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Shaping HIV Care and Prevention
Shaping the Future of HIV Care and Prevention

Released: November 21, 2025

Darcy Wooten
Darcy Wooten, MD, MS
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Key Takeaways
  • Zoster vaccination may be associated with a lower risk of major cardiovascular events and all-cause mortality in people living with HIV.
  • Weekly oral islatravir plus lenacapavir may be a promising investigational alternative to daily antiretroviral therapy.
  • With both intramuscular cabotegravir and subcutaneous lenacapavir approved for PrEP in the US, people have greater choices for long-acting options.

There were numerous outstanding studies at European AIDS Clinical Society (EACS) and IDWeek 2025 with the potential to be practice changing for prevention and treatment of HIV. Below, I’ve highlighted several that I found particularly exciting.

Benefits of Zoster Vaccination in People Living With HIV 
First was a retrospective, propensity-matched cohort study that used the TriNetX network to evaluate whether prior zoster vaccination mitigates adverse outcomes among people living with HIV. Investigators hypothesized that “silent reactivation” of herpes zoster, which occurs often among people living with HIV, contributes to inflammation and accelerates vascular injury.

After matching across 85 variables, zoster vaccination was associated with significantly lower risks of major adverse cardiovascular events and all-cause mortality. However, the observational design of this study introduces potential residual confounding, such as healthier individuals being more likely to receive vaccination. Of note, much of the observed benefit occurred 90-540 days post vaccination, raising questions about the optimal timing of immunization. Current US guidelines recommend zoster vaccination for all adults living with HIV.

Additional LA ART Options
Long-acting (LA) injectable antiretroviral therapy (ART) has transformed HIV care, with recent updates from IDWeek and EACS demonstrating the efficacy and tolerability of LA cabotegravir (CAB) plus rilpivirine in diverse populations, including older adults (RELATIVITY), individuals with advanced renal disease (CAPRI), and those with adherence challenges (PREFER-LA).

owever, LA injectables are not ideal for all patients, and additional options are still needed for people who cannot or prefer not to use injectables. For such individuals, emerging data on the investigational weekly oral islatravir plus lenacapavir (LEN) are particularly promising.

In a randomized, active-controlled, phase II trial, participants living with virologically suppressed HIV on  bictegravir/emtricitabine/tenofovir alafenamide who switched to weekly oral islatravir plus LEN maintained virologic suppression through Week 96, with no participants exceeding 50 copies/mL of HIV-1 RNA at study discontinuation. The regimen was well tolerated without lymphopenia (as was observed in prior studies with higher doses of islatravir) and mean adherence exceeded 99%. Phase III trials are now underway.

PrEP Preferences
The recent approval of twice-yearly SC LEN pre-exposure prophylaxis (PrEP) expanded injectable PrEP options from just IM CAB every 2 months. The CLARITY study, presented at EACS, was an open-label, randomized crossover trial comparing IM CAB and SC LEN in healthy adults to determine which injectable PrEP option patients preferred.

It was a small study, but participants overwhelmingly preferred IM CAB (90%) by Day 22 with the top 2 reasons being less pain during administration and less pain or soreness following administration. Pain scores were initially higher with SC LEN, but by Days 3, 5, and 8 they were similar between agents.

Although these findings highlight differences in tolerability, future studies incorporating both injection experience and dosing intervals will be essential to understand real-world preference patterns. Patient-centered research of this kind is crucial to optimizing uptake and sustained engagement in PrEP care.

Your Thoughts
How have patient preferences such as tolerability, dosing frequency, and injection experience shaped the real-world adoption of different PrEP modalities and ART options in your practice? Leave a comment to join the discussion!

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