jofinЖурнал инфектологииJournal Infectology2072-6732IPO “АIDSSPbR"10.22625/2072-6732-2022-14-1-78-86jofin-1311Research ArticleОригинальное исследованиеOriginal ResearchРезультаты применения этравирина в течение 48 недель у пациентов в Санкт-Петербурге в реальной клинической практикеThe results of the use of etravirine within 48 weeks in patients in Saint-Petersburg in real clinical practiceСизоваН. В.SizovaN. V.

Сизова Наталия Владимировна – заместитель по амбулаторно-поликлинической помощи, д.м.н. 

Санкт-Петербург

Saint-Petersburg

natalia_v_sizova@mail.ruМайороваС. О.MajorovaS. O.

Майорова Светлана Олеговна – заведующая поликлиническим инфекционным отделением, к.м.н. 

Санкт-Петербург

Saint-Petersburg

svetlana.majorova11@jandex.ruАладьинаЯ. В.Alad’inaYа. V.

Аладьина Яна Владимировна – врач-инфекционист 

Санкт-Петербург

Saint-Petersburg

yanaaladina@jandex.ruДенисенкоЛ. В.DenisenkoL. V.

Денисенко Лада Викторовна – врач-инфекционист 

Санкт-Петербург

Saint-Petersburg

zaches80@jandex.ruЦентр по профилактике и борьбе со СПИД и инфекционными заболеваниямиРоссияCenters for AIDS and Other Infections DiseasesRussian Federation2022050420221417886Copyright © Сизова Н.В., Майорова С.О., Аладьина Я.В., Денисенко Л.В., 20222022Сизова Н.В., Майорова С.О., Аладьина Я.В., Денисенко Л.В.Sizova N.V., Majorova S.O., Alad’ina Y.V., Denisenko L.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.niidi.ru/jofin/article/view/1311Цель

Цель: оценка эффективности, безопасности и переносимости схем, содержащих этравирин, у пациентов с опытом лечения в реальной клинической практике.

Материалы и методы

Материалы и методы. Проведен ретроспективный анализ 300 амбулаторных карт ВИЧ-инфицированных пациентов с опытом лечения, которые были переведены на схемы, содержащие в качестве 3-го компонента препарат этравирин (ETR, ETV). Причинами переключения на ETR-содержащие схемы были нежелательные явления, сопутствующие заболевания, а также вирусологическая неэффективность. Основным критерием эффективности схемы явилась доля пациентов с неопределяемым уровнем вирусной нагрузки на 48-й неделе лечения. Дополнительными критериями оценки эффективности и безопасности схемы являлись динамика количества CD4+-лимфоцитов, частота и характер нежелательных побочных реакций.

Результаты

Результаты. Доля пациентов с вирусологической супрессией менее 50 коп/мл составила 83% против 77,3% на момент переключения (p <0,005). Доля пациентов, имеющих уровень CD4+-лимфоцитов более 500 кл/мкл., возросла с 40,3% до 58%, а доля пациентов, имеющих уровень CD4+-лимфоцитов менее 200 кл/мкл, уменьшилась более чем в 2 раза с 13% до 6% (p<0,005). Получено достоверное снижение среднего уровня АЛТ с 47,52±66,45 Ед/л до 42,65±55,18 Ед/л (p=0,019). Средний уровень общего холестерина снизился на 8,7% с 5,64±1,37 ммоль/л до 5,15±0,98 ммоль/л (p<0,001). Средний ИМТ после переключения на ETV не изменился и составил 24,07±4,07, 24,2±4,05 соответственно (p=0,347).

Выводы

Выводы. Результаты этого исследования подтверждают, что этравирин хорошо переносится и может быть вариантом для пациентов, у которых наблюдается супрессия РНК ВИЧ на АРТ, но развились побочные реакции, а также может стать частью схемы АРТ второго ряда у пациентов с неэффективностью схемы первого ряда.

The aim of the work was to evaluate the efficacy, safety and tolerability of etravirine-containing regimens in patients with treatment experience in real clinical practice.

Materials and methods

Materials and methods. A retrospective analysis of 300 outpatient records of HIV-infected patients with treatment experience, which were converted to regimens containing etravirine (ETR) as the third component, was performed. The reasons for switching to ETR-containing regimens were adverse events, comorbidities, and virological failure. The main criterion for the effectiveness of the scheme was the proportion of patients with an undetectable level of viral load at 48 weeks of treatment. Additional criteria for evaluating the effectiveness and safety of the scheme were the dynamics of the number of CD4-lymphocytes, the frequency and nature of adverse reactions.

Results

Results. The proportion of patients with virologic suppression less than 50 kop/mL was 83% versus 77,3% at the time of switching (p<0.005). The percentage of patients with CD4-lymphocytes level >500 ctlls/um increased from 40,3% to 58%, and the percentage of patients with CD4 level <200 cells/um decrease more than twice from 13% to 6% (p<0.005). The mean level os ALT decreased significantly from 47,52±66,45 units/L to 42,65±55,18 units/L (p=0,019). The average level of total cholesterol decreased by 8.7% from 5,64±1,37 mmol/L to 5.15±0.98 mmol/L (p<0,001). The average BMI after switching to ETR did not change and amounted to 24,07±4,07, 24,2±4,05, respectively (p=0,347).

Conclusions

Conclusions. The results of this study confirm that etravirine is well tolerated and may be an option for patients who have HIV RNA suppression on ART but develop adverse reactions, and may also be part of a second-line ART regimen in patients who fail first-line regimen.

ВИЧ-инфекцияэтравиринвирусологическая и иммунологическая эффективностьметаболические нарушенияHIV infectionetravirinevirological and immunological efficacymetabolic disordersReferencesКлинические рекомендации МЗ РФ «ВИЧ-инфекция у взрослых», 2020 г.Clinical guidelines of the Ministry of Health of the Russian Federation “HIV infection in adults”, 2020US Food and Drug Administration. Etravirine. accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=022187. Accessed August 2, 2021.US Food and Drug Administration. Etravirine. accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=022187. Accessed August 2, 2021.Das K, Clark AD, Jr., Lewi PJ, et al. Roles of conformational and positional adaptability in structure-based design of TMC125-R165335 (etravirine) and related non-nucleoside reverse transcriptase inhibitors that are highly potent and effective against wild-type and drug-resistant HIV-1 variants. Journal of Medicinal Chemistry. 2004;47(10):2550–2560.Das K, Clark AD, Jr., Lewi PJ, et al. Roles of conformational and positional adaptability in structure-based design of TMC125-R165335 (etravirine) and related non-nucleoside reverse transcriptase inhibitors that are highly potent and effective against wild-type and drug-resistant HIV-1 variants. Journal of Medicinal Chemistry. 2004;47(10):2550–2560.Andries K, Azijn H, Thielemans T, et al. TMC125, a novel next-generation nonnucleoside reverse transcriptase inhibitor active against nonnucleoside reverse transcriptase inhibitorresistant human immunodeficiency virus type 1. Antimicrobial Agents and Chemotherapy. 2004;48(12):4680–4686.Andries K, Azijn H, Thielemans T, et al. TMC125, a novel next-generation nonnucleoside reverse transcriptase inhibitor active against nonnucleoside reverse transcriptase inhibitorresistant human immunodeficiency virus type 1. Antimicrobial Agents and Chemotherapy. 2004;48(12):4680–4686.Katlama C, Haubrich R, Lalezari J, et al. Efficacy and safety of etravirine in treatment-experienced, HIV-1 patients: pooled 48 week analysis of two randomized, controlled trials. AIDS. 2009;23(17):2289–2300.Katlama C, Haubrich R, Lalezari J, et al. Efficacy and safety of etravirine in treatment-experienced, HIV-1 patients: pooled 48 week analysis of two randomized, controlled trials. AIDS. 2009;23(17):2289–2300.Katlama C, Clotet B, Mills A, et al. Efficacy and safety of etravirine at week 96 in treatment-experienced HIV type1-infected patients in the DUET-1 and DUET-2 trials. Antiviral Therapy. 2010;15(7):1045–1052.Katlama C, Clotet B, Mills A, et al. Efficacy and safety of etravirine at week 96 in treatment-experienced HIV type1-infected patients in the DUET-1 and DUET-2 trials. Antiviral Therapy. 2010;15(7):1045–1052.Schöller-Gyüre M, Kakuda TN, Raoof A, de Smedt G, Hoetelmans RMW. Clinical pharmacokinetics and pharmacodynamics of etravirine. Clinical Pharmacokinetics. 2009;48(9):561–574.Schöller-Gyüre M, Kakuda TN, Raoof A, de Smedt G, Hoetelmans RMW. Clinical pharmacokinetics and pharmacodynamics of etravirine. Clinical Pharmacokinetics. 2009;48(9):561–574.C. Scott, N. Khatib, M. Bower, B. G. Gazzard, and M. Nelson, “Etravirine use in clinical practice: 48-week data from a single-centre cohort,” Journal of the International AIDS Society, vol. 11, supplement 1, article P49, 2008.C. Scott, N. Khatib, M. Bower, B. G. Gazzard, and M. Nelson, “Etravirine use in clinical practice: 48-week data from a single-centre cohort” Journal of the International AIDS Society, vol. 11, supplement 1, article P49, 2008.P. Echeverria, A. Bonjoch, J. Puig et al., “Pilot study to assess the efficacy and safety of switching protease inhibitor to once-daily etravirine in HIV-infected subjects with viral suppression (ETRA-SWITCH STUDY),” in Proceedings of the International Conference on Antimicrobial Agents and Chemotherapy (ICAAC ‘11), September 2011.P. Echeverria, A. Bonjoch, J. Puig et al., “Pilot study to assess the efficacy and safety of switching protease inhibitor to once-daily etravirine in HIV-infected subjects with viral suppression (ETRA-SWITCH STUDY),” in Proceedings of the International Conference on Antimicrobial Agents and Chemotherapy (ICAAC ‘11), September 2011.P. Monteiro, I. Perez, M. Laguno et al., “Dual therapy with etravirine plus raltegravir for virologically suppressed HIV-infected patients: a pilot study” Journal of Antimicrobial Chemotherapy, vol. 69, no. 3, pp. 742–748, 2014.P. Monteiro, I. Perez, M. Laguno et al., “Dual therapy with etravirine plus raltegravir for virologically suppressed HIV-infected patients: a pilot study,” Journal of Antimicrobial Chemotherapy, vol. 69, no. 3, pp. 742–748, 2014.R. Calin, L. Paris, A. Simon et al., “Dual raltegravir/etravirine combination in virologically suppressed HIV-1-infected patients on antiretroviral therapy,” Antiviral Therapy, vol. 17, no. 8, pp. 1601–1604, 2012.R. Calin, L. Paris, A. Simon et al., “Dual raltegravir/etravirine combination in virologically suppressed HIV-1-infected patients on antiretroviral therapy,” Antiviral Therapy, vol. 17, no. 8, pp. 1601–1604, 2012.S. Nozza, L. Galli, F. Visco et al., “Raltegravir, maraviroc, etravirine: an effective protease inhibitor and nucleoside reverse transcriptase inhibitor-sparing regimen for salvage therapy in HIV-infected patients with triple-class experience,” AIDS, vol. 24, no. 6, pp. 924–928, 2010.S. Nozza, L. Galli, F. Visco et al., “Raltegravir, maraviroc, etravirine: an effective protease inhibitor and nucleoside reverse transcriptase inhibitor-sparing regimen for salvage therapy in HIV-infected patients with triple-class experience,” AIDS, vol. 24, no. 6, pp. 924–928, 2010.Vingerhoets J, Tambuyzer L, Azijn H, et al. Resistance profile of etravirine: combined analysis of baseline genotypic and phenotypic data from the randomized, controlled Phase III clinical studies. AIDS. 2010;24:503-514.Vingerhoets J, Tambuyzer L, Azijn H, et al. Resistance profile of etravirine: combined analysis of baseline genotypic and phenotypic data from the randomized, controlled Phase III clinical studies. AIDS. 2010;24:503-514.Stamler J, Wentworth D, Neaton JD. Is relationship between serum cholesterol and risk of premature death from coronary heart disease continuous and graded? Findings in 356,222 primary screenees of the multiple risk factor intervention trial (MRFIT) JAMA. 1986;256(20):2823–2828Stamler J, Wentworth D, Neaton JD. Is relationship between serum cholesterol and risk of premature death from coronary heart disease continuous and graded? Findings in 356,222 primary screenees of the multiple risk factor intervention trial (MRFIT) JAMA. 1986;256(20):2823–2828Barragan P, Fisac C, Podzamczer D. Switching strategies to improve lipid profile and morphologic changes. AIDS Rev. 2006;8(4):191–203Barragan P, Fisac C, Podzamczer D. Switching strategies to improve lipid profile and morphologic changes. AIDS Rev. 2006;8(4):191–203Whitcomb JM, Parkin NT, Chappey C, Hellmann NS and Petropoulos CJ. Broad nucleoside reverse-transcriptase inhibitor cross-resistance in human immunodeficiency virus type 1 clinical isolates. J Infect Dis 2003.Whitcomb JM, Parkin NT, Chappey C, Hellmann NS and Petropoulos CJ. Broad nucleoside reverse-transcriptase inhibitor cross-resistance in human immunodeficiency virus type 1 clinical isolates. J Infect Dis 2003.Madruga JV, Cahn P, Grinsztejn B, et al. Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1-infected patients in DUET-1: 24-week results from a randomized, double-blind, placebo-controlled trial. Lancet. 2007;370:29-38.Madruga JV, Cahn P, Grinsztejn B, et al. Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1-infected patients in DUET-1: 24-week results from a randomized, double-blind, placebo-controlled trial. Lancet. 2007;370:29-38.Lazzarin A, Campbell T, Clotet B, et al. Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1-infected patients in DUET-2: 24-week results from a randomised, double-blind, placebo-controlled trial. Lancet. 2007;370:39-48Lazzarin A, Campbell T, Clotet B, et al. Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1-infected patients in DUET-2: 24-week results from a randomised, double-blind, placebo-controlled trial. Lancet. 2007;370:39-48Katlama C, Haubrich R, Lalezari J, et al. Efficacy and safety of etravirine in treatment-experienced, HIV-1 patients: pooled 48 week analysis of two randomized, controlled trials. AIDS. 2009;23(17):2289–2300.Katlama C, Haubrich R, Lalezari J, et al. Efficacy and safety of etravirine in treatment-experienced, HIV-1 patients: pooled 48 week analysis of two randomized, controlled trials. AIDS. 2009;23(17):2289–2300.

The authors declare that there are no conflicts of interest present.