| Objective: We conducted two cross-sectional studies to learn the drug resistance among Chinese patients 9-18 months after receiving first-line antiretroviral treatment and the prevalence of drug resistance after stopping the antiretroviral treatment.Method:1. The survey protocol was taken from the National Center for AIDS/STD Control and Prevention recommended cross-sectional survey on acquired HIVDR in adult patients receiving ART. We conducted a cross-sectional survey in eight provinces or cities of China: Beijing, Jilin,Hunan, Guangxi, Sichuan, Guizhou, Yunnan and Xinjiang Province. Patients included were 18 years or older, had begun free ART treatment in 2013, and had received first-line ART for 9-18 months at enrollment. Eligible patients were enrolled at routine clinic visits in 2014. All participants provided written informed consent.2. Surveys were performed at six provinces or cities of China: Sichuan, Chongqing, Yunnan,Guangxi, Henan and Hunan province. Patients included were 18 years or older, and had stopped ART beyond 1 month at enrollment. Eligible patients were enrolled at routine clinic visits and provided written informed consent.Results:1. This survey included 765 patients having received ART for 9-18 months among eight provinces. The mean age was 44.7 years. The majority of the subjects were male (71.4%), of Han ethnicity (79.3%), and had received Junior high school or lower education (70.7%). 42.5% were married and 35.3% were farmers. About two-thirds of the patients were infected by heterosexual transmission, followed by homosexual contact (19.2%), and intravenous drug use (8.5%). Most patients started ART included AZT+3TC+EFV/NVP (56.0%), D4T+3TC+EFV/NVP (7.6%), or TDF+3TC+EFV/NVP (29.9%). 8.2% of the patients initiated ART with PI (LPV/r)-based second-line regimens. At the time of the survey, the median duration of ART was 13.9 months(interquartile range [IQR] 12.6-15.0). The median CD4 count before ART increased from 222(IQR, 215) cells/ul to 303 (IQR, 258) cells/ul at the time of the survey. The great majority of patients (700/765, 91.5%) had a plasma HIV viral load failure (VLF)1000 copies/ml). Among the individuals with VLF, 64 were successful genotyped, and 33 had one or more HIVDR mutations. Among the 33 patients identified with HIVDR mutations, all patients harbored HIV-1 strains resistant to non-nucleoside reverse transcriptase inhibitors (NNRTIs). 81.8% of these patients were also resistant to nucleoside reverse transcriptase inhibitors (NRTIs), but only 3%were resistant to both NNRTIs and PIs. The most common NNRTIs mutations were K103N(54.5%), G190A/S/R/ (27.3%), and Y181C (24.2%) in the reverse transcriptase (RT) region.NRTIs mutations were most frequently seen as M184I/V (66.7%) and K65R (39.4%) in the RT region, while PI mutations were only found to be M46L in the protease (PR) region. In the multivariate model, the following two factors were independently correlated with HIVDR: the rate of HIVDR among patients with <90% of drug intake in the past month were 6.0 folds higher than in patients with >90% of drug intake (95%CI: 1.7-20.7; P=0.005), and Sichuan and Guizhou Provinces were 7.3 times higher than the other provinces (95%CI: 3.6-15.2; P<0.0001).2. We totally included 481 patients who had stopped antiretroviral treatment, and 365 patients received questionnaire survey. All of the participants had the laboratory test. The majority of the questionnaire subjects were male (70.3%), of Han ethnicity (60.8%). 70.9% were rural, 60.5% of the subjects were heterosexual transmission, 4.7% were homosexual transmission, 27.4% were drug transmission. Discontinuation of 1-6 months had 86 (23.6%) patients, 6-12 months 75(20.6%),12-24 months 85(23.3%), 24-36 months 36(9.7%),?36 months 42(11.5%). Among the subjects, 52 (10.8%) had stopped with treatment failure, and the side effects were 124 patients(25.8%), and bad adherence were 177 (36.8%).Among the 481 patients with drug stopped, 337 (70.1%) patients had viral load ? 1000 copies/ml during the investigation. The 337 patients who had no-suppress of viral load were amplified, and 336 (99.7%, 336/337) patients were successfully obtained, of which there were at least 65 patients with drug-resistant mutations. 65 of the patients with drug resistance were resistant to NNRTIs, and 4.6% (3) were resistant to NRTIs, while 10.8% (7) had drug resistance to PIs. The most common resistance mutation site of NNRTIs is K103N (56.9%). M184I/V located in the RT region which is the most common NRTIs mutation, while the PIs mutation site only occurs at the site of 154 V.Two variables in the multivariate model were correlated with HIVDR: no medical insurance withdrawal people were 2.8 times than medical insurance patients (95%CI:1.2-6.6; P=0.02); 0-199 CD4 count patients were 3.6 times than CD4?350 count patients (95%CI:1.4-8.9; P=0.006),200-350 CD4 count patients were 3.5 times than CD4 ?350 count patients (95%CI: 1.4-8.4;P=0.006). In the multivariate model, there were two variables related to the viral load no-supression: patients getting medicine from county or city hospital were 2.9(95%CI: 1.6-5.3;P=0.0003 ) times than patients getting medicine from township hospitals concerning with the viral load no-supression; patients with CD4 counts 0-199 havingthe risk of viral load no-supression were 10.3 times than CD4 count ?350 patients (95%CI:4.9-21.7;P<0.0001), patients with CD4 counts 200-350 having the risk of viral load no-supression were 4.6 times than CD4 count ?350 patients (95%CI:2.6-8.3; P<0.0001).Conclusion: In summary, our study showed that the rate of viral suppression in patients who had been consistently taking free ART for 9-18 months has reached 90% of WHO viral load standard, with the CD4 count improving. The rate of drug resistance was 4.3%, but the drug resistance differed largely among Sichuan and Guizhou. The viral no-suppression and drug resistance among withdrawal ART patients were bad, the rate of drug resistance was 13.5%. And the lower CD4 count during investigation had more risk of drug resistance and viral no-suppression. Patients stopping ART were mainly due to adverse drug reactions and bad compliance. We should pay attention to the stopped ART groups, and provide scientific basis for long-term treatment. Although the rate of consistently taking-drug patients is relatively low, the study found that there is still a certain proportion of resistance occurred among stopping ART patients. We should take measures to maintain long-term antiviral treatment effect in China. |
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