Immune-based therapies - an alternative to PrEP with HAART drugs?

The early termination of the FEM-PrEP trial was disappointing, but PrEP using antiviral drugs is not the only prevention game in town. NAPWA supports development of therapeutic vaccines and other immune-based therapies enabling people living with HIV to control their virus with less use of antiviral drugs. And the same immune-based therapies that may someday help infected people live healthy lives without drugs might, just might, also give uninfected people some protection from infection. We hosted a Community Forum on immune-based therapies in development at last summer's IAS conference in Vienna, and we are moving forward with plans to hold a second community forum on emerging but underfunded HIV therapies, focusing on potential next-generation breakthroughs, at this summer's IAS Pathogenesis Conference in Rome.

So we were more than happy last week to see National Institute of Allergy and Infectious Diseases' announcement of a new $4.5 million request for grant proposals (RFP) to support collaborative functional cure research. $4.5 million isn't much money in the context of NIAID's nearly $5 billion budget, but the announcement shows that one of the world's most influential funders of HIV research is looking beyond antivirals.

The RFP's title is a story in itself: "Beyond HAART: Innovative Therapies to Control HIV-1." The program takes up again the almost abandoned pursuit of a "functional cure," which, in the RFP's words, "would be expected to delay or eliminate rebound of virus when ART is interrupted, reduce exposure to drugs and consequent toxicities, free infected persons from the complexities of continuous drug taking, decrease the potential to transmit virus, and perhaps lower levels of immune activation and resulting long-term morbidities." In short, the program supports researchers in looking for ways to take patients off of HAART.

A small number of tiny biotech companies sprinkled across the globe are already working to see whether a therapeutic vaccine really can bring about such a "functional cure." The research is targeted initially at people already living with HIV, but a successful therapeutic vaccine might also give uninfected people lasting if not permanent protection against infection. A successful therapeutic vaccine would offer significant benefits:

· Better health without sometimes toxic drugs for people living with HIV

· Reduced community viral load and less transmission of HIV to new hosts

· Preservation of immune system function and stimulation of HIV-specific immunity

· Minimal administration and less dependence on taking pills every day - only a few injections and boosters are necessary to improve patient immune system function

· Lower cost than current HAART drugs

· Progress towards a possible permanent "functional cure" for AIDS.

Several therapeutic vaccine candidates have moved into human trials and show varying degrees of promise. Trials are expensive, though, the global financial crisis has dried up venture capital funding, and researchers desperately need funds to bring promising new therapies through testing and into clinical use. We hope major funders of HIV research, like the International AIDS Vaccine Initiative (IAVI), The Bill & Melinda Gates Foundation, The Elizabeth Glaser Pediatric AIDS Foundation, will take a careful look at NIAID's new grant opportunity and ask how they too could begin to fund the immune-based pursuits for functional cures.

Nobel prize winner Françoise Barré-Sinoussi recently joined the call on funders to develop immune based therapies and preventive vaccines simultaneously so that advances in one field can lead to breakthroughs in the other ("HIV persistence and the prospect of long-term, drug-free remissions for HIV infected individuals," Science, Didier et al., 339: 174 / 2010). Concurrent development of preventive and therapeutic vaccines and other new broad range therapeutic interventions for HIV/AIDS and co-morbidities will help lead to breakthroughs faster.

Examples of projects in need of funding include:

VRX1273, a therapeutic vaccine from VIRxSYS and the only vaccine candidate using a lentiviral vector. The vaccine may also work as a preventative. Leveraging technology spun off from Johns Hopkins University, VRX1273 has been found to provide a "functional cure" (no detectable disease 24 months after a series of three vaccinations) to 40 percent of monkeys infected with SIV, the monkey analogue of HIV. The results of the primate study so far have been extraordinary, turning heads of some of the top HIV researchers in the world. And these results were achieved using a massive dose of a very virulent form of SIV (SIVmac251). VRX1273 has undergone rigorous FDA review and is in the process of being cleared for use human trials.

DermaVir, a topically applied HIV synthetic DNA nanomedicine designed to "train" the immune system specifically to recognise and kill HIV-infected cells. DermaVir has demonstrated excellent safety, immunogenicity, and antiviral efficacy in preclinical and human studies. Phase I/II trials to date have confirmed safety and tolerability, indicate the induction of long-lasting HIV-specific T cells, and show reduced viral load in therapy-naive individuals following four three-hour applications. DermaVir contains no vectors or boosters that could limit its ability to be administered repeatedly over time to maintain immune control of viral replication throughout the body and in reservoir sites.

AGS-004, a personalized immunotherapy from Argos Therapeutics, derived from the company's Arcelis technology platform. Arcelis is Argos' proprietary technology for harvesting dendritic cells from individual patients' bodies, loading them with signature RNA from HIV or other diseases, and returning the cells to the patient to search for and destroy infected cells displaying the signature. AGS-004 recently demonstrated a positive outcome with the primary endpoint of viral load control and a favorable safety and immunogenicity profile in a Phase 2a clinical trial.

We invite readers interested in seeing therapeutic vaccine research move forward to join NAPWA and let us know we can add your voice to the growing number of patients, researchers, and other advocates who would like to see more spent on finding functional cures for people living with HIV/AIDS and alternatives to PrEP with HAART drugs for uninfected people.

From NAPWA

By Stephen Bailous, Vice President for Treatment Advocacy and Community Affairs, National Association for People with AIDS. Originally published in NAPWA Positive Voice 4/25/2011.