Revised adult treatment guidelines focus on NNRTIs

Pediatric guidelines include amprenavir info

Two HIV panels released their updated treatment guidelines early this year, with each reflecting changes in antiretroviral drug therapies.

The 17-member International AIDS Society, in its updated recommendations published in JAMA, acknowledged that a greater availability of new antiretroviral drugs has expanded treatment options for adults, including the use of nonnucleoside reverse transcriptase inhibitors (NNRTIs).1

With so many treatment options now available, treating HIV patients is more of a challenge than ever, says Douglas Richman, MD, a physician at the San Diego Veterans Administration Medical Center and a professor of medicine and pathology at the University of California at San Diego. Richman is a member of the panel that wrote the updated recommendations.

"It’s becoming more and more clear that this is a very complicated field," Richman says. "The use of antiretroviral drugs is at least as complicated as oncology. You can’t provide a simple algorithm for the use of these drugs. It really requires expertise and a fairly significant commitment."

The adult recommendations discuss the three NNRTIs approved in the United States: nevirapine, delavirdine, and efavirenz. The recommendations also discuss the potency of combinations that include efavirenz-lamivudine-zidovudine, nevirapine-zidovudine-didanosine, and delavirdine-zidovudine-lamivudine. The panel says that because of the potential for high-level resistance and cross-resistance, NNRTIs should be only used in regimens that will maximally suppress HIV.1

Also, the panel notes that physicians should consider possible drug-drug interactions between the NNRTI class and protease inhibitors (PIs).

Guidelines touch on resistance testing

The updated guidelines briefly address drug resistance testing, saying only that testing for HIV drug resistance is available and such information may assist physicians in improving patient treatment and reducing antiretroviral cost and toxicity.

Later this year, there will be another set of consensus guidelines with revised and more detailed recommendations about resistance testing that will be published in JAMA, Richman says.

The guidelines also suggest clinicians may delay treatment initiation in patients who have CD4 cell counts above 500 X 106 /L and HIV RNA levels below 5,000 copies/mL.

In these cases, the guidelines say, patients are at low risk of progressing to AIDS within three years, so other issues should be considered before starting therapy, including patients’ quality of life, adherence, adverse effects, and development of drug resistance.

The consensus on what thresholds to use in determining when to start therapy is more generous now than what it was previously, reflecting the input of the panel’s international physicians, Richman says.

The panel’s recommendations on protease inhibitors includes information about their adverse effects and which forms of the five approved PIs are better tolerated.

"One thing we tried to do is reinforce general principles of using the most effective and reasonable combinations of drugs," Richman says. "We acknowledge there are more drugs and drug combinations to choose from, and physicians can make decisions more individualized."

Physicians treating HIV/AIDS patients now deal with a drug regimen that is at least as complicated as those in oncology practice, Richman adds. "It’s not something people can do in their spare time for a small number of patients."

The revised "Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection," were released in January on the Web site of the HIV/AIDS Treatment Information Service (ATIS) at www.hivatis.org.

Pediatric guidelines note use of amprenavir

The guidelines have added information about amprenavir, the drug manufactured under the trade name of Agenerase by Glaxo Wellcome Inc. of Research Triangle Park, NC. Amprenavir, which is available in a liquid formulation, may be used as initial therapy under special circumstances in a combination with two nucleoside reverse transcriptase inhibitors, according to the revised guidelines.2

Physicians should not use amprenavir as initial therapy in children under three years of age because of the lack of data.

The guidelines advise the use of amprenavir in a treatment regimen for children who have failed prior protease inhibitor therapy.

Another addition to the pediatric guidelines is a section on antiretroviral drug resistance testing. The six-paragraph section discusses why resistance testing may be important in monitoring patients’ disease, and it briefly describes genotypic assays and phenotypic assays. However, the guidelines stop short of recommending resistance testing, due in part to the fact that no controlled clinical trials of resistance testing have been performed in children.

References

1. Carpenter CCJ, Cooper DA, Fischl MA, et al. Antiretroviral therapy in adults: Updated recommendations of the International AIDS Society — USA Panel. JAMA 2000; 283:381-390.

2. Abrams E, Ammann A, Anderson M, et al. Guidelines for the use of antiretroviral agents in pediatric HIV infection. Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children convened by the National Pediatric and Family HIV Resource Center, the Health Resources and Services Administration, and the National Institutes of Health. ATIS Web site [www.hivatis. org]. January 7, 2000:1-61.