Nine efficacy trials. One flicker of success. And a prevention line that, while the world waited, quietly won. This is the whole ledger — with sources.
At an April 23 press conference, U.S. Health Secretary Margaret Heckler announced the discovery of the virus that causes AIDS — and promised a vaccine "ready for testing in approximately two years." Forty-two years later, that sentence is still the most quoted promise in AIDS history.
The U.S. government launched its first HIV vaccine clinical trials. Early candidates targeted gp120, the envelope protein — the same target that would dominate — and disappoint — the field's first decade.
After fifteen years of small safety studies, AIDSVAX became the first HIV vaccine ever tested for efficacy — 5,000 volunteers in North America, with a parallel trial in Thailand. The field held its breath.
No protection, on either continent. The lesson that antibodies to gp120 alone were not enough would steer — and haunt — every design that followed.
The Partnership for AIDS Vaccine Evaluation, a consortium of U.S. agencies and government-funded organizations, launched to coordinate HIV vaccine trials and stop duplicated effort. This site now continues that record-keeping, independently. What PAVE was →
The STEP trial was stopped early: no protection — and a worrying hint of increased infection risk in men with prior immunity to the cold virus used as the vector. T-cell vaccines staggered. The field entered what many called its deepest winter.
16,402 volunteers in Thailand delivered the only efficacy success HIV has ever seen: 31.2% protection (95% CI 1.2–51.1). Modest, fading within a year — and unmistakably real. Every strategy since has cited it.
While vaccine trials regrouped, the U.S. FDA approved daily oral PrEP. The two lines of this ledger — the vaccine line and the prevention line — started running in parallel. Follow the parallel line →
Uhambo tried to repeat RV144's success in southern Africa with clade C. The AMP trials tested whether a lab-made antibody (VRC01) could prevent infection by infusion. The field placed its largest bets since 2009.
On February 3, 2020, Uhambo was stopped for futility: 138 infections in the vaccine arm vs 133 in placebo. Months later, mRNA vaccines ended a coronavirus pandemic in under a year — a triumph of the same platform that had failed for HIV for four decades. The contrast reshaped the field's questions.
Janssen's mosaic Ad26 regimen — the last big non-mRNA hope — showed no protection in young women across five African countries. Its sister trial Mosaico would follow in 2023. And on the parallel line: long-acting injectable cabotegravir was approved for PrEP.
PrEPVacc, Africa's last running vaccine efficacy trial, reported no protection. The same year, PURPOSE 1: zero infections among 2,134 women on twice-yearly lenacapavir — 100% efficacy. Science named it Breakthrough of the Year. The ledger's two lines had never diverged further.
FDA approved lenacapavir (Yeztugo) as PrEP — two injections a year, after PURPOSE 1 (100%) and PURPOSE 2 (99.9%). For the first time since 1984, ending the epidemic no longer depends on waiting for a vaccine. But a vaccine remains the only tool that could end HIV everywhere, for everyone, at once.
No HIV vaccine efficacy trial is running anywhere. The next generation — germline-targeting mRNA designed to teach the body to grow its own broadly neutralizing antibodies — is in Phase 1. In IAVI G002/G003, priming induced the targeted bnAb precursors in "substantial frequencies," and boosting drove them further toward maturity (Science, May 2025). The earliest a new efficacy trial could launch: late this decade. See the full trial archive →