April 02, 2024
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HHS recommends ART for all children with HIV, regardless of clinical stage or CD4+ count, and rapid initiation of ART within days of diagnosis in all patients unless they have an opportunistic infection at the time of diagnosis.
High rates of adherence to ART are required for viral suppression and prevention of transmission. Therefore, concerns for suboptimal adherence have led to advances in therapeutic formulations, such as long-acting injectables.
Epidemiology
According to the CDC, approximately 20% of new HIV diagnoses in 2022 were among people aged 13 to 24 years, although there has been an overall decline in high-risk sexual behaviors over the last decade in this age group.
Only 6% of high school students have ever been tested for HIV, which is important because regardless of the results, testing services can connect patients with STI prevention resources. Almost half of young people with HIV are unaware they are infected.
In 2019, less than 1% of new HIV diagnoses were due to perinatal transmission, and data show the prevalence was highest among Black and Hispanic patients. Although perinatal transmission is the most common way patients aged younger than 13 years in the United States contract HIV, the rate decreased approximately 40% from 2015 to 2019.
Adherence concerns
Children and adolescents with HIV encounter various adherence obstacles when it comes to treatment regimens. Factors such as parental schedule and support, health insurance issues, stigma, poor taste of medications, and forgetfulness can contribute to difficulty with adherence.
Poor adherence can result in subtherapeutic drug levels, which facilitates the development of resistance to one or more of the components of ART and potentially cross-resistance to other drugs in the same class, therefore limiting future treatment options and increasing the risk for transmitting drug resistant virus.
The U.S. Pediatric HIV/AIDS Cohort Study showed that nonadherence rates increase with age, which may be in part due to loss in follow-up as patients age out of treatment by pediatricians and need to transition to another provider.
Once-daily regimens and regimens with low pill burden should be used, when possible, to improve rates of adherence and simplify regimens. The availability of once-daily, single-tablet regimens and formulations that have acceptable flavoring for children is limited.
Long-acting injectables
Because of adherence and resistance concerns, long-acting injectable therapy is an attractive option for adolescents.
In 2021, the FDA approved injectable cabotegravir and rilpivirine as the first long-acting HIV treatment for adults. The approval was expanded to include adolescents aged 12 years or older the following year, although the therapy is not approved or recommended as initial ART in treatment-naive patients. It can be administered monthly or every 2 months.
Eligible patients
Virologically suppressed adolescents aged 12 years or older who weigh at least 35 kg are eligible for treatment with cabotegravir and rilpivirine. Patients must be on a stable antiretroviral regimen and have no history of treatment failure or resistance to either cabotegravir or rilpivirine.
Administration
Before initiating the long-acting injectable, an oral 28-day lead in period using 30 mg cabotegravir and 25 mg rilpivirine daily can assess tolerability of the individual components of the regimen.
The therapy is injected intramuscularly by a health care provider into the gluteal muscle as two separate injections and is initiated on the last day of the oral lead in or a patient’s current regimen.
Dosing regimens for adolescents are the same as for adult patients. For once-monthly regimens, the initiation dose is cabotegravir 600 mg/rilpivirine 900 mg, followed monthly with cabotegravir 400 mg/rilpivirine 600 mg. For bimonthly regimens, the initiation dose of cabotegravir 600 mg/rilpivirine 900 mg is administered once monthly for two doses, followed by maintenance treatment with the same dose every 8 weeks.
Although residual concentrations of each component may remain for up to 1 year or longer after injection, an alternative ART regimen should be initiated within 1 month of discontinuing cabotegravir and rilpivirine.
Efficacy and safety
The FDA approval for adolescents was supported by efficacy data from studies conducted among adults, and a Week 16 interim analysis of the multicenter phase 1/2 More Options for Children and Adolescents (MOCHA) trial to confirm dosing strategies and assess safety, tolerability and efficacy among children aged 12 to 17 years old.
Data from the interim analysis of 23 adolescents in the United States who were enrolled in MOCHA showed that 61% of participants reported adverse effects, with injection site pain accounting for most reports. Additionally, the results showed the regimen was reaching goal pharmacokinetic levels in the adolescent population.
More recently, researchers presented 24-week data from MOCHA at the Conference on Retroviruses and Opportunistic Infections that showed the long-acting regimen safely suppresses HIV in adolescents when administered every 8 weeks.
Among 144 adolescents enrolled in the trial, all but three had completed visits through 24 weeks. There were no recorded virologic failures among the participants, who almost universally indicated that they preferred the long-acting therapy. Just over a third of them reported injection site reactions, which mostly resolved within a week, the researchers reported.
Looking into the future
Data on the use of long-acting injectable cabotegravir and rilpivirine in patients with adherence concerns, and adolescents specifically, are still being collected. The combination is currently the only long-acting injectable ART on the market. However, long-acting injectables are emerging as a treatment strategy for various disease states with advances in pharmacotherapy.
References:
- Brizzi M, et al. Ther Adv Infect Dis. 2023;doi:10.1177/20499361221149773.
- Cabenuva (cabotegravir, rilpivirine) Prescribing Information. US Approval March 2022.
- CDC. Diagnoses of HIV infection in the United States and dependent areas, 2020. https://www.cdc.gov/hiv/library/reports/hiv-surveillance/vol-33/index.html. Last reviewed May 24, 2022. Accessed March 28, 2024.
- CDC. HIV testing and youth. https://www.cdc.gov/healthyyouth/youth_hiv/hiv-information-and-youth.htm. Last reviewed March 26, 2024. Accessed March 27, 2024.
- CDC. YRBS summary & trends report. https://www.cdc.gov/healthyyouth/data/yrbs/yrbs_data_summary_and_trends.htm. Last reviewed April 27, 2023. Accessed March 28, 2024.
- Gaur A, et al. Abstract 188. Presented at: Conference on Retroviruses and Opportunistic Infections; March 3-6, 2024; Denver.
- HHS. Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/adult-adolescent-arv/guidelines-adult-adolescent-arv.pdf. Accessed March 27, 2024.
- HHS. Guidelines for the use of antiretroviral agents in pediatric HIV infection. https://clinicalinfo.hiv.gov/en/guidelines/pediatric-arv/regimens-not-recommended-initial-therapy-antiretroviral-naive-children. Accessed March 28, 2024.
- Lowenthal E, et al. Abstract 729. Presented at: Conference on Retroviruses and Opportunistic Infections; Feb. 12-16, 2022; virtual.
- Moore CB, et al. Abstract 738. Presented at: Conference on Retroviruses and Opportunistic Infections; Feb. 12-16, 2022; virtual.
- Orkin C, et al. N Engl J Med. 2020;doi:10.1056/NEJMoa1909512.
- Overton ET, et al. Lancet. 2020;doi:10.1016/S0140-6736(20)32666-0.
For more information:
Lauren Steil, PharmD, is a PGY-1 pharmacy resident at Denver Health Medical Center. Steil can be reached at [email protected].
Kati Shihadeh, PharmD, BCIDP, is a clinical pharmacy specialist in infectious diseases at Denver Health Medical Center. Shihadeh can be reached at [email protected].
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