Vaccine candidates like HTVN 702 are needed to build momentum
by Jeannie Wraight
[dropcap]I[/dropcap]f current HIV diagnoses rates persist, about 1 in 2 black men who have sex with men (MSM) and 1 in 4 Latino MSM in the United States will be diagnosed with HIV during their lifetime,” stated a February 23, 2016, CDC press release about the agency’s new analysis by researchers.
A second quote reads, “As alarming as these lifetime risk estimates are, they are not a foregone conclusion. They are a call to action,” said Jonathan Mermin, M.D., director of CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD, and Tuberculosis Prevention.
We recently marked the thirty-fifth anniversary of the first reported case of HIV. In the past three and a half decades we have made a great deal of progress in HIV therapies and decreasing new HIV transmissions. However, to read statistics such as these, we have to question whether we’re progressing fast enough in the right direction. Comfortingly the recent announcement of HVTN 702, a large preventative vaccine trial, has us moving a step forward in vaccine research, a field where tangible results have been slow to materialize in recent years.
As highlighted in Destination: Cure’s last column, “Orphaned Vaccines,” a vaccine should optimally be both a preventative and a therapeutic vaccine that can be utilized globally. Unfortunately, in the HVTN 702 trial, the regimen being studied is neither a therapeutic vaccine nor a vaccine that, in its current form, could be used against any clade other than Clade C. Clade C is the predominant clade seen in sub-Saharan Africa. Although not ideal, HTVN 702 may help achieve some degree of protection in a region such as South Africa where 16.6 percent of the adult population aged fifteen to forty-nine are living with HIV/AIDS.
HTVN 702 stems from the controversial 2009 RV144 study, which showed a 31.2 percent protection rate against HIV. This Phase III study raised eyebrows and voices from its inception—predominantly due to the amount of money spent on the singular trial that, even if found wholly effective, would still have needed further studies to determine the individual effects of its components (particularly ALVAC, as the other component, AIDSVAX, had already been shown to be ineffective as a singular component).
RV144 did show the greatest protection benefit thus far. Further research concluded that the rate of protection reached sixty percent during the first year of the study. A research initiative called the Pox-Protein Public-Private Partnership (P5) was formed to build on the success of the RV144 study. P5 is a collaboration of the National Institute of Allergy and Infectious Diseases (NIAID), The Gates Foundation, the U.S. Military HIV Research Program, Sanofi Pasteur, the HIV Vaccine Research Network (HVTN) and Novartis Vaccines and Diagnostics. P5 initiated several further studies based on the RV144 study: RV305 and RV306, where additional boosting of ALVAC, AIDSVAX or a combination was given; and RV328, where AIDSVAX was studied alone for intense immunologic assessment.
The P5 also launched HVTN 100, a two-year study of the components of the RV144 regimen initiated in February 2015. HVTN 702 is a direct follow-up to this study. Both studies will evaluate a vaccine regimen modified from the RV144 vaccines to work specifically against Clade C where, according to the NIH, “the composition and schedule of the RV144 vaccine regimen have been adjusted to try to increase the magnitude and duration of vaccine-elicited immune responses, and to extend the higher level of protection seen at one year in RV144 throughout the entire three-year follow-up period of HVTN 702.”
The vaccine regimen will consist of a canary pox-based vaccine called ALVAC-HIV and a bivalent gp120 protein subunit vaccine with an adjuvant that enhances the body’s immune response to the vaccine and is combined with an adjuvant called MF59 to potentially generate greater robust immune response. The vaccine regimen will include booster shots at the one-year mark in an effort to prolong the early protective effect observed in RV144.
HVTN 702 will test the safety, tolerability, and efficacy of the vaccine regimen and will enroll 5,400 at-risk HIV-negative men and women. To ensure that women are adequately represented, a minimum of forty percent of participants will be women. In all, fifteen sites in South Africa will participate in the NIAID-sponsored study. Participants will be randomized to either the vaccine regimen or placebo and given five injections over a one-year period of time. They will then be followed for one or two years.
A therapeutic and preventative vaccine that can be used against all clades for a widespread protective benefit is essential in preventing new infections and controlling existing immune responses in people already living with HIV. HVTN 702 may help us move towards these goals. Its results, predicted to be released in 2020, are much anticipated.
Jeannie Wraight is the former editor-in-chief and co-founder of HIV and HCV Haven (www.hivhaven.com) and a blogger and writer for TheBody.com. She is a member of the Board of Directors of Health People, a community-based organization in the South Bronx and an advisor to TRW (Teach me to Read and Write), a community-based organization in Kampala, Uganda. She lives with her husband in New York City.