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Injectables for HIV Treatment and Prevention: How They Work

Posted on July 21, 2022
Medically reviewed by
Barry S. Zingman, M.D.
Article written by
Jennifer Berger, Ph.D.

Modern antiretroviral therapy (ART) — the term for HIV treatment regimens — has come a long way over the past four decades. Now, many people live full lives with well-controlled HIV, without developing AIDS. However, for some people, ART has drawbacks.

Most therapies come in pill form, which poses problems for people who have trouble taking them. Additionally, all oral ART must be taken daily — sometimes, multiple times per day — and remembering to take the medication can be challenging. Research has found that about 30 percent of people living with HIV have trouble sticking to their treatment.

Being inconsistent with your HIV medications can have serious ramifications: You can develop what’s called drug-resistant HIV, a form of the condition that can’t be controlled by treatments that may have previously worked.

New injectable therapies are promising long-lasting alternatives that don’t require daily administration. In this article, we’ll look at some of the newer injectable treatments for HIV and how they compare to oral treatments.

Injectable Medication for HIV Treatment

This past January, the U.S. Food and Drug Administration (FDA) approved an HIV treatment called Cabenuva. Cabenuva is a combination of cabotegravir and rilpivirine — both extended-release injectable medications. It’s the first injectable treatment for HIV approved by the FDA.

Cabenuva is designed to be administered once per month as an injection into the muscle of the buttocks. In the future, that regimen could be extended to every eight weeks.

Cabenuva is designed to replace the current ART regimen of daily pills for people with well-controlled HIV. People who have well-controlled HIV are considered virologically suppressed or “undetectable.” A person is considered to have well-controlled HIV if their viral load (HIV levels in the blood) is less than 20 to 50 copies per milliliter, depending on what test is used. People who receive Cabenuva should also have no known drug resistance to either drug in Cabenuva.

Before starting injectable Cabenuva, a person is typically required to take oral formulations of cabotegravir (Vocabria) and rilpivirine (Edurant) for one month. This practice is called oral tablet lead-in. It’s generally recommended to establish how well the person tolerates these medications and to determine if they experience any side effects.

If you can tolerate the oral tablet lead-in well, you should be able to start monthly injections of Cabenuva. If a person plans to miss an injection by more than seven days, they can take cabotegravir and rilpivirine orally until the next injection of Cabenuva.

Injectable Medication for HIV Prevention

In December of 2021, the FDA approved Apretude — an extended-release injectable formulation of cabotegravir — as a preventive treatment for adolescents and adults who are HIV-negative but at high risk of being infected by HIV. Preventive treatment for HIV that is given before high-risk exposure is called pre-exposure prophylaxis (PrEP).

Apretude works by stopping a protein called integrase that HIV uses to reproduce itself. The drug is administered as an injection into the buttocks initially once a month for two months and then every two months after that.

Both Cabenuva and Apretude contain extended-release injectable cabotegravir, although the drugs have different purposes. Cabotegravir alone can be used to prevent HIV infection in high-risk populations.

The extended-release cabotegravir component of Cabenuva and Apretude can last up to 12 months in the body. This is why an oral tablet lead-in is often recommended to assess tolerance and toxicity before a person starts receiving the injections. The lead-in is less frequently used for Apretude.

How These Medications Work

Both cabotegravir and rilpivirine lead to viral suppression in someone living with HIV, but in different ways. Cabotegravir is an integrase inhibitor. This means it stops the integrase protein, thereby preventing the virus from integrating into the human DNA and then making more copies of HIV.

Rilpivirine is an HIV non-nucleoside reverse transcriptase inhibitor (NNRTI). Drugs in this class stop an HIV protein called reverse transcriptase. Reverse transcriptase is also necessary for HIV to make copies of itself, and NNRTIs prevent this from occurring.

Benefits of Extended-Release Injectables

Sticking to ART or PrEP medicines can be difficult because the pills must be taken as often as every day in order to control or prevent HIV infection. An online survey by pharma company ViiV uncovered some reasons why people struggle with taking pills daily, including:

  • Emotional issues, such as anxiety over missing a dose or taking it late
  • Privacy concerns, such as fear that carrying around and taking medications every day increases the chances of others learning about their HIV status

Although injections can be painful and require administration by a nurse, Cabenuva and Apretude are only administered every one to two months. The relatively low level of maintenance can be beneficial. Two clinical trials observed that most individuals receiving Carbenuva injections didn’t miss injections, with 97 percent of injections occurring within the required timeframe. This study suggests that the burden of receiving an injection once a month may not be as severe as daily pills in certain highly motivated people.

Researchers have observed some side effects from these injectables, although few have been severe. The most common side effects of Carbenuva are injection-site reactions (like redness, swelling, or pain) and headache. Other uncommon side effects include fatigue, fever, nausea, and muscle or bone pain. Liver toxicity (damage to the liver) can occur, especially in people previously diagnosed with hepatitis B or hepatitis C.

Cabenuva is just as, if not more, effective at treating HIV as the oral pill alternatives cabotegravir and rilpivirine. In clinical trials, a higher percentage of participants receiving the injectable therapy maintained low levels of HIV with well-controlled HIV by the end of each clinical trial, compared to those taking the pill alternatives.

Moreover, long-acting injectable cabotegravir administered as PrEP was found to be more effective at preventing HIV infection than emtricitabine/tenofovir (Truvada), a once-daily pill used for PrEP. This is likely due to better maintenance of therapeutic levels of the medicine with Apretude.

In clinical trials to date, researchers have found injectable cabotegravir taken either every month or two months to be well-tolerated. Mild injection-site reactions were the most common side effect. If a person acquires HIV despite having taken cabotegravir PrEP, they face the risk of developing an HIV strain that can no longer be treated by some, or even all, medicines in the integrase inhibitor class of ART. This can make it difficult to treat HIV later, in some cases.

People starting PrEP with this medicine must be well screened for HIV at the start of therapy, one month into treatment, and then at least every two months while on treatment. If a person goes longer than two months from their most recent injection, they must switch to oral PrEP treatment and/or use condoms or abstinence consistently in order to avoid developing HIV infection resistant to the integrase class of medicines.

U=U Campaign

The U=U campaign is spreading awareness about the power of HIV therapy. U=U stands for “undetectable equals untransmittable.” The name of the campaign refers to the fact that people who are HIV-positive and have undetectable viral loads are unable to spread the virus.

The campaign is based on three large clinical trials — from the New England Journal of Medicine, the Journal of the American Medical Association, and The Lancet HIV — that determined that HIV-positive individuals didn’t pass HIV on to their partners if their HIV was undetectable. These studies illustrate the importance of becoming undetectable by sticking with a modern ART treatment plan.

MyHIVteam Members and Injectables

Although new injectable HIV medications may not be the best choice for everyone, they offer a promising way for many to gain better viral control — and therefore improved quality of life. Many myHIVteam members are excited about the possibilities of these new formulations.

One member stated, “I’m so very excited for the injectables tomorrow morning!”

“I’m currently on a once-a-month injectable study. I love it,” shared another member. “I do experience soreness at the injection site, but that lasts maybe two days at most. Sometimes, not at all.”

Research into injectable HIV therapies is ongoing, and the future looks bright for people living with HIV. If you think injectables are a good fit for your goals while living with HIV, contact your health care provider.

Talk With Others Who Understand

On myHIVteam, the social support network for those diagnosed with HIV, you can connect with others. Members come together to ask questions, give advice, and share their stories with others who understand.

Are you interested in injectables for HIV treatment? Share your insights in the comments below, or start a conversation by posting on myHIVteam.

References
  1. HIV Drug Resistance — World Health Organization
  2. FDA Approves Cabenuva and Vocabria for the Treatment of HIV-1 Infection — U.S. Food & Drug Administration
  3. FDA Approves First Injectable Treatment for HIV Pre-Exposure Prevention — U.S. Food & Drug Administration
  4. Drug Database: Cabotegravir — Clinical Info HIV.gov
  5. HIV/AIDS — Mayo Clinic
  6. The Importance of Treatment Adherence in HIV — The American Journal of Managed Care
  7. Therapeutic Review of Cabotegravir/Rilpivirine Long-Acting Antiretroviral Injectable and Implementation Considerations at an HIV Specialty Clinic — Pharmacotherapy
  8. Drug Database: Cabotegravir / Rilpivirine — Clinical Info HIV.gov
  9. Long-Acting Injectable form of HIV Prevention Outperforms Daily Pill in NIH Study — National Institutes of Health
  10. U=U: Ending Stigma and Empowering People Living With HIV — Harvard Health Publishing
  11. Prevention of HIV-1 Infection With Early Antiretroviral Therapy — The New England Journal of Medicine
  12. Sexual Activity Without Condoms and Risk of HIV Transmission in Serodifferent Couples When the HIV-Positive Partner Is Using Suppressive Antiretroviral Therapy — JAMA
  13. Viral Suppression and HIV Transmission in Serodiscordant Male Couples: An International, Prospective, Observational, Cohort Study — The Lancet HIV
  14. Undetectable = Untransmittable — Prevention Access Campaign
  15. Swapping Daily Pills for Monthly Shots Could Transform HIV Treatment and Prevention — Science
  16. Two-Thirds of People Living With HIV Would Like To Try Injectable Treatment, According to European Survey — NAM

All updates must be accompanied by text or a picture.
Barry S. Zingman, M.D. specializes in HIV/AIDS medicine and general infectious disease. Review provided by VeriMed Healthcare Network. Learn more about him here.
Jennifer Berger, Ph.D. is a microbiologist at the University of Colorado Anschutz Medical Center. Learn more about her here.

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