By the Editorial Team — referencing Dr. Jay K. Varma’s article on Psychology Today
Read more of Dr. Varma’s research and commentary at DrJayVarma.com

A breakthrough drug could change the landscape of HIV prevention. In his Fevered Mind column for Psychology Today, infectious-disease expert Dr. Jay K. Varma explains how lenacapavir, a twice-yearly injection, has shown near-complete protection against HIV infection in clinical trials — and what challenges remain to bring it to everyone who needs it.

The approval of lenacapavir marks a potential turning point in the fight against HIV, offering hope for populations who face barriers to daily pill-based prevention methods like PrEP.

A New Era in HIV Prevention

For decades, HIV prevention has relied on three strategies: behavior, barriers, and biomedicine.

Early public-health efforts focused on reducing risk behaviors and promoting condom use. But since 2010, landmark trials like iPrEx and HPTN 052 have proven that antiretroviral medications can not only prevent infection but also stop transmission when viral loads are undetectable — the foundation of the “U = U” principle (Undetectable = Untransmittable).

This paved the way for biomedical prevention through daily pre-exposure prophylaxis (PrEP), now a standard of care. Yet even with these advances, more than 30,000 Americans are infected with HIV each year, disproportionately affecting gay and bisexual men, transgender women, and people of color in the South — groups often facing systemic barriers to care and insurance.

What Makes Lenacapavir Different?

Lenacapavir belongs to a new class of capsid inhibitors — drugs that target the protective shell around the HIV virus. Unlike oral PrEP, it’s administered as a subcutaneous injection every six months, offering a low-maintenance, long-duration option for prevention.

In the PURPOSE 1 trial in South Africa and Uganda, involving over 5,000 adolescent girls and young women, no participants receiving lenacapavir became infected — compared to 55 infections across oral PrEP control groups. The follow-up PURPOSE 2 study in men, transgender women, and nonbinary individuals who have sex with men showed a 96% reduction in HIV incidence compared to background rates.

These findings suggest lenacapavir could function much like an HIV vaccine, dramatically reducing infections if widely deployed.

The Challenges Ahead

Despite its promise, lenacapavir is not without hurdles.

At the individual level, most participants reported mild injection-site reactions. More concerning are the rare cases of infection by drug-resistant strains when doses were delayed or missed — a risk caused by the drug’s long “pharmacologic tail,” when levels remain too low to prevent infection but high enough to foster resistance.

At the system level, Dr. Varma notes that health care infrastructure must evolve: clinics need new systems for scheduled injections, reminders, and follow-up, and national programs must monitor emerging resistance. With Medicaid and HIV-prevention budget cuts looming, these logistics could become major obstacles to equitable access.

Access, Equity, and the Future of HIV Prevention

Dr. Varma emphasizes that medical innovation alone won’t end the epidemic — access and delivery matter just as much. The people most at risk for HIV often face the greatest barriers to insurance, transportation, and stigma-free care.

Long-acting injectables like lenacapavir could revolutionize prevention — but only if the health system adapts to make them available to everyone, not just the privileged few.

Encouragingly, a once-yearly version of lenacapavir is already in early trials, with results expected later in 2025. If approved, it could simplify prevention even further — turning HIV prophylaxis into a routine, annual visit rather than a daily responsibility.

Learn More

Read Dr. Varma’s full article, “Could This Shot Prevent HIV?” on Psychology Today.
For more on his ongoing work in HIV prevention and public health, visit DrJayVarma.com.

FAQs

• How does lenacapavir work differently from daily PrEP pills?
• What are the risks of drug resistance in long-acting HIV prevention?
• Could lenacapavir replace current PrEP regimens?
• How might health-care cuts affect access to new HIV treatments?
• What would a once-a-year HIV shot mean for public-health strategy?