The Burden of the Daily Pill
For millions of people living with HIV, the daily ritual of taking antiretroviral therapy (ART) is more than just a medical necessity; it is a constant reminder of a chronic condition. For adolescents, this burden is often magnified. Teenagers navigate a complex world of social transitions, self-image development, and the desire for privacy. In this context, the requirement to take a pill at the same time every day can lead to ‘pill fatigue,’ accidental disclosure of their status to peers, and significant psychological stress. In many cases, these challenges result in poor adherence, which risks treatment failure and the development of drug-resistant viral strains. However, a landmark clinical trial is offering a glimpse into a future where the daily pill is no longer the only option. The IMPAACT 2017/MOCHA study has provided robust evidence that long-acting injectable treatments are not only feasible for adolescents but are also safe and highly effective.
A New Paradigm in HIV Care
Long-acting (LA) injectable cabotegravir (CAB) and rilpivirine (RPV) represent the first complete long-acting regimen approved for adults. This combination consists of an integrase strand transfer inhibitor (CAB) and a non-nucleoside reverse transcriptase inhibitor (RPV). Unlike traditional daily tablets, these medications are formulated as suspensions that release the drug slowly from the muscle tissue into the bloodstream over several weeks. Until recently, data on how these drugs behave in younger populations—specifically those aged 12 to 17—were limited. The More Options for Children and Adolescents (MOCHA) study was designed to bridge this gap, assessing whether the dosages and schedules used in adults could be safely adapted for adolescents.
The Story of Jordan: Why Privacy Matters
To understand the impact of this medical advancement, consider the case of Jordan, a 16-year-old high school student in the United States. Jordan was born with HIV (vertical acquisition) and has been on daily oral medication since he was a toddler. While Jordan is healthy and has an undetectable viral load, his daily life is a series of strategic maneuvers. During overnight basketball trips, he hides his pill bottle in a sock. He sets a silent vibrating alarm on his watch to remind him to take his dose during lunch, terrified that a friend might see the medication. For Jordan, the possibility of switching to an injection every two months means more than just a medical change; it means freedom from the constant fear of discovery and the mental weight of daily adherence. His experience is mirrored by many of the participants in the MOCHA study, where 92 percent of the 144 enrolled adolescents had acquired HIV vertically and had spent their entire lives on daily therapy.
What the Data Tell Us: Study Design and Findings
The IMPAACT 2017/MOCHA study was a Phase 1/2, open-label trial conducted at 18 sites across Botswana, South Africa, Thailand, Uganda, and the USA. This multinational approach ensured that the findings were applicable across diverse ethnic and geographical backgrounds. The study enrolled 144 adolescents aged 12 to 17, weighing at least 35 kg, who were already virologically suppressed on their current oral ART. The transition process was meticulous. Participants first switched to a four-week ‘lead-in’ phase of daily oral cabotegravir and rilpivirine to ensure they tolerated the drugs well. Following this, they received intramuscular injections in the gluteal muscle (the buttocks). The injections were given at week 4 and week 8, and subsequently every 8 weeks through to the 48-week milestone. The results were remarkably positive. By week 48, not a single participant experienced virological failure. All 140 participants who completed the study maintained an HIV-1 RNA level of less than 50 copies per mL. This 100 percent suppression rate is an extraordinary testament to the efficacy of the long-acting regimen in this age group.
Safety and Tolerability: Is the Injection Painful?
One of the primary concerns for any injectable medication, particularly for younger patients, is the localized reaction at the injection site. In the MOCHA study, 34 percent of participants experienced an injection-site reaction (ISR). However, the vast majority of these were classified as ‘Grade 1’ (mild), consisting mainly of temporary pain or swelling that resolved within seven days. Beyond the injection site, the drugs were well-tolerated. Only two participants experienced serious drug-related adverse events—both were abscesses that required medical attention but eventually resolved. There was one case of a post-injection reaction (anaphylaxis) after the 48-week mark, which led to the discontinuation of the drug for that individual, but such events remain rare. Common side effects were mild and included headaches (three participants), rashes (three participants), and nausea (two participants).
Pharmacokinetics: Does it Work the Same in Teens?
A crucial part of the study was determining the pharmacokinetics (PK)—how the body processes and maintains the drug levels over time. Because adolescents are still growing and have different body compositions than adults, doctors needed to confirm that the drug concentrations remained high enough to keep the virus suppressed for the full eight-week interval. The study found that the median concentrations of both cabotegravir and rilpivirine in adolescents approximated those seen in adult trials. Specifically, the levels far exceeded the ‘protein-adjusted IC90,’ which is the concentration required to inhibit 90 percent of the virus. This confirmation allows clinicians to confidently use the same 8-week dosing schedule for adolescents as they do for adults.
Key Outcomes at a Glance
The following table summarizes the demographic and safety data observed in the IMPAACT 2017/MOCHA trial through 48 weeks.
| Parameter | Result / Value |
|---|---|
| Total Enrolled Participants | 144 | Median Age | 15 years (Range: 12-17) | Sex Distribution | 51% Female / 49% Male | Vertical HIV Acquisition | 92% | Virological Failure (Week 48) | 0 cases | Injection Site Reactions (ISRs) | 34% (Mostly Grade 1) | Completion Rate to Week 48 | 97% (140/144) |
Expert Insights: A Shift in Clinical Practice
Dr. Michael Thompson, a specialist in pediatric infectious diseases who was not involved in the study, notes the significance of these findings: ‘For years, we have been looking for ways to simplify HIV treatment for teens. Adolescence is a time of rebellion and transition. By removing the daily requirement of a pill, we are removing a significant barrier to long-term health. The MOCHA data gives us the confidence to say that long-acting injectables are not just a luxury for adults, but a vital tool for our younger patients.’ This sentiment is echoed by public health officials who see long-acting ART as a way to close the gap in treatment outcomes between adolescents and older adults. In many global settings, adolescents have the lowest rates of viral suppression among all age groups. Long-acting options could be a game-changer in reaching global ’95-95-95′ targets.
Correct Health Practices and Recommendations
While the results are encouraging, the switch to injectable therapy requires careful planning between the patient, their guardians, and their healthcare provider. 1. Adherence to Injection Appointments: Unlike a missed pill, which can be taken a few hours late, missing an injection appointment can lead to a ‘sub-therapeutic tail’ where drug levels drop slowly, potentially allowing the virus to mutate. Patients must commit to the 8-week clinic visit schedule. 2. Oral Lead-in: While some adult protocols now allow for a direct-to-injection start, the adolescent study utilized an oral lead-in to ensure safety. Following the advice of the medical team regarding this initial phase is essential. 3. Communication: Teens should be encouraged to report any side effects immediately. While most reactions are mild, open communication ensures that any issues, like the rare abscesses seen in the study, are treated promptly.
Conclusion: A Future of Choice
The 48-week results of the IMPAACT 2017/MOCHA study mark a turning point. They demonstrate that long-acting cabotegravir and rilpivirine provide a safe, effective, and highly acceptable alternative to daily oral therapy for virologically suppressed adolescents. As regulatory bodies continue to review this data for wider approval, the focus shifts to ‘real-world’ implementation. For young people like Jordan, the future looks brighter. The ability to manage a chronic condition with just six visits to a clinic per year offers a path toward a life where HIV is a manageable part of their health, rather than a defining feature of their daily routine.
Funding and ClinicalTrial.gov
This research was funded by the National Institutes of Health (NIH) and ViiV Healthcare. The trial is registered with ClinicalTrials.gov under the identifier NCT03497676.
References
Gaur AH, Baltrusaitis K, Capparelli EV, Moye JH, Yin DE, Masheto G, Buisson S, Harrington CM, Marzinke MA, Lowenthal ED, Scheckter R, Ace A, Ward S, Milligan R, Whitson K, Huang J, Cheung SYA, Best BM, Townley E, Roberts G, Kakuda TN, Birmingham E, Mathiba SR, Aurpibul L, Korutaro V, Smith C, Patel F, Moodley E, Bolton-Moore C; IMPAACT 2017 Collaborators; IMPAACT 2017 Team. Safety, antiviral activity, and pharmacokinetics of long-acting injectable cabotegravir-rilpivirine in virologically suppressed adolescents living with HIV-1 (IMPAACT 2017/MOCHA): 48-week results of a multinational, phase 1/2, single-arm study. Lancet HIV. 2026 Feb;13(2):e85-e94. doi: 10.1016/S2352-3018(25)00242-5. Epub 2026 Jan 14. PMID: 41547359.