Magazine article Clinical Psychiatry News

Pivotal Phase III HIV Vaccine Efficacy Trial Set to Begin

Magazine article Clinical Psychiatry News

Pivotal Phase III HIV Vaccine Efficacy Trial Set to Begin

Article excerpt

DURBAN, SOUTH AFRICA -- A new optimism regarding the possibility of creating a safe and effective HIV preventive vaccine was very much in evidence at the 21st International AIDS Conference.

"The HIV vaccine field is open for business," an exuberant Larry Corey, MD, declared in a plenary address highlighting recent major progress in HIV vaccine development.

Three extremely important HIV vaccine efficacy clinical trials testing diverse promising strategies are now either in progress or soon to start, noted Dr. Corey, professor of laboratory medicine and medicine at the University of Washington and emeritus director of the Fred Hutchinson Cancer Research Center in Seattle.

"We are finally moving the needle forward with human efficacy trials that are commensurate with the need for developing an HIV vaccine," Dr. Corey said.

He emphasized that HIV is "still the world's most pressing global health issue," with more than 45,000 new infections occurring annually in the United States and more than 2 million annually worldwide. And while numerous nonvaccine prevention methods have been developed, they share a major limitation: Their extended effectiveness requires continuous adherence.

"With asymptomatic acquisition, prolonged subclinical infection, and sexual transmission, getting to an AIDS-free generation will require a vaccine," Dr. Corey predicted.

After years of discouragingly negative HIV vaccine studies, researchers finally turned a corner in 2009 with the reported results of the U.S. Military HIV Research Program-led RV144 trial, commonly known as the Thai trial, Anthony S. Fauci, MD, recalled in an interview.

The trial, which randomized more than 16,000 young adult Thais, showed a modest 31% efficacy at 3.5 years, but a more substantial and encouraging 60% efficacy at 12 months (N Engl J Med. 2009 Dec 3;361[23]:2209-20). More importantly, the Thai trial opened up a whole new avenue to HIV vaccine development.

"We thought the Thai vaccine would induce neutralizing antibodies, but it didn't. Instead, it induced nonneutralizing antibodies against a component of the V1V2 loop region of the HIV envelope, which was associated with protection.

So the good news about that study was that, even though that vaccine wasn't efficacious enough to make it a usable vaccine, it gave us something we could improve upon by using the same platform and enhancing the response to provide greater depth, breadth, and durability," explained Dr. Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID).

The improved vaccine consists of a canarypox-based vaccine called ALVAC-HIV and a bivalent gp120 protein subunit vaccine with MF59, a different adjuvant from that used in the Thai trial, in an effort to achieve a more robust immune response. Also, the four-injection series studied in the Thai trial is now bolstered by a booster injection at the 12-month mark. This vaccine has been altered to be specific to HIV clade C, the predominant HIV subtype in southern Africa, where the bulk of new HIV infections occur.

At the AIDS 2016 conference, Linda-Gail Bekker, MD, presented the primary immunogenicity results from the HIV Vaccine Trials Network (HVTN) 100 trial, a phase 1/2, double-blind, placebo-controlled study of the improved version of the Thai trial vaccine, known as the Clade C ALVAC-(vCP2438) and bivalent subtype C gp120/MF59 vaccine, in 252 HIV-uninfected South African adults.

The ALVAC / protein vaccine achieved cellular and humoral immune responses that exceeded all four predetermined criteria as correlates of protection. …

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