Toward an HIV vaccine and cure
More than three decades have passed since AIDS was recognized and its etiologic agent, HIV, was discovered. Extraordinary scientific progress has been made in understanding, diagnosing, treating, and preventing HIV/AIDS. Globally, new HIV infections and deaths from AIDS fell by more than one-third over the past decade.
While continued scale-up of existing HIV treatment and prevention tools will likely continue to reduce new HIV infections and AIDS deaths, further innovation is needed if we are to realize the goal of a world without AIDS and sustain that landmark success. In this regard, two areas loom large: developing a vaccine to prevent HIV infection, and finding a therapeutic regimen that induces permanent or at least prolonged suppression of viremia, thereby sparing HIV-infected individuals a lifetime of antiretroviral therapy (ART).
The history of HIV vaccine development has been marked by disappointments, but recent research advances have provided reason for optimism. Notably, candidate vaccines have proven protective in various animal models of HIV infection, and modest efficacy was seen in a large human HIV vaccine trial conducted in Thailand. Ongoing analyses of the data from the Thai trial have identified possible leads for improved vaccines, and clinical trials are planned to build on the results. Furthermore, a growing array of potent, broadly neutralizing monoclonal antibodies targeting at least five structures on the HIV envelope protein have been identified. Alone or in combination, these antibodies can neutralize most HIV strains circulating globally. Scientists are working to characterize these antibodies and the viral structures to which they bind and to trace antibody development in the bodies of HIV-infected individuals, with an eye to eliciting such broadly neutralizing antibodies in uninfected individuals.
A second key area of innovation in HIV science is finding a cure for AIDS. The stunning successes achieved with ART for HIV-infected individuals is tempered by the fact that these lifesaving drugs are not curative; the virus persists in a latent form in cellular reservoirs even when a patient responds well to treatment. Although medicines can suppress HIV to very low levels in the blood, the virus in these reservoirs of latently infected cells resurges if treatment is stopped.
Two strategies emerge when the concept of a cure is considered: viral eradication, in which HIV is no longer present in the body, and sustained virologic remission, in which viral replication is completely suppressed or kept at very low levels in the absence of daily ART. The latter approach is likely the more feasible of the two. The extended virologic remission seen in an HIV-infected infant called the “Mississippi child” treated very soon after birth suggests that therapy, if initiated early enough in HIV infection, can perhaps preempt formation of a sustained viral reservoir. Furthermore, a cohort of patients in France was identified who started treatment early in the course of infection and later discontinued ART without viral rebound. Since very early therapeutic intervention is not always feasible, other approaches are being pursued in the quest for a cure, including activating and eliminating latently infected cells, immunotoxic therapy directed at the HIV reservoir, gene therapy, and other novel strategies including a therapeutic vaccine.
In summary, although both an HIV vaccine and a cure remain within the uncertain realm of discovery, recent advances give cause for hope that both can be achieved with further innovation. Added to our existing HIV treatment and prevention tools, an HIV vaccine and cure would help bring us closer to our goal of ending AIDS.
Photo: PATH/Gabe Bienczycki.