贾小芳;谭智汨;张丽军;

• 1:上海市公共卫生临床中心

摘要(Abstract)：

艾滋病又称为获得性免疫缺陷综合征(acquired immunodeficiency syndrome,AIDS),是由人类免疫缺陷病毒(human immunodeficiency virus,HIV)感染引起的。目前临床上一般采用高效抗反转录病毒联合治疗法(high active antiretroviral therapy,HAART),即鸡尾酒疗法来治疗艾滋病,该疗法联合使用至少3种类型的抗HIV药物,可有效控制患者体内的病毒载量,极大地延长艾滋病患者的生存时长,提高了患者的生存质量,但同时不可避免地造成了一些副反应,如皮疹、肝损伤和注意力不集中等神经精神症状。本文将对鸡尾酒疗法治疗艾滋病过程中的药物毒副作用的研究进展作一综述。

关键词(KeyWords)： 艾滋病;人类免疫缺陷病毒;高效抗反转录病毒联合治疗;鸡尾酒疗法;副作用

Abstract:

Keywords:

基金项目(Foundation): 国家重大新药专项(2017ZX09304027);; 国家自然科学基金(81801991);; 上海市卫生计生委重点课题(201640005)

作者(Authors): 贾小芳;谭智汨;张丽军;

DOI: 10.13200/j.cnki.cjb.002731

参考文献(References)：

• [1]朱礼胜,戴骁意,陈飞,等.艾滋病治疗的研究进展[J].国际流行病学传染病学杂志,2017,44(5):348-352.
• [2]WHO.HIV AIDS[EB/OL].[2018-05-11].Http://www.who.int/hiv/data/en/.
• [3]BANDEIRA A,ELIAS D B D,CAVALCANTE M G,et al.Antiretroviral changes during the first year of therapy[J].Rev Assoc Med Bras(1992),2017,63(7):606-612.
• [4]SHAH A,GANGWANI M R,CHAUDHARI N S,et al.Neurotoxicity in the post-HAART era:caution for the antiretroviral therapeutics[J].Neurotox Res,2016,30(4):677-697.
• [5]ZHANG L,LI X,LIN Z,et al.Side effects,adherence selfefficacy,and adherence to antiretroviral treatment:a mediation analysis in a Chinese sample[J].AIDS Care,2016,28(7):919-926.
• [6]DE CLERCQ E.Anti-HIV drugs:25 compounds approved within 25 years after the discovery of HIV[J].Int J Antimicrob Agents,2009,33(4):307-320.
• [7]MANFREDI R,CALZA L,CHIODO F.An extremely different dysmetabolic profile between the two available nonnucleoside reverse transcriptase inhibitors:efavirenz and nevirapine[J].JAcquir Immune Defic Syndr,2005,38(2):236-238.
• [8]CAI J,XIAO J,ZHANG Q.Side effects and tolerability of post-exposure prophylaxis with zidovudine,lamivudine,and lopinavir/ritonavir:a comparative study with HIV/AIDS patients[J].Chin Med J(Engl),2014,127(14):2632-2636.
• [9]ONOYA D,HIRASEN K,VAN DEN BERG L,et al.Adverse drug reactions among patients initiating second-line antiretroviral therapy in South Africa[J].Drug Saf,2018,41(12):1343-1353.
• [10]USACH I,MELIS V,PERIS J E.Non-nucleoside reverse transcriptase inhibitors:a review on pharmacokinetics,pharmacodynamics,safety and tolerability[J].J Int AIDS Soc,2013,16:1-14.
• [11]杨蓉蓉,桂希恩,熊勇,等.两种非核苷类逆转录酶抑制剂治疗艾滋病的不良反应分析[J].国际流行病学传染病学杂志,2017,44(4):233-236.
• [12]PATIL R,ONA M A,PAPAFRAGKAKIS H,et al.Acute liver toxicity due to efavirenz/emtricitabine/tenofovir[J].Case Reports Hepatol,2015,2015:280353.
• [13]TAN Z,JIA X,MA F,et al.Increased MMAB level in mitochondria as a novel biomarker of hepatotoxicity induced by E-favirenz[J].PLoS One,2017,12(11):e0188366.
• [14]LV Z,CHU Y,WANG Y.HIV protease inhibitors:a review of molecular selectivity and toxicity[J].HIV AIDS(Auckl),2015,7:95-104.
• [15]COHEN C J,DUSEK A,GREEN J,et al.Long-term treatment with subcutaneous T-20,a fusion inhibitor,in HIV-infected patients:patient satisfaction and impact on activities of daily living[J].AIDS Patient Care STDS,2002,16(7):327-335.
• [16]QUASHIE P K,SLOAN R D,WAINBERG M A.Novel therapeutic strategies targeting HIV integrase[J].BMC Med,2012,10:34.
• [17]WEI X,DECKER J M,LIU H,et al.Emergence of resistant human immunodeficiency virus type 1 in patients receiving fusion inhibitor(T-20)monotherapy[J].Antimicrob Agents Chemother,2002,46(6):1896-1905.
• [18]MANFREDI R,CALZA L,MARINACCI G,et al.Raltegravir use prospectively assessed in a major HIV outpatient clinic in Italy:sample population,virological-immunological activity,and tolerability profile[J].Infez Med,2014,22(4):288-295.
• [19]SMITH S J,ZHAO X Z,BURKE T R,et al.HIV-1 integrase inhibitors that are broadly effective against drug-resistant mutants[J].Antimicrob Agents Chemother,2018,62(9):e01035-1018.
• [20]PODANY A T,SCARSI K K,FLETCHER C V.Comparative clinical pharmacokinetics and pharmacodynamics of HIV-1 integrase strand transfer inhibitors[J].Clin Pharmacokinet,2017,56(1):25-40.
• [21]DEEKS E D.Raltegravir once-daily tablet:a review in HIV-1infection[J].Drugs,2017,77(16):1789-1795.
• [22]TAN Q,ZHU Y,LI J,et al.Structure of the CCR5 chemokine receptor-HIV entry inhibitor maraviroc complex[J].Science,2013,341(6152):1387-1390.
• [23]BRELOT A,CHAKRABARTI L A.CCR5 revisited:how mechanisms of HIV entry govern AIDS pathogenesis[J].J Mol Biol,2018,430(17):2557-2589.
• [24]FGIAQUINTO C,MAWELA M P,CHOKEPHAIBULKIT K,et al.Pharmacokinetics,safety and efficacy of maraviroc in treatment-experienced pediatric patients infected with CCR5-tropic HIV-1[J].Pediatr Infect Dis J,2018,37(5):459-465.
• [25]DEGLI ANTONI A,WEIMER L E,MANFREDI R,et al.Areduced grade of liver fibro-steatosis after raltegravir,maraviroc and fosamprenavir in an HIV/HCV co-infected patient with chronic hepatitis,cardiomyopathy,intolerance to nelfinavir and a marked increase of serum creatine phosphokinase levels probably related to integrase inhibitor use[J].West Indian Med J,2012,61(9):932-936.
• [26]MANFREDI R,CALZA L,MARINACCI G,et al.A prospective evaluation of maraviroc administration in patients with advanced HIV disease and multiple comorbidities:focus on efficacy and tolerability issues[J].Infez Med,2015,23(1):36-43.
• [27]HE X,WANG W,XU K,et al.Evaluation of the efficacy of a therapeutic HIV vaccine by in vitro stimulation assay[J].Cell Immunol,2017,313:67-71.
• [28]LEAL L,LUCERO C,GATELL J M,et al.New challenges in therapeutic vaccines against HIV infection[J].Expert Rev Vaccines,2017,16(6):587-600.
• [29]FABBIANI M,DI GIAMBENEDETTO S,CINGOLAMI A,et al.Relationship between self-reported adherence,antiretroviral drug concentration measurement and self-reported symptoms in patients treated for HIV-1 infection[J].Infect Dis(Lond),2016,48(1):48-55.
• [30]PUNYAWUDHO B,SINGKHAM N,THAMMAJARUK N,et al.Therapeutic drug monitoring of antiretroviral drugs in HIV-infected patients[J].Expert Rev Clin Pharmacol,2016,9(12):1583-1595.
• [31]CALCAGNO A,PAGANI N,ARIAUDO A,et al.Therapeutic drug monitoring of boosted PIs in HIV-positive patients:undetectable plasma concentrations and risk of virological failure[J].J Antimicrob Chemother,2017,72(6):1741-1744.