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Kiểm soát virus trong phản ứng với liệu pháp điều trị kháng retrovirus mặc dù có kháng thuốc rộng rãi trong RT của HIV-1 sau thất bại virologic lần đầu tiên
Tóm tắt
Việc kiểm soát vi sinh vật không đầy đủ dẫn đến các đột biến liên quan đến kháng thuốc và là một trở ngại lớn trong việc kiểm soát bệnh. Chúng tôi đã phân tích hồ sơ gen của bệnh nhân HIV-1 vào thời điểm thất bại virologic lần đầu tiên và phản ứng với liệu trình cứu chữa sau 48 tuần. Nghiên cứu này là một nghiên cứu phân tích hồi cứu cắt ngang dựa trên dữ liệu thu thập từ hồ sơ y tế và các xét nghiệm gen trong khoảng thời gian từ 2006 đến 2016. Mẫu nghiên cứu bao gồm dữ liệu của những cá nhân sống với HIV (PLWH) từ ba trung tâm tham khảo chính. Tổng cộng có 184 bệnh nhân đã được đưa vào phân tích dữ liệu. Phân loại virus B là phổ biến nhất (81,3%), cũng như các đột biến codon M184 V/I (85,3%) và K103 (65,8%). Sau 48 tuần khi chuyển sang liệu trình cứu chữa, 67,3% bệnh nhân đạt được tải lượng virus không thể phát hiện. Số lượng đột biến liên quan đến thuốc ức chế men sao chép ngược nucleos(t)ide (NRTI(t)s) không ảnh hưởng đến việc kiểm soát virus (9,3% cho không có đột biến NRTI(t) so với 48,6% cho 1-2 đột biến NRTI(t) so với 42,1% cho ≥3 đột biến NRTI(t), p=0,179). Thời gian điều trị ARV (thời điểm bắt đầu liệu trình ARV đầu tiên cho đến khi genotyping) >36 tháng là yếu tố bảo vệ cho tải lượng virus có thể phát hiện (PR=0,60, 95% CI=0,39–0,92, p=0,020) và là yếu tố nguy cơ cho sự phát triển ≥3 đột biến liên quan đến NRTI(t) (PR=2,43, 95% CI 1,38–4,28, p=0,002). Chúng tôi phát hiện rằng kháng thuốc rộng rãi đối với NRTI(t)s vào thời điểm thất bại virologic lần đầu tiên không ảnh hưởng đến việc kiểm soát virus sau 48 tuần khi chuyển sang liệu pháp thứ hai dựa trên NRTI(t)s cộng với thuốc ức chế protease.
Từ khóa
#HIV #virologic suppression #antiretroviral therapy #NRTI #drug resistanceTài liệu tham khảo
1 Joint United Nations Programme on HIV/AIDS. Global AIDS Update. 2016. http://www.unaids.org/en/topic/treatment. (Accessed Dec 20, 2017).
Strategies for Management of Antiretroviral Therapy (SMART) Study Group, El- Sadr WM, Lundgren J, Neaton JD, et al. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med. 2006;355:2283–96.
Rodger AJ, Cambiano V, Bruun T, et al. PARTNER study group. Sexual activity without condoms and risk of hiv transmission in serodifferent couples when the HIV- positive partner is using suppressive antiretroviral therapy. JAMA. 2016;316(2):171–81.
World Health Organization. HIV drug resistance report 2017. (https://www.who.int/hiv/pub/drugresistance/hivdr-report-2017/en/).
Campbell TB, Smeaton LM, Kumarasamy N, et al. Efficacy and safety of three antiretroviral regimens for initial treatment of HIV-1: a randomized clinical trial in diverse multinational settings. PLoS Med 2012; 9:e1001290. [sPubMed: 22936892].
Tilghman M, Tsai D, Buene TP, et al. Pooled nucleic acid testing to detect antiretroviral treatment failure in HIV-infected patients in Mozambique. J Acquir Immune Defic Syndr. 2015;70:256–261. [PubMed: 26135327].
Joint United Nations Programme on HIV/AIDS. Global AIDS Update. 2016. In:. Accessed 20 Dec 2017.
Brasil. Protocolo Clínico e Diretrizes Terapêuticas para Manejo da Infecção pelo HIV em Adultos. Data de publicação: 03/10/2013. Data última atualização: 31/07/2015. Available at https://www.aids.gov.br/tags/publicacoes/protocolo-clinico-e-diretrizes-terapeuticas. (Accessed 20 Aug 2017).
Brasil. Protocolo Clínico e Diretrizes Terapêuticas para Manejo da Infecção pelo HIVem Adultos. Data de publicação: 2017. Available at www.aids.gov.br/tags/publicacoes/protocolo-clinico-e-diretrizes-terapeuticas. (Accessed 01 Dec 2017).
Matsuda EM, Coelho LP, Romero G, et al. High prevalence of drug resis- tance mutations among patients failing first-line antiretroviral therapy and predictors of virological response 24 weeks after switch to second-line therapy in São Paulo state, Brazil. AIDS Res Hum Retroviruses. 2017;34(2):1–27. http://doi.org/10.1089/aid.2017.0052.
Brites C, Pinto-Neto L, Medeiros M, et al. Extensive variation in drug-resistance mutational profile of Brazilian patients failing antiretroviral therapy in five large Brazilian cities. Braz J Infect Dis. 2016;20(4):323–9.
World Health Organization. Consolidated Guidelines on the use of antiretrovi- ral drugs for treating and preventing HIV infection. https://www.who.int/hiv/pub/arv/treatment-monitoring-info-2017/en/ (Accessed 20 Dec 2017).
Boyd MA, Kumarasamy N, Moore CL, et al. for the second-line study group. Ritonavir-boosted lopinavir plus nucleoside or nucleotide reverse transcriptase inhibitors versus ritonavir-boosted lopinavir plus raltegravir for treatment of HIV-1 infection in adults with virological failure of a standard first-line ART regimen (SECOND-LINE): a randomised, open-label, non-inferiority study. Lancet. 2013;381:2091–9.
Paton NI, Kityo C, Hoppe A, et al. EARNEST trial team. Assessment of second- line antiretroviral regimens for HIV therapy in Africa. N Engl J Med. 2014;371(3):234–47.
La Rosa AM, Harrison LJ, Taiwo B, et al. Raltegravir in second-line antiretroviral therapy in resource-limited settings (SELECT): a randomised, phase 3, non- inferiority study. Lancet HIV. 2016;3:e247–58.
2017 Resistance Mutations Update. Volume 24, Issue 4, Dec. 2016/January 2017. Available at https://www.iasusa.org/sites/default/files/uploads/2017hiv-muta-article.pdf. Accessed in 01/20/2017.
Cavalcanti AM, Lacerda HR, Brito AM, et al. Antiretroviral resistance in individuals presenting therapeutic failure and subtypes of the human immunodeficiency virus type 1 in the northeast region of Brazil. Mem Inst Oswaldo Cruz. 2007;102:785–92.
Lacerda HR, Medeiros LB, Cavalcanti AM, et al. Comparison of the epidemi- ology, profile of mutations, and clinical response to antiretrovirals among subtypes B and F of the human immunodeficiency virus type 1. Mem Inst Oswaldo Cruz. 2007;102:693–9.
Lima K, de Souza Leal É, AMS C, Salustiano DM, de Medeiros LB, da Silva SP, et al. Epidemiological, Clinical and Antiretroviral Susceptibility Characterization of Human Immunodeficiency Virus Subtypes B and Non-B in Pernambuco, Northeast Brazil. PLoS One. 2016;11(5):e0155854.
Kanters S, Socias ME, Paton NI, et al. Comparative efficacy and safety of second- line antiretroviral therapy for treatment of HIV/AIDS: a systematic review and network meta-analysis. The Lancet HIV. 2017;3018(17):1–9.
Gräf T, Vrancken B, Maletich Junqueira D, et al. Contribution of epidemiological predictors in unraveling the phylogeographic history of HIV-1 subtype C in Brazil. J Virol. 2015;89:12341–8.
Velasco-de-Castro CA, Grinsztejn B, Veloso VG, et al. HIV-1 diversity and drug resistance mutations among people seeking HIV diagnosis in voluntary counseling and testing sites in Rio de Janeiro, Brazil. PLoS One. 2014;9(1):e87622.
Miller MD, Margot N, Lu B, Zhong L, et al. Genotypic and phenotypic predictors of the magnitude of response to tenofovir disoproxil fumarate treatment in antiretroviral- experienced patients. J Infect Dis. 2004;189(5):837–46.
Melikian GL, Rhee SY, Taylor J, et al. Standardized comparison of the relative impacts of HIV-1 reverse transcriptase (RT) mutations on nucleoside RT inhibitor susceptibility. Antimicrob Agents Chemother. 2012;56(5):2305–13.
Lopes CA, Soares MA, Falci DR, Sprinz E. The evolving genotypic profile of HIV- 1 mutations related to antiretroviral treatment in the north region of Brazil. Biomed Res Int. 2015;2015:738528e.
Hamers RL, Sigaloff KC, Wensing AM, et al. PharmAccess African studies to evaluate resistance (PASER). Patterns of HIV-1 drug resistance after first-line antiretroviral therapy (ART) failure in 6 sub-Saharan African countries: implications for second-line ART strategies. Clin Infect Dis. 2012;54(11):1660–9.
Sivamalar S, Dinesha TR, Gomathi S, et al. Accumulation of HIV-1 drug resistance mutations after first-line immunological failure to evaluate the options of recycling NRTI drugs in second-line treatment: a study from South India. AIDS Res Hum Retrovir. 2017;33(3):271–4.
The TenoRes Study Group. Global epidemiology of drug resistance after failure of WHO recommended fi rst-line regimens for adult HIV-1 infection: a multicentre retrospective cohort study. Lancet Infect Dis. 2016;16:565–75.
Ford N, Shubber Z, Hill A, et al. Comparative efficacy of lamivudine and Emtricitabine: a systematic review and meta-analysis of randomized trials. PLoS One. 2013;8(11):e79981.
Von Wyl V, Yerly S, Böni J, et al. Swiss HIV cohort study. Incidence of HIV-1 drug resistance among antiretroviral treatment-naive individuals starting modern therapy combinations. Clin Infect Dis. 2012;54(1):131–40.
Van Zyl GU, Liu TF, Claassen M, Engelbrecht S, et al. Trends in genotypic HIV-1 antiretroviral resistance between 2006 and 2012 in south African patients receiving first and second-line antiretroviral treatment regimens. PLoS One. 2013;8(6):e67188.
Stevens WS, Wallis CL, Sanne I, Venter F. Will etravirine work in patients failing nonnucleoside reverse transcriptase inhibitor-based treatment in southern Africa? J Acquir Immune Defic Syndr. 2009;52(5):655–6.
Kiertiburanakul S, Wiboonchutikul S, Sukasem C, Chantratita W, Sungkanu- parph S. Using of nevirapine is associated with intermediate and reduced response to etravirine among HIV-infected patients who experienced virologic failure in a resource- limited setting. J Clin Virol. 2010;47(4):330–4.
Taiwo B, Chaplin B, Penugonda S, et al. Suboptimal Etravirine activity is common during failure of Nevirapine-based combination antiretroviral therapy in a cohort infected with non-B subtype HIV-1. Curr HIV Res. 2010;8(3):194–8.
Paton, N, Kityo, C, Thompson, J, et al. Impact of NRTI cross-resistance on second-line PI + NRTI therapy outcomes in Africa; Conference on Retrovirus and Opportunistic Infections; Seattle, WA, USA. Feb 23–26, 2015;119 (abstr).
Lam EP, Moore CL, Gotuzzo E, et al. Antiretroviral resistance ater first-line anti- retroviral therapy failure in diverse HIV-1 subtypes in the SECOND-LINE study. AIDS Res Hum Retrovir. 2016;32:841–50.
Cozzi-Lepri A, Phillips AN, Martinez-Picado J, et al. EuroSIDA study group. Rate of accumulation of thymidine analogue mutations in patients continuing to receive virologically failing regimens containing zidovudine or stavudine: implications for antiretroviral therapy programs in resource-limited settings. J Infect Dis. 2009;200(5):687–97.
Molina JM, Cohen C, Katlama C, Grinsztejn B, Timerman A, Pedro RD. et al.Safety and efficacy of darunavir (TMC114) with low-dose ritonavir in treatment- experienced patients: 24-week results of POWER 3. J Acquir Immune Defic Syndr. 2007;46:24–31.
Grinsztejn B, Nguyen B-Y, Katlama C, et al. For the Protocol 005Team. Safety and efficacy of the HIV-1 integrase inhibitor raltegravir (MK-0518) in treatment- experienced patients with multidrug-resistant virus: a phase II randomised controlled trial. Lancet. 2007;369:1261–9.
Duani H, Aleixo AW, Tupinambás U. Trends and predictors of HIV-1 acquired drug resistance in Minas Gerais, Brazil: 2002-2012. Braz J Infect Dis. 2017;21(2):148–54.
Nucleoside reverse-transcriptase inhibitor cross-resistance and outcomes from second-line antiretroviral therapy in the public health approach: an observational analysis within the randomised, open-label, EARNEST trial.
Horizons/Population Council, International Centre for Reproductive Health and Coast Province General Hospital, Mombasa-Kenya. Adherence to Antiretroviral Therapy in Adults: A Guide for Trainers. Nairobi: Population Council. 2004. Available from: http://www.popcouncil.org/uploads/pdfs/horizons/mombasaarvtrainingguide.pdf. Accessed 6 Feb 2018.
Shigdel R, Klouman E, Bhandari A, et al. Factors associated with adherence to antiretroviral therapy in HIV-infected patients in Kathmandu District, Nepal. HIV AIDS (Auckl). 2014;6:109–16.
Vandenhende MA, Ingle S, May M, et al. Impact of low-level viremia on clinical and virological outcomes in treated HIV-1-infected patients: the antiretroviral therapy cohort collaboration (ART-CC). AIDS. 2015;29(3):373–83.