Activists Caution About Dolutegravir's Expanded Access Program

AIDS activists and physician advocates welcome the news that ViiV Healthcare will be providing compassionate-use expanded access of dolutegravir (DTG), a new integrase inhibitor for HIV patients with few remaining HIV treatment options. However, they warn patients and physicians to avoid functional monotherapy, or the introduction of dolutegravir as an "add-on" to a failing treatment regimen if the patient's virus is resistant to all other currently available antiretroviral drugs (ARVs). Functional monotherapy has been shown to permit rapid HIV resistance to new medications, which can result in more rapid disease progression, health deterioration, and death.

Currently, the Department of Health and Human Services (DHHS) adult HIV treatment guidelines recommend three ARVs be given in combination to suppress HIV. But many patients have HIV that has mutated, rendering their virus multi-drug resistant (MDR-HIV). Those with MDR-HIV cannot construct a viable HIV-suppressive regimen with current FDA approved and commercially available ARVs.

"The DHHS guidelines specify that patients who have developed HIV drug resistance to all commercially available antiretrovirals require access to at least two new active drugs to maximize their chances for treatment response. However, another new drug to combine with dolutegravir will not be commercially available for at least two years, and some patients cannot wait that long," said Nelson Vergel, an activist and founder of SalvageTherapies.org. "For them, access to another research drug in combination with DTG is the only hope for survival," added Vergel.

In studies to date, dolutegravir (DTG) appears to be the most potent integrase inhibitor to soon enter the HIV ARV market. Unlike Gilead's soon-to-be-released elvitegravir, DTG has been shown to be effective against HIV that has developed resistance to Merck's Isentress (raltegravir), the only FDA approved integrase inhibitor currently on the market.

Fortunately, another new ARV that can help patients with MDR-HIV is in active development and clinical trials. Ibalizumab, a monoclonal antibody from a small biotech firm called Taimed Biologics, may soon be available via patient participation in research studies. While ibalizumab has yet to enter Phase 3 studies, it can be provided to patients at risk of death via a named (or single) patient access application permitted by the FDA via a physician's direct request to Taimed. Any physician who has a patient with MDR-HIV who is in dire need of two new unapproved ARVs may use this form.

There are no documented statistics on how many people in the United States have uncontrolled HIV due to MDR-HIV. A report in the Journal of Clinical Infectious Diseases estimates that about 260,000 patients are being treated for HIV in the U.S. However, it is virtually impossible to know how many of them have run out of treatment options since no registries for those patients exist.

A coalition of activists and physicians have been working with both Taimed and ViiV for two years to obtain access to two active ARVs for those with MDR-HIV in greatest need of new treatment options. The AIDS Community Research Initiative of America (ACRIA), a New York City-based community research and education organization, and physicians in San Francisco have proposed solutions to overcome this "two-drug barrier" in an effort to secure urgent access to patients across the country. This access program may start in Spring 2012.