Efficacy and safety of antiretroviral therapy regimens containing etravirine for HIV-infected patients


Kravchenko A.V., Kanestri V.G., Gankina N.Yu.

1Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Welfare, Moscow; 2Krasnoyarsk Territorial Center for Prevention and Control of AIDS and Communicable Diseases
The paper gives the results of a number of studies (DUET, TRIO, and others) that demonstrate the virological and immunological efficacies and safety of antiretroviral treatment (ART) regimens containing etravirine (ETR) for patients who have been previously treated with ART and had drug- or multidrug-resistant HIV. The SENSE study shows that Grade 1–4 neuropsychiatric adverse events (AEs) are significantly less frequently recorded in patients taking ETR than in those receiving efavirenz. There are two clinical examples of successfully switching patients to an ETR-containing ART regimen for previous treatment-emergent AEs. Based on both the results of foreign studies and own findings, the authors establish that ETR used in the ART regimens in patients with HIV/CHC co-infection, including in those treated for CHC with Peg, IFN, and ribavirin, is effective and safe. Elevated Al/AT levels in some patients suggest the activity of CHC or its inadequate treatment efficiency rather than the hepatotoxicity of an ABT regimen containing ETR. The performed investigations provide a rationale for the use of ETR as part in the ART regimens in case of both previous treatment failure and current treatment-emergent AEs, as well as in patients with HIV/CHC co-infection.

Literature



  1. Покровский В.В., Юрин О.Г., Кравченко А.В., Беляева В.В., Канестри В.Г., Афонина Л.Ю., Ермак Т.Н., Буравцова Е.В., Шахгильдян В.И., Козырина Н.В., Нарсия Р.С., Зимина В.Н., Покровская А.В., Ефремова О.С. Протоколы диспансерного наблюдения и лечения больных ВИЧ-инфекцией. Эпидемиол. инфекц. болезни. Актуал. вопр. 2014; 6 (приложение). 48 с.

  2. Wit F.W., Weverling G.J., Weel J. Incidence of and risk factors for severe hepatotoxicity associated with antiretroviral combination therapy. J. Infect. Dis. 2002; 186: 23–31.

  3. Mauelshagen A., Horst H., Stellbrink H., Hoffmann C. Long-term safety and tolerability of nevirapine and efavirenz-containing regimens in HIV/HCV-co-infected patients. J. Int. AIDS Soc. 2012; 15(6): 18416. doi: 10.7448/IAS.15.6.18416.

  4. Croxlall D.J. Etravirine. A review of its use in the Management of Treatment-Experienced Patients with HIV-1 Infection. AIDS 2012; 72 (6): 847–869.

  5. Katlama C., Cloter B., Mills A. Efficacy and safety of etravirine at week 96 in treatment-experienced HIV type-1-infected patients in the DUET-1 and DUET-2 trials. Antivir. Ther. 2010; 15(7): 1045–1052.

  6. Clumeck N., Katlama C., Nijs S., Witek J. Safety of etravirine in HIV-1/hepatitis B and/or C virus co-infected patients: pooled 96 week results from the Phase III DUET trials. J. Antimicrob. Chemother. 2010; 65(11): 2450–2454.

  7. Fagard C., Colin C., Charpentier C., Rami A., Jacomet C., Yeni P. Long-term efficacy and safety of raltegravir, etravirine, and darunavir/ritonavir in treatment-experienced patients: week 96 results from the ANRS 139 TRIO trial. J. Acquir. Immune Defic. Syndr. 2012; 59: 489–493.

  8. Nozza S., Galli1 L., Bigoloni A., Gianotti N., Spagnuolo V., Carbone A. Four-year outcome of a PI and NRTI-sparing salvage regimen: maraviroc, raltegravir, etravirine. New Microbiologica 2014; 37: 145–151.

  9. Munoz-Moreno J., Fumaz C., Ferrer M., Gonzalez-Garcia M., Molto J., Negredo E., Clotet B. Neuropsychiatric symptoms associated with efavirenz: prevalence, correlates and management. A neurobehavioral review. AIDS Rev. 2009; 11: 103–109.

  10. Gazzard B., Balkin A., Hill A. Analysis of neuropsychiatric adverse events during clinical trials of efavirenz in antiretroviral-naive patients: a systematic review. AIDS Rev. 2010; 12: 67–75.

  11. Gazzard B., Di Perri G., Furrer H., Domingo P., Hill A., Van Delft Y., Vingerhoets J., Stark T., Marks S. The SENSE trial: etravirine (ETR) shows fever neuropsychiatric adverse events than efavirenz (EFV) in treatment-naïve HIV-1 infected patients. JIAS 2010. Abstract LBPE19.

  12. Waters L., Ftsher M., Winston A., Higgs C., Hadley W., Garvey L., Mandalia S., Perry N., Mackie N., Nelson M. A phase IV, double blind, multi centre, randomized, placebo controlled, pilot study to assess the feasibility of switching individuals receiving efavirenz (EFV) with continuing central nervous system (CNS) adverse events (AE) to etravirine (ETR). JIAS, 2010. Abstract MOPDB103.

  13. Покровский В.В., ред. ВИЧ-инфекция и СПИД. Национальное руководство. М.: ГЭОТАР-Медиа, 2013. 608 с.

  14. Канестри В.Г. Новый ненуклеозидный ингибитор обратной транскриптазы ВИЧ рилпивирин: обзор международных клинических исследований. Эпидемиол. инфекц. болезни. Актуал. вопр. 2012; 3: 54–61.

  15. Casado J.L., Mena A., Banon S., Moreno A., Castro M.A., Perez-Elias M., Pedreira J., Moreno S. Efficacy and safety of etravirine-containing regimens in a large cohort of HIV/HCV coinfected patients according to liver fibrosis. J. Int. AIDS Soc. 2014; 17(4, Suppl 3): 19574.

  16. Ганкина Н.Ю., Кравченко А.В., Куимова У.А., Канестри В.Г. Выбор нуклеозидных ингибиторов в схемах антиретровирусной терапии у больных ВИЧ-инфекцией, получающих лечение хронического гепатита С. Эпидемиол. и инфекц. бол. 2010; 3: 42–46.


About the Autors


For correspondence:
Prof. Kravchenko Aleksey Viktorovich, MD; Leading Researcher, Specialized Research Department of AIDS Epidemiology and Prevention, Central Research Institute of Epidemiology, Russian Inspectorate for the Protection of Consumer Rights and Human Welfare
Address: 15, Eighth Sokolinaya Gora St., Build. 2, Moscow 105275
Telephone: +7(495) 366-05-18
E-mail: kravtchenko@hivrussia.net


Similar Articles


Бионика Медиа