Twice-Yearly Promise: How Lenacapavir Could Redefine HIV Prevention in the Global South

HIV (human immunodeficiency virus) remains one of the world’s most persistent public health challenges. Since its identification in the 1980s, it has claimed millions of lives and affected countless families. Thanks to advances in antiretroviral therapy (ART), HIV shifted from a near-certain death sentence to a manageable chronic condition for many—but prevention is still key to ending the epidemic.

Over decades, prevention strategies have evolved: condoms; behavioral change; male circumcision; needle exchange; and more recently, PrEP (pre-exposure prophylaxis)—mostly daily oral pills (e.g. tenofovir/emtricitabine). But daily adherence, stigma, pharmacy access, and supply chain constraints have limited uptake in many settings.

Enter lenacapavir, a long-acting injectable designed for HIV prevention, requiring only two doses per year. It promises to overcome many of the barriers that stick to daily pills. But a drug’s power is only as good as the access people have to it—and that’s where the new pricing and licensing deals become crucial.

Lenacapavir to redefine HIV Prevention and Treatment

1. The Changing Landscape of HIV Prevention & Treatment

From ART to Prevention

• After the era of treating full-blown AIDS, scientists established ART regimens combining multiple drugs, reducing viral loads, preventing opportunistic infections, and transforming life expectancy for people with HIV.

• Over time, treatment guidelines improved (less toxic drugs, simpler regimens, fixed-dose combinations).

• Parallel to treatment, the idea of prevention with antiretrovirals grew. PrEP showed that uninfected people could take medicines to prevent HIV acquisition.

• Yet, daily PrEP has drawbacks: people forget, face social stigma, have erratic access, or simply “pill fatigue."

The Promise of Long-Acting Technologies

• In recent years, attention has turned to long-acting injectables as a way to reduce burden: fewer clinic visits, lower adherence demands, more discreet use.

• Cabotegravir (injectable PrEP given every 2 months) already showed the feasibility and superior effectiveness over oral PrEP in some trials (e.g. HPTN 083) .

• Lenacapavir pushes this further—with dosing every six months.

2. What Is Lenacapavir — Mechanism & Approved Uses

Mechanism

• Lenacapavir is an antiretroviral in a class called capsid inhibitors: it targets the HIV capsid (the protein shell of the virus) and interferes with multiple stages of the viral life cycle.

• Because its mechanism is distinct from many other drug classes, there is no known cross-resistance in vitro to existing antiretroviral classes.

• Its long residence and stability make it suitable for slow release / sustained activity over months.

Approved Uses & Regulatory Status

• Initially, lenacapavir has been used in treatment: for people with multi-drug resistant HIV, in combination with other antiretrovirals.

• In 2025, regulatory bodies have started approving its preventive use. In the U.S., it got approval (branded as Yeztugo) for HIV prevention.

• In July 2025, the World Health Organization issued guidelines recommending injectable lenacapavir twice per year as an additional PrEP option.

• The European Commission has authorized lenacapavir (brand name Yeytuo in Europe) as a twice-yearly injection for HIV prevention.

3. Efficacy & Safety — What the Trials Show

Efficacy

• In the PURPOSE 2 trial, lenacapavir achieved a 96% reduction in HIV incidence relative to background incidence; among those receiving lenacapavir, 99.9% remained HIV negative.

• In a trial in cisgender women (PURPOSE 1), none of the women receiving the injection contracted HIV.

• Comparisons with daily oral PrEP: lenacapavir was more effective and more forgiving of inconsistent use.

Safety & Tolerability

• The drug was generally well tolerated in trials, with primary side effects being injection site reactions and mild systemic symptoms.

• No new or unexpected safety concerns emerged in the prevention trials.

• Because lenacapavir for prevention is used as monotherapy (i.e. not combined with other ART drugs as in treatment), drug-interaction and resistance dynamics are somewhat different. But its strong barrier and distinct mechanism help mitigate those worries.

Bottom line: in trial settings, lenacapavir has come very close to “100%” prevention for many populations (within confidence intervals). That’s rare in HIV prevention.

4. The Price Slash & Global Access Deal

This is where things get really interesting—because a drug that’s powerful but unaffordable is wasted.

The Original Price & Barriers

• In U.S. markets, the cost was set extremely high (tens of thousands of dollars per year) for the branded version.

• That price puts it out of reach for most governments, health systems, or individuals in low- and middle-income countries.

The New Deal: $40/year

• In September 2025, an agreement was announced involving Unitaid, CHAI (Clinton Health Access Initiative), Wits RHI, and Dr. Reddy’s (an Indian generic manufacturer) to make lenacapavir available for US$40/year in 120 low- and middle-income countries (starting in 2027).

• Gilead had earlier granted royalty-free licenses to six generics for those same countries.

• The agreement includes technical, regulatory, and supply chain support to ensure quality, scale, and competition.

• This $40 is roughly 0.14% of the original price (if compared to $28,000) — a drastic reduction. (Your CFA figure of ~17M CFA corresponds to such high U.S. or European pricing.)

• Some projections suggest that with very large scale demand, cost per person-year could drop further, even to $25.

Why This Matters

• The price point is now competitive with (or even below) many oral PrEP regimens—making PrEP with lenacapavir potentially cost-neutral for health budgets in many settings.

• Because it’s injectable and less frequent, it may reduce costs tied to adherence support, supply chain leaks, pill wastage, etc.

• The model of licensing, technical support, and early generics is reminiscent of how older ARVs dropped in price drastically via generics in the 2000s.

Caveats / Critiques

• The licensing deal covers 120 low- and middle-income countries, but many upper-middle-income countries or “middle-income non-license countries” (e.g. parts of Latin America) may be excluded from the deal.

• Activist groups are pushing to expand the license, challenge patent barriers, and ensure inclusion of populations that often get left behind (e.g. transgender people, sex workers).

• The rollout is set for 2027, so there remains a gap of several years before broad access.

• Even with a low price, implementation challenges (cold chain, clinic infrastructure, trained staff, regulatory approvals, supply logistics) could slow uptake.

5. Implementation Realities & Challenges

Even a perfect drug won’t save lives if people can’t get it.

Regulatory & National Approval

• National regulatory authorities must approve lenacapavir for preventive use; WHO prequalification can help accelerate that.

• Some high-incidence countries are already prioritized for regulatory submissions (e.g. Gilead aims for 18 countries representing 70% of burden).

Infrastructure & Distribution

• Clinics must be ready to give injections twice a year, monitor patients, manage side effects, track follow-up.

• Cold chain, storage, inventory management, supply forecasting—all classic hurdles in global health.

• Many communities may lack trust in new interventions; outreach and engagement will matter.

Demand, Awareness & Acceptability

• People may hesitate to switch from oral PrEP or to try a new injection.

• Education, community acceptance, combating myths will be critical.

• Stigma and marginalization remain major barriers—especially for key populations (sex workers, LGBTQ+, people who inject drugs).

Sustainability & Financing

• Donors (Global Fund, PEPFAR, national governments) must commit to fund and procure.

• The low price helps, but budgets are tight; competition with other health priorities.

• Strategic planning needed to ensure no interruption in supply, no “start-stop” cycles.

6. What This Means for the Global HIV Agenda

If implemented well, lenacapavir could shift the balance:

• Acceleration toward the 2030 “End AIDS” goals: fewer new infections, fewer transmissions, faster decline in prevalence.

• Reduced burden on health systems: less frequent clinic visits, fewer monitoring demands.

• Better reach into “last mile” populations that struggle with daily adherence.

• New models for how breakthrough drugs reach low-resource settings: pricing, licensing, generics from the start, not waiting a decade.

But it won’t be a silver bullet. It must be paired with testing, linkage to care, treatment (for those who have HIV), behavioral interventions, harm reduction, stigma reduction.

Conclusion

Lenacapavir is a potentially paradigm-shifting tool in HIV prevention: a twice-yearly injection with near-perfect trial results. The newly negotiated drop from ~$28,000 to ~$40 per year in 120 low- and middle-income countries is bold, historic, and hopeful.

Yet, the devil is in the detail: inclusion (which countries, which populations), regulatory readiness, infrastructure, funding, community trust. If those pieces align, we may finally see tools that match the ambition of ending HIV. If not, it risks becoming another “breakthrough that never reaches people.”