Immunologic effects of combined protease inhibitor and reverse transcriptase inhibitor therapy in previously treated chronic HIV-1 infection.
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.


METHODS
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.
Giorgi
J V
JV
Multicenter AIDS Cohort Study and University of California Los Angeles School of Medicine, 90095-1745, USA.
Majchrowicz
M A
MA
Johnson
T D
TD
Hultin
P
P
Matud
J
J
Detels
R
R
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal; D018791:CD4 Lymphocyte Count; D002908:Chronic Disease; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005455:Fluorescent Antibody Technique; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D020276:HIV Long-Term Survivors; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D018023:HIV Seronegativity; D015497:HIV-1; D018451:Homosexuality, Male; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014779:Virus Replication
D019380:Anti-HIV Agents; D000911:Antibodies, Monoclonal; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors