Genotypic resistance tests for the clinical management of patients with primary HIV infection.

Abstract

Witness for the prosecution: Assays to detect antiretroviral drug resistance have recently become available, but several factors limit the clinical utility of resistance testing in patients with primary HIV infection (PHI). First, there is a great uncertainty in the prevalence of PHI due to resistant virus, which may vary from 2% to over 50%. Moreover, studies on temporal trends give discordant results. Secondly, the reported degree of resistance is also variable since low levels of resistance are reported in some cases. The clinical significance of such low-level baseline reduced susceptibility to some antiretrovirals is uncertain. Thirdly, current resistance testing might not detect minority populations of drug-resistant species. Reversion of mutations conferring drug resistance was described in patients who acquired drug-resistant strains, and viral strains harbouring drug-resistant mutations may become minor species in untreated patients owing to the absence of drug pressure. Finally, no prospective clinical trials have been conducted to test the clinical or virological utility of resistance testing in PHI. Witness for the defence: A suboptimal initial regimen in subjects infected with drug-resistant virus may be associated with multiple treatment failures in the early stage of the disease and hence with a more rapid disease progression. When treating PHI, immediate, complete and long-lasting suppression of virus replication is desired both to limit total body viral burden and to preserve HIV-1 specific immune responses. Transmission of resistant virus has been identified for each therapeutic class. A greater than 2.5-fold resistance to one or more antiretroviral agent has been observed in 26% of patients with PHI and resistance among newly infected patients has increased over the past 3 y. Treatment should not be delayed to wait for the result of the test. However, once a resistant virus has been identified, one or more drugs can be readily substituted. Prospective randomized studies to address the need for baseline resistance testing in the setting of PHI are warranted.