title: Immunological and virological effects of structured treatment interruptions following exposure to hydroxyurea plus didanosine.
abstract: Both hydroxyurea (HU) and structured treatment interruptions (STI) have been investigated as therapeutic approaches to enhance immune responses in chronically HIV-infected individuals. HIV-specific T cell responses as well as T cell activation were analyzed longitudinally in 31 HIV-infected individuals who had been treated for the prior 12 months with didanosine (ddI) plus HU and thereafter completed three STI cycles consisting of 2 months off and 2 months on ddI-HU. Similar increases in plasma HIV-RNA were seen in each of the three cycles off therapy, whereas CD4 counts remained fairly stable along the study period. T cell activation paralleled the evolution of plasma HIV-RNA during the first STI cycle and waned afterward. At baseline most patients presented a high level of CD8+ responses to different HIV peptide pools and 23% of them had CD4+ responses to Gag and/or Env. The level of CD8+ responses against each pool was stable and did not increase during STI cycles, while CD4 responses tended to decline. However, the contribution of Nef-specific response to the total CD8 response tended to increase. In a multivariate model, both a higher baseline plasma HIV-RNA and a higher level of Nef-specific response contribution to the total CD8+ response were independently associated with lower plasma HIV-RNA increases during each of the three STI cycles. Nef-specific CD8+ responses might contribute to a better virological control of HIV replication following treatment interruptions in HIV-infected individuals and might be boosted by the immunomodulatory effect of HU.
authors.affiliation: Department of Infectious Diseases, Hospital Carlos III, Madrid 28029, Spain. jbenito@hotmail.com
authors.forename: José Miguel
authors.initials: JM
authors.lastname: Benito
authors.forename: Mariola
authors.initials: M
authors.lastname: López
authors.forename: Celia
authors.initials: C
authors.lastname: Ballesteros
authors.forename: Sara
authors.initials: S
authors.lastname: Lozano
authors.forename: Laura
authors.initials: L
authors.lastname: Capa
authors.forename: Pablo
authors.initials: P
authors.lastname: Barreiro
authors.forename: José
authors.initials: J
authors.lastname: Sempere
authors.forename: Juan
authors.initials: J
authors.lastname: Gonzalez-Lahoz
authors.forename: Vincent
authors.initials: V
authors.lastname: Soriano
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000276:immunology; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D016009:Chi-Square Distribution; D016049:Didanosine / Q000008:administration & dosage* / Q000276:immunology; D004359:Drug Therapy, Combination; D005260:Female; D015693:Gene Products, nef / Q000097:blood; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage* / Q000276:immunology; D007111:Immunity, Cellular; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D012044:Regression Analysis; D054311:nef Gene Products, Human Immunodeficiency Virus
chemical_list: D019380:Anti-HIV Agents; D015693:Gene Products, nef; D012367:RNA, Viral; D054311:nef Gene Products, Human Immunodeficiency Virus; D051997:ADP-ribosyl Cyclase 1; D016049:Didanosine; D006918:Hydroxyurea