New Debates Over Therapy Goals

In January the federal governmemt revised its guidelines for HIV therapy to reflect the progress and setbacks that have come with the prevailing hit early-hit hard model of combination antiretroviral therapy. These updates reflect experts’ more realistic expectations about how well this approach can work over time, based on the knowledge they’ve gained using the current drug arsenal. HIV specialists are reassessing when to start or switch therapy, what doses to use, how to best restore the ability of the immune system to contain HIV, and the potential role of vaccination.

They are also weighing the risks versus benefits of this approach in light of new reports about toxicities and side effects such as lactic acidosis, mitochondrial toxicity, and loss of bone density —- the latest in a laundry list of problems linked to HIV drugs, which also include metabolic changes that increase the risk of heart attack and diabetes. Some people now question the wisdom of continual, long-term therapy and instead suggest that drug holidays, a.k.a. "structured treatment interruptions," or STI, may be the wave of the future.

A battery of tantalizing small-scale studies presented at the seventh Conference on Retroviruses and Opportunistic Infections in San Francisco in early February support a controlled STI approach, showing it can lower viral load and boost immune defenses in recently infected individuals and those with chronic infection. While this stop-’n-go therapy isn’t addressed in the updated guidelines, it represents the cutting edge of HIV treatment. It’s also a risky strategy, warn experts, since not everyone may be able to control viral rebound. Individuals should not try this at home, but should discusss updates with their physicians.

The new guidelines do look at how to use resistance testing, how to take drugs sequentially to maxmize their benefits, and how to avoid drug resistance. There’s also the encouraging suggestion that it may not be necessary to throw out all the drugs in a failing regimen.

In the meantime, drug companies continue to strive for simpler dosing. Coming up: Look for a single capsule of ddI (now dosed as two pills, once a day) and Trizivir (Glaxo Wellcome), a single pill containing AZT, 3TC, and Ziagen (one pill twice a day). Looking down the pipeline, both lopinavir (ABT-378; Abbott) and tenofovir (Gilead) have enlarged their expanded access programs* (see charts). It’s possible that T-20, Trimeris’ novel fusion inhibitor, could also make it into expanded access by the end of 2000.

The chart below specifies the main features of each drug. For a more complete list and updates, check with your doctor or community organization.

— ACD, EB