广西壮族自治区海洛因成瘾的HIV感染者和艾滋病患者抗病毒治疗效果及耐药性分析

The efficacy of antiviral therapy and drug resistance analysis among HIV/AIDS patients with heroin addiction in Guangxi Zhuang Autonomous Region

目的了解广西壮族自治区海洛因成瘾的HIV感染者和艾滋病患者抗病毒治疗效果及耐药、突变情况。方法2008年4月至2009年10月，在柳州和百色市的美沙酮门诊、艾滋病门诊和自愿咨询检测点招募调查对象，根据抗病毒治疗情况及海洛因使用情况进行分组。共纳入435例调查对象，其中抗病毒治疗＋海洛因组108例、抗病毒治疗＋不吸毒组93例、不抗病毒治疗＋海洛因组105例、不抗病毒治疗＋不吸毒组129例。通过问卷调查了解基本信息，测定病毒载量水平和CD4^＋T淋巴细胞计数评价抗病毒治疗效果；从血浆中提取HIV-1RNA，扩增pol区基因并测序，进行基因型耐药性分析。结果抗病毒治疗者海洛因组病毒载量lg值为（2．61±1．24），高于不吸毒组（2．08±0．80），差异有统计学意义（t=3．54，P〈0．05）；海洛因组病毒载量〈1000拷贝／ml的比例（63．9％，69／108）低于不吸毒组（86．0％，80／93），差异有统计学意义（Х^2=12．76，P〈0．05）。抗病毒治疗者海洛因组CD4^＋T淋巴细胞计数（337．92±181．66）个／ml与不吸毒组（326．14±254．98）个／ml比较，差异无统计学意义（t=0．38，P=0．703）；不抗病毒治疗者海洛因组CD4^＋T淋巴细胞计数（373。73±155．97）个／ml与不吸毒组（337．53±209．26）个／ml比较，差异无统计学意义（t=1．47，P=0．143）。抗病毒治疗者海洛因组CD4^＋T淋巴细胞计数大于350个／ml的比例（48．1％，52／108）与不吸毒组（43．0％，40／93）比较，差异无统计学意义（Х^2=0．53，P=0．466）。成功扩增的319例HIV-1 pol区序列中，抗病毒治疗的HIV感染者或艾滋病患者中海洛因组出现M184V／I、T215Y／F、L210W和T69N／S突变的频率高于不吸毒组[分别为14．9％（11／74）比4．4％（3／68）、12．2％（9／74）比1．5％（1／68）、12．2％（9／74）比1．5％（1／68）以及10．8％（8／74）比1．5％（1／68）]，差异有统计学意义（P〈0．05）。结论海洛因可能会促进HIV感染者或艾滋病患者体内HIV复制，降低抗病毒治疗的病毒学应答，增加耐药位点出现的频率，故戒毒可能会获得更好的抗病毒治疗效果。

Objective To investigate the impact of heroin for antiviral treatment, drug resistance, mutation types and frequency in HIV/AIDS patients in Guangxi Zhuang Autonomous Region. Methods HIV/AIDS patients were recruited in Methadone Maintenance Treatment Clinics, HIV/AIDS Clinic and HIV Voluntary Counseling and Testing Center Liuzhou and Baise city from April 2008 to October 2009. The patients were grouped by the situation of antiviral treatment and use of heroin. A total of 435 HIV/AIDS patients were recruited, among which 108 cases in antiviral treatment and heroin group ,93 cases in antiviral treatment and never using drug group, 105 cases in no antiviral treatment and using heroin group, 129 cases in no antiviral treatment and never using drug group. The effect of antiviral treatment was evaluated by questionnaire survey, viral load measurement and CD4^ ＋ T lymphocyte count. HIV-1 RNA from plasma was extracted,and then the pol genes were amplified and sequenced. The sequences were analyzed for HIV-1 genotype drug-resistance. Results For the patients who received antiviral treatment, the viral load in heroin group was higher than that in never using drug group（lg（2. 61 ±1.24） vs lg（2. 08 ±0. 80） ,t =3. 54,P 〈 0.05 ） , and the percentage of viral load lower than 1 000 copies/ml in heroin group was significantly less than that in never using drug group （63.9% vs 86. 0% ,Х^2 = 12. 76,P 〈0. 05）. For the patients who received antiviral treatment, the difference has no significance in CD4 ^＋ T lymphocyte count between heroin group and never using drug group（ （337.92 ±181.66） vs （326. 14 ±254. 98 ）, t = 0. 38, P = 0. 703 ）. For the patients who didn＇t receive antiviral treatment,the difference also has no significance in CD4^＋ T lymphocyte count between heroin group and never using drug group （ （373.73 ±155.97 ） vs （337.53 ±209.26 ） , t = 1.47,P = 0. 143 ）. For the patients who received antiviral treatment, there was no difference in the percentage of the CD4 ＋ T lymphocyte count more than 350/ml between heroin group and never using drug group （48. 1% vs 43.0% ,Х^2 = 0. 53, P = 0. 466）. 319 HIV-1 pol gene sequences were obtained. Among the patients who received antiviral treatment, the mutation frequency of M184V/I, T215Y/F, L210W and T69N/S in heroin abuser group were significantly higher than that in never using drug group （14. 9% （11/74） vs 4.4% （3/68） ,12. 2% （9/74） vs 1.5% （ 1/68）, 12. 2% （9/74） vs 1.5% （1/68） and 10. 8% （8/74） vs 1.5% （ 1/68 ） respectively） （ P 〈 0.05 ）. Conclusion Using heroin may promote HIV replication, reducing the virological response to antiviral treatment and increasing the frequencies of drug resistance loci among HIV/AIDS patients. Heroin rehabilitation may benefit from the antiviral treatment and obtain better antiviral effect.