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Restoration of Human Immunodeficiency Virus‐1‐Specific Responses in Patients Changing from Protease to Non‐Nucleoside Reverse Transcriptase Inhibitor‐Based Antiretroviral Therapy
Author(s) -
Sullivan A. K.,
Burton C. T.,
Nelson M. R.,
Moyle G.,
Mandalia S.,
Gotch F. M.,
Gazzard B. G.,
Imami N.
Publication year - 2003
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1046/j.1365-3083.2003.01276.x
Subject(s) - reverse transcriptase , virology , protease inhibitor (pharmacology) , viral load , reverse transcriptase inhibitor , immunology , virus , antigen , biology , nucleoside reverse transcriptase inhibitor , didanosine , lentivirus , immune system , viral disease , medicine , antiretroviral therapy , rna , biochemistry , gene
The effect of altering antiretroviral therapy (ART) on responses to viral, recall and human immunodeficiency virus (HIV)‐1‐specific recombinant antigens and interleukin‐2 (IL‐2) in HIV‐1‐infected patients was assessed. A longitudinal cohort study in eight HIV‐1 infected individuals following a clinically indicated therapy change (seven for drug intolerance and one for virological failure) from protease inhibitor (PI) to non‐nucleoside reverse transcriptase inhibitor (NNRTI)‐based antiretroviral regimens was performed. CD4 T‐cell counts, viral loads, lymphoproliferative responses, cytokine production and latent proviral deoxyribonucleic acid (DNA) were measured at baseline and at weeks 12 and 24 after therapy substitution. Following therapy‐switch there was a 33% proportional increase in mitogen response (95% confidence interval (CI), 3–33%) and a 31% increase (95% CI, 15–48%) in viral and recall‐antigen responses. Six patients developed proliferative responses to low concentration IL‐2 stimulation. All patients demonstrated an increase in median HIV‐1‐specific responses, as three had detectable virus at baseline (two being viral rebound); this may reflect an autovaccination effect. Proviral DNA changes largely reflected plasma HIV‐1 ribonucleic acid (RNA). In conclusion, NNRTI substitution for a PI may favour immune reconstitution with an improvement in HIV‐1‐specific responses, which may reflect differential effects on antigen processing and presentation, an autovaccination effect or alternatively a potential suppressive effect of the PI.