ROME – In a conference abuzz about new strategies for preventing HIV infection with antiretroviral medications, excitement about the potential for a vaccine was comparably subdued.
With so much success at preventing the transmission of the virus by using antiretroviral therapy prophylactically, one might ask, "Do we still need a vaccine?" The answer is an unequivocal ‘yes,’ according to Dr. Gary J. Nabel of the Vaccine Research Center at the National Institutes of Health.
Dr. Myron S. Cohen of the University of North Carolina Chapel Hill, agreed. Though Dr. Cohen presented the conference’s most celebrated finding – that early initiation of antiretroviral therapy was associated with a 96% reduction in transmission to an uninfected partner in heterosexual serodiscordant couples – he cautioned that transmission can occur at "any CD4 count. ... The bottom line: Make a vaccine and that will solve the problem."
Concerns about the costs and logistics of scaling up antiretroviral therapy for use in prevention, particularly in settings where eligible HIV-infected people have limited access to such agents in the first place, further underscored the urgency to produce a durable, effective vaccine.
"We need to maintain our devotion to an HIV vaccine. ... We mustn’t forget how cost effective an HIV vaccine is," Dr. Nabel said at the International AIDS Society Conference on HIV Pathogenesis and Treatment.
While many were disappointed by 2009 results from a Phase III trial in Thailand (n = 16,402) of a prime-boost vaccine that lowered the risk of HIV infection by less than a third compared to placebo (N. Engl. J. Med. 2009;361:2209-20), Dr. Nabel asserted that opportunities for vaccine development have never been more promising. The past year has seen a surge of optimism about vaccines thanks to the discovery of VRCO2 and VRCO1, two potent antigens that neutralize more than 90% of all known HIV strains, he noted.
The pre-VRCO1 era, Dr. Nabel said, should now be regarded as "the dark ages" for HIV vaccine development.
Further, a better understanding of HIV-1 entry "has provided an opportunity for AIDS vaccine development through the definition of highly conserved invariant viral structures" that can be targeted by broadly neutralizing antibodies, he said.
Several scientists presented an overview and update of the more than 40 ongoing investigations – most of them in Phase I – of HIV vaccines with therapeutic and eradication targets.
Susan B. Zolla-Pazner, Ph.D., of New York University, discussed the prime-boost vaccination strategies in development that "can focus the antibody response on selected epitopes." Early in vivo work has shown a long-lasting response to this type of strategy in animals, "with neutralizing antibodies detectable more than a year after the last boost," she said.
While a vaccine offering durable, complete protection remains an obvious goal, Robin Shattock, Ph.D., of Imperial College London questioned whether it was time to consider the value of vaccines offering incomplete or shorter-term protection as part of a combination strategy that includes microbicides, male circumcision, condoms, and, where available, antiretroviral prophylaxis.
"A partially efficacious vaccine is a truly viable option if combined" with other approaches, Dr. Shattock said, adding that it was time not only to consider combining proven partially effective interventions, but to initiate randomized controlled trials comparing combinations.
Dr. Shattock said he envisioned a large, four-arm trial comparing two or three combined interventions in each arm. "The effect size of each intervention adds up," he said. "You don’t have to be a mathematician to see that combining the values is likely to give significant improvement."
VRCO2 and VRCO1 were identified by Dr. Nabel’s department, the Vaccine Research Center at the National Institutes of Health. Dr. Zolla-Pazner, Dr. Shattock and Dr. Cohen did not disclose whether or not they had conflicts of interest.