Large-Scale HIV Vaccine Trial to Launch in South Africa

NIH-Funded Study Will Test Safety, Efficacy of Vaccine Regimen
May 18, 2016

An early-stage HIV vaccine clinical trial in South Africa has determined that an investigational vaccine regimen is safe and generates comparable immune responses to those reported in a landmark 2009 study showing that a vaccine can protect people from HIV infection. Consequently, the National Institute of Allergy and Infectious Diseases (NIAID) and its partners have decided to advance the experimental HIV vaccine regimen into a large clinical trial. This new study, called HVTN 702, is designed to determine whether the regimen is safe, tolerable and effective at preventing HIV infection among South African adults. The trial is slated to begin in November 2016, pending regulatory approval.

“For the first time in seven years, the scientific community is embarking on a large-scale clinical trial of an HIV vaccine, the product of years of study and experimentation,” said Anthony S. Fauci, M.D., director of NIAID, part of the National Institutes of Health and a co-funder of the trial. “A safe and effective HIV vaccine could help bring about a durable end to the HIV/AIDS pandemic and is particularly needed in southern Africa, where HIV is more pervasive than anywhere else in the world.”

The experimental vaccine regimen that will be studied in HVTN 702 is now being tested in the smaller initial trial, named HVTN 100, and is based on the regimen investigated in the U.S. Military HIV Research Program-led RV144 clinical trial in Thailand that delivered landmark results in 2009. The current regimen is designed to provide greater protection than the RV144 regimen and has been adapted to the HIV subtype that predominates in southern Africa.

The experimental vaccine regimen tested in the RV144 trial was found to be 31.2 percent effective at preventing HIV infection during the 3.5 years after vaccination, although the regimen appears to have been 60 percent effective one year after vaccination. In the HVTN 702 study, the design and schedule of the RV144 vaccine regimen have been adjusted to try to increase the magnitude and duration of vaccine-elicited immune responses.

NIAID is responsible for all operational aspects of the pivotal Phase 2b/3 trial, which will enroll 5,400 HIV-uninfected men and women ages 18 to 35 years who are at risk for HIV infection. The NIAID-funded HIV Vaccine Trials Network (HVTN) will conduct the study. Results are expected in late 2020.

The HVTN 702 study will be led by protocol Chair Glenda Gray, MBBCH, FCPaed (SA). Dr. Gray is president and chief executive officer of the South African Medical Research Council, research professor of pediatrics at the University of the Witwatersrand, Johannesburg, and a director of the Perinatal HIV Research Unit at Chris Hani Baragwanath Hospital in Soweto, South Africa.

“HVTN 702 will tell us whether the initial success observed in HVTN 100 will bear fruit in the form of a safe and effective HIV vaccine designed for the people of southern Africa,” said Dr. Gray.

HVTN 100 and HVTN 702 are part of a larger HIV vaccine research endeavor led by a group called the Pox-Protein Public-Private Partnership, or P5—a diverse set of public and private organizations committed to building on the success of the RV144 trial. The P5 aims to produce an HIV vaccine that could have a significant public health benefit in southern Africa and to deepen scientists’ understanding of the immune responses associated with preventing HIV infection. P5 members are NIAID, the Bill & Melinda Gates Foundation, the South African Medical Research Council, HVTN, Sanofi Pasteur, GSK and the U.S. Military HIV Research Program.

The HVTN 702 vaccine regimen consists of two experimental vaccines: a canarypox-based vaccine called ALVAC-HIV and a bivalent gp120 protein subunit vaccine with an adjuvant that enhances the body’s immune response to the vaccine. Both ALVAC-HIV (supplied by Sanofi Pasteur) and the protein vaccine (supplied by GSK) have been modified from RV144 to be specific to HIV subtype C, the predominant HIV subtype in southern Africa. In addition, the protein subunit vaccine in HVTN 702 is combined with MF59 (also supplied by GSK), a different adjuvant than the one used in RV144, in the hope of generating a more robust immune response. Finally, the HVTN 702 vaccine regimen will include booster shots at the one-year mark in an effort to prolong the early protective effect observed in RV144.

All study participants will receive a total of five injections over one year. The volunteers will be randomly assigned to receive either the investigational vaccine regimen or a placebo.

The safety of HVTN 702 study participants will be closely monitored throughout the trial, and participants will receive the standard of care for preventing HIV infection. Study participants who become infected with HIV during the trial will be referred to local medical providers for care and treatment and will be counseled on how to reduce their risk of transmitting the virus

Read today’s statement by Dr. Fauci marking HIV Vaccine Awareness Day.

Question & Answer: 

The HVTN 702 HIV Vaccine Study

What is the HVTN 702 study?

The HVTN 702 study is a Phase 2b/3 efficacy clinical trial that aims to determine if an investigational HIV vaccine regimen is safe, tolerable and effective at preventing HIV infection among South African adults. This experimental vaccine regimen is based on the one tested in the first study to show that a vaccine can protect people from HIV infection—the U.S. Military HIV Research Program-led RV144 clinical trial in Thailand. The HVTN 702 vaccine regimen has been adapted to the HIV subtype that predominates in southern Africa, where the pandemic is most pervasive.

How effective was the vaccine tested in the RV144 clinical trial?

The experimental vaccine regimen tested in the RV144 trial was found to be 31 percent effective at preventing HIV infection during the 3.5 years after vaccination; the regimen appears to have been 60 percent effective one year after vaccination. In the HVTN 702 study, the composition and schedule of the RV144 vaccine regimen have been adjusted to try to increase the magnitude and duration of vaccine-elicited immune responses, and to extend the higher level of protection seen at one year in RV144 throughout the entire three-year follow-up period of HVTN 702.

Who will participate in HVTN 702?

Approximately 5,400 healthy men and women ages 18 to 35 years who are at risk for HIV infection will participate in HVTN 702. To ensure a balance of the sexes, at least 40 percent of enrolled participants will be male and at least 40 percent will be female.

Where will HVTN 702 take place? When will it begin and end?

The study will take place at 15 sites in South Africa beginning in November 2016, pending regulatory approval. Results are expected in late 2020.

Who will sponsor and fund HVTN 702?

The NIAID-funded HIV Vaccine Trials Network (HVTN) will conduct the trial.

Glenda Gray, MBBCH, FCPaed (SA), is chair of the HPTN 702 protocol. Dr. Gray is president and chief executive officer of the South African Medical Research Council, a research professor of pediatrics at the University of the Witwatersrand, and a director of the Perinatal HIV Research Unit at Chris Hani Baragwanath Hospital in Soweto, South Africa.

The protocol co-chairs are Linda-Gail Bekker, MD, PhD, and Fatima Laher, MD. Dr. Bekker is deputy director of the Desmond Tutu HIV Centre at the University of Cape Town and chief operating officer of the Desmond Tutu HIV Foundation in South Africa. Dr. Laher is a director of the Perinatal HIV Research Unit at Chris Hani Baragwanath Hospital.

What is the study design?

HVTN 702 study participants will be randomly assigned to receive either the investigational HIV vaccine regimen or a placebo. Neither the volunteers nor the study team will know who receives which type of injection until the end of the trial. Participants will receive a total of five injections over one year and then will be followed for another one or two years

What HIV preventive care will study participants receive?

Study participants will receive the standard of care for preventing HIV infection, including condoms and lubricant, counseling on how to reduce behaviors that increase risk for infection, access to management of other sexually transmitted infections, information on voluntary medical male circumcision and referral to circumcision services, and counseling and referral for antiretrovirals to take immediately following suspected exposure to HIV (post-exposure prophylaxis).

In addition, study participants will be referred to available local programs where they may obtain the oral medication Truvada to take daily for HIV prevention, a highly effective practice called pre-exposure prophylaxis (PrEP). HVTN 702 has been designed so investigators will be able to discern a preventive effect from the vaccine regimen even if some participants are taking PrEP.

What will happen to study participants who acquire HIV infection during the trial?

Study participants who become HIV-infected during the trial will be referred to local medical providers for care and treatment and will be counseled on how to reduce their risk of transmitting the virus. The study team will follow these participants for about 6 months after confirmation of diagnosis.

How will the study team ensure the safety of study participants?

An independent Data and Safety Monitoring Board (DSMB) will carefully monitor participants’ safety. A DSMB is composed of clinical research experts, statisticians, ethicists and community representatives who meet periodically during a study to review safety and efficacy data as it is gathered. A statistician who is not part of the study team presents interim data to the DSMB. Because the study team is blinded to interim study data, they are excluded from portions of meetings when data are presented. The DSMB alerts the study team if anything appears to compromise the safety of study participants, if there is compelling evidence that the study intervention is effective, or if it becomes clear that the study cannot answer one of the questions it was designed to address.

In addition, a Protocol Safety Review Team (PSRT) designated for HVTN 702 will conduct ongoing oversight of the safety of study participants. The PSRT will include a medical officer from the NIAID Division of AIDS, the study’s protocol chair and co-chairs, and principal investigators and clinicians from study sites. Periodically throughout the study, reports of safety data will be sent to the Medicines Control Council, the South African national regulatory authority for medications.

What are the components of the HVTN 702 investigational vaccine regimen? How are they intended to improve upon the regimen tested in the RV144 clinical trial?

The HVTN 702 vaccine regimen consists of two experimental vaccines: a canarypox-based vaccine called ALVAC-HIV and a bivalent gp120 protein subunit vaccine with an adjuvant that enhances the body's immune response to the vaccine. Both ALVAC-HIV (supplied by Sanofi Pasteur) and the protein subunit vaccine (supplied by GSK) have been modified from RV144 to be specific to HIV subtype C, the predominant HIV subtype in southern Africa. In addition, the protein subunit vaccine in HVTN 702 is combined with MF59 (also supplied by GSK), a different adjuvant than the one used in RV144, in the hope of generating a more robust immune response. Finally, the HVTN 702 vaccine regimen will include booster shots at the one-year mark in an effort to prolong the early protective effect observed in RV144.

What is the relationship of the HVTN 100 study to HVTN 702?

The HVTN 100 study is an early stage, Phase 1/2 clinical trial that was designed to be a litmus test for the HIV vaccine regimen that will be tested in HVTN 702. The HVTN 100 investigators sought to determine whether or not the investigational vaccine regimen was safe and elicited a set of key immune responses that were comparable to the immune responses elicited by the RV144 vaccine regimen. Once it was clear that the regimen in HVTN 100 met these criteria, the study’s funders decided to go forward with plans to test the safety, tolerability and efficacy of the regimen in the much larger HVTN 702 clinical trial..

Will HVTN 100 continue? If so, why?

The HVTN 100 study will continue through December 2016 because it is expected to generate important information about the experimental HIV vaccine regimen, including the duration of protective immune responses. These findings will help inform future HIV vaccine research.

What is the P5 and its relationship to HVTN 702?

P5 stands for the Pox-Protein Public-Private Partnership, a diverse set of public and private organizations committed to building on the success of the RV144 trial. The P5 aims to produce an HIV vaccine that could have a significant public health benefit and to deepen scientists’ understanding of the immune responses associated with preventing HIV infection. HVTN 100 and HVTN 702 are part of the P5 research program.

P5 members are NIAID, the Bill & Melinda Gates Foundation (BMGF), the South African Medical Research Council (SAMRC), HVTN, Sanofi Pasteur, GSK and the U.S. Military HIV Research Program. NIAID, BMGF and SAMRC fund the P5.

Content last reviewed on May 18, 2016