Virologic and immunologic outcomes of treatment with integrase inhibitors in a real-world setting: The RESPOND cohort consortium
Por:
Neesgaard, B, Mocroft, A, Zangerle, R, Wit, F, Lampe, F, Gunthard, HF, Necsoi, C, Law, M, Mussini, C, Castagna, A, Monforte, AD, Pradier, C, Chkhartisvilli, N, Reyes-Uruena, J, Vehreschild, JJ, Wasmuth, JC, Sonnerborg, A, Stephan, C, Greenberg, L, Llibre, JM, Volny-Anne, A, Peters, L, Pelchen-Matthews, A, Vannappagari, V, Gallant, J, Rieger, A, Youle, M, Braun, D, De Wit, S, Petoumenos, K, Borghi, V, Spagnuolo, V, Tsertsvadze, T, Lundgren, J and Ryom, L
Publicada:
31 dic 2020
Ahead of Print:
31 dic 2020
Resumen:
Objectives
To compare virologic and immunologic outcomes of integrase inhibitor (INSTI)-containing, contemporary boosted protease inhibitor (PI/b)-containing and non-nucleotide reverse transcriptase inhibitor (NNRTI)-containing regimens in a real-life setting.
Methods
Using logistic regression, virologic and immunologic outcomes of INSTI use were compared to outcomes of PI/b or NNRTI treatment 12 months after treatment start or switch, for participants in the RESPOND cohort consortium. A composite treatment outcome (cTO) was used, defining success as viral load (VL) <200 copies/mL and failure as at least one of: VL >= 200 copies/mL, unknown VL in the time window, any changes of antiretroviral therapy (ART) regimen, AIDS, or death. In addition, on-treatment analysis including only individuals with known VL and no regimen changes was performed. Favorable immunologic response was defined as a 25% increase in CD4 count or as reaching >= 750 CD4 cells/mu L.
Results
Between January 2012 and January 2019, 13,703 (33.0% ART-naive) individuals were included, of whom 7,147 started/switched to a regimen with an INSTI, 3,102 to a PI/b and 3,454 to an NNRTI-containing regimen. The main reason for cTO failure in all treatment groups were changes in ART regimen. Compared to INSTIs, the adjusted odds ratio (aOR) of cTO success was significantly lower for PI/b (0.74 [95% confidence interval, CI 0.67-0.82], p <0.001), but similar for NNRTIs (1.07 [CI 0.97-1.17], p = 0.11). On-treatment analysis and sensitivity analyses using a VL cut-off of 50 copies/mL were consistent. Compared to INSTIs, the aORs of a 25% increase in CD4 count were lower for NNRTIs (0.80 [CI 0.71-0.91], p<0.001) and PI/b (0.87 [CI 0.76-0.99], p = 0.04).
Conclusion
In this large analysis of a real-world population, cTO and on-treatment success were similar between INSTIs and NNRTIs, but lower for PI/b, though residual confounding cannot be fully excluded. Obtaining favorable immunologic outcomes were more likely for INSTIs than the other drug classes.
Filiaciones:
Neesgaard, B:
Univ Copenhagen, Dept Infect Dis, CHIP, Rigshosp, Copenhagen, Denmark
Mocroft, A:
UCL, Inst Global Hlth, Ctr Clin Res Epidemiol Modelling & Evaluat CREME, London, England
Zangerle, R:
Med Univ Innsbruck, Austrian HIV Cohort Study AHIVCOS, Innsbruck, Austria
Wit, F:
AIDS Therapy Evaluat Netherlands Cohort ATHENA, Stichting HIV Monitoring SHM, Amsterdam, Netherlands
Lampe, F:
UCL, Royal Free Hosp, London, England
Gunthard, HF:
Univ Zurich Hosp, Div Infect Dis & Hosp Epidemiol, Zurich, Switzerland
Univ Zurich, Inst Med Virol, Zurich, Switzerland
Necsoi, C:
CHU St Pierre, Ctr Rech Malad Infect Asbl, Brussels, Belgium
Law, M:
UNSW, Australian HIV Observat Database AHOD, Sydney, NSW, Australia
Mussini, C:
Univ Modena, Modena HIV Cohort, Modena, Italy
Castagna, A:
Univ Vita Salute San Raffaele, San Raffaele Sci Inst, Milan, Italy
Monforte, AD:
ASST Santi Paolo & Carlo, Italian Cohort Naive Antiretrovirals ICONA, Milan, Italy
Pradier, C:
Univ Cote dAzur, Nice HIV Cohort, Nice, France
CHU Nice, Nice, France
Chkhartisvilli, N:
AIDS & Clin Immunol Res Ctr, Infect Dis, Tbilisi, Georgia
Reyes-Uruena, J:
CIBERESP, PISCIS Cohort, Ctr Estudis Epidemiol Infecc Transmiss Sexual & S, Badalona, Spain
Vehreschild, JJ:
Univ Hosp Frankfurt, Med Dept 2, Hematol Oncol, Frankfurt, Germany
Univ Hosp Cologne, Dept Internal Med, Cologne, Germany
Wasmuth, JC:
Univ Hosp Bonn, Bonn, Germany
Sonnerborg, A:
Karolinska Univ Hosp, Swedish InfCare HIV Cohort, Stockholm, Sweden
Stephan, C:
Goethe Univ, Frankfurt Univ Hosp, Med Dept 2, Infect Dis Unit, Frankfurt, Germany
Greenberg, L:
UCL, Inst Global Hlth, Ctr Clin Res Epidemiol Modelling & Evaluat CREME, London, England
:
Hosp Badalona Germans Trias & Pujol, Infect Dis & Fight AIDS Fdn, Barcelona, Spain
Volny-Anne, A:
European AIDS Treatment Grp EATG, Brussels, Belgium
Peters, L:
Univ Copenhagen, Dept Infect Dis, CHIP, Rigshosp, Copenhagen, Denmark
Pelchen-Matthews, A:
UCL, Inst Global Hlth, Ctr Clin Res Epidemiol Modelling & Evaluat CREME, London, England
Vannappagari, V:
ViiV Healthcare, Res Triangle Pk, NC USA
Gallant, J:
Gilead Sci, Foster City, CA USA
Rieger, A:
Wiener Med Univ, Vienna, Austria
Youle, M:
UCL, Royal Free Hosp, London, England
Braun, D:
Univ Zurich Hosp, Div Infect Dis & Hosp Epidemiol, Zurich, Switzerland
Univ Zurich, Inst Med Virol, Zurich, Switzerland
De Wit, S:
CHU St Pierre, Ctr Rech Malad Infect Asbl, Brussels, Belgium
Petoumenos, K:
UNSW, Australian HIV Observat Database AHOD, Sydney, NSW, Australia
Borghi, V:
Univ Modena, Modena HIV Cohort, Modena, Italy
Spagnuolo, V:
Univ Vita Salute San Raffaele, San Raffaele Sci Inst, Milan, Italy
Tsertsvadze, T:
AIDS & Clin Immunol Res Ctr, Infect Dis, Tbilisi, Georgia
Lundgren, J:
Univ Copenhagen, Dept Infect Dis, CHIP, Rigshosp, Copenhagen, Denmark
Green Published, gold, Green Accepted
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