Investigation On The Failure And Drug Resistance Of HIV Virus In HIV Antiviral Therapy

BackgroundAntiretroviral drugs (ARVs) had been developed rapidly across the world since Zidovudine (AZT) was emerged as the first ARV in 1987. Until late 20th century, along with the application of highly active antiretroviral therapy (HAART), more and more HIV/AIDS patients could acquire effective therapy, which not only suppressed replication of virus in plasma and improved immune reconstitution, but also decreased AIDS-related death and enhanced quality of life. National free antiretroviral treatment program (NFATP) had been implemented in China in 2003, after ten years of efforts, the national coverage of antiretroviral therapy (ART) was over 70%, about 3000 free ART clinic had been established nationwide, and accumulated number of adult patients who had received ART was more than 360,000. However, along with widely use of ARVs, the epidemic of HIV-1 drug resistance strains got worse, which could compromise therapeutic effect for an individual. Meanwhile, under current situation of shortage of medical resources, if first-line regime couldn’t be used constantly, most patients would switch to second-line regimen because of drug resistance, which might increase social economic burden as well. To expand ART in China more effectively and prevent the rapid epidemic of HIV-1 drug resistance strains, our study investigated the prevalence of virological suppression and drug resistance among the patients who received ART, and we also analyzed the treatment effect of some high-risk population, including injecting drug users and former blood donors.Objective1、To understand the prevalence of virological failure and drug resistance among patients who received ART from 2003 to 20132、To investigated HIV virological failure and drug resistance among injecting drug users receiving ART3、To determine HIV virological failure and drug resistance among former blood donors receiving ARTMethodsData was collected from the Chinese National HIV Drug Resistance (HIVDR) Surveillance and Monitoring Network, which patients started ART from 2003 to 2013. Personal information, including demographic characteristics, HIV risk behaviors, HAART regimes and predictors for adherence, was acquired with questionnaires, and blood specimens were collected to test CD4 count, viral load (VL) and HIV drug resistance mutations. Two people were needed to enter questionnaire data respectively using Epidata 3.1, then consistency checks were conducted and wrong information should be modified. SAS 9.2 was used for data cleaning and analysis.ResultsThe first sectionAccording to the inclusion criteria,10129 patients were enrolled in our study eventually. For these patients, the mean duration of treatment was (29.5±25.2) months and the median duration was 23.3 months. After testing,2094 of the 10129 patients (20.7%) experienced virological failure (VL≥1000 copies/ml). The results of multivariate logistic regression with virological failure as dependent variable demonstrated that patients who were junior high school or more, or residence of Guangxi and Yunnan, had lower prevalence of virological failure; however, blood/plasma transmission or drug injection, DDI based initial ART regimen, CD4 count before ART was 200-349 cells/mm3 or 350-499 cells/mm3, self-reported missing doses in the past month, residence of Anhui and Henan provinces were predictors for development of virological failure.The overall prevalence of HIVDR was 11.0%(1114/10129). Among those with HIVDR,80.8% of patients had drug resistance to NNRTIs, followed by NRTIs (69.0%) and PIs (4.2%). Besides,51.2% had multidrug resistance to NNRTIs and NRTIs. The most common NRTI mutations were M184I/V, M41L and D67G/N; NNRTI mutations were frequently occurred at position 103 in reverse transcriptase (RT) region; and PI mutations were found at condon 46 and 54 in protease (PR) region.Compared with patients who had not drug resistance, patients who infected HIV through blood/plasma transmission (AOR=1.3; 95% CI=1.0～1.7) or drug injection (AOR=1.9; 95% CI=1.5～2.4), taken DDI based initial regimen (AOR=2.7; 95% CI=2.3～3.2), self-reported missing doses in the past month (AOR=1.5; 95% CI=1.2～1.8), were residence of Anhui and Henan (AOR=1.4; 95% CI=1.1～1.7), had higher prevalence of drug resistance. Patients who were junior high school or more (AOR=0.8; 95% CI=0.7～0.9), starting treatment from 2008 to 2010 (AOR=0.8; 95% CI=0.6～0.9) or 2011 to 2013 (AOR=0.6; 95% CI=0.4～0.8), living in Guangxi and Yunnan (AOR=0.6; 95% CI=0.4～0.8), had low risk for drug resistance.The second sectionIn our study,1395 patients were injecting drug users. For them, the mean duration of treatment was (23.9±20.9) months and median duration was 17.0 months. After ART,20%(298/1395) had plasma viral load≥1000 copies/ml.Samples with VL≥1000 copies/ml should be selected for HIV drug resistance testing.278 were successfully genotyped, and among these,117 had drug resistance mutations. Of these patients, the prevalence of drug resistance to NRTIs, NNRTIs, and PIs was 65.0%,69.2%, and 7.7%, respectively.37.6% were resistant to both NRTIs and NNRTIs. The majority of NRTI mutations were resistant to 3TC, and M184I/V was the most common NRTIs mutations. EFV was the most frequent resistant NNRTIs drug, and K103N/R was the most common NNRTIs mutation site. The type of HIV subtype was varied, in which CRF07_BC was the majority, accounting for 54.0%.The prevalence of HIV drug resistance was 8.4%(117/1395). The results of multivariate analysis indicated that injecting drug users who were minority ethnics (AOR=2.5; 95% CI=1.5～3.9), using DDI based regimen at initial time (AOR=6.8; 95% CI=2.4～19.4), had higher risk for drug resistance.The third sectionA total of 3690 patients were infected with HIV through blood donating. The mean duration of treatment of these people was (38.6±30.0) months and median duration was 32.7 months.1178 (31.9%) patients had failure of viral suppression (VL ≥1000 copies/ml).Among patients with virological failure,689 had resisted at least one drug. The prevalence of HIV drug resistance of former blood donors was 18.7%. NRTIs and NNRTIs were the most common drug resistance mutations, and the most frequent resistance to NRTIs and NNRTIs was ABC and NVP, respectively. M41L was the most common NRTIs mutation site; most NNRTIs mutations were found at position 103 in RT region. Moreover,22 patients had PIs mutations.93.5% had HIV subtype B.The outcomings of multivariate analysis showed that patients, who were age 40-59 years old (AOR=0.7; 95% CI=0.6～0.9) or≥60 years old (AOR=0.6; 95% CI=0.4～0.9), junior high school or more (AOR=0.8; 95% CI=0.7～1.0), farmer (AOR=0.5; 95% CI=0.4～0.6), had low prevalence of drug resistance. Those, who self-reported missing doses in the past month (AOR=1.7; 95% CI=1.3～2.2), were more likely to develop drug resistance.ConclusionThe overall prevalence of virological failure among patients who received ART in China was still high, especially among former blood donors and injecting drug users. In our study, the useage of DDI based initial ART regimen and poor adherence of ART were the most significant factors associated with virological failure and drug resistance.