Does Use of Resistance Testing Improve Long-term Virologic Outcomes in HIV Patients?

Resistance to antiretroviral therapy (ART) is an important cause of treatment failure in patients infected with HIV.  Resistance to ART has also been noted in HIV isolates recovered from treatment-naive, newly infected patients, with a prevalence that appears to be increasing.

There are 2 types of assays available for measurement of ART resistance. Genotype tests identify polymorphisms in the HIV genome associated with resistance, and phenotype tests measure ART susceptibility in vitro.

Genetic polymorphisms associated with drug resistance have been retrospectively shown to be associated with treatment failure, development of AIDS, and death.

Several prospective studies have shown short-term improvement in virus load (VL) suppression in patients when genotype testing, phenotype testing, or genotyping with the advice of expert virologists was used to guide therapy. Other recent studies showed either transient or no benefit associated with the use of resistance assays.

An International AIDS Society-USA panel has recommended that resistance testing be used to help guide ART selection at the time of treatment failure and that they be considered for treatment-naive patients at the time of therapy initiation.

The major impediment to the routine use of either genotype or phenotype assays is cost ($400-$1000 per assay), which is outside of the range of affordability for many HIV patients. A more fundamental concern is the lack of information about the long-term efficacy of the routine use of resistance tests in the management of HIV-1 infection.

Researchers conducted a prospective, randomized, multicenter study at 6 US military hospitals comparing the therapeutic efficacy of routine access to and use of genotype and phenotype resistance testing and results with those for clinical management without resistance testing in a cohort of HIV positive beneficiaries of US Department of Defense (DoD) health care.

The study's goal was to determine the long-term efficacy of routinely available resistance testing, as defined by an increase in the time to refractory treatment failure. Emulation of actual clinical practice patterns was reflected in the study design. Results from commercially available resistance tests were provided to treating clinicians without expert recommendations regarding test interpretation.

The HIV positive volunteers were randomized to have routine access to phenotype resistance testing (PT arm), access to genotype resistance testing (GT arm), or no access to either test (VB arm).

The primary outcome measure was time to persistent treatment failure despite change(s) in antiretroviral therapy (ART) regimen.

Results

Overall, routine access to resistance testing did not significantly increase the time to end point. Time to end point was significantly prolonged in the PT arm for subjects with a history of treatment with 4 different ART regimens or a history of treatment with non nucleoside reverse-transcriptase inhibitors (NNRTIs) before the study, compared with that in the VB arm.

The authors conclude, “These results suggest that routine access to resistance testing can improve long-term virologic outcomes in HIV-infected patients who are treatment experienced but may not impact outcome in patients who are naive to or have had limited experience with ART.”

03/03/04

S A Wegner and others. Long-Term Efficacy of Routine Access to Antiretroviral-Resistance Testing in HIV Type 1Infected Patients: Results of the Clinical Efficacy of Resistance Testing Trial. Clinical Infectious Diseases 38(5): 723-730. March 1, 2004.