Updates in HIV Care

HIV, a chronic viral illness that affects over 30 million individuals, has been a global pandemic since the 1980s. 1 Global rates of HIV-related fatalities and HIV transmission are declining; between 2010 and 2022, HIV-related deaths decreased by 51%.1 New medical advances aim to further decrease these rates. As of 2022, an estimated 86% of people living with HIV (PLWH) worldwide are aware of their HIV status, and among those, 93% have achieved suppression of viral load through antiretroviral therapy (ART).1

“ART has been a medical gamechanger for saving lives as treatment and as a potent prevention tool. […] Yet, we have substantial gaps that remain for people who face co-occurring health, housing, and other socio-economic challenges,” stated Carl Dieffenbach, PhD, director of the National Institute of Allergy and Infectious Diseases (NIAID) Division of AIDS. “Making progress against the HIV pandemic necessitates that societies prioritize reaching those who have historically been left behind, yet stand to benefit the most from making newer, easier formulations of ART available.”2

Currently, the standard of care for HIV treatment requires at least 2 agents from 2 separate ART classes.3 Modern ART regimens are much simplified compared with those of decades past; in some cases, treatment involves a single daily combination pill. However, treatment adherence remains suboptimal.4 This is particularly concerning when treating HIV, a chronic and transmissible condition that requires lifelong treatment. Socioeconomic factors such as stigma, substance abuse, complex treatment regimens, pill fatigue, and medication availability contribute to decreased adherence rates.4 Consequently, ART adherence rates for PLWH on oral treatments range from 27% to 80%.3

In general, the use of long-acting (LA) agents as treatment or prevention of chronic conditions improves adherence, which leads to better outcomes and care.5 Thus, recent introduction of LA medications for the management of HIV has been favorably received. “The HIV community is just beginning to unpack the enormous potential of long-acting antiretroviral medications for HIV treatment and prevention” said NIAID Director Jeanne Marrazzo, MD.6 

Studies show that LA ART for both the prevention and treatment of HIV is effective at maintaining viral suppression and is generally well-accepted by patients.7,8 Furthermore, PLWH transitioning from oral ART to LA ART report enhanced treatment satisfaction.8 Importantly, adherence rates among PLWH using injectable ART are consistent, regardless of the presence or absence of vulnerable factors such as mental health issues, substance use, financial instability, or lack of social support.9

Treatments available 

Currently, 5 LA ARTs are available globally for HIV treatment.10 

Two medications, lenacapavir and ibalizumab, are approved in the US for use as adjuncts to therapy for patients with extensive drug resistance.7,11 While both are LA agents, patients receiving treatment with either lenacapavir or ibalizumab still require additional daily oral ART.7 Lenacapavir is a subcutaneous injection given on a 6-month schedule, whereas ibalizumab, an intravenous treatment, is administered every 2 weeks.7,11 

Cabotegravir and rilpivirine are approved in the US as a joint regiment LA ART, and is co-administered as a comprehensive HIV treatment regimen for eligible PLWH.7 These intramuscular injections are dosed every 4 or 8 weeks and are co-packaged for convenience in the US.7 Cabotegravir–rilpivirine is non-inferior to conventional oral therapy for maintaining viral suppression.12 Contraindications include known resistance to either agent, hepatitis B co-infection, pregnancy or planned pregnancy.12

Lastly, dapivirine, an LA ART in the form of a monthly vaginal ring, is not currently approved in the US.10

Obstacles to LA ART

The introduction of LA ART is not without its challenges. For example, the cabotegravir–rilpivirine combination is approved only for PLWH who are virally suppressed and are already being treated with oral ART.2 Patients must also complete a one-month oral lead-in period to confirm tolerability before switching to the injectable formulation.⁵ This requirement may pose a barrier for patients with difficulties adhering to oral medications.

Additionally, implementation of LA regimens requires a change in practice. LA ART requires more frequent clinic visits for injections, increasing both patient and clinic burdens.¹³ Clinics must adapt by training personnel, ensuring appropriate storage, and expanding capacity to accommodate higher patient volumes.¹³ Additional limitations to LA ART include high costs and injection-site reactions.⁴

The implementation of intramuscular injections requires comprehensive patient counseling. Counseling topics should include the oral lead-in process, the importance of maintaining the injection schedule, protocols for missed doses, the importance of reliable contact information and ongoing communication, and potential side effects.3 

Treatment preference and the importance of choice

When asked about treatment preference, most PLWH on oral ART would prefer to switch to LA regimens.14 Specifically, PLWH with access to a car, higher income, and suboptimal adherence are most interested in switching to LA ART.14 Conversely, PLWH with limited social supports are more inclined to remain on oral therapy.14 

PLWH who opt for LA ART do so for many reasons, including reducing stigma, reducing inadvertent disclosure of their HIV status, and avoiding swallowing issues.12 However, some clients prefer daily oral medications over injectable formulations, either for convenience or needle phobia.12,15 

“The most effective treatments are those that fit into the lives of people who need them,” stated Dr Joshua A. Gordon.2 Offering multiple treatment options empowers patients to take control of their health and improves adherence.¹⁵

Next steps 

LA ARTs are available in only a few countries.7 As a result, very few eligible PLWH worldwide have access to these novel therapies.7 Expanding access is essential for enabling patients to choose treatments that best align with their lifestyles.

Efforts to increase access should include further simplifying ART regimens, reducing drug-drug interactions, and enhancing healthcare coordination for PLWH.4 Specifically for injectable LA ART, improving access requires optimization of the manufacturing processes, researching extended dosing intervals, improving LA ART long-term storage and transportation stability, and decreasing injection-site reactions.4 

Ongoing research aims to address these issues. For example, clinical trials are currently investigating the efficacy of a longer-acting cabotegravir, which would be dosed every 4 months.4,16

“With the right support, long-acting ART can make it easier for people with HIV who face barriers in adhering to daily oral treatment to keep the virus under control,” said Joshua Gordon, MD, director of the National Institute of Mental Health.2 

References 

  1. World Health Organization. HIV statistics, globally and by WHO region, 2023. Accessed November 20, 2024. https://iris.who.int/bitstream/handle/10665/376793/WHO-UCN-HHS-SIA-2023.01-eng.pdf?sequence=1

  2. Long-acting antiretroviral therapy suppresses HIV among people with unstable housing, mental illnesses, substance use disorders. News release. National Institutes of Health. February 21, 2023. Accessed November 20, 2024. https://www.nih.gov/news-events/news-releases/long-acting-antiretroviral-therapy-suppresses-hiv-among-people-unstable-housing-mental-illnesses-substance-use-disorders

  3. Brizzi M, Pérez SE, Michienzi SM, Badowski ME. Long-acting injectable antiretroviral therapy: will it change the future of HIV treatment?. Ther Adv Infect Dis. 2023;10:20499361221149773. doi:10.1177/20499361221149773

  4. Ullah Nayan M, Sillman B, Hasan M, et al. Advances in long-acting slow effective release antiretroviral therapies for treatment and prevention of HIV infection. Adv Drug Deliv Rev. 2023;200:115009. doi:10.1016/j.addr.2023.115009

  5. Nachega JB, Scarsi KK, Gandhi M, et al. Long-acting antiretrovirals and HIV treatment adherence. Lancet HIV. 2023;10(5):e332-e342. doi:10.1016/S2352-3018(23)00051-6

  6. Long-acting HIV treatment benefits adults with barriers to daily pill taking and adolescents with suppressed HIV. National Institutes of Health (NIH). Published March 6, 2024. Accessed October 23, 2024. https://www.nih.gov/news-events/news-releases/long-acting-hiv-treatment-benefits-adults-barriers-daily-pill-taking-adolescents-suppressed-hiv

  7. Venter WDF, Gandhi M, Sokhela S, et al. The long wait for long-acting HIV prevention and treatment formulations. Lancet HIV. 2024;11(10):e711-e716. doi:10.1016/S2352-3018(24)00173-5

  8. Konishi K, Onozuka D, Okubo M, Kasamatsu Y, Kutsuna S, Shirano M. Long-acting antiretroviral therapy effectiveness and patient satisfaction using patient questionnaires: data from a real-world setting. BMC Infect Dis. 2024;24(1):979. doi:10.1186/s12879-024-09904-x

  9. John M, Williams L, Nolan G, Bonnett M, Castley A, Nolan D. Real-world use of long-acting cabotegravir and rilpivirine: 12-month results of the inJectable Antiretroviral therapy feasiBility Study (JABS). HIV Med. 2024;25(8):935-945. doi:10.1111/hiv.13647

  10. Sherman EM, Agwu AL, Ambrosioni J, et al. Consensus recommendations for use of long-acting antiretroviral medications in the treatment and prevention of HIV-1: Endorsed by the American Academy of HIV Medicine, American College of Clinical Pharmacy, Canadian HIV and Viral Hepatitis Pharmacists Network, European AIDS Clinical Society, and Society of Infectious Diseases Pharmacists: An executive summary. Pharmacotherapy. 2024;44(7):488-493. doi:10.1002/phar.2921

  11. FDA approves new HIV treatment for patients who have limited treatment options. News Release. Food and Drug Administration. March 6, 2018. Accessed November 18, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-new-hiv-treatment-patients-who-have-limited-treatment-options

  12. Halani S, Tan D, Andany N. Long-acting injectable antiretroviral therapy for HIV-1 infection in adults. CMAJ. 2024;196(10):E341-E342. doi:10.1503/cmaj.231498

  13. Collins LF, Koester KA, McNulty MC, et al. Patient Attitudes Toward Self- or Partner-, Friend-, or Family-Administered Long-acting Injectable Antiretroviral Therapy: A Mixed-Methods Study Across 3 Urban Human Immunodeficiency Virus Clinics. Open Forum Infect Dis. 2024;11(6):ofae265. doi:10.1093/ofid/ofae265

  14. Fisk-Hoffman RJ, Liu Y, Somboonwit C, et al. Who wants long-Acting injectable antiretroviral therapy? Treatment preferences among adults with HIV in Florida. AIDS Care. 2024;36(11):1545-1554. doi:10.1080/09540121.2024.2383872

  15. Aziz R. AIDS 2024: Studies show strong user preference for long-acting, injectable PrEP. Infectious Disease Society of America. Published July 23, 2024. Accessed November 20, 2024. https://www.idsociety.org/science-speaks-blog/2024/aids-2024-studies-show-strong-user-preference-for-long-acting-injectable-prep/

  16. Highleyman L. Ultra-long-acting cabotegravir could be taken three times a year for HIV PrEP and treatment. Aidsmap.com. Published March 12, 2024. Accessed November 20, 2024. https://www.aidsmap.com/news/mar-2024/ultra-long-acting-cabotegravir-could-be-taken-three-times-year-hiv-prep-and-treatment