TY - JOUR

T1 - Virologic and immunologic outcomes of treatment with integrase inhibitors in a real-world setting

T2 - The RESPOND cohort consortium

AU - Neesgaard, Bastian

AU - Mocroft, Amanda

AU - Zangerle, Robert

AU - Wit, Ferdinand

AU - Lampe, Fiona

AU - Günthard, Huldrych F

AU - Necsoi, Coca

AU - Law, Matthew

AU - Mussini, Cristina

AU - Castagna, Antonella

AU - Monforte, Antonella d'Arminio

AU - Pradier, Christian

AU - Chkhartisvilli, Nikoloz

AU - Reyes-Uruena, Juliana

AU - Vehreschild, Jörg Janne

AU - Wasmuth, Jan-Christian

AU - Sönnerborg, Anders

AU - Stephan, Christoph

AU - Greenberg, Lauren

AU - Llibre, Josep M

AU - Volny-Anne, Alain

AU - Peters, Lars

AU - Pelchen-Matthews, Annegret

AU - Vannappagari, Vani

AU - Gallant, Joel

AU - Rieger, Armin

AU - Youle, Mike

AU - Braun, Dominique

AU - De Wit, Stephane

AU - Petoumenos, Kathy

AU - Borghi, Vanni

AU - Spagnuolo, Vincenzo

AU - Tsertsvadze, Tengiz

AU - Lundgren, Jens

AU - Ryom, Lene

AU - RESPOND Study Group

PY - 2020

Y1 - 2020

N2 - 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/μL.RESULTS: Between January 2012 and January 2019, 13,703 (33.0% ART-naïve) 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.

AB - 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/μL.RESULTS: Between January 2012 and January 2019, 13,703 (33.0% ART-naïve) 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.

KW - Adult

KW - CD4 Lymphocyte Count

KW - Cohort Studies

KW - Female

KW - HIV/drug effects

KW - HIV Infections/drug therapy

KW - HIV Integrase Inhibitors/therapeutic use

KW - HIV Protease Inhibitors/therapeutic use

KW - Humans

KW - Male

KW - Middle Aged

KW - Reverse Transcriptase Inhibitors/therapeutic use

KW - Treatment Outcome

KW - Viral Load/drug effects

U2 - 10.1371/journal.pone.0243625

DO - 10.1371/journal.pone.0243625

M3 - Journal article

C2 - 33382756

VL - 15

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 12

M1 - e0243625

ER -