September 24th, 2009, marked the first major breakthrough in the search for the HIV vaccine in nearly a decade, as a study conducted by the United States Army demonstrated a 31.2% positive vaccination efficacy rate (BBC 2009). This result is the first of its kind in a search that was on the verge of being condemned as futile (Lancet 2009).
The Thai Phase III HIV vaccine clinical trial, commonly known as “RV 144,” tested the primer-booster combination of two previously tested vaccines on a population of 16,402 Thai adults, ranging in age from 18 to 30 and possessing an average risk of infection. Half of the population received the vaccine, a combination of the ALVAC HIV vaccine and the AIDSVAX B/E vaccine, while the other half received a placebo version (Phase III 2009). The study was designed to both test the vaccination strategy’s capacity to prevent HIV infection as well as its ability to reduce the amount of HIV in the blood of infected individuals. The results indicate that out of the test population, 74 non-vaccinated adults became infected three years after vaccination, while 51 vaccinated adults became infected during the same time period.
These results are the product of a search for an HIV vaccine that has spanned more than two decades, dating back to 1984, when it was confirmed that HIV was the virus responsible for the development of AIDS. After this was realized, the then U.S. Health and Human Services Secretary Margaret Heckler made a John F. Kennedy-esque declaration that a vaccine would be available within two years (Lancet 2009). A quarter of a century later, however, it seems like science has barely brushed the surface of the complexity surrounding the HIV virus. Despite the positive light surrounding the efficacy produced by RV144, much work remains to be done to move anywhere near a reliable vaccine.
Multiple questions immediately arise from these published results. Most importantly, the statistical significance of these results has not been completely analyzed (Lancet 2009). Furthermore, even if these results are not by chance, the pragmatism of the vaccine is limited, as the strategy entails six injections over the course of four visits. Additionally, the vaccine only dealt with B and E strains of the virus, while the most prevalent strain found in Africa, the HIV epicenter, is strain C (Lancet 2009). Finally, the fact that positive efficacy was paired with a neutral effect on the viral load of infected patients raises questions about the mechanism with which the vaccine may operate.
Nonetheless, multiple positives can be derived from these results as well. The prime-boost vaccine strategy relies on a combinatory effect of two vaccination strategies. The primer vaccination, the ALVAC HIV vaccine, relies on components that stimulate the cell-mediated immune response, activating viral-specific cytoxic T-cells. The AIDSVAX booster then uses a recombinant DNA component to stimulate the antibody-mediated, or “humoral” response from the human immune system (Lancet 2009). Such results demonstrate that the fight against HIV may lie in combining many facets of the human immune system, as each of these vaccines independently failed lower-scale clinical trials.
Inevitably, more large-scale human trials similar to RV144’s test population will have to be conducted, and careful moral and ethical lines will have to be drawn. Performing these tests in developing countries will create a wealth of moral ambiguities that will need to be scrutinized by society as a whole. Already, the U.S. Army is recruiting volunteers for a follow up cohort study, known as RV152, which is due to be conducted in 2013. Another prime-boost efficacy trial—HTVN 505—is recruiting circumcised men who have sex with men in the United States (Lancet 2009). Most certainly, as the results of RV144 are more carefully analyzed, clues to the direction in which to take future studies and vaccination strategy designs will emerge, more clinical trials will be designed, and more volunteers will be recruited. This progression will require close monitoring, as the advantages of using developing countries as the setting for further human trials may distort the ethics associated with widespread human testing.
Clearly, the initial results of RV144 indicate a step in the right direction in the fight against the HIV pandemic. The search for a vaccine has been energized for the first time in years, and the media attention being given to the Thailand trial serves only as confirmation (BBC 2009). However, as biomedical scientists continue to search, they must always survey the long-run implications of their research and the societal concerns associated with their methods. A fine-line will inevitably be drawn, helping to balance scientific progress and social responsibility.
“A (prime) boost for HIV vaccine research?” The Lancet. Vol. 374, Issue 9696, pg 1119. 3 October 2009
“HIV Vaccine ‘reduces infection.’” BBC News. 24 September 2009
“HIV Vaccine Trial in Thai Adults.” Clinical Trials.gov. Last updated 22 June 2009.
“Phase III Trial-Thailand” www.hivresearch.org. 4 September 2009.
“RV144 Phase III HIV Vaccine Trial Press Release.” U.S. Military HIV Research Program. 24 September 2009