PEPFAR, defined its structure and funding, and created a new position of U.S. Global AIDS Coordinator at the Department of State, with the rank of Ambassador.[4] The legislation defines the duties of the Coordinator as to: “(1) operate internationally to carry out prevention, care, treatment, support, capacity development, and other activities for combating HIV/AIDS; and (2) provide grants to, and enter into contracts with, nongovernmental organizations, including faith-based and community-based organizations, to carry out such activities.”[1] PEPFAR funding also includes contributions to the Global Fund to Fight AIDS, Tuberculosis, and Malaria. Significant PEPFAR endeavors include expanding access to HIV treatment and prevention, strengthening health systems, and providing services to children with HIV/AIDS. Many of the children are vulnerable and orphaned. The initial motivation behind PEPFAR was the devastation President George W. Bush saw occurring with the HIV/AIDS epidemic in Africa.

Providing antiretroviral therapy (ART) is a strong focus of PEPFAR. As of 2022, 20 million patients in 54 countries have received PEPFAR-funded ART. This is a 300-fold increase from 66,500 people in 2004.[5] The initial goal was to treat 2 million people, prevent 7 million infections, and provide humane care. At PEPFAR’s inception, it was estimated that 30 million people in Africa were infected with HIV, but only 50,000 were on ART.[5] To date, it is estimated that over 25 million lives have been saved with ART, and millions of infections prevented. ART not only preserves the lives of those living with HIV but prevents its spread through sexual contact and mother-to-child transmission through birth. Of those on PEPFAR-funded ART, viral suppression has increased from 80% to 95%.

The positive outcomes of PEPAR are not just HIV related. Due to the initiatives, public health infrastructures have been created and strengthened. Thus, countries were better prepared to deal with labs and testing necessary for COVID-19. Additionally, H.R. 1298 contained provisions to help with debt cancellation and restructuring of underdeveloped, heavily indebted countries overburdened by the HIV/AIDS epidemic and other public health crises.[1] PEPFAR has been hailed as one of the greatest achievements of the Bush Administration.

Photo Source: The Borgen Project

Data shows that in 2021 approximately 38.4 million people were living with HIV, 28.7 million people were on treatment, 1.5 million became newly infected, and 40.1 million have died from  AIDS-related illnesses since the start of the epidemic.[6] The fight against HIV/AIDS is far from over. It is imperative that Congress reauthorizes PEPFAR. Is it up for its fourth reauthorization this year. If Congress does not reauthorize PEPFAR, funding for it will not end. However, not reauthorizing it would mean that specific key time-bound provisions would sunset. This could adversely affect the way funds are allocated, the way oversight is conducted, and even how studies concerning its effectiveness and outcomes are conducted, ultimately affecting the appropriation of funds.

[1] H.R.1298 - United States Leadership Against HIV/AIDS, Tuberculosis, and Malaria Act of 2003. Retrieved from https://www.congress.gov/bill/108th-congress/house-bill/1298

[2] Cohen, J (2023, March 14). On Its 20th Anniversary, Reflecting On PEPFAR’s Success In Saving Millions Of Lives In Developing Nations From The Scourge Of HIV/AIDS. Retrieved from https://www.forbes.com/sites/joshuacohen/2023/03/14/on-its-20th-anniversary-reflecting-on-pepfars-success-in-saving-millions-of-lives-in-developing-nations-from-the-scourge-of-hivaids/?sh=44e55f494873

[3] Kaiser Family Foundation. (2022, July 12). The U.S. President’s Emergency Plan for AIDS Relief (PEPFAR). Retrieved from https://www.kff.org/global-health-policy/fact-sheet/the-u-s-presidents-emergency-plan-for-aids-relief-pepfar/

[4] Moss, K., Kates, J. (2023, March 13). PEPFAR Reauthorization 2023: Key Issues. Retrieved from https://www.kff.org/policy-watch/pepfar-reauthorization-2023-key-issues/

[5] CDC. (2023, March 14). Vital Signs: Progress Toward Eliminating HIV as a Global Public Health Threat Through Scale-Up of Antiretroviral Therapy and Health System Strengthening Supported by the U.S. President’s Emergency Plan for AIDS Relief — Worldwide, 2004–2022. Retrieved from https://www.cdc.gov/mmwr/volumes/72/wr/mm7212e1.htm?s_cid=mm7212e1_w

[6] UNAIDS. (2023) Global HIV & AIDS statistics — Fact sheet. Retrieved from https://www.unaids.org/en/resources/fact-sheet

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.