Treatment of primary HIV-1 infection with cyclosporin A coupled with highly active antiretroviral therapy.
Primary HIV-1 infection causes extensive immune activation, during which CD4(+) T cell activation supports massive HIV-1 production. We tested the safety and the immune-modulating effects of combining cyclosporin A (CsA) treatment with highly active antiretroviral therapy (HAART) during primary HIV-1 infection. Nine adults with primary HIV-1 infection were treated with CsA along with HAART. At week 8, all patients discontinued CsA but maintained HAART. Viral replication was suppressed to a comparable extent in the CsA + HAART cohort and in 29 control patients whose primary infection was treated with HAART alone. CsA restored normal CD4(+) T cell levels, both in terms of percentage and absolute numbers. The increase in CD4(+) T cells was apparent within a week and persisted throughout the study period. CsA was not detrimental to virus-specific CD8(+) or CD4(+) T cell responses. At week 48, the proportion of IFN-gamma-secreting CD4(+) and CD4(+)CCR7(-) T cells was significantly higher in the CsA + HAART cohort than in the HAART-alone cohort. In conclusion, rapid shutdown of T cell activation in the early phases of primary HIV-1 infection can have long-term beneficial effects and establish a more favorable immunologic set-point. Appropriate, immune-based therapeutic interventions may represent a valuable complement to HAART for treating HIV infection.
Rizzardi
G Paolo
GP
Laboratory of AIDS Immunopathogenesis, Division of Immunology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
Harari
Alexandre
A
Capiluppi
Brunella
B
Tambussi
Giuseppe
G
Ellefsen
Kim
K
Ciuffreda
Donatella
D
Champagne
Patrick
P
Bart
Pierre-Alexandre
PA
Chave
Jean-Philippe
JP
Lazzarin
Adriano
A
Pantaleo
Giuseppe
G
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008875:Middle Aged; D011446:Prospective Studies; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000378:metabolism; D012449:Safety; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects
D000276:Adjuvants, Immunologic; C515370:CCR7 protein, human; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D016572:Cyclosporine