OBJECTIVE: To evaluate the efficacy of combination protease and reverse transcriptase inhibitor therapy in correcting HIV-1-induced lymphocyte subset abnormalities in previously treated adults. DESIGN: A 48-week observational study of lymphocyte subsets in 12 participants in the Multicenter AIDS Cohort Study who were already taking at least one reverse transcriptase inhibitor and added a protease inhibitor to their treatment regimen. Comparison groups were HIV-seronegative homosexual men, HIV-seronegative heterosexual men, and homosexual HIV-1-infected men who were long-term non-progressors. METHODS: Three-color immunofluorescence and monoclonal antibodies were used to assess HIV-1-induced lymphocyte subset alterations related to immune deficiency and immune activation. Plasma HIV-1 RNA levels were monitored to assess suppression of viral replication. RESULTS: CD4+ cell counts significantly increased and lymphocyte activation measured as CD38 and HLA-DR expression on CD8+ T cells significantly decreased by 48 weeks. CD4+ cell values remained abnormal even in those who were fully suppressed. Some T-cell activation markers decreased to levels observed in long-term non-progressors. The increase in CD4+ T-cell numbers reached a plateau by week 24, but the increase in resting HLA-DR- CD38-T cells was sustained through week 48. Proportions of CD45RA+ CD62L-selectin+ and CD28+ CD4+ T-cell subsets and Fas expression were not abnormal at baseline compared with seronegative homosexual controls. CONCLUSIONS: The most significant impact of suppression of viral replication was reversal of T-cell activation. However, normalization of lymphocyte subset perturbations associated with chronic HIV-1 infection was not achieved after 1 year of treatment with current combination antiretroviral regimens. More profound viral suppression, therapy for longer than 1 year, or immunologic augmentation may be needed to fully reverse the abnormalities.
OBJECTIVE: To evaluate the efficacy of combination protease and reverse transcriptase inhibitor therapy in correcting HIV-1-induced lymphocyte subset abnormalities in previously treated adults. DESIGN: A 48-week observational study of lymphocyte subsets in 12 participants in the Multicenter AIDS Cohort Study who were already taking at least one reverse transcriptase inhibitor and added a protease inhibitor to their treatment regimen. Comparison groups were HIV-seronegative homosexual men, HIV-seronegative heterosexual men, and homosexual HIV-1-infectedmen who were long-term non-progressors. METHODS: Three-color immunofluorescence and monoclonal antibodies were used to assess HIV-1-induced lymphocyte subset alterations related to immune deficiency and immune activation. Plasma HIV-1 RNA levels were monitored to assess suppression of viral replication. RESULTS: CD4+ cell counts significantly increased and lymphocyte activation measured as CD38 and HLA-DR expression on CD8+ T cells significantly decreased by 48 weeks. CD4+ cell values remained abnormal even in those who were fully suppressed. Some T-cell activation markers decreased to levels observed in long-term non-progressors. The increase in CD4+ T-cell numbers reached a plateau by week 24, but the increase in resting HLA-DR- CD38-T cells was sustained through week 48. Proportions of CD45RA+ CD62L-selectin+ and CD28+ CD4+ T-cell subsets and Fas expression were not abnormal at baseline compared with seronegative homosexual controls. CONCLUSIONS: The most significant impact of suppression of viral replication was reversal of T-cell activation. However, normalization of lymphocyte subset perturbations associated with chronic HIV-1 infection was not achieved after 1 year of treatment with current combination antiretroviral regimens. More profound viral suppression, therapy for longer than 1 year, or immunologic augmentation may be needed to fully reverse the abnormalities.
Authors: Katherine Tassiopoulos; Alan Landay; Ann C Collier; Elizabeth Connick; Steven G Deeks; Peter Hunt; Dorothy E Lewis; Cara Wilson; Ronald Bosch Journal: J Infect Dis Date: 2012-03-23 Impact factor: 5.226
Authors: S Zanussi; C Simonelli; M T Bortolin; M D'Andrea; C Crepaldi; E Vaccher; G Nasti; D Politi; L Barzan; U Tirelli; P De Paoli Journal: Clin Exp Immunol Date: 1999-06 Impact factor: 4.330
Authors: Christian R Aguilera-Sandoval; Otto O Yang; Nebojsa Jojic; Pietro Lovato; Diana Y Chen; Maria Ines Boechat; Paige Cooper; Jun Zuo; Christina Ramirez; Marvin Belzer; Joseph A Church; Paul Krogstad Journal: AIDS Date: 2016-03-13 Impact factor: 4.177
Authors: Peter W Hunt; Jason Brenchley; Elizabeth Sinclair; Joseph M McCune; Michelle Roland; Kimberly Page-Shafer; Priscilla Hsue; Brinda Emu; Melissa Krone; Harry Lampiris; Daniel Douek; Jeffrey N Martin; Steven G Deeks Journal: J Infect Dis Date: 2008-01-01 Impact factor: 5.226
Authors: Salvador Resino; Isabel Galán; José M Bellón; M Luisa Navarro; Juan Antonio León; M Angeles Muñoz-Fernandez Journal: J Clin Immunol Date: 2003-07 Impact factor: 8.317