HIV Vaccine Trials Network

The HIV Vaccine Trials Network (HVTN) is a nonprofit clinical research organization that coordinates physicians, scientists, trial volunteers, activists, and community educators in the evaluation of HIV vaccine candidates. Its work centers on human clinical research rather than vaccine design: candidate products are developed by commercial, academic, governmental, and nonprofit partners, while the HVTN organizes studies that assess safety, immune responses, and—where appropriate—whether a product can prevent HIV infection. This distinction is central to the network’s identity. HVTN is a testing and evidence-generation infrastructure, not a conventional vaccine manufacturer or consumer-facing pharmaceutical brand. The network operates in collaboration with the U.S. National Institute of Allergy and Infectious Diseases (NIAID) and the Division of AIDS (DAIDS), with government-supported research funding administered through the National Institutes of Health. It is headquartered at the Fred Hutchinson Cancer Center in Seattle and has functioned as the only HIV vaccine research network sponsored by the U.S. government. Its international role has been especially important in Africa, where HIV incidence and viral diversity create different scientific and operational requirements from those encountered in North American studies. HVTN has helped establish and operate trial capacity in countries including Botswana and South Africa, and has coordinated multinational studies involving sites across Africa, the Americas, and Europe. A defining feature of HVTN’s model is structured community participation. In addition to institutional review boards and other formal research-ethics safeguards, the network uses community advisory boards. These groups allow local residents and affected communities to review study plans, discuss risks and benefits, contribute to educational activities, and raise concerns about recruitment, informed consent, confidentiality, access, and scientific priorities. HVTN’s community-engagement approach reflects the sensitivity of HIV research, the history of exploitation in medical research, the urgency of the epidemic, and the need to ensure that volunteers understand that experimental vaccines may be ineffective and cannot cause HIV infection when they contain no HIV virus. The network has coordinated several influential HIV prevention studies. HVTN 503, known as Phambili, was an early large-scale African efficacy study and was halted after concerns arising from the related STEP study and the similarity of the vaccine strategies. HVTN 502, or STEP, tested an adenovirus-based candidate in a randomized, double-blind design in the United States and other locations; the trial was stopped after interim findings showed no preventive benefit and an imbalance in HIV infections that prompted extensive scientific analysis. HVTN 505 tested a DNA prime followed by a recombinant adenovirus type 5 boost and was stopped in 2013 after monitoring showed no evidence of protection. HVTN also participated in studies building on the partially efficacious RV144 trial in Thailand. HVTN 097 examined a related pox-protein regimen in South Africa, while later programs tested alternative approaches, including passive administration of broadly neutralizing antibodies and mosaic antigen designs intended to address global HIV diversity. HVTN 702, HVTN 703 (the Antibody Mediated Prevention study), HVTN 705 (Imbokodo), and HVTN 706 (MOSAICO) illustrate the network’s broad portfolio. Results have been mixed: some candidates were safe but ineffective, while others generated scientific and operational knowledge without producing a deployable vaccine. Imbokodo and MOSAICO were discontinued after their primary analyses found insufficient or absent efficacy. HVTN’s present significance lies in maintaining the clinical, laboratory, regulatory, and community infrastructure needed for a difficult long-term research program. Its activities connect early…

The HIV Vaccine Trials Network was created as a specialized clinical research system for evaluating HIV vaccine candidates in people. Unlike a pharmaceutical company, HVTN does not have a product-development pipeline of its own and does not design the vaccines it studies as part of its core mission. Instead, it links research institutions, clinical investigators, laboratories, government agencies, trial volunteers, and affected communities so that candidate products from different developers can be assessed under common scientific and ethical standards. The network’s operating model places community participation alongside conventional clinical research oversight. Institutional review boards and regulatory authorities review protocols, but HVTN also established community advisory boards to give non-specialists a formal role in examining study plans and communicating with researchers. Community representatives can address informed consent, risk communication, recruitment, confidentiality, local priorities, and the practical meaning of trial results. This approach was considered particularly important for HIV research because of the epidemic’s urgency, the social stigma associated with HIV, the novelty of some biological technologies, and the possibility that enthusiasm for finding a vaccine could lead volunteers to underestimate experimental risks. HVTN works with the U.S. National Institute of Allergy and Infectious Diseases and its Division of AIDS under National Institutes of Health support. Its Seattle headquarters is located at the Fred Hutchinson Cancer Center. The network has also developed a substantial international footprint. In 2003, it worked with Harvard University to establish a vaccine trials unit in Botswana. The early objectives included understanding local HIV prevalence, assessing trial feasibility, and building grassroots support and research capacity. In 2007, HVTN launched Phambili, one of the first large-scale HIV vaccine efficacy programs in Africa, with support from the South African AIDS Vaccine Initiative. The study was halted after the failure and safety concerns surrounding a related vaccine approach tested in STEP. Following the partial efficacy signal from Thailand’s RV144 trial, HVTN collaborated with South African investigators, including Glenda Gray, on HVTN 097 in 2011. The study examined a related pox-protein regimen and extended evaluation of a strategy that had shown limited protection in Thailand. The network subsequently became involved in multiple large African and international programs. HVTN 702 tested a pox-protein regimen in South Africa; HVTN 703 studied whether passively administered antibodies could prevent HIV; and HVTN 705, known as Imbokodo, evaluated a mosaic-antigen vaccine designed to address the genetic diversity of HIV. In the United States, HVTN managed HVTN 502/STEP, a double-blind randomized trial of an adenovirus-based vaccine candidate. The study was stopped early after more HIV infections were observed in the vaccine group than in the control group. Because the candidate contained no HIV, it could not infect volunteers with HIV, but the imbalance prompted extensive investigation into whether the product, the vector, participant characteristics, or chance could explain the findings. The early termination limited the ability to reach a definitive explanation. HVTN 505 began in 2009 to test a DNA vaccine followed by a recombinant adenovirus type 5 vaccine. The candidates had been developed for HIV subtypes A, B, and C by the U.S. National Institutes of Health Vaccine Research Center. In 2013, monitoring authorities recommended stopping vaccinations because interim data showed no evidence of protection against HIV. The regimen was considered safe and generally well tolerated, but it did not demonstrate efficacy and did not treat established HIV infection. The network later coordinated HVTN 706/HPX3002, known as MOSAICO, a multinational Phase 3 study of a Johnson & Johnson mosaic-based vaccine candidate. The trial targeted populations at elevated risk, including men who have sex with men and transgender participants, across sites in the Americas, Europe, and the United States. In 2023, the study was discontinued after failing to show preventive efficacy. Imbokodo had similarly been discontinued after its 2021 analysis found insufficient protection. These setbacks have not eliminated HVTN’s role. HIV presents unusually complex vaccine challenges because of rapid viral variation, the difficulty of inducing broadly protective immunity, and the absence of a simple correlate of protection. HVTN continues to provide the clinical sites, laboratories, community relationships, and trial expertise required to test new concepts. Its historical contribution is therefore not limited to successful products: negative results, safety findings, participant protections, and improved methods have all shaped the broader HIV vaccine and biomedical-prevention field.

1. 2023MOSAICO discontinued after no efficacy signal

   HVTN 706/HPX3002/MOSAICO was stopped after analysis found no evidence that the candidate prevented HIV infection.

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2. 2021Imbokodo discontinued after insufficient efficacy

   The primary analysis of HVTN 705/Imbokodo found insufficient protection against HIV in the study cohort, and the program was discontinued.

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3. 2019MOSAICO Phase 3 trial announced

   Johnson & Johnson announced the planned HVTN 706/HPX3002/MOSAICO Phase 3 trial of a mosaic-based HIV vaccine candidate at sites in the Americas, Europe, and the United States.

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4. 2016Expansion of African efficacy programs

   HVTN began collaborating with African researchers and communities on several major efficacy and prevention studies, including HVTN 702, HVTN 703, and HVTN 705.

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5. 2013HVTN 505 stopped for futility

   Vaccinations in HVTN 505 were stopped after interim analysis found no evidence that the DNA/rAd5 regimen prevented HIV infection.

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6. 2011HVTN 097 evaluates RV144-related regimen

   The network collaborated with South African researchers on HVTN 097, a study of a pox-protein regimen related to the partially efficacious approach tested in Thailand’s RV144 trial.

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7. 2007Phambili large-scale African trial begins

   HVTN launched HVTN 503/Phambili with support from the South African AIDS Vaccine Initiative; the study was later halted in the context of findings from the related STEP program.

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8. 2003Botswana vaccine trials unit established

   HVTN partnered with Harvard University to establish a vaccine trials unit in Botswana, helping assess HIV prevalence, trial feasibility, and community support for future studies.

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A nonprofit, publicly supported global clinical research network specializing in rigorous and community-engaged evaluation of HIV vaccines and related biomedical prevention strategies.

• HVTN 502 / STEPHIV vaccine efficacy trial

  A double-blind, randomized clinical trial evaluating an adenovirus-based HIV vaccine candidate. The candidate did not contain HIV and therefore could not cause HIV infection. The study was stopped early after an imbalance in HIV infections between vaccine and control groups. The result generated extensive analysis of vector biology, participant factors, trial conduct, and potential correlates of risk, although early termination prevented a conclusive explanation for the imbalance.

• HVTN 503 / PhambiliAfrican HIV vaccine efficacy trial2007

  A major African HIV vaccine trial developed to test a candidate regimen and to strengthen large-scale vaccine research capacity in the region. The program was conducted with South African partners and financial assistance from the South African AIDS Vaccine Initiative. It was halted in 2007 after the related STEP study raised concerns about the vaccine approach and provided no basis for continuing vaccination.

• HVTN 097HIV vaccine regimen study2011

  A South African study of a pox-protein vaccine regimen related to the approach that had shown partial efficacy in Thailand’s RV144 trial. Conducted with African research leadership, the study helped examine whether immune responses and operational experience associated with the Thai regimen could be evaluated in another epidemic and population context.

• HVTN 505DNA and adenovirus HIV vaccine trial2009

  A U.S. clinical trial testing a DNA plasmid prime followed by a recombinant adenovirus type 5 boost. The candidates were designed for HIV subtypes A, B, and C and were developed by the NIH Vaccine Research Center. Vaccination was stopped in 2013 when interim monitoring showed no evidence of protection against HIV. The regimen was reported to be safe and well tolerated but did not prevent infection or treat HIV.

• HVTN 702African HIV vaccine efficacy trial2016

  A large South African efficacy study evaluating a pox-protein HIV vaccine regimen in a population and epidemic setting distinct from the original RV144 trial. It formed part of HVTN’s broader effort to test whether partially promising vaccine concepts could be adapted and evaluated in southern Africa.

• HVTN 703 / AMPPassive immunization prevention study2016

  The Antibody Mediated Prevention study evaluated passive administration of antibodies as an HIV-prevention strategy. Rather than asking participants’ immune systems to generate protection through vaccination, the approach tested whether externally supplied antibodies could prevent infection and provide information about antibody sensitivity and protection.

• HVTN 705 / ImbokodoMosaic HIV vaccine efficacy trial2016

  A multinational study of a mosaic-antigen vaccine regimen intended to broaden coverage across the genetic diversity of HIV. The trial enrolled young women in southern Africa. Johnson & Johnson announced in 2021 that the primary analysis showed insufficient protection, and the study was discontinued.

• HVTN 706 / HPX3002 / MOSAICOPhase 3 mosaic HIV vaccine trial2019

  A Johnson & Johnson and Janssen-sponsored Phase 3 study of a mosaic-based HIV vaccine candidate. HVTN coordinated the trial across sites in Argentina, Brazil, Italy, Mexico, Peru, Poland, Spain, and the United States, focusing on populations including men who have sex with men and transgender people. The study was discontinued in 2023 after no evidence of preventive efficacy was found.

• 2023Discontinuation of MOSAICOOther

  MOSAICO was a Phase 3 multinational study of a Johnson & Johnson and Janssen mosaic-based HIV vaccine candidate.

  What changed. The trial was stopped after analysis found no evidence of efficacy in preventing HIV infection.

  Aftermath. The negative result ended that candidate’s efficacy program but added to the field’s evidence about the limitations of the tested mosaic vaccine strategy.

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• 2021Discontinuation of ImbokodoOther

  HVTN 705 tested a mosaic-based vaccine strategy intended to address the diversity of HIV in a cohort of young women in southern Africa.

  What changed. The study was discontinued after its primary analysis found insufficient protection against HIV.

  Aftermath. The result showed that the mosaic approach had not yet produced a sufficiently effective vaccine in the tested population, while the trial generated additional safety and immunology data.

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• 2013Stopping HVTN 505 vaccinationsOther

  Interim data from the DNA/rAd5 study showed no evidence that the candidate regimen could prevent HIV infection.

  What changed. Following a recommendation from the data and safety monitoring board, HVTN stopped vaccinations in the trial.

  Aftermath. The candidates were considered safe and well tolerated, but the study did not support further efficacy testing of the regimen in its existing form.

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• 2007Halt of HVTN 503/PhambiliOther

  Phambili was a large-scale African HIV vaccine efficacy study, and a related adenovirus-based strategy had produced concerning findings in the STEP study.

  What changed. The study was halted and vaccination was discontinued while the implications of the STEP findings were assessed.

  Aftermath. The outcome reinforced the need for careful assessment of vaccine vectors and demonstrated the importance of coordinated safety monitoring in large international trials.

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• 2023MOSAICO HIV vaccine efficacy study discontinued

  HVTN 706/HPX3002/MOSAICO was discontinued after analysis found no evidence that the mosaic-based vaccine regimen prevented HIV infection.

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• 2021Johnson & Johnson reports insufficient protection in Imbokodo study

  Johnson & Johnson reported that the primary analysis of HVTN 705/Imbokodo found that its mosaic-based vaccine regimen did not provide sufficient protection for the participating cohort of young women, leading to discontinuation of the study.

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• 2013HVTN 505 vaccinations stopped for lack of preventive efficacy

  An independent data and safety monitoring board recommended stopping vaccinations in the U.S. HVTN 505 study because the DNA and adenovirus-based regimen showed no evidence that it could prevent HIV infection.

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• 2007HVTN 503/Phambili halted during African HIV vaccine research program

  The large-scale Phambili efficacy study was stopped after concerns related to the vaccine strategy tested in the STEP trial and the absence of evidence supporting continued vaccination.

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1. HIV Vaccine Trials Network
2. HIV Vaccine Trials Network official website