Three-year immune reconstitution in PI-sparing and PI-containing antiretroviral regimens in advanced HIV-1 disease
Identifieur interne : 009277 ( Main/Exploration ); précédent : 009276; suivant : 009278Three-year immune reconstitution in PI-sparing and PI-containing antiretroviral regimens in advanced HIV-1 disease
Auteurs : Assia Samri [France] ; Ruth Goodall [Royaume-Uni] ; Catherine Burton [Royaume-Uni] ; Nesrina Imami [Royaume-Uni] ; Giuseppe Pantaleo [Suisse] ; Anthony Kelleher [Australie] ; Guido Poli [Italie] ; Frances Gotch [Royaume-Uni] ; Brigitte Autran [France]Source :
- Antiviral therapy : (London) [ 1359-6535 ] ; 2007.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
Abstract
Background: The long-term immunological benefit of protease inhibitor (Pl)-sparing antiretroviral therapy (ART) using non-nucleoside reverse transcriptase inhibitors (NNRTIs) remains poorly investigated. Methods: A total of 120 ART-naive, HIV-1 -infected participants were included in the immunology substudy of INITIO, an international randomized trial comparing two NRTIs (didanosine + stavudine) combined with either: one NNRTI (efavirenz; EFV), one non-boosted PI (nelfinavir; NFV), or one NNRTI + one PI (EFV/NFV). CD4+ T-cell counts, HIV-1 plasma RNA load (VL), T-cell phenotype, T-cell proliferation and IFN-y production against opportunistic/recall and HIV-1 antigens/peptides were compared at baseline and at week (W) 96 and W156. Results: Participants (37 EFV, 44 NFV, 39 EFV/NFV) had similar baseline VL; median CD4+ T-cell counts/mm3 were: 144 (64-303) EFV, 212 (42-313) NFV and 257 (86-331) EFV/NFV. At W156, the proportion of patients with VL ≤50 copies/ml was not different between the arms (P=0.3). From baseline to W156 there was a significant increase in CD4+ T-cell counts (P<0.001) and in naive CD4+ T cells (P<0.001), with no difference between arms and percentages of total and activated CD8+ T cells decreased significantly (P<0.001) in all arms. The decrease in activated memory CD4+ T-cells was significantly greater in the EFV arm at W96 (P=0.03) and W156 (P=0.01), but did not persist after adjusting for baseline CD4+ T-cell counts. During follow-up, responses to opportunistic pathogens increased in all patients while specific T-cell responses to HIV-1-p24 and gp160 recombinant proteins or to Gag and Nef peptides were not restored. Conclusion: Regimens using/sparing Pls provide similar levels of long-term immune reconstitution even in patients with low CD4+ T-cell counts.
Affiliations:
- Australie, France, Italie, Royaume-Uni, Suisse
- Angleterre, Canton de Vaud, Grand Londres, Lombardie, Île-de-France
- Lausanne, Londres, Milan, Paris
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INSERM UMR S 543; Université Pierre et Marie Curie-Paris 6</s1><s2>Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Goodall, Ruth" sort="Goodall, Ruth" uniqKey="Goodall R" first="Ruth" last="Goodall">Ruth Goodall</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>MRC Clinical Trials Unit</s1><s2>London</s2><s3>GBR</s3><sZ>2 aut.</sZ></inist:fA14><country>Royaume-Uni</country><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Burton, Catherine" sort="Burton, Catherine" uniqKey="Burton C" first="Catherine" last="Burton">Catherine Burton</name><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Department of Immunology, Imperial College</s1><s2>London</s2><s3>GBR</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Royaume-Uni</country><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Imami, Nesrina" sort="Imami, Nesrina" uniqKey="Imami N" first="Nesrina" last="Imami">Nesrina Imami</name><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Department of Immunology, Imperial College</s1><s2>London</s2><s3>GBR</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Royaume-Uni</country><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Pantaleo, Giuseppe" sort="Pantaleo, Giuseppe" uniqKey="Pantaleo G" first="Giuseppe" last="Pantaleo">Giuseppe Pantaleo</name><affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois</s1><s2>Lausanne</s2><s3>CHE</s3><sZ>5 aut.</sZ></inist:fA14><country>Suisse</country><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author><author><name sortKey="Kelleher, Anthony" sort="Kelleher, Anthony" uniqKey="Kelleher A" first="Anthony" last="Kelleher">Anthony Kelleher</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>National Centre in HIV Epidemiology and Clinical Research, University of New South Wales</s1><s2>Darlinghurst</s2><s3>AUS</s3><sZ>6 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Darlinghurst</wicri:noRegion></affiliation></author><author><name sortKey="Poli, Guido" sort="Poli, Guido" uniqKey="Poli G" first="Guido" last="Poli">Guido Poli</name><affiliation wicri:level="3"><inist:fA14 i1="06"><s1>San Raffaele Scientific Institute</s1><s2>Milan</s2><s3>ITA</s3><sZ>7 aut.</sZ></inist:fA14><country>Italie</country><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Gotch, Frances" sort="Gotch, Frances" uniqKey="Gotch F" first="Frances" last="Gotch">Frances Gotch</name><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Department of Immunology, Imperial College</s1><s2>London</s2><s3>GBR</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Royaume-Uni</country><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Autran, Brigitte" sort="Autran, Brigitte" uniqKey="Autran B" first="Brigitte" last="Autran">Brigitte Autran</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Laboratoire d'lmmunologie Cellulaire, AP-HP, Hôpital Pitié-Salpêtrière; INSERM UMR S 543; Université Pierre et Marie Curie-Paris 6</s1><s2>Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author></analytic><series><title level="j" type="main">Antiviral therapy : (London)</title><title level="j" type="abbreviated">Antivir. ther. : (Lond.)</title><idno type="ISSN">1359-6535</idno><imprint><date when="2007">2007</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Antiviral therapy : (London)</title><title level="j" type="abbreviated">Antivir. ther. : (Lond.)</title><idno type="ISSN">1359-6535</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>AIDS</term><term>Advanced stage</term><term>HIV-1 virus</term><term>Immune reconstitution</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Immunorestauration</term><term>SIDA</term><term>Stade avancé</term><term>Virus HIV1</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Background: The long-term immunological benefit of protease inhibitor (Pl)-sparing antiretroviral therapy (ART) using non-nucleoside reverse transcriptase inhibitors (NNRTIs) remains poorly investigated. Methods: A total of 120 ART-naive, HIV-1 -infected participants were included in the immunology substudy of INITIO, an international randomized trial comparing two NRTIs (didanosine + stavudine) combined with either: one NNRTI (efavirenz; EFV), one non-boosted PI (nelfinavir; NFV), or one NNRTI + one PI (EFV/NFV). CD4<sup>+</sup> T-cell counts, HIV-1 plasma RNA load (VL), T-cell phenotype, T-cell proliferation and IFN-y production against opportunistic/recall and HIV-1 antigens/peptides were compared at baseline and at week (W) 96 and W156. Results: Participants (37 EFV, 44 NFV, 39 EFV/NFV) had similar baseline VL; median CD4<sup>+</sup> T-cell counts/mm<sup>3</sup> were: 144 (64-303) EFV, 212 (42-313) NFV and 257 (86-331) EFV/NFV. At W156, the proportion of patients with VL ≤50 copies/ml was not different between the arms (P=0.3). From baseline to W156 there was a significant increase in CD4<sup>+</sup> T-cell counts (P<0.001) and in naive CD4<sup>+</sup> T cells (P<0.001), with no difference between arms and percentages of total and activated CD8<sup>+</sup> T cells decreased significantly (P<0.001) in all arms. The decrease in activated memory CD4<sup>+</sup> T-cells was significantly greater in the EFV arm at W96 (P=0.03) and W156 (P=0.01), but did not persist after adjusting for baseline CD4<sup>+</sup> T-cell counts. During follow-up, responses to opportunistic pathogens increased in all patients while specific T-cell responses to HIV-1-p24 and gp160 recombinant proteins or to Gag and Nef peptides were not restored. Conclusion: Regimens using/sparing Pls provide similar levels of long-term immune reconstitution even in patients with low CD4<sup>+</sup> T-cell counts.</div></front></TEI><affiliations><list><country><li>Australie</li><li>France</li><li>Italie</li><li>Royaume-Uni</li><li>Suisse</li></country><region><li>Angleterre</li><li>Canton de Vaud</li><li>Grand Londres</li><li>Lombardie</li><li>Île-de-France</li></region><settlement><li>Lausanne</li><li>Londres</li><li>Milan</li><li>Paris</li></settlement></list><tree><country name="France"><region name="Île-de-France"><name sortKey="Samri, Assia" sort="Samri, Assia" uniqKey="Samri A" first="Assia" last="Samri">Assia Samri</name></region><name sortKey="Autran, Brigitte" sort="Autran, Brigitte" uniqKey="Autran B" first="Brigitte" last="Autran">Brigitte Autran</name></country><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Goodall, Ruth" sort="Goodall, Ruth" uniqKey="Goodall R" first="Ruth" last="Goodall">Ruth Goodall</name></region><name sortKey="Burton, Catherine" sort="Burton, Catherine" uniqKey="Burton C" first="Catherine" last="Burton">Catherine Burton</name><name sortKey="Gotch, Frances" sort="Gotch, Frances" uniqKey="Gotch F" first="Frances" last="Gotch">Frances Gotch</name><name sortKey="Imami, Nesrina" sort="Imami, Nesrina" uniqKey="Imami N" first="Nesrina" last="Imami">Nesrina Imami</name></country><country name="Suisse"><region name="Canton de Vaud"><name sortKey="Pantaleo, Giuseppe" sort="Pantaleo, Giuseppe" uniqKey="Pantaleo G" first="Giuseppe" last="Pantaleo">Giuseppe Pantaleo</name></region></country><country name="Australie"><noRegion><name sortKey="Kelleher, Anthony" sort="Kelleher, Anthony" uniqKey="Kelleher A" first="Anthony" last="Kelleher">Anthony Kelleher</name></noRegion></country><country name="Italie"><region name="Lombardie"><name sortKey="Poli, Guido" sort="Poli, Guido" uniqKey="Poli G" first="Guido" last="Poli">Guido Poli</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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