Phase II Trial Offers ‘Proof of Concept’ for Therapeutic HIV Vaccine.

A peptide-based vaccine against HIV-1 reduces viral load set-point after combination antiretroviral therapy (cART), a new phase II trial demonstrates.

However, there was no difference between the vaccine and placebo groups in the study’s two primary endpoints, the proportion of patients who resumed treatment after cART interruption or CD4 cell count.

“We believe the study reported here provides initial proof of concept to support a role for therapeutic HIV vaccines, since the finding that Vacc-4x is immunogenic and capable of changing plasma viral load setpoint after an analytical treatment interruption of cART,” Dr. Richard Pollard of U.C. Davis Medical Center in Sacramento and colleagues stated in The Lancet Infectious Disease, in a paper online February 11.

Vacc-4x (Bachem AG, Bubendorf, Switzerland) targets domains on the HIV-1 core protein, p24Gag. The study, at 18 sites in the U.S. and Europe, enrolled 137 patients who were virologically controlled on cART, with data available for 135 patients.

Patients were given a dose of the vaccine weekly for the first four weeks of the study, and then booster immunizations at week 16 and week 18. Patients continued on cART for an additional 10 weeks, and then cART was stopped in individuals with a CD4 count above 350 x 1,000,000/L who were under virologic control. Patients resumed cART if their CD4 counts dropped below this level or fell to more than half of their levels at week 28; if their viral load went above 300,000 copies per mL on two consecutive measurements; or if they developed HIV- or AIDS-related events. The study ended at week 52, and patients were followed to week 104.

Thirty patients (34%) given Vacc-4x began taking cART again between week 28 and week 52, versus 11 patients (29%) on placebo (p=0.89). Time to resuming cART was a median 198 days in the vaccine group and 175 days in the placebo group (p=0.77).

At week 48, patients in the vaccine group had a viral load of 23,100 copies per mL, vs 71,800 copies per mL in the patients on placebo (p=0.025).

At week 52, median viral load was 19,550 in the vaccine group and 51,000 in the placebo group (p=0.041).

The vaccine was well tolerated, with most adverse events involving injection site reactions. Nine patients, including five in the vaccine group, had serious events.

“It is recognized that because of the smaller number of recruited participants than originally planned (137 vs. 345) and the use of additional analyses, done on a subgroup of participants who achieved a 52 week off-ART period, these data need to be considered as exploratory,” Dr. Pollard and colleagues write.

“It’s an encouraging first step,” Dr. Merlin Robb, of the US Military HIV Research Program at the Walter Reed Army Institute of Research in Silver Spring, Maryland, told Reuters Health. Dr. Robb co-wrote an editorial on the new study. “If we could arm the immune system to better control the virus after a period of suppression under drugs, then we might have an important avenue to improve treatment outcomes and possibly achieve a cure.”

He and his colleagues are currently conducting clinical trials of HIV vaccine in individuals in the acute phase of HIV infection, when it may be easier to reduce the reservoir of infected T cells, he added.

The SMART trial, which looked at the effect of interrupting cART in HIV patients, found that patients who interrupted cART therapy were actually at greater risk of side effects than those who continued on cART, Dr. Robb noted. Dr. Pollard and his colleagues attributed the difficulty they had recruiting patients to the current trial to the “climate after the release of the SMART data.”

But studies like the current investigation, which are seeking curative treatments, are different from SMART, which looked at management of HIV, Dr. Robb said. “We need to brace ourselves to do these treatment interruptions safely and carefully, because we don’t want to do any harm, but we also want to see if these interventions have any impact.”