Clinical and laboratory guidelines have been recently published for use of HIV—1 drug resistance testing as part of treatment management; AIDS 2001; 15: 309-320.
From the 3rd Surgeon Symposium on Clinical Implications of HIV Drug Resistance — Frankfurt, Germany, February, 2001
From Clifford Lane, NIH: HIV infection is characterized by the development of immunodeficiency occurring simultaneously with an increase in immune activation. Use of IL-2 may expand T-cell pool and extend half-life of CD4 cells. The clinical benefit of this strategy remains to be demonstrated.
From C. Craig of Roche Discovery, England: The level of unbound protease inhibitor (PI) is associated with antiretroviral activity, and because most PIs are highly protein bound, the level of protein in serum may have a significant effect on the efficiency of PIs in vivo. Alpha-acid glycoprotein provides the greatest contribution to PI protein binding. Use of serum in drug testing to assay antiretroviral activity of PIs may underestimate the role of serum proteins in vivo.
Treatment options for persons who have failed all 3 currently available classes of antiretroviral agents are extremely limited. A trial of amprenavir and lopinavir/r as part of lopinavir/r Easy Access Program showed moderate viral suppression and immunologic recovery for patients with documented treatment failure with all 3 classes of available agents.
Data from Wayne State/Detroit Medical Center (R. MacArthur) were presented which examined use of ritonovir-boosted indinavir in highly experienced HIV-infected patients. Using retrospective chart review of 17 patients, at 24 weeks after initiating the combination therapy, 5 patients achieved full virologic response and 6 patients had a partial response. However, 4/17 patients had confirmed or probable episodes of nephrolithiasis, with 2 of 4 discontinuing the regimen.
In terms of defining resistance, the final analysis of the HAVANA trial was presented by B. Clotet of Spain. These data, using 326 patients with first, second or third drug failure, demonstrated that, at week 24, individuals who had genotypic testing and access to expert opinion had a significant difference in viral load below detection and HIV-1 RNA reduction compared with those who did not receive genotypic testing and/or expert opinion.
Discussing transmission of resistant virus, R. Comacho of Portugal demonstrated a prevalence of 16.7% (9/54) primary resistance mutations in newly HIV-infected patients. Similarly, O. Donoso of Spain showed resistant genotypes in 14/130 (10.8%) therapy-naïve HIV-infected persons in 18 outpatient clinics in Spain.