Background: Despite successful suppression of HIV-1 with HAART, some patients do not have robust immunological recovery. Chronic inflammation from persistent immune activation could contribute to this poor response, resulting in HIV-1 disease progression and the development of some non-HIV-1 comorbidities.
Methods: We conducted a pilot study of 30 HIV-1-infected patients with undetectable viral loads and poor CD4(+) T-cell responses on long-term stable HAART to assess whether the addition of raltegravir would have an effect on biomarkers of chronic inflammation. A total of 26 patients were followed for 1 year on the intensified regimen. In addition to T-cell responses, we evaluated changes in activated CD4(+) and CD8(+) T-cells, several pro-inflammatory cytokines and chemokines and memory cell responses to HIV-1-associated peptides.
Results: Although there was no improvement in CD4(+) T-cell counts, the percentage change in CD4(+)%, CD4(+)/CD8(+) ratios and RANTES (regulated on activation normal T-cells expressed and secreted) increased significantly while the percentage change in CD8(+) T-cell counts and CD8(+)%, activated CD4(+) T-cells and several pro-inflammatory chemokines and cytokines decreased significantly. The percentage change in HIV-1-specific nef, pol set 1, gag and env memory T-cells also declined.
Conclusions: The addition of raltegravir to a virologically suppressive HAART regimen in patients with poor immunological responses resulted in the reduction of several pro-inflammatory biomarkers; increases were seen in RANTES levels and CD4(+)/CD8(+) T-cell ratios. The clinical relevance of these observations is beyond the scope of this study.