HIV-2型感染流行病学诊疗方案及防控策略
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摘要
艾滋病病毒(HIV)包含HIV-1和HIV-2两种类型。到目前为止,在HIV感染的临床筛查中,发现的感染类型绝大多数为HIV-1型,极少数为HIV-2型。国外HIV-2型主要集中在西非地区,我国偶有发现HIV-2型的感染病例。由于临床中遇到的HIV-2型感染病例数较少,所以对HIV的研究多集中在了HIV-1型上。随着全球化的推进和人员交流日益频繁,HIV-2型感染的风险正在不断增加,临床上遇到的HIV-2型感染病例也会增加,应引起科研人员和临床医生足够的重视。本文从HIV-2型感染的流行病学、诊断方案及抗病毒防治措施等几个方面进行探讨,以期为我国HIV-2型的预防及诊治策略的制定提供参考意见。
Human immunodeficiency virus(HIV) is divided into two types, HIV-1 and HIV-2. To date, HIV-1 has accounted predominately in the clinical screening of HIV infection, while there are few cases of HIV-2 discovered. HIV-2 isolate is mainly prevalent in the West Africa, and its infection has occasionally been found in China. Because of the small number of HIV-2 infections encountered in the clinic, the researches mainly focus on HIV-1. However, the globalization is accelerating exchanges around the world and the risk of HIV-2 infection is increasing. Therefore, there will be an increase in the number of HIV-2-infected patients, which should get sufficient attention by researchers and clinicians. This article will review the epidemiology, diagnosis, antiretroviral treatment of HIV-2, in order to provide advice for prevention and therapeutic strategies against HIV-2 infection in China.
Human immunodeficiency virus(HIV) is divided into two types, HIV-1 and HIV-2. To date, HIV-1 has accounted predominately in the clinical screening of HIV infection, while there are few cases of HIV-2 discovered. HIV-2 isolate is mainly prevalent in the West Africa, and its infection has occasionally been found in China. Because of the small number of HIV-2 infections encountered in the clinic, the researches mainly focus on HIV-1. However, the globalization is accelerating exchanges around the world and the risk of HIV-2 infection is increasing. Therefore, there will be an increase in the number of HIV-2-infected patients, which should get sufficient attention by researchers and clinicians. This article will review the epidemiology, diagnosis, antiretroviral treatment of HIV-2, in order to provide advice for prevention and therapeutic strategies against HIV-2 infection in China.
引文
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[2] UNAIDS.90-90-90:an ambitious treatment target to help end the AIDS epidemic[EB/OL] (2018).[2019-04-19].http://www.unaids.org/en/resources/909090,2018.
[3] Gottlieb GS,Raugi DN,Smith RA.90-90-90 for HIV-2 Ending the HIV-2 epidemic by enhancing care and clinical management of patients infected with HIV-2[J].Lancet HIV,2018,5(7):e390-e399.
[4] 中华医学会感染病学分会艾滋病丙型肝炎学组,中国疾病预防控制中心.中国艾滋病诊疗指南(2018版)[J].中国艾滋病性病,2018,24(12):1266-1282.
[5] 严延生,郑兆双,陈舸,等.福建发现首例HIV-2感染者[J].海峡预防医学杂志,1999,5(1):6-7.
[6] 彭瑾瑜,郑军,贺健梅,等.湖南省首次诊断2例非输入性HIV-2感染病例与流行病学个案调查[J].中华流行病学杂志,2018,39(8):1077-1081.
[7] Clavel F,Mansinho K,Chamaret S,et al.Human immunodeficiency virus type 2 infection associated with AIDS in West Africa[J].N Engl J Med,1987,316(19):1180-1185.
[8] Clavel F,Guetard D,Brun-Vezinet F,et al.Isolation of a new human retrovirus from West African patients with AIDS[J].Science,1986,233(4761):343-346.
[9] Visseaux B,Damond F,Matheron S,et al.HIV-2 molecular epidemiology[J].Infect Genet Evol,2016(46):233-240.
[10] Lemey P,Pybus OG,Wang B,et al.Tracing the origin and history of the HIV-2 epidemic[J].Proc Natl Acad Sci USA,2003,100(11):6588-6592.
[11] Raugi DN,Gottlieb GS,Sow PS,et al.HIV-1 outcompetes HIV-2 in dually infected Senegalese individuals with low CD4(+) cell counts[J].AIDS,2013,27(15):2441-2450.
[12] Leonard G,Chaput A,Courgnaud V,et al.Characterization of dual HIV-1 and HIV-2 serological profiles by polymerase chain reaction[J].AIDS,1993,7(9):1185-1189.
[13] Esbjornsson J,Mansson F,Kvist A,et al.Long-term follow-up of HIV-2-related AIDS and mortality in Guinea-Bissau:a prospective open cohort study[J].Lancet HIV,2018 Nov 1.pii:S2352-3018(18)30254-6.[Epub ahead of orint].
[14] Gottlieb GS,Sow PS,Hawes SE,et al.Equal plasma viral loads predict a similar rate of CD4+ T cell decline in human immunodeficiency virus (HIV) type 1-and HIV-2-infected individuals from Senegal,West Africa[J].J Infect Dis,2002,185(7):905-914.
[15] Marlink R,Kanki P,Thior I,et al.Reduced rate of disease development after HIV-2 infection as compared to HIV-1[J].Science,1994,265(5178):1587-1590.
[16] Simon F,Matheron S,Tamalet C,et al.Cellular and plasma viral load in patients infected with HIV-2[J].AIDS,1993,7(11):1411-1417.
[17] van der Loeff MF,Larke N,Kaye S,et al.Undetectable plasma viral load predicts normal survival in HIV-2-infected people in a West African village[J].Retrovirology,2010(7):46.
[18] Honge BL,Jespersen S,Medina C,et al.The challenge of discriminating between HIV-1,HIV-2 and HIV-1/2 dual infections[J].HIV Medicine,2018,19(6):403-410.
[19] Branson BM,Owen SM,Wesolowski LG,et al.Laboratory Testing for the Diagnosis of HIV Infection:Updated Recommendations[J].Atlanta,GA:Centers for Disease Control and Prevention,2014.[Epub ahead of orint].
[20] Chang M,Wong AJ,Raugi DN,et al.Clinical validation of a novel diagnostic HIV-2 total nucleic acid qualitative assay using the Abbott m2000 platform:Implications for complementary HIV-2 nucleic acid testing for the CDC 4th generation HIV diagnostic testing algorithm[J].J Clin Virol,2017(86):56-61.
[21] Lindman J,Honge BL,Kjerulff B,et al.Performance of Bio-Rad HIV-1/2 Confirmatory Assay in HIV-1,HIV-2 and HIV-1/2 dually reactive patients-comparison with INNO-LIA and immunocomb discriminatory assays[J].J Virol Methods,2019(268):42-47.
[22] Parker MM,Bennett SB,Sullivan TJ,et al.Performance of the Alere Determine HIV-1/2 Ag/Ab Combo Rapid Test with algorithm-defined acute HIV-1 infection specimens[J].J Clin Virol,2018(104):89-91.
[23] Matheron S,Descamps D,Gallien S,et al.First-line Raltegravir/Emtricitabine/Tenofovir Combination in Human Immunodeficiency Virus Type 2 (HIV-2) Infection:A Phase 2,Noncomparative Trial (ANRS 159 HIV-2)[J].Clin Infect Dis,2018,67(8):1161-1167.
[24] Menendez-Arias L,Alvarez M.Antiretroviral therapy and drug resistance in human immunodeficiency virus type 2 infection[J].Antiviral Res,2014(102):70-86.
[25] Balestre E,Ekouevi DK,Tchounga B,et al.Immunologic response in treatment-naive HIV-2-infected patients:the IeDEA West Africa cohort[J].Journal of the International Aids Society,2016,19(1):20044.
[26] Benard A,van Sighem A,Taieb A,et al.Immunovirological response to triple nucleotide reverse-transcriptase inhibitors and ritonavir-boosted protease inhibitors in treatment-naive HIV-2-infected patients:The ACHIEV2E Collaboration Study Group[J].Clin Infect Dis,2011,52(10):1257-1266.
[27] Smith RA,Anderson DJ,Pyrak CL,et al.Antiretroviral drug resistance in HIV-2:three amino acid changes are sufficient for classwide nucleoside analogue resistance[J].J Infect Dis,2009,199(9):1323-1326.
[28] Gottlieb GS,Badiane NM,Hawes SE,et al.Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal:implications for HIV-2 treatment in resouce-limited West Africa[J].Clin Infect Dis,2009,48(4):476-483.
[29] Ntemgwa ML,d'Aquin Toni T,Brenner BG,et al.Antiretroviral drug resistance in human immunodeficiency virus type 2[J].Antimicrob Agents Chemother,2009,53(9):3611-3619.
[30] Witvrouw M,Pannecouque C,Switzer WM,et al.Susceptibility of HIV-2,SIV and SHIV to various anti-HIV-1 compounds:implications for treatment and postexposure prophylaxis[J].Antiviral Therapy,2004,9(1):57-65.
[31] Raugi DN,Smith RA,Ba S,et al.Complex patterns of protease inhibitor resistance among antiretroviral treatment-experienced HIV-2 patients from Senegal:implications for second-line therapy[J].Antimicrob Agents Chemother,2013,57(6):2751-2760.
[32] Requena S,Trevino A,Cabezas T,et al.Drug resistance mutations in HIV-2 patients failing raltegravir and influence on dolutegravir response[J].J Antimicrob Chemother,2017,72(7):2083-2088.
[33] Tsiang M,Jones GS,Goldsmith J,et al.Antiviral Activity of Bictegravir (GS-9883),a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile[J].Antimicrob Agents Chemother,2016,60(12):7086-7097.
[34] Smith RA,Raugi DN,Pan C,et al.In vitro activity of dolutegravir against wild-type and integrase inhibitor-resistant HIV-2[J].Retrovirology,2015(12):10.
[35] Roquebert B,Damond F,Collin G,et al.HIV-2 integrase gene polymorphism and phenotypic susceptibility of HIV-2 clinical isolates to the integrase inhibitors raltegravir and elvitegravir in vitro[J].J Antimicrob Chemother,2008,62(5):914-920.
[36] Visseaux B,Hurtado-Nedelec M,Charpentier C,et al.Molecular determinants of HIV-2 R5-X4 tropism in the V3 loop:development of a new genotypic tool[J].J Infect Dis,2012,205(1):111-120.
[37] Trevino A,Cabezas T,Lozano AB,et al.Dolutegravir for the treatment of HIV-2 infection[J].J Clin Virol,2015(64):12-15.
[38] Descamps D,Peytavin G,Visseaux B,et al.Dolutegravir in HIV-2-Infected Patients With Resistant Virus to First-line Integrase Inhibitors From the French Named Patient Program[J].Clin Infect Dis,2015,60(10):1521-1527.
[39] Ba S,Raugi DN,Smith RA,et al.A Trial of a Single-tablet Regimen of Elvitegravir,Cobicistat,Emtricitabine,and Tenofovir Disoproxil Fumarate for the Initial Treatment of Human Immunodeficiency Virus Type 2 Infection in a Resource-limited Setting:48-Week Results From Senegal,West Africa[J].Clin Infect Dis,2018,67(10):1588-1594.
[40] 李敬云.HIV耐药的现状趋势与应对[J].中国艾滋病性病,2018,24(6):635-642.
[41] Desbois D,Roquebert B,Peytavin G,et al.In vitro phenotypic susceptibility of human immunodeficiency virus type 2 clinical isolates to protease inhibitors[J].Antimicrob Agents Chemother,2008,52(4):1545-1548.
[42] Organization WH.Consolidated guidelines on HIV testing services.5Cs:consent,confidentiality,counselling,correct results and connection 2015[EB/OL].(2015)[2019-04-19].http://apps.who.int/iris/handle/10665/179870,2015.
[43] 李敬云.提高对HIV-1急性感染和HIV-2诊断能力的检测策略[J].中国艾滋病性病,2016,22(2):138-140.
[2] UNAIDS.90-90-90:an ambitious treatment target to help end the AIDS epidemic[EB/OL] (2018).[2019-04-19].http://www.unaids.org/en/resources/909090,2018.
[3] Gottlieb GS,Raugi DN,Smith RA.90-90-90 for HIV-2 Ending the HIV-2 epidemic by enhancing care and clinical management of patients infected with HIV-2[J].Lancet HIV,2018,5(7):e390-e399.
[4] 中华医学会感染病学分会艾滋病丙型肝炎学组,中国疾病预防控制中心.中国艾滋病诊疗指南(2018版)[J].中国艾滋病性病,2018,24(12):1266-1282.
[5] 严延生,郑兆双,陈舸,等.福建发现首例HIV-2感染者[J].海峡预防医学杂志,1999,5(1):6-7.
[6] 彭瑾瑜,郑军,贺健梅,等.湖南省首次诊断2例非输入性HIV-2感染病例与流行病学个案调查[J].中华流行病学杂志,2018,39(8):1077-1081.
[7] Clavel F,Mansinho K,Chamaret S,et al.Human immunodeficiency virus type 2 infection associated with AIDS in West Africa[J].N Engl J Med,1987,316(19):1180-1185.
[8] Clavel F,Guetard D,Brun-Vezinet F,et al.Isolation of a new human retrovirus from West African patients with AIDS[J].Science,1986,233(4761):343-346.
[9] Visseaux B,Damond F,Matheron S,et al.HIV-2 molecular epidemiology[J].Infect Genet Evol,2016(46):233-240.
[10] Lemey P,Pybus OG,Wang B,et al.Tracing the origin and history of the HIV-2 epidemic[J].Proc Natl Acad Sci USA,2003,100(11):6588-6592.
[11] Raugi DN,Gottlieb GS,Sow PS,et al.HIV-1 outcompetes HIV-2 in dually infected Senegalese individuals with low CD4(+) cell counts[J].AIDS,2013,27(15):2441-2450.
[12] Leonard G,Chaput A,Courgnaud V,et al.Characterization of dual HIV-1 and HIV-2 serological profiles by polymerase chain reaction[J].AIDS,1993,7(9):1185-1189.
[13] Esbjornsson J,Mansson F,Kvist A,et al.Long-term follow-up of HIV-2-related AIDS and mortality in Guinea-Bissau:a prospective open cohort study[J].Lancet HIV,2018 Nov 1.pii:S2352-3018(18)30254-6.[Epub ahead of orint].
[14] Gottlieb GS,Sow PS,Hawes SE,et al.Equal plasma viral loads predict a similar rate of CD4+ T cell decline in human immunodeficiency virus (HIV) type 1-and HIV-2-infected individuals from Senegal,West Africa[J].J Infect Dis,2002,185(7):905-914.
[15] Marlink R,Kanki P,Thior I,et al.Reduced rate of disease development after HIV-2 infection as compared to HIV-1[J].Science,1994,265(5178):1587-1590.
[16] Simon F,Matheron S,Tamalet C,et al.Cellular and plasma viral load in patients infected with HIV-2[J].AIDS,1993,7(11):1411-1417.
[17] van der Loeff MF,Larke N,Kaye S,et al.Undetectable plasma viral load predicts normal survival in HIV-2-infected people in a West African village[J].Retrovirology,2010(7):46.
[18] Honge BL,Jespersen S,Medina C,et al.The challenge of discriminating between HIV-1,HIV-2 and HIV-1/2 dual infections[J].HIV Medicine,2018,19(6):403-410.
[19] Branson BM,Owen SM,Wesolowski LG,et al.Laboratory Testing for the Diagnosis of HIV Infection:Updated Recommendations[J].Atlanta,GA:Centers for Disease Control and Prevention,2014.[Epub ahead of orint].
[20] Chang M,Wong AJ,Raugi DN,et al.Clinical validation of a novel diagnostic HIV-2 total nucleic acid qualitative assay using the Abbott m2000 platform:Implications for complementary HIV-2 nucleic acid testing for the CDC 4th generation HIV diagnostic testing algorithm[J].J Clin Virol,2017(86):56-61.
[21] Lindman J,Honge BL,Kjerulff B,et al.Performance of Bio-Rad HIV-1/2 Confirmatory Assay in HIV-1,HIV-2 and HIV-1/2 dually reactive patients-comparison with INNO-LIA and immunocomb discriminatory assays[J].J Virol Methods,2019(268):42-47.
[22] Parker MM,Bennett SB,Sullivan TJ,et al.Performance of the Alere Determine HIV-1/2 Ag/Ab Combo Rapid Test with algorithm-defined acute HIV-1 infection specimens[J].J Clin Virol,2018(104):89-91.
[23] Matheron S,Descamps D,Gallien S,et al.First-line Raltegravir/Emtricitabine/Tenofovir Combination in Human Immunodeficiency Virus Type 2 (HIV-2) Infection:A Phase 2,Noncomparative Trial (ANRS 159 HIV-2)[J].Clin Infect Dis,2018,67(8):1161-1167.
[24] Menendez-Arias L,Alvarez M.Antiretroviral therapy and drug resistance in human immunodeficiency virus type 2 infection[J].Antiviral Res,2014(102):70-86.
[25] Balestre E,Ekouevi DK,Tchounga B,et al.Immunologic response in treatment-naive HIV-2-infected patients:the IeDEA West Africa cohort[J].Journal of the International Aids Society,2016,19(1):20044.
[26] Benard A,van Sighem A,Taieb A,et al.Immunovirological response to triple nucleotide reverse-transcriptase inhibitors and ritonavir-boosted protease inhibitors in treatment-naive HIV-2-infected patients:The ACHIEV2E Collaboration Study Group[J].Clin Infect Dis,2011,52(10):1257-1266.
[27] Smith RA,Anderson DJ,Pyrak CL,et al.Antiretroviral drug resistance in HIV-2:three amino acid changes are sufficient for classwide nucleoside analogue resistance[J].J Infect Dis,2009,199(9):1323-1326.
[28] Gottlieb GS,Badiane NM,Hawes SE,et al.Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal:implications for HIV-2 treatment in resouce-limited West Africa[J].Clin Infect Dis,2009,48(4):476-483.
[29] Ntemgwa ML,d'Aquin Toni T,Brenner BG,et al.Antiretroviral drug resistance in human immunodeficiency virus type 2[J].Antimicrob Agents Chemother,2009,53(9):3611-3619.
[30] Witvrouw M,Pannecouque C,Switzer WM,et al.Susceptibility of HIV-2,SIV and SHIV to various anti-HIV-1 compounds:implications for treatment and postexposure prophylaxis[J].Antiviral Therapy,2004,9(1):57-65.
[31] Raugi DN,Smith RA,Ba S,et al.Complex patterns of protease inhibitor resistance among antiretroviral treatment-experienced HIV-2 patients from Senegal:implications for second-line therapy[J].Antimicrob Agents Chemother,2013,57(6):2751-2760.
[32] Requena S,Trevino A,Cabezas T,et al.Drug resistance mutations in HIV-2 patients failing raltegravir and influence on dolutegravir response[J].J Antimicrob Chemother,2017,72(7):2083-2088.
[33] Tsiang M,Jones GS,Goldsmith J,et al.Antiviral Activity of Bictegravir (GS-9883),a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile[J].Antimicrob Agents Chemother,2016,60(12):7086-7097.
[34] Smith RA,Raugi DN,Pan C,et al.In vitro activity of dolutegravir against wild-type and integrase inhibitor-resistant HIV-2[J].Retrovirology,2015(12):10.
[35] Roquebert B,Damond F,Collin G,et al.HIV-2 integrase gene polymorphism and phenotypic susceptibility of HIV-2 clinical isolates to the integrase inhibitors raltegravir and elvitegravir in vitro[J].J Antimicrob Chemother,2008,62(5):914-920.
[36] Visseaux B,Hurtado-Nedelec M,Charpentier C,et al.Molecular determinants of HIV-2 R5-X4 tropism in the V3 loop:development of a new genotypic tool[J].J Infect Dis,2012,205(1):111-120.
[37] Trevino A,Cabezas T,Lozano AB,et al.Dolutegravir for the treatment of HIV-2 infection[J].J Clin Virol,2015(64):12-15.
[38] Descamps D,Peytavin G,Visseaux B,et al.Dolutegravir in HIV-2-Infected Patients With Resistant Virus to First-line Integrase Inhibitors From the French Named Patient Program[J].Clin Infect Dis,2015,60(10):1521-1527.
[39] Ba S,Raugi DN,Smith RA,et al.A Trial of a Single-tablet Regimen of Elvitegravir,Cobicistat,Emtricitabine,and Tenofovir Disoproxil Fumarate for the Initial Treatment of Human Immunodeficiency Virus Type 2 Infection in a Resource-limited Setting:48-Week Results From Senegal,West Africa[J].Clin Infect Dis,2018,67(10):1588-1594.
[40] 李敬云.HIV耐药的现状趋势与应对[J].中国艾滋病性病,2018,24(6):635-642.
[41] Desbois D,Roquebert B,Peytavin G,et al.In vitro phenotypic susceptibility of human immunodeficiency virus type 2 clinical isolates to protease inhibitors[J].Antimicrob Agents Chemother,2008,52(4):1545-1548.
[42] Organization WH.Consolidated guidelines on HIV testing services.5Cs:consent,confidentiality,counselling,correct results and connection 2015[EB/OL].(2015)[2019-04-19].http://apps.who.int/iris/handle/10665/179870,2015.
[43] 李敬云.提高对HIV-1急性感染和HIV-2诊断能力的检测策略[J].中国艾滋病性病,2016,22(2):138-140.