title: Immunological function restoration with lopinavir/ritonavir versus efavirenz containing regimens in HIV-infected patients: a randomized clinical trial.
abstract: CD4(+) count increase has been reported to be different with lopinavir/r (LPV/r) and efavirenz (EFV)-containing regimens. The different effect of these two regimens on other immune function parameters and the relationship with the gain of CD4(+) count have not been assessed in a randomized clinical trial. Fifty antiretroviral treatment (cART) naïve HIV-infected individuals were randomized to receive LPV/r or EFV both with tenofovir/emtricitabine for 48 weeks. A substudy of immunological function restoration was performed in 22 patients (LPV/r n=10 and EFV n=12). Activation, thymic function, apoptosis, senescence, exhaustion, Treg cells, interleukin (IL)-7-receptor/IL-7 system, thymic volume, and lymphoid tissue fibrosis were evaluated at baseline and at week 48. Both groups experienced a CD4(+) count increase that was higher in the EFV group (ΔCD4(+) 88 vs. 315 cells/μl LPV/r vs. EFV, respectively, p<0.001). Despite this difference in CD4(+) gain, the change in other immune function parameters was similar in both treatment groups. Most of parameters evaluated tended to normalize after 48 weeks of cART. A significant decrease in levels of activation, senescence, exhaustion, and apoptosis on CD4(+) and CD8(+) T cells (p<0.001 for all) and a significant increase in markers of thymic function, IL-7 receptor, and in the levels of central memory CD4(+) T cells and naive subsets of CD8(+) T cells (p<0.001 for all) with respect to baseline values were observed without any difference between groups. These data indicate that the differences in CD4(+) gain with different cART regimens are not immunologically meaningful and might explain the similar clinical efficacy of these regimens.
authors.affiliation: 1 Hospital Clinic, IDIBAPS, University of Barcelona , Barcelona, Spain .
authors.forename: Berta
authors.initials: B
authors.lastname: Torres
authors.forename: Norma I
authors.initials: NI
authors.lastname: Rallón
authors.forename: Montserrat
authors.initials: M
authors.lastname: Loncá
authors.forename: Alba
authors.initials: A
authors.lastname: Díaz
authors.forename: Llucia
authors.initials: L
authors.lastname: Alós
authors.forename: Esteban
authors.initials: E
authors.lastname: Martínez
authors.forename: Anna
authors.initials: A
authors.lastname: Cruceta
authors.forename: Joan Albert
authors.initials: JA
authors.lastname: Arnaiz
authors.forename: Lorna
authors.initials: L
authors.lastname: Leal
authors.forename: Constanza
authors.initials: C
authors.lastname: Lucero
authors.forename: Agathe
authors.initials: A
authors.lastname: León
authors.forename: Marcelo
authors.initials: M
authors.lastname: Sánchez
authors.forename: Eugenia
authors.initials: E
authors.lastname: Negredo
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.forename: José M
authors.initials: JM
authors.lastname: Gatell
authors.forename: José M
authors.initials: JM
authors.lastname: Benito
authors.forename: Felipe
authors.initials: F
authors.lastname: Garcia
mesh_terms: D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D048588:Benzoxazines / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D003521:Cyclopropanes; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007107:Immune System / Q000502:physiology*; D061466:Lopinavir / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D019438:Ritonavir / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D061466:Lopinavir; C098320:efavirenz; D019438:Ritonavir