INTERRUPTING THERAPY MAY MAKE AIDS TREATMENT CHEAPER, LESS TOXIC

By E. J. Mundell

Reuters 11 July 2000

Durban -- Although successful in keeping AIDS at bay in many patients, HIV-suppressing combination drug therapies remain very expensive and are often accompanied by a variety of side effects. But in a speech delivered Tuesday at the XIII International AIDS Conference here, AIDS pioneer Dr. Anthony Fauci outlined a treatment strategy of 'structured interrupted therapy,' which could free many patients from both side effects and expense for large periods of time.

The idea, Fauci told Reuters Health, "is to try and have people off therapy for a finite period of time, intermittently, so that you can get them to a course where they're not feeling that they need to be on a drug every single day.'' The practice has already produced positive results in two clinical trials.

According to Fauci, who is the director of the US National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, complete eradication of HIV is probably not within the reach of even the most sophisticated highly active antiretroviral therapies (HAART) available today.

This means that "people are going to be essentially confined to having to take the drug for the rest of their lives,'' he said.

However, HAART can be so toxic that it is often difficult for patients to continue to tolerate the drugs when they are taken every day over the life span. "You don't want them to just stop their drug,'' Fauci explained, "so we have to figure out a way that's safe and hopefully effective, that would get them on less total time on drugs.''

To tackle this problem, Fauci and his colleagues began experimenting with the short-term interruption of therapy for patients whose drug therapy had already caused HIV levels to decline to near-undetectable levels (less than 50 copies of the virus per milliliter of blood).

Speaking to conference attendees, Fauci noted that, even at these low levels, hidden reservoirs of active virus can cause HIV levels to shoot up again "with a vengeance'' within 4 weeks after therapy is discontinued. This was the case when Fauci's team tested interrupted therapy in 9 patients using a 2-month-on/1-month-off schedule.

But what about discontinuing therapy for even shorter periods of time? "We looked at what would happen if we interrupted therapy every other week,'' Fauci said. In a study involving 5 patients, the researchers found that "the virus did, in fact, come back after discontinuation of therapy. However, in no individual did it go above several hundred copies per millimeter cubed.'' While that level was higher than the 50 copies recorded during active HAART, it was still too low to have a significant negative impact on immune health. Fauci noted that when HAART was resumed, HIV again plunged to previous levels.

He also noted that levels of CD8+ T cells--immune cells known as "killer'' T cells, which are thought to help fight HIV--normally drop precipitously under the HIV-suppressing influence of HAART.

During week-on/week-off interrupted therapy, however, CD8+ cells began to rise as HIV crept upwards. Fauci said re-instatement of HAART causes CD8 to drop again along with HIV, "but (they) seem to stabilize at least temporarily at a level that is somewhat higher than (that seen) prior to the interruption.'' The result, Fauci explained, is a kind of weak 'vaccination' against HIV, due to an enlarged pool of virus-fighting CD8.

The Bethesda researcher stressed that this therapy would probably only work in patients whose viral load had already fallen to near-undetectable levels. And he said it remains unknown whether or not HIV might, over the long term, mutate and develop some type of resistance to this type of therapy.

However, the strategy could enable more people to be treated with antiretroviral drugs, including those who have difficulty tolerating the medications or who have until now been unable to afford the costly drugs.

"One might be able to interrupt therapy at regular cycles such that the patient may be able to be without therapy for a substantial fraction of the year, perhaps even 6 or 8 months,'' Fauci explained, "as long as the virus continues to remain sensitive to HAART.'' The findings could have important implications for the availability of antiretroviral drugs in poorer countries, he said.

Fauci's speech was just one of a series of talks delivered at the same session by eminent AIDS researchers such as Dr. Mauro Schechter of the Hospital Universitario Clementino Fraga Filho in Rio de Janeiro, Brazil, and Dr. David Ho of the Aaron Diamond AIDS Research Center, New York. Ho, Time Magazine's Man of the Year for 1996, is largely credited with discovering and developing HIV-suppressing antiretroviral therapies.

The assembled crowd broke into applause as Ho opened his speech with a direct attack on South African President Thabo Mbeki, who has publicly sought advice from researchers who claim that HIV does not, in fact, cause AIDS. Pointing to a slide of HIV entering a human cell, Ho said, "This is, ladies and gentlemen, the cause of AIDS.'' He went on to state that ''failure to address the modern plague caused by HIV is an act of irresponsibility that will be judged harshly by history. President Mbeki, I beg you to not let your legacy be defined by inaction on this human catastrophe.''