How many HIV vaccine efficacy trials have there been?

Nine major programs have reported efficacy or futility results between 2003 and 2024 — VaxGen (two trials), STEP, RV144, HVTN 702, HVTN 705, HVTN 706, AMP (two trials), and PrEPVacc. Only RV144 showed any protection: 31.2%.

Is any HIV vaccine efficacy trial running now?

No. As of September 2026, no Phase IIb/III HIV vaccine efficacy trial is recruiting or running anywhere in the world. Active HIV vaccine trials are Phase 1, mainly germline-targeting mRNA designs.

Why did every trial after RV144 fail?

RV144's mild success depended on a specific antibody-and-cell balance that did not survive transfer to clade C (HVTN 702) or to mosaic designs (HVTN 705/706). HIV's diversity defeats one-antigen strategies; the field is now rebuilding from first principles.

HIV vaccine trial archive: every efficacy trial, graded

The trial archive

9 REPORTED · 2 ACTIVE · SOURCED

Every HIV vaccine efficacy program in history, in order — with what was tested, what happened, and where the result was published. Red stopped for futility or harm; amber partial signal; green running now.

CASE 01 · 1998–2003AIDSVAX B/B

The first efficacy trial — and first failure

Phase III · North America · gp120 protein subunit · N=5,000 · NCT00002441

No protection. The field learned that antibodies to gp120 alone do not stop the virus — a lesson that shaped, and limited, the next decade.

STOPPED0% EFFICACY · 2003

CASE 02 · 1999–2003AIDSVAX B/E

The Bangkok IDU cohort

Phase III · Thailand · gp120 · injecting drug users · N=2,500

The sister trial also failed. Both VaxGen trials closed the book on first-generation envelope vaccines.

STOPPED0% EFFICACY · 2003

CASE 03 · 2004–2007STEP

The trial that froze the field

Phase IIb · Americas/Australia · Ad5 vector, T-cell design · N=3,000 · NCT00095576

Halted early — no protection, and a signal of increased acquisition risk in Ad5-immune men. T-cell vaccines staggered; grant budgets with them.

STOPPEDHALTED 2007

CASE 04 · 2003–2009RV144

The Thai trial — the only flicker

Phase III · Thailand · ALVAC + AIDSVAX prime-boost · N=16,402 · NCT00223080

31.2% protection (95% CI 1.2–51.1, p=0.04). Modest and transient — but proof a vaccine can work at all. Correlate analyses still anchor modern design.

31.2%PARTIAL SIGNAL · 2009

CASE 05 · 2016–2020HVTN 702

Uhambo: history repeats, then stops

Phase IIb/III · South Africa · ALVAC clade C + gp120/MF59 · N=5,404 · NCT02968849

Stopped Feb 3, 2020 for futility: 138 infections (vaccine) vs 133 (placebo), HR 1.02. RV144's formula did not transfer. NEJM 2021.

FUTILEHALTED 02/2020

CASE 06 · 2017–2021HVTN 705

Imbokodo: the mosaic bet

Phase IIb · 5 African countries · Ad26.Mos4.HIV mosaic + gp140 · N=2,636 · NCT03060629

Janssen announced no sufficient protection in June 2021. The mosaic approach — hoping broader antigen coverage would beat HIV's diversity — fell short.

STOPPED0% EFFICACY · 2021

CASE 07 · 2019–2023HVTN 706

Mosaico: the last of its kind

Phase III · Americas/Europe · Ad26 mosaic + gp140 · N=3,900 · NCT03964415

Terminated January 2023 for lack of efficacy. With it ended the era of large non-mRNA HIV vaccine efficacy trials.

STOPPED0% EFFICACY · 2023

CASE 08 · 2016–2020AMP

Antibody infusions: proof of concept

Phase IIb ×2 · global · VRC01 bnAb infusions q8wk · N=1,924+2,699 · NCT02568215/02716675

VRC01 did not prevent overall acquisition — but against VRC01-sensitive strains, 75.4% prevention (95% CI 45.5–88.9). First human proof bnAbs can work. NEJM 2021.

75.4%SENSITIVE STRAINS ONLY

CASE 09 · 2020–2024PrEPVacc

Africa's last standing trial falls

Phase IIb · Uganda/Tanzania/Zambia/Mozambique · DNA + Ad35 + oral PrEP arms · N=1,512 · NCT04066881

December 2024: neither vaccine regimen protected. The last HIV vaccine efficacy trial on Earth concluded without success.

STOPPED0% EFFICACY · 2024

ACTIVE · Phase 1IAVI G002

Germline targeting goes mRNA

Phase I · North America · eOD-GT8 60mer mRNA prime + core-g28v2 boost · N=56 · NCT05001373

Priming induced VRC01-class precursors at substantial frequencies, with boosting driving further maturation, affinity and neutralization activity (Science, May 2025). The seed of the next efficacy generation.

PHASE 1SIGNAL · 2025

ACTIVE · Phase 1IAVI G003

The same question, in Africa

Phase I · Rwanda/South Africa · eOD-GT8 mRNA · NCT05414786

G002's strategy tested in African volunteers — where an eventual vaccine is needed most. Safety and immunogenicity readouts ahead.

PHASE 1ONGOING

What "efficacy" means here. Vaccine efficacy (VE) is the percentage reduction in infections versus placebo under trial conditions. A trial can be stopped "futile" while safe — futility means the data already show protection will not reach the bar. Registry links: each NCT number above resolves at clinicaltrials.gov.

Straight answers

FAQ

How many HIV vaccine efficacy trials have there been?: Nine major programs have reported efficacy or futility results between 2003 and 2024 — VaxGen (two trials), STEP, RV144, HVTN 702, HVTN 705, HVTN 706, AMP (two trials), and PrEPVacc. Only RV144 showed any protection: 31.2%.
Is any HIV vaccine efficacy trial running now?: No. As of September 2026, no Phase IIb/III HIV vaccine efficacy trial is recruiting or running anywhere in the world. Active HIV vaccine trials are Phase 1, mainly germline-targeting mRNA designs.
Why did every trial after RV144 fail?: RV144's mild success depended on a specific antibody-and-cell balance that did not survive transfer to clade C (HVTN 702) or to mosaic designs (HVTN 705/706). HIV's diversity defeats one-antigen strategies; the field is now rebuilding from first principles.