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Clinical Trial
. 2020 Dec 31;15(12):e0243625.
doi: 10.1371/journal.pone.0243625. eCollection 2020.

Virologic and immunologic outcomes of treatment with integrase inhibitors in a real-world setting: The RESPOND cohort consortium

Bastian Neesgaard  1 , Amanda Mocroft  2 , Robert Zangerle  3 , Ferdinand Wit  4 , Fiona Lampe  5 , Huldrych F Günthard  6   7 , Coca Necsoi  8 , Matthew Law  9 , Cristina Mussini  10 , Antonella Castagna  11 , Antonella d'Arminio Monforte  12 , Christian Pradier  13 , Nikoloz Chkhartisvilli  14 , Juliana Reyes-Uruena  15 , Jörg Janne Vehreschild  16   17 , Jan-Christian Wasmuth  18 , Anders Sönnerborg  19 , Christoph Stephan  20 , Lauren Greenberg  2 , Josep M Llibre  21 , Alain Volny-Anne  22 , Lars Peters  1 , Annegret Pelchen-Matthews  2 , Vani Vannappagari  23 , Joel Gallant  24 , Armin Rieger  25 , Mike Youle  5 , Dominique Braun  6   7 , Stephane De Wit  8 , Kathy Petoumenos  9 , Vanni Borghi  10 , Vincenzo Spagnuolo  11 , Tengiz Tsertsvadze  14 , Jens Lundgren  1 , Lene Ryom  1 ; RESPOND study group
Affiliations
Clinical Trial

Virologic and immunologic outcomes of treatment with integrase inhibitors in a real-world setting: The RESPOND cohort consortium

Bastian Neesgaard et al. PLoS One. .

Abstract

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.

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Conflict of interest statement

RESPOND is externally funded by Gilead sciences and ViiV Healthcare. Funding companies have no direct involvement in the conduct of scientific projects. However academic personnel from funders can be included in the writing group for RESPOND projects, if they satisfy the ICMJE criteria, as specified in RESPOND’s governance (https://chip.dk/Portals/0/files/RESPOND/RESPOND%20governance%20and%20procedures_v6_2019SEP30.pdf?ver=2019-10-02-144419-230). This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Proportions of individuals with composite treatment outcome (cTO) success, on-treatment success, or favorable immunologic response after 12±3 months.
Error bars and numbers in the 3rd row in the table indicate 95% confidence intervals. * cTO failure was defined as ≥1 of VL ≥200 cp/mL, unknown VL, any ART regimen change, AIDS events, or death. ** Individuals with known VL at 12±3 months without ART regimen change in the periods (N = INSTI 4513; PI/b 1721; NNRTI 2263). *** Persons with known CD4 counts at 12±3 months (N = INSTI 5823; PI/b 2550; NNRTI 2882). ****Persons with known CD4 counts at 12±3 months, excluding those with ≥750 CD4 cells/μL at baseline (N = INSTI 4297; PI/b 2160; NNRTI 2253).
Fig 2
Fig 2. Adjusted odds ratios (aOR) of composite treatment outcome (cTO) success and on-treatment success at 12±3 months.
Forest plots showing the aOR of cTO success (A) or on-treatment success (B). A controlled viral load was defined as <200 cp/mL. The multivariable models were adjusted for: Age (per ten years older), ethnicity, mode of transmission, baseline date (per year later), baseline smoking status, hypertension, diabetes, HBV and HCV status, prior AIDS event, cardiovascular disease, chronic kidney disease, end stage liver disease, non-AIDS-defining malignancies and prior fractures, viral load(<200 cp/mL, ≥200 cp/mL at baseline) and treatment status, CD4 count (nadir and baseline; both per 100 cells higher), treatment regimen and number of drugs in regimen. * cTO failure was defined as ≥1 of VL ≥200 cp/mL, unknown VL, any ART regimen change, AIDS events, or death. ** Individuals with known VL at 12±3 months without ART regimen change in the period.
Fig 3
Fig 3. Reasons for cTO failure at 12±3 months.
Error bars and 3rd row in the table indicate 95% confidence intervals. Total numbers with cTO failure: INSTI: 2749/7147; PI/b: 1396/3102; NNRTI 1253/3454. *cTO failure: ≥1 of: VL ≥200 cp/mL, unknown VL, any antiretroviral treatment (ART)-regimen change, AIDS, or death (note it was possible to fail more than one parameter).
Fig 4
Fig 4. Adjusted odds ratios (aOR) of a favorable immunologic response at 12±3 months.
Immunologic response was defined as a 25% increase in CD4 cell counts (A) or reaching a CD4 cell count ≥750 cells/μL (B). Models were adjusted for age (per ten years older), ethnicity, mode of transmission, baseline date (per year later), baseline smoking status, hypertension, diabetes, HBV and HCV status, prior AIDS event, cardiovascular disease, chronic kidney disease, end stage liver disease, non-AIDS-defining malignancies and prior fractures, viral load (<200 cp/mL, ≥200 cp/mL at baseline) and treatment status, CD4 count (nadir and baseline; both per 100 cells higher), treatment regimen and number of drugs in regimen. *Excluding individuals with a CD4 cell count ≥750 cells/μL at baseline.
Fig 5
Fig 5. Sensitivity analysis: Adjusted odds ratios (aOR) of cTO and on-treatment analysis with VL cut-off <50 cp/mL at 12±3 months.
Multivariable models were adjusted for age (per ten years older), ethnicity, mode of transmission, baseline date (per year later), smoking status, hypertension, diabetes, prior AIDS event- cardiovascular disease, chronic kidney disease, end stage liver disease, non-AIDS-defining malignancies and fractures, HBV and HCV status, viral load (<200 cp/mL, ≥200 cp/mL at baseline), CD4 count (nadir and baseline; both per 100 cells higher), treatment regimen and number of drugs in regimen. * cTO failure was defined as ≥1 of VL ≥50 cp/mL, unknown VL, any ART regimen change, AIDS events, or death. ** Individuals with known VL at 12±3 months without ART regimen change in the period.
Fig 6
Fig 6. Adjusted odds ratios of cTO success, on-treatment success and favorable immunologic outcomes at 12 ± 3 months for ART-naïve individuals initiating treatment after 16th January 2014.
Forest plots showing the aOR of cTO success, on-treatment success, and immunologic response as a 25% increase in CD4 cell counts or reaching a CD4 cell count ≥750 cells/μL. A controlled viral load was defined as <200 cp/mL. Multivariable models were adjusted for age (per ten years older), ethnicity, mode of transmission, baseline date (per year later), baseline smoking status, hypertension, diabetes, HBV and HCV status, prior AIDS event, cardiovascular disease, chronic kidney disease, end stage liver disease, non-AIDS-defining malignancies and prior fractures, viral load (<200 cp/mL, ≥200 cp/mL at baseline), CD4 count (nadir and baseline; both per 100 cells higher, treatment regimen and number of drugs in regimen. *cTO failure was defined as ≥1 either of VL ≥200 cp/mL, unknown VL, ART regimen change, AIDS events, or death. ** Individuals with known VL at 12±3 months without ART regimen change in the period. ***Excluding individuals with ≥750 CD4 cells/μL at baseline.
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References

    1. Clotet B, Feinberg J, van Lunzen J, Khuong-Josses MA, Antinori A, Dumitru I, et al. Once-daily dolutegravir versus darunavir plus ritonavir in antiretroviral-naive adults with HIV-1 infection (FLAMINGO): 48 week results from the randomised open-label phase 3b study. Lancet. 2014;383(9936):2222–31. Epub 2014/04/05. 10.1016/S0140-6736(14)60084-2 . - DOI - PubMed
    1. Molina JM, Clotet B, van Lunzen J, Lazzarin A, Cavassini M, Henry K, et al. Once-daily dolutegravir versus darunavir plus ritonavir for treatment-naive adults with HIV-1 infection (FLAMINGO): 96 week results from a randomised, open-label, phase 3b study. Lancet HIV. 2015;2(4):e127–36. Epub 2015/10/02. 10.1016/S2352-3018(15)00027-2 . - DOI - PubMed
    1. Molina JM, Lamarca A, Andrade-Villanueva J, Clotet B, Clumeck N, Liu YP, et al. Efficacy and safety of once daily elvitegravir versus twice daily raltegravir in treatment-experienced patients with HIV-1 receiving a ritonavir-boosted protease inhibitor: randomised, double-blind, phase 3, non-inferiority study. Lancet Infect Dis. 2012;12(1):27–35. Epub 2011/10/22. 10.1016/S1473-3099(11)70249-3 . - DOI - PubMed
    1. Sax PE, DeJesus E, Mills A, Zolopa A, Cohen C, Wohl D, et al. Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus co-formulated efavirenz, emtricitabine, and tenofovir for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3 trial, analysis of results after 48 weeks. Lancet. 2012;379(9835):2439–48. Epub 2012/07/04. 10.1016/S0140-6736(12)60917-9 . - DOI - PubMed
    1. Walmsley SL, Antela A, Clumeck N, Duiculescu D, Eberhard A, Gutierrez F, et al. Dolutegravir plus abacavir-lamivudine for the treatment of HIV-1 infection. N Engl J Med. 2013;369(19):1807–18. Epub 2013/11/08. 10.1056/NEJMoa1215541 . - DOI - PubMed

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