Promising Developments in HIV Treatment: Lenacapavir's Role

Lenacapavir, a long-acting injectable medication administered every six months, has shown significant promise as a component of combination regimens for individuals initiating HIV treatment. The final results from the CALIBRATE study indicate that nearly 100% of participants maintained viral suppression after 132 weeks of treatment. This long-acting treatment option could enhance adherence and convenience for patients, although it currently requires daily antiretroviral medications alongside it. The U.S. Food and Drug Administration (FDA) approved lenacapavir (brand name Sunlenca) in 2022 for heavily treatment-experienced individuals with multidrug-resistant HIV and later for pre-exposure prophylaxis (PrEP) under the brand name Yeztugo.

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The Phase II CALIBRATE trial enrolled 183 previously untreated individuals with HIV, focusing on a racially diverse population. Participants were divided into four groups, with varying regimens involving lenacapavir and other antiretrovirals. Initial results presented at the 2021 International AIDS Society Conference showed high rates of undetectable viral loads across all groups. By 132 weeks, viral suppression rates ranged from 98% to 100% for those receiving lenacapavir injections. The treatment was generally well tolerated, with mild to moderate injection-site reactions being the most common side effects.

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Research is ongoing to explore additional long-acting injectable therapies. Gilead Sciences is testing new integrase inhibitors and a pro-drug of islatravir, while ViiV Healthcare is developing long-acting formulations of integrase inhibitors and capsid inhibitors. Combining lenacapavir with other long-acting agents may also be a viable strategy, as indicated by preliminary studies. Furthermore, broadly neutralizing antibodies (bnAbs) are being investigated as potential long-acting HIV treatments, with promising results from recent trials.

Twice-yearly lenacapavir could be an option for initial HIV treatment

Despite the advancements, challenges remain in achieving a complete long-acting regimen. Currently, lenacapavir must be combined with daily oral medications, and the only fully long-acting regimen available, Cabenuva, is limited to individuals transitioning from daily treatments. Critics emphasize the need for more comprehensive solutions that do not rely on daily adherence, especially in populations with high rates of stigma and discrimination.

Twice-yearly lenacapavir could be an option for initial HIV treatment

Health officials, including South Africa's Minister of Health Aaron Motsoaledi, have hailed lenacapavir as a "miracle tool" for HIV prevention, particularly for young women. The South African Health Products Regulatory Authority (SAHPRA) has approved lenacapavir for use, with plans for rollout in early 2026. The minister highlighted the importance of accessible prevention methods to combat the ongoing HIV epidemic.

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• “Lenacapavir-containing combinations achieved and maintained high rates of virologic suppression in treatment-naive participants through Week 132,” — Debbie Hagins, MD, Coastal District CARE Clinic

Twice-yearly lenacapavir could be an option for initial HIV treatment

• “We need prevention methods that fit into people’s lives, that address the gaps left by existing tools.” — Aaron Motsoaledi, Minister of Health, South Africa

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As lenacapavir becomes available in South Africa, efforts will focus on reducing costs and increasing accessibility. Ongoing clinical trials will further assess the efficacy of lenacapavir in combination with other treatments, aiming to enhance long-term viral suppression and explore potential curative strategies.

Twice-yearly lenacapavir could be an option for initial HIV treatment