IAS: Remune slows viral load rise and CD4 cell count fall during treatment interruptions

HIV-positive patients receiving the therapeutic vaccine Remune show slowed rises in viral load and falls in CD4 cell count during an interruption of antiretroviral therapy, according to a presentation on July 27^th at the Third International AIDS Society Conference on HIV Pathogenesis and Treatment in Rio de Janeiro.

The investigators found that this was linked to an increased number of CD4 and CD8 T-cells with anti-HIV activity.

Therapeutic vaccines are designed to stimulate the immune system to recognise HIV and boost the body’s responses against the virus in infected patients. One of these vaccines, called Remune, is made from inactivated HIV particles, which lack the gp120 molecule on the outer ‘envelope’ of the virus.

Researchers from Spain have previously shown that Remune improved the duration of HIV suppression in patients taking highly active antiretroviral therapy (HAART). This study, called STIR-2102, was extended to examine the effects of therapeutic vaccination on the levels of HIV and CD4 T-cells during an interruption of anti-HIV therapy.

“Therapeutic vaccination with Remune induces a statistically significant reduction of viral load rebound and CD4⁺ decline in comparison with the placebo group during analytical treatment interruption,” they conclude. “Long term vaccination with HIV-1 immunogen may enhance host HIV-1 CD4 and CD8 T-cell responses and result in a better control of plasma viral load after antiretroviral therapy withdrawal.”

In the preceding STIR-2102 study, 243 patients had been randomised to receive Remune or placebo for 36 months, after which they all received the vaccine for a further 24 months. After the completion of this trial, the 39 patients who had had viral loads below 2000 copies/ml and CD4 cell counts above 500 cells/mm³ for at least a year were selected for the treatment interruption study, called REMIT.

The patients were randomised to receive four injections of Remune or dummy injections, once every three months. All of the patients stopped taking their antiretroviral drugs when they received their first injection.

Although both groups of patients showed an increase in viral load, they remained lower in the patients who received the vaccine (p Remune-treated patients (p = 0.028).

However, the vaccination did not bring about a statistically significant extension of the time required for the patients to reach a viral load above 55,000 copies/ml (p = 0.1). Dr Eduardo Fernández-Cruz, presenting, said that this may have been due to the small numbers of patients in his study.

Remune caused an increase in the numbers of ‘central memory’ CD4 (p = 0.005) and CD8 T-cells (p = 0.004), with high levels of these cells being associated with lower viral loads at 48 weeks (p = 0.026 and 0.01, respectively). High levels of anti-HIV activity were also linked to lower viral loads (p Remune stimulated the production of cells with potent anti-HIV activity, explaining their reduced viral loads.

Since the control group in this study had received Remune during the preceding STIR-2102 study, the investigators also examined the anti-HIV activity of the immune systems of 19 patients who had never received the vaccine, but who had stopped anti-HIV therapy. These patients did not show any increase in central memory T-cells and had lower anti-HIV responses than both of the groups of patients who were enrolled in STIR-2102.

However, the patients with the strongest anti-HIV activity were those who were randomised to receive Remune during both trials.

Despite these findings, further trials of this and other therapeutic vaccines will be necessary before they can be considered for use in mainstream anti-HIV therapy.