Pam Harrison

July 22, 2016

DURBAN, South Africa — Immune responses to candidate vaccines designed to match the main strain of HIV circulating in southern Africa are robust, interim results from the phase 1/2 HIV Vaccine Trials Network (HVTN) 100 suggest.

"It is gratifying to see vaccines that were designed and manufactured specifically for South Africa meet and even exceed the criteria established to advance them into the large efficacy trial," Larry Corey, MD, from the Fred Hutchinson Cancer Research Center in Seattle, said in a statement.

"In many instances, the HVTN 100 outcomes exceeded both our own criteria and the immune responses seen in RV144," a previous HIV vaccine trial conducted in Thailand, Linda-Gail Bekker, MD, from the Desmond Tutu HIV Centre in Cape Town, South Africa, told reporters.

In the RV144 trial, the vaccines used were 60% effective against HIV infection 1 year after vaccination, but only 31% effective at 3.5 years (Procedia Vaccinol. 2013;7:49-56).

In the HVTN 100 study, presented here at the International AIDS Conference 2016, vaccines tested in the RV144 trial were modified to make them specific to the clade C subtype of HIV that is widespread in southern Africa.

The investigators also changed the adjuvant used with one of the vaccines to elicit more powerful immune responses and added a booster to prolong the duration of response.

Of the uninfected participants in HVTN 100, 185 received the candidate vaccines and 37 received placebo.

"We wanted to make sure these vaccine candidates were safe in HIV-uninfected individuals and, if safe, what the immunogenicity was," Dr Bekker explained during a news conference.

The fact that we are now talking about a vaccine is a sure sign that progress has been made.

The treatment regimen consisted of five injections. The ALVA-HIV vaccine was administered at months 0 and 1, and the ALVA-HIV vaccine plus the bivalent subtype C gp120/MF59 vaccine were administered at months 3, 6, and 12.

Investigators analyzed primary immunogenicity data at 6.5 months and compared blood samples with archived specimens from RV144 recipients.

The development of neutralizing antibodies to several key vaccine antigens was seen in 100% of participants in the active treatment group (P < .001).

In addition, T-cell responses were significantly higher with the HVTN 100 regimen than with the RV144 regimen. The cumulative response to two key regions on the HIV envelope (V1 and V2) was 80% — well above the 63% threshold established to model a 50% vaccine efficacy if response to the V1 and V2 regions was the sole correlate of protection, Dr Bekker reported.

On the basis of these results, investigators expect to launch the HVTN 702 phase 2b/3 efficacy trial in November. They plan to recruit 5400 HIV-negative men and women 18 to 35 years who are at risk for HIV infection.

Participants will receive the same vaccine regimen as in HVTN 100, but will be followed for another 2 years to verify that the regimen provides a sustained protective effect.

"HVTN 702 is a pivotal study that could lead to a licensed HIV vaccine in South Africa — the first preventive HIV vaccine worldwide," Dr Corey, who is principle investigator, said.

"Sixteen years ago, when I first came to Durban, a vaccine was nowhere near the main stage. The fact that we are now talking about a vaccine is a sure sign that progress has been made," he told reporters.

The development of an effective vaccine will be to help rein in the HIV epidemic, said Carl Dieffenbach, PhD, director of the division of AIDS at the National Institute of Allergy and Infectious Diseases.

"Fundamentally, we need prevention tools, similar to adult circumcision, that are so generalizable they can be given to the general population," he explained during the news conference.

"We really need to do something to overcome the extraordinarily high incidence of HIV in South Africa, and the best way to attack that is with a safe, durable, and effective vaccine," he added.

Vaccination is the ultimate female-empowered strategy.

"Vaccination is the ultimate female-empowered strategy," said Glenda Gray, MBBCH, chair of the HVTN 702 protocol and president and chief executive officer of the South African Medical Research Council.

"You put a needle in your arm and nobody knows that you've been vaccinated. You don't have to negotiate safe sex and you're still protected," she explained. "To put control over protection from HIV in the hands of a woman is what you want, and the best thing you can do to help her do that is find a vaccine."

GlaxoSmithKline and Sanofi Pasteur supplied the vaccines used in the study. HVTN 702 is being led by the National Institute of Allergy and Infectious Diseases. Dr Corey, Dr Bekker, Dr Dieffenbach, and Dr Gray have disclosed no relevant financial relationships.

International AIDS Conference 2016: Abstract TUAX102LB. Presented July 19, 2016.


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