Immune response may persist after emergence of protease inhibitor-resistant HIV

For nearly a quarter of HIV-infected patients on highly active antiretroviral therapy (HAART) that includes protease inhibitors, immune recovery persists even after virologic failure of therapy due to the emergence of resistant HIV strains.

Dr. Laurent Belec of the Hopital Broussais in Paris, France, and colleagues assessed genotypic viral resistance in participants in a 12-month trial of indinavir with two nucleoside analogs as a first-line protease inhibitor-containing regimen. Virologic response was defined as achievement of undetectable levels or decrease in the plasma HIV load by at least 1 log copies/mL. Immune response referred to an increase in CD4+ T-cell counts of at least 50 cells per microliter over baseline.

Three groups of patients were compared: 27 ‘discrepant’ responders, 24 responders and 8 nonresponders. In the discrepant responders, plasma HIV RNA levels remained above 4 log copies/mL at 12 months, but their CD4+ T-cell counts increased from 71.5 to 213.2 cells per microliter.

As reported in the May issue of the Journal of Infectious Diseases, the number of primary and secondary mutations increased significantly in both nonresponders and discrepant responders.

‘These findings clearly indicate that the development of resistance mutations to protease inhibitor drugs does not interfere with immunologic restoration under HAART,’ Dr. Belec and his associates state. They question whether evaluations of genotypic resistance to protease inhibitors and measurements of viral load are useful markers of HAART efficacy in patients with sustained CD4+ T-cell response.

More data is needed to document whether such patients, who may represent up to 25% in currently reported clinical cohorts, should remain on the same treatment despite the presence of high levels of HIV RNA and protease inhibitor-resistant virus or whether treatment should be changed despite immune reconstitution,’ the investigators conclude.