154 AIDS, ðóññêîå èçäàíèå, 2009, òîì 2, N¹ 2 A. Carr, J. AminBristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline,Merck <strong>и</strong> Roche; спонсорск<strong>и</strong>е пожертвован<strong>и</strong>я на проведен<strong>и</strong>елекц<strong>и</strong>й от компан<strong>и</strong>й Abbott, Boehringer-Ingelheim,Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline,Merck <strong>и</strong> Roche; а также являлся членом консультат<strong>и</strong>вногосовета компан<strong>и</strong>й Abbott, Bristol-Myers Squibb,Gilead Sciences, GlaxoSmithKline, Merck <strong>и</strong> Roche.Janaki Amin заявляет об отсутств<strong>и</strong><strong>и</strong> конфл<strong>и</strong>кта <strong>и</strong>нтересов.Австрал<strong>и</strong>йск<strong>и</strong>й нац<strong>и</strong>ональный центр эп<strong>и</strong>дем<strong>и</strong>олог<strong>и</strong><strong>и</strong><strong>ВИЧ</strong> <strong>и</strong> кл<strong>и</strong>н<strong>и</strong>ческ<strong>и</strong>х <strong>и</strong>сследован<strong>и</strong>й (NationalCentre in HIV Epidemiology and Clinical Research) существуетпр<strong>и</strong> поддержке Австрал<strong>и</strong>йского департаментаздравоохранен<strong>и</strong>я <strong>и</strong> проблем старен<strong>и</strong>я (CommonwealthDepartment of Health and Aging). Andrew Carr получалст<strong>и</strong>пенд<strong>и</strong>ю, предоставленную Австрал<strong>и</strong>йск<strong>и</strong>м советомпо <strong>и</strong>сследован<strong>и</strong>ям в област<strong>и</strong> мед<strong>и</strong>ц<strong>и</strong>ны <strong>и</strong> здравоохранен<strong>и</strong>я(Australian National Health and Medical ResearchCouncil).Ëèòåðàòóðà1. World Health Organization. 2006 Antiretroviral therapy for HIVinfection in adults and adolescents: recommendations for a publichealth approach — 2006 revision. Accessed on 5 July 2008. http://www.who.int/<strong>hiv</strong>/pub/guidelines/artadultguidelines.pdf.2. Panel on Antiretroviral Guidelines for Adult and Adolescents, Departmentof Health and Human Services. 29 January 2008. Guidelinesfor the use of antiretroviral agents in HIV-infected adults andadolescents. Accessed on 5 July 2008. http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf.3. Hammer SM, Saag MS, Schechter M, et al., International AIDS Society— USA panel. Treatment for adult HIV infection: recommendationsof the International AIDS Society — USA Panel. JAMA 2006;296:827–843.4. Gazzard B, Bernard AJ, Boffito M, et al., Writing Committee, BritishHIV Association. British HIV Association (BHIVA) guidelines forthe treatment of HIV-infected adults with antiretroviral therapy. HIVMed 2006; 7:487–503.5. European AIDS Clinical Society. Guidelines for the clinical managementand treatment of HIV-infected adults in Europe. Accessed on 5July 2008. http://www.eacs.eu/guide/index.htm.6. Yazdanpanah Y, Sissoko D, Egger M, et al. Clinical efficacy of antiretroviralcombination therapy based on protease inhibitors or nonnucleosideanalogue reverse transcriptase inhibitors: indirect comparisonof controlled trials. BMJ 2004; 328:249–<strong>25</strong>5; doi: 10.1136/bmj.37995.435787.A6.7. Chou R, Fu R, Huffman LH, Korthuis PT. Initial highly-active antiretroviraltherapy with a protease inhibitor versus a non-nucleosidereverse transcriptase inhibitor: discrepancies between direct and indirectmeta-analyses. Lancet 2006; 368:1503–1515.8. Bartlett JA, Fath MJ, DeMasi R, et al. An updated, systematic overviewof triple combination therapy in antiretroviral-naive, HIV-infectedadults. AIDS 2006; 20:2051–2064.9. May M, Sterne JA, Sabin C, et al., Antiretroviral Therapy CohortCollaboration. Antiretroviral Therapy (ART) Cohort Collaboration.Prognosis of HIV-1-infected patients up to 5 years after initiation ofHAART: collaborative analysis of prospective studies. AIDS 2007;21:1185–1197.10. Maggiolo F, Ripamonti D, Gregis G, et al. Once-a-day therapy forHIV infection: a controlled, randomised study in antiretroviral-naiveHIV-1-infected patients. Antiviral Ther 2003; 8:339–346.11. Maggiolo F, Migliorino M, Maserati R, et al., Once Study Group.Virological and immunological responses to a once-a-day antiretroviralregimen with didanosine, lamivudine and efavirenz. AntiviralTher 2002; 6:249–<strong>25</strong>3.12. U.S. Department of Health and Human Services Food and D<strong>ru</strong>gAdministration Center for D<strong>ru</strong>g Evaluation and Research (CDER).Guidance for industry. Antiretroviral d<strong>ru</strong>gs using plasma HIV RNAmeasurements: clinical considerations for accelerated and traditionalapproval. Accessed on 5 July 2008. http://www.fda.gov/cder/guidance/3647fnl.pdf.13. Building models stepwise. In: Practical statistics for medical research.Altman DG, Chapman and Hall, London; 1991. pp. 340–351.14. Sterne JAC, Egger M, Davey Smith G. Investigating and dealing withpublication and other biases in meta-analysis. BMJ 2001; 323:101–105.15. Mocroft A, Ledergerber B, Zilmer K, et al., EuroSIDA study group andthe Swiss HIV Cohort Study. Short-term clinical disease progressionin HIV-1-positive patients taking combination antiretroviral therapy:the EuroSIDA risk-score. AIDS 2007; 21:1867–1875.16. Lactic Acidosis International Study Group. Risk factors for lactic acidosisand severe hyperlactataemia in HIV-1-infected adults exposedto antiretroviral therapy. AIDS 2007; 21:2455–2464.17. Berenguer J, Gonzalez J, Ribera E, et al. Didanosine, lamivudine andefavirenz vs zidovudine and efavirenz, for initial treatment of HIVinfection over 48 weeks: a randomised, noninferiority clinical trial,GESIDA. In: Abstracts of the 46th International Conference on AntimicrobialAgents and Chemotherapy, Chicago, USA, September,2007, Abstract 383.18. Carr A, Cooper DA. Adverse effects of antiretroviral therapy. Lancet2000; 356:1423–1430.19. Friis-Moller N, Sabin CA, Weber R, et al., Data Collection on AdverseEvents of Anti-HIV D<strong>ru</strong>gs (DAD) Study Group. Combinationantiretroviral therapy and the risk of myocardial infarction. N Engl JMed 2003; 349:1993–2003.20. Strategies for Management of Anti-Retroviral Therapy Study Group.CD4R count-guided inter<strong>ru</strong>ption of antiretroviral treatment. N Engl JMed 2006; 355:2283–2296.21. Baker J, Peng G, Rapkin J, et al., Terry Beirn Community Programsfor Clinical Research on AIDS (CPCRA). CD4R count and risk of non-AIDS diseases following initial treatment for HIV infection. AIDS2008; 22:841–848.22. Mallal S, Phillips E, Carosi G, et al. PREDICT-1 Study Team. HLA-BM5701 screening for hypersensitivity to abacavir. N Engl J Med2008; 358:568–579.23. Sax P, Tierney C, Collier A, et al. ACTG 5202: shorter time to virologicfailure (VF) with abacavir/lamivudine (ABC/3TC) than tenofovir/emtricitabine(TDF/FTC) as part of combination therapy in treatment-naivesubjects with screening HIV RNA ≥ 100,000 c/mL. In:Abstracts of the 17th — International AIDS Conference, 3–8 August2008, Mexico City, Mexico, Abstract THAB0303.
ÊËÈÍÈ×ÅÑÊÈÅ ÈÑÑËÅÄÎÂÀÍÈßÊîíöåíòðàöèÿ èíãèáèòîðîâ ïðîòåàçû â âîëîñàõñëóæèò ÷åòêèì ïðîãíîñòè÷åñêèì ôàêòîðîìâèðóñîëîãè÷åñêîãî îòâåòà íà ëå÷åíèå.ÐåôåðàòMonica Gandhi a , Niloufar Ameli b , Peter Bacchetti c , Stephen J. Gange d ,Kathryn Anastos e , Alexandra Levine f,g , Charles L. Hyman h , MardgeCohen i , Mary Young j , Yong Huang b , Ruth M. Greenblatt a,b,c, äëÿêîîïåðèðîâàííîãî èññëåäîâàíèÿ WIHSЦель. Есл<strong>и</strong> в с<strong>и</strong>лу поведенческ<strong>и</strong>х <strong>и</strong> б<strong>и</strong>олог<strong>и</strong>ческ<strong>и</strong>х обстоятельств соблюден<strong>и</strong>е реж<strong>и</strong>ма ант<strong>и</strong>ретров<strong>и</strong>руснойтерап<strong>и</strong><strong>и</strong> нарушается, лечен<strong>и</strong>е терп<strong>и</strong>т неудачу. В настоящее время методы оценк<strong>и</strong>соблюден<strong>и</strong>я реж<strong>и</strong>ма ант<strong>и</strong>ретров<strong>и</strong>русной терап<strong>и</strong><strong>и</strong> огран<strong>и</strong>чены. Концентрац<strong>и</strong>я ант<strong>и</strong>ретров<strong>и</strong>русныхпрепаратов в волосах отражает сывороточную концентрац<strong>и</strong>ю препарата на протяжен<strong>и</strong><strong>и</strong> нескольк<strong>и</strong>хнедель <strong>и</strong> месяцев <strong>и</strong> может быть новым прогност<strong>и</strong>ческ<strong>и</strong>м фактором ответа на лечен<strong>и</strong>е.Методы. Коопер<strong>и</strong>рованное <strong>и</strong>сследован<strong>и</strong>е WIHS (Women’s Interagency HIV Study) — проспект<strong>и</strong>вноекогортное <strong>и</strong>сследован<strong>и</strong>е с участ<strong>и</strong>ем <strong>ВИЧ</strong>-<strong>и</strong>нф<strong>и</strong>ц<strong>и</strong>рованных женщ<strong>и</strong>н с целью разработк<strong>и</strong> <strong>и</strong>оценк<strong>и</strong> методов <strong>и</strong>змерен<strong>и</strong>я содержан<strong>и</strong>я часто <strong>и</strong>спользуемых <strong>и</strong>нг<strong>и</strong>б<strong>и</strong>торов протеазы (лоп<strong>и</strong>нав<strong>и</strong>р/р<strong>и</strong>тонав<strong>и</strong>р <strong>и</strong> атазанав<strong>и</strong>р) в малых образцах волос. Мы <strong>и</strong>сследовал<strong>и</strong> связь между концентрац<strong>и</strong>ей<strong>и</strong>нг<strong>и</strong>б<strong>и</strong>торов протеазы в волосах <strong>и</strong> начальным в<strong>и</strong>русолог<strong>и</strong>ческ<strong>и</strong>м ответом на лечен<strong>и</strong>е с помощьюмодел<strong>и</strong> многофакторной лог<strong>и</strong>ст<strong>и</strong>ческой регресс<strong>и</strong><strong>и</strong>.Результаты. Концентрац<strong>и</strong>я ант<strong>и</strong>ретров<strong>и</strong>русных препаратов в волосах была четко <strong>и</strong> незав<strong>и</strong>с<strong>и</strong>моот друг<strong>и</strong>х факторов связана с ответом на лечен<strong>и</strong>е у 224 женщ<strong>и</strong>н, проход<strong>и</strong>вш<strong>и</strong>х лечен<strong>и</strong>е схемойна основе новых <strong>и</strong>нг<strong>и</strong>б<strong>и</strong>торов протеазы. Для участн<strong>и</strong>ц, начавш<strong>и</strong>х лечен<strong>и</strong>е лоп<strong>и</strong>нав<strong>и</strong>ром/р<strong>и</strong>тонав<strong>и</strong>ром,отношен<strong>и</strong>е шансов для подавлен<strong>и</strong>я в<strong>и</strong>руса состав<strong>и</strong>ло 39,8 (95%-й довер<strong>и</strong>тельный <strong>и</strong>нтервал2,8–564) у женщ<strong>и</strong>н, у которых уровень лоп<strong>и</strong>нав<strong>и</strong>ра наход<strong>и</strong>лся в самом высоком кварт<strong>и</strong>ле(> 1,9 нг/мг), по сравнен<strong>и</strong>ю с пац<strong>и</strong>енткам<strong>и</strong>, у которых уровень препарата был в н<strong>и</strong>жнем кварт<strong>и</strong>ле(< 0,41 нг/мг), пр<strong>и</strong> коррекц<strong>и</strong><strong>и</strong> по так<strong>и</strong>м факторам, как самооценка соблюден<strong>и</strong>я реж<strong>и</strong>ма терап<strong>и</strong><strong>и</strong>,возраст, раса, начальная в<strong>и</strong>русная нагрузка, ч<strong>и</strong>сло л<strong>и</strong>мфоц<strong>и</strong>тов CD4 <strong>и</strong> лечен<strong>и</strong>е <strong>и</strong>нг<strong>и</strong>б<strong>и</strong>торам<strong>и</strong>протеазы в анамнезе. У женщ<strong>и</strong>н, получавш<strong>и</strong>х атазанав<strong>и</strong>р, скоррект<strong>и</strong>рованное отношен<strong>и</strong>ешансов в<strong>и</strong>русолог<strong>и</strong>ческого ответа состав<strong>и</strong>ло 7,7 (95%-й довер<strong>и</strong>тельный <strong>и</strong>нтервал 2,0–29,7) дляучастн<strong>и</strong>ц <strong>и</strong>з верхнего кварт<strong>и</strong>ля (> 3,4 нг/мг) по сравнен<strong>и</strong>ю с пац<strong>и</strong>енткам<strong>и</strong> <strong>и</strong>з н<strong>и</strong>жнего кварт<strong>и</strong>ля(< 1,2 нг/мг).Выводы. Концентрац<strong>и</strong>я <strong>и</strong>нг<strong>и</strong>б<strong>и</strong>торов протеазы в образцах волос была четк<strong>и</strong>м, не зав<strong>и</strong>сящ<strong>и</strong>м отдруг<strong>и</strong>х факторов пред<strong>и</strong>ктором в<strong>и</strong>русолог<strong>и</strong>ческого успеха лечен<strong>и</strong>я у разнородной группы <strong>ВИЧ</strong><strong>и</strong>нф<strong>и</strong>ц<strong>и</strong>рованныхвзрослых. Этот не<strong>и</strong>нваз<strong>и</strong>вный метод оценк<strong>и</strong> соблюден<strong>и</strong>я реж<strong>и</strong>ма ант<strong>и</strong>ретров<strong>и</strong>руснойтерап<strong>и</strong><strong>и</strong> может быть особенно ценен в услов<strong>и</strong>ях огран<strong>и</strong>ченных ресурсов в связ<strong>и</strong> с простотойполучен<strong>и</strong>я <strong>и</strong> хранен<strong>и</strong>я образцов волос для <strong>и</strong>сследован<strong>и</strong>я.© 2009 Wolters Kluwer Health / Lippincott Williams & WilkinsAIDS 2009, 23:471–478aDepartment of Medicine; b Department of Clinical Pharmacy; c Department of Epidemiology/Biostatistics, University of California, SanFrancisco, San Francisco, California; d Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland; e Departmentof Medicine, Albert Einstein College of Medicine, Bronx, New York; f Department of Medicine, University of Southern California;gCity of Hope National Medical Center, Los Angeles, California; h Department of Medicine, SUNY Downstate Medical Center, Brooklyn,New York; i Cook County Bureau of Health Services, Chicago, Illinois; j Department of Medicine, Georgetown University MedicalCenter, Washington DC, USA.155
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