HIV vaccine regimen more efficacious at 1 year, among low-risk patients

Issue: July 2012

An HIV vaccine regimen that included ALVAC-HIV and AIDSVAX B/E was more efficacious among those at low risk for HIV, according to a post-hoc analysis of the Thai phase 3 HIV vaccine trial RV 144.

The RV 144 trial was a randomized, multicenter, double blind, placebo-controlled efficacy trial testing the combination vaccines of ALVAC-HIV (Sanofi-Pasteur) and AIDSVAX B/E (VaxGen) to prevent HIV infection or reduce set point viral load. It included men and women aged 18 to 30 years recruited regardless of risk for HIV. For the post-hoc analysis, 16,395 participants were included.

“RV 144 was the first HIV vaccine trial to show efficacy in humans, roughly 31% after 42 months follow-up,” Col. Jerome Kim, MD, deputy director and chief, department of molecular virology and pathogenesis, Walter Reed Army Institute of Research, US Military HIV Research Program, told Infectious Disease News. “This analysis looks in greater detail at questions that the primary study was not designed to answer and has raised some intriguing points. Interestingly, we found that vaccine efficacy in RV144 was 60% at 1 year.”

Jerome Kim

HIV risk behavior was assessed by questionnaires that were self-administered at the initial vaccination and then every 6 months for 3 years. Participants’ behavior was classified as low, medium or high risk. Throughout the study, the proportion of participants classified as low risk increased, whereas the proportion of participants classified as medium risk or high risk decreased.

Although the risk for HIV acquisition was low for each group, most HIV infections were identified in those who reported high-risk behaviors at baseline or during at least one subsequent visit. Vaccine efficacy was lowest among participants who reported a high-risk behavior at least once during the study (P=.01). For those who maintained low-risk or medium-risk status, the vaccine efficacy estimate was 68% (95% CI, 34-84). For those in the high-risk group, the vaccine efficacy was 5% (95% CI, –46 to 38).

In addition, the vaccine efficacy was highest within the 12 months after initial vaccination, but declined quickly.

“This study confirmed that efficacy was higher in persons whose risk was always low,” Kim said. “This observation may be linked to the second analysis, that efficacy in RV 144 decreased with time. It is not uncommon for vaccines to require booster doses to improve immune responses that waned with time.”

Kim said the findings also raise two important questions: Will the vaccines work in traditional high-risk groups, such as commercial sex workers or men who have sex with men, and can the vaccines in RV 144 be “boosted” and immune responses made more potent and/or durable?

Future efficacy studies are anticipated in southern Africa and Thailand with vaccines matched to circulating subtypes of HIV-1, Kim added. Based upon these findings, these planned studies have incorporated a 12 month “booster” vaccination to hopefully improve upon vaccine potency and durability.

“Our hope is that this research, in combination with the recent correlates studies published in the New England Journal of Medicine, will help us extend the results seen in the RV144 trial and lead to a better and longer-lasting HIV vaccine,” Kim said.

“At this point, the vaccines are not ready for use as a public health intervention,” he said. “Importantly, vaccines are a part of the HIV prevention equation, and new and exciting developments in microbicides and pre-exposure prophylaxis contribute to a growing sense that a combination of modalities may eventually be successful in controlling the HIV pandemic.”

References:

Robb ML. Lancet Infect Dis. 2012;doi:10.1016/S1473-3099(12)70088-9.

Disclosures:

Two of the study researchers are employees of Sanofi-Pasteur.