New Resistance Assays for HIV ‘Must Prove Value’

SAN DIEGO—With several new ultrasensitive HIV viral load assays soon to be available, Jonathan Schapiro, MD, questioned to what degree they will be able to predict or help physicians manage clinical HIV resistance. “We will be seeing both genotypic and phenotypic resistance assays for use with zidovudine [Retrovir], abacavir [investigational], and protease inhibitor resistance,” he said at ICAAC.

Genotypic resistance assays identify the complete sequence of the HIV protease gene, a large portion of the RT gene, and mutations at key codons, he said. Phenotypic resistance assays are a direct assay of HIV resistance to specific drugs. The two assays may be combined, he said.

Resistance assays play several potentially important roles in HIV management, said Dr. Schapiro, of Tel Hashomer Hospital, Tel Aviv. They may help rule out infection with resistant virus in a newly infected patient before starting therapy. They may assist in determining the patient’s cause of drug failure—eg, poor compliance, absorption metabolism, or viral resistance. They could help determine the next appropriate drug regimen in a patient with a failing current regimen—a classic indication. They could assist in the decision to discontinue antiretroviral therapy in an advanced patient with multidrug-resistant mutations.

However, he said, “there are a number of hoops resistance assays must always jump through.” They must prove they can predict which drugs will no longer clinically benefit the patient—in other words, “what not to use”—as well as which drugs will benefit the patient most; and they must prove that their use will improve clinical outcomes over use of current tools.