Prevalence And Influence Factors Of HIV-1 Drug Resistance In HIV/AIDS Patients In Shandong Province

Objective1. To understand the epidemiological status of HIV-1 drug-resistant strains and to identify the influence factors of HIV-1 drug resistance in HIV/AIDS patients receiving HAART and having not received HAART in Shandong province in 2013;2. To monitor the HIV-1 subtypes by analyzing the major strain of pol, env and gag gene in HIV/AIDS patients re ving not received HAART in Shandong province;3. By identifying the rules and evidence of the spread of drug-resistant strains, to help forecasting the development of the AIDS epidemic and establishing prevention and control measures, and provide scientific basis for the development of detection reagent, vaccines and antiviral drugs.MethodsHIV/AIDS patients receiving HAART and having not received HAART were separated from the anticoagulatory whole blood during April and December in 2013. The whole blood were used for CD4+T cell count and viral load detection. The entire protease gene and part of the reverse transcriptase gene were amplified by RT-PCR and nest-PCR in the samples with viral load larger than 1000 copies/ml and all the recently reported HIV-infected individuals, then sequenced the gene fragments. The distribution of HIV-1 genotypes was studied by phylogenetic analyses of pol、gag and env genes.Mutation of drug resistant gene and drug susceptibility to nucleoside reverse transcriptase inhibitors (NRTIs), non nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs) was analyzed by the online tool HIV db program developed by Stanford University. On the basis of the resistant strains spread level analysis. The prevalence of transmitted HIV drug resistance was evaluated by pol sequences.Epidemiological data was established using EpiData3.1,statistical software SPSS 17.0 was used for statistical analysis of data, the influence factors of drug-resistant strains do uniariate chi-square test, statistically significant (P< 0.05) variables is analyzed by multivariate logistic regression analysis.Results1. Among 1352 HIV/AIDS patients, the rate of virological failure in patients was 9.5% (129/1352). A total of 110 gene sequences were used for genotypic resistance analysis. Based on the pol sequences, the distribution of HIV-1 genotypes was as follows: CRF01_AE(60/110,54.5%), B(37/110,33.6%), BC (13/110,11.8%).60 patients were indicated HIV-1 drug resistance with the total of 4.4% (60/1352). The primary mutation types of drug resistance were M184V, K103N, G190A、Y181C, M46L for NRTI, NNRTI and PI, respectively. Drug resistance rates of NRTI, NNRTI and PI were 3.3%　(45/1352), 4.4%　(59/1352),0.1%　(2/1352), respectively. Multivariate logistic regression analysis showed that the main risk factors associated with the prevalence of drug resistance included age below 16 years (OR=0.209,95%　CI=0.082～0.533), and anti-retroviral therapy (ART) with LPV/r (ART with EFV:OR= 0.316,95%　CI= 0.140-0.710; ART with　NVP:OR= 0.412,95%　CI= 0.194～0.873).2. Of the 83 plasma samples,77 and 78 were successfully sequenced on pol, gag and env sequences, respectively. Phylogenetic analyses showed that the HIV-1 subtypes including CRF01_AE (50.6%), CRF07_BC (41.0%), CRF08_BC (1.2%), and B (1.2%). Three individuals were found to contain HIVDR mutations. One has resistant mutation to NRTIs, resistance location is L210W; One has resistant mutation to NNRTIs, resistance location are V108IV and V179E; One has resistant mutation to PIs, resistance location are Q58E and A71AT.3. According to the HIV drug resistance threshold survey method developed by the World Health Organization(WHO), the first 47 sequenced samples were used for HIV-1 drug resistance prevalence analysis. The prevalence of transmitted HIV-1 drug resistance to all relevant drugs was classified as moderate (5%～15%). The prevalence of TDR to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs) were estimated as low (<5%).Conclusions1. Prevalence rate of HIV drug resistance is 4.4% in Shandong Province. The prevalence rate is relatively in a low level compared with other provinces. But mutation diversity was found in drug resistant gene, and the problem of dual NRTI and NNRTI resistance was serious, even appeared the resistance to PI. Based on the condition, relevant departments should attach great importance to it.2. Multivariate logistic regression analysis showed that the main risk factors associated with the prevalence of drug resistance included age below 16 years. We should strengthen the monitor to improve the children and adolescent patients’medication adherence.3. According to the WHO classification standard, the prevalence of transmitted HIV-1 drug resistance to all relevant drugs was classified as low (<5%).4. Antiviral treatment strategy is effective in Shandong province, the current treatment strategy is feasible.