2025-12-03
Twice-yearly injections to change the game?
Infectiology
By Ana Espino | Published on December 3rd, 2025 | 3 min read
HIV remains a major global challenge, with more than 1.3 million new infections recorded in 2024, particularly affecting marginalized populations. Although oral pre-exposure prophylaxis (PrEP) has proven effective, its real-world impact is limited by adherence barriers such as stigma, daily pill fatigue, and inconsistent access to care. Similarly, currently available prevention options (TDF/FTC, TAF/FTC, CAB-LA, dapivirine vaginal ring) also present significant limitations: frequent dosing schedules, reliance on medical infrastructures, or moderate efficacy depending on the context.
A key challenge is the need for an effective, durable, and acceptable alternative — especially for the populations at highest risk. In this context, lenacapavir, a capsid inhibitor administered twice a year via subcutaneous injection and recently approved, is emerging as a promising approach in HIV prevention.
The objective of this review is to assess the potential of lenacapavir as an innovative solution to improve PrEP adherence and access.
Lenacapavir acts at multiple stages of the HIV replication cycle. It is administered by subcutaneous injection every six months, following a short oral lead-in phase. It has an exceptionally long half-life, a favorable safety profile, and sustained efficacy even in the presence of certain resistance mutations. To assess its potential in HIV prevention, two major clinical trials — PURPOSE 1 and PURPOSE 2 — were conducted.
In the PURPOSE 1 trial, no HIV infections were observed in the lenacapavir arm, compared with 16 cases in the oral PrEP arm (TDF/FTC). Similarly, in PURPOSE 2, only two infections occurred among lenacapavir recipients — both linked to pre-existing infections or interrupted follow-up — compared with nine cases in the TDF/FTC arm.
These results demonstrate near 100% efficacy, very high acceptability (with >75% of participants expressing a preference for lenacapavir), and strong potential to overcome adherence barriers associated with PrEP.
HIV continues to represent a major global public health threat. Although PrEP is effective, its uptake remains limited due to adherence constraints, social barriers, and unequal access. The real challenge is to develop prevention strategies that are simpler, more durable, and better tailored to the needs of the most vulnerable populations. In this context, the study aimed to assess the potential of lenacapavir, recently approved, as an innovative twice-yearly injectable PrEP option.
The PURPOSE clinical trials confirm its near-total efficacy and high acceptability. Moreover, lenacapavir appears capable of overcoming several limitations of existing PrEP approaches, particularly regarding adherence.
However, major obstacles remain: limited access in low-resource settings, high cost, storage requirements, disparities in prescribing practices, and the need for training among healthcare providers. These limitations highlight the need for further research. Lenacapavir will need to be integrated into national prevention strategies, and its availability extended to community-level structures such as pharmacies and mobile clinics. Finally, real-world data will be essential to confirm its long-term safety and effectiveness.
About the author – Ana Espino
As a scientific writer, Ana is passionate about bridging the gap between research and real-world impact. With expertise in immunology, virology, oncology, and clinical studies, she makes complex science clear and accessible. Her mission: to accelerate knowledge sharing and empower evidence-based decisions through impactful communication.
HIV remains a major global challenge, with more than 1.3 million new infections recorded in 2024, particularly affecting marginalized populations. Although oral pre-exposure prophylaxis (PrEP) has proven effective, its real-world impact is limited by adherence barriers such as stigma, daily pill fatigue, and inconsistent access to care. Similarly, currently available prevention options (TDF/FTC, TAF/FTC, CAB-LA, dapivirine vaginal ring) also present significant limitations: frequent dosing schedules, reliance on medical infrastructures, or moderate efficacy depending on the context.
A key challenge is the need for an effective, durable, and acceptable alternative — especially for the populations at highest risk. In this context, lenacapavir, a capsid inhibitor administered twice a year via subcutaneous injection and recently approved, is emerging as a promising approach in HIV prevention.
The objective of this review is to assess the potential of lenacapavir as an innovative solution to improve PrEP adherence and access.
Could the future of PrEP rely on just two injections?
Lenacapavir acts at multiple stages of the HIV replication cycle. It is administered by subcutaneous injection every six months, following a short oral lead-in phase. It has an exceptionally long half-life, a favorable safety profile, and sustained efficacy even in the presence of certain resistance mutations. To assess its potential in HIV prevention, two major clinical trials — PURPOSE 1 and PURPOSE 2 — were conducted.
In the PURPOSE 1 trial, no HIV infections were observed in the lenacapavir arm, compared with 16 cases in the oral PrEP arm (TDF/FTC). Similarly, in PURPOSE 2, only two infections occurred among lenacapavir recipients — both linked to pre-existing infections or interrupted follow-up — compared with nine cases in the TDF/FTC arm.
These results demonstrate near 100% efficacy, very high acceptability (with >75% of participants expressing a preference for lenacapavir), and strong potential to overcome adherence barriers associated with PrEP.
Lenacapavir: a silent revolution in HIV prevention?
HIV continues to represent a major global public health threat. Although PrEP is effective, its uptake remains limited due to adherence constraints, social barriers, and unequal access. The real challenge is to develop prevention strategies that are simpler, more durable, and better tailored to the needs of the most vulnerable populations. In this context, the study aimed to assess the potential of lenacapavir, recently approved, as an innovative twice-yearly injectable PrEP option.
The PURPOSE clinical trials confirm its near-total efficacy and high acceptability. Moreover, lenacapavir appears capable of overcoming several limitations of existing PrEP approaches, particularly regarding adherence.
However, major obstacles remain: limited access in low-resource settings, high cost, storage requirements, disparities in prescribing practices, and the need for training among healthcare providers. These limitations highlight the need for further research. Lenacapavir will need to be integrated into national prevention strategies, and its availability extended to community-level structures such as pharmacies and mobile clinics. Finally, real-world data will be essential to confirm its long-term safety and effectiveness.
Read next: HIV & young people: what if we changed the rules?
About the author – Ana Espino
PhD in Immunology, specialized in Virology
Last press reviews
Twice-yearly injections to change the game?
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