CAPE TOWN, SOUTH AFRICA—More than 30 years into the HIV/AIDS pandemic that has claimed an estimated 35 million lives, a preventive vaccine has remained elusive. The only HIV-vaccine clinical trial that has shown potential so far is the United States’ and Thai military’s vaccine, RV144, the results of which were announced in 2009. RV144 demonstrated a “modest” 31 percent efficacy at the end of the three-year study. The vaccine apparently peaked early—it was 60 percent effective at the one-year mark, reported the U.S. Military HIV Research Program. But the effect quickly declined.
The first in a series of trials designed to build on the success of RV144 has now passed a key test in South Africa. A safety trial using the same vaccine regimen from RV 144—but with an added booster shot 12 months afterward—has has shown to be safe for South Africans and demonstrated “robust” immune responses. A successful safety trial was necessary to move forward with extensive clinical research. The research was first presented in late October by South African scientists in Cape Town. Clinical trials of a modified vaccine tailored to Southern Africa will begin in early 2015.
Southern Africa desperately needs such a vaccine. Sub-Saharan Africa is home to two-thirds of all people living with HIV/AIDS and the main driver is unprotected heterosexual sex, according to the Joint United-Nations Program on HIV/AIDS, or UNAIDS. South Africa has the unfortunate distinction of claiming the world’s highest HIV/AIDS burden, with an estimated 6.3 million people living with HIV/AIDS. New infections, called seroconversions, are increasing at about 370,000 per year in that region. That’s about 1,000 new infections every day. About 20 percent of South African adults—that’s one in five people—are living with the virus, reports UNAIDS. Young women are twice as likely to be infected as young men.
This most recent trial was a small Phase I trial to ensure that the vaccine tested in Thailand was safe and tolerable for South Africans. The study enrolled 100 participants and was evenly split among men and women. More than half of the women in the study were overweight or obese.
“We know from previous studies that high body mass index, gender, age, and genetics impact HIV vaccine-induced responses. Given the rising prevalence of obesity in South Africa and the distinct differences in genetic backgrounds [from Thailand], we needed to validate whether the regimen in Thailand was immunogenic in South Africa,” said Dr. Glenda E. Gray, executive director of the Perinatal HIV Research Unit at the University of the Witwatersrand and the first woman to lead the South African Medical Research Council. Gray was also the co-principal investigator of the trial.
“We saw no significant difference in CD4 T-cell responses for body mass, gender, or age,” Gray said. “Females responded slightly better than males and young slightly better than older age groups.”
CD-4 cells—sometimes known as T4 or T-helper cells—are white blood cells that are a critical part of the human immune system. These are called “helper” cells because they send signals to activate the body’s immune response when an “intruder”—such as a virus or bacteria—is detected. HIV infection leads to a gradual reduction in these cells. The virus mutates and hides in CD-4 cell reservoirs. When these cells multiply to fight an infection, they end up making more copies of the virus. Scientists have attempted to develop a vaccine for HIV for more than three decades. But the genetic diversity of the virus and its unique ability to “replicate unrelentingly despite everything the immune system can throw at it”—in the words of Harvard University virologist Ron Desrosiers—“are among the reasons this has proven to become a extraordinary challenge.” The South African study investigated safety and immune response. It did not measure how effective the vaccine was against preventing HIV. The study found that the vaccine produced immune responses—triggered the production of CD-4 cells—in all healthy adults who received the vaccination. Sixty-eight of the 100 participants had responses that were "comparable to or better than those induced in RV144,” note researchers. The results were announced at the HIV Research for Prevention 2014 conference.
Starting in January 2015, Phase 1 and Phase 2 trials will modify the Thai regimen to make it more “friendly” to South Africa. There are up to 10 HIV subtypes—these are called “clades”—and the subtype “C” in Southern Africa is different than subtypes B and E found in Thailand. South African researchers will modify the vaccine with a Clade “C”-specific insert. Researchers will also add a protein adjuvant—sort of a “turbocharge” to increase the body’s immune response. A second vaccination—known as a “booster”–will be given at 12 months to make the regimen stronger and more durable.
An efficacy trial is expected to enroll about 7,000 participants, and results are expected in 2018. “If everything goes well, we could take a product to licensure as early as 2019,” Gray said.
The Bill & Melinda Gates Foundation and other partners funding the vaccine’s research, development, and trials have mandated that any funded HIV vaccine or prevention product must have “global access”—meaning the product and its technology have to become widely available at an affordable price. There is already “significant” interest from the South African government in the vaccine and there will be discussions on how to scale it up, Gray said.
The investment in HIV vaccine research marks a substantial policy shift from only 10 years ago for the South African government. Former President Thabo Mbeki “denied the existence of AIDS and claimed that AIDS antiretroviral drugs were in fact poison,” the BBC reported in 2003. The government could have prevented the deaths of at least 365,000 people from 2000 to 2005 “if it had provided antiretroviral drugs to [people living with HIV/AIDS] and to help prevent pregnant mothers from infecting their babies,” according to a 2008 study conducted by the Harvard School of Public Health.
Mbeki was ousted in 2008. Since then, the government has “massively scaled up HIV prevention and treatment” to operate the largest HIV-treatment program in the world, reports UNAIDS. Unlike most other nations in the region, South Africa “largely funds its own response” to the crisis and “spends $1 billion annually on HIV and AIDS programs,” reports AVERT, a UK-based HIV/AIDS charity.
Despite considerable resource limitations—almost half the country lives in poverty according to the World Bank—researchers are confident that a vaccine could be introduced and scaled-up to the general population. South Africa boasts the second largest economy on the continent, and “has a very good track record of rolling out interventions,” Gray said.