Phylogenetic Analysis And Transmitted Antiretroviral Drug Resistance Of HIV Among MSM

Introduction and Objective: MSM contribute to the majority of new cases in China. Combined with the behavior way, culture influence and the improveme nt of the social tolerance, the unrelenting HIV burden among MSM suggests th at HIV intervention remains an urgent priority. Explore the spread of HIV amo ng the MSM populations can help us to understand the source of the infection of the virus and the propagation path, to reduce the probability of HIV trans mission to uninfected, to explore the implementation of the various prevention measures. We conducted two cross-sectional studies: 1.The phylogenetic relation-ship and the characteristic of transmission, the transmitted drug resistance of HIV among MSM in Beijing. 2. Trends of HIV subtypes and phylogenetic dyn amics among young MSM in China (13 provinces and municipalities)Methods: A serial cross-sectional study1. This study is designed in a cross-sectional manner to assess the genetic relatedness of HIV viruses among HIV+ MSM participating in Beijing, China.Molecular phylogeny will be used to reconstruct transmission events and highlight clusters or networks of HIV transmission. The study will collect de-id entified behavioral and general socio-demographic information that will remain linked to each sequence generated, and we will overlay this data onto our phylogenetic analysis to more completely characterize the phylogenetic clusters identified in the sampled populations.2. A serial cross-sectional study was conducted from 2009 and 2014 in 13 provinces or cities, China. The subjects were enrolled from newly diagnosed HIV cases at the local Center for Disease Control and Prevention. Subjects eligible for study included males, between 16 and 25 years of age, newly diagnosed HIV positive MSM,unaware of treatment, and able to provide written informed consent. Criteria selection of patient’s age between 16 and 25 was newly diagnosed HIV-infected.All study participants completed a questionnaire administered by trained interviewers in a private room. The research staff collected 8 mL of peripheral blood samples that were anti-coagulated with EDTA-3K. Plasma was separated within 6 hours after collection, tested for antibodies and HIV-1 RNA, and frozen at -80℃ for further analysis. This study was approved by institutional review board at the National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention. All data were analyzed using SAS 9.2 software packages. The proportion of HIV subtypes over time was assessed using the chi-square trend test. P values <0.05 were considered statistically significant.Results:1. A total of 3618 patients, including 485 patients with HIV+ were enrolled into this study between 2013 and 2014 in Beijing, the infection rate is 13.4%. We got 405 sequences, Half of the patients were identified to be CRF01_AE (n = 226, 55.7%).More than one quarter of patients were identified as subtype CRF07 BC (n = 114,28.1%), and the remaining were subtype B (n = 42. 10.3%). Additionally, 23 patients(5.7%) were denoted as unique recombinant forms (URFs). We find a distinct cluster of CRF07 BC by phylogenetic analysis, which transmitted to MSM in about 2004,and has been the fast spread among MSM and been the biggest cluster for over ten years. Our study results showed that the use of nitrite inhalants was alarmingly prevalent among MSM in Beijing, and 33.4% of the participants used nitrite inhalants which were associated with high-risks of HIV infection. We find several multiple recombinant strains among CRF01_AE with CRF07_BC and subtype B. The TDR is 4.4% (18/405).2. A total of 1205 HIV-1 nucleotide sequences of the 1.0-kb pol gene (HXB2:2253-3278 nts) from newly diagnosed MSM between 2009 and 2014 from 13 Chinese provinces were determined and genotyped by phylogenetic tree analysis. As shown in Table 1, there were three known major Chinese circulating subtypes:CRF01_AE, 45.3%. CRF07_BC 37.8%. and subtype B_EU(U.S.-European origin)6.1%, plus minor subtype B’ (Thailand) 3.7%, and other recombinants 7.1% in the MSM population. The total of CRF01_AE and CRF07_BC genotypes accounted for 83.1% (1001/1205) of the HIV-1 infections among MSM. The chi-square trend test was used to compare the changes of HIV-1 subtypes over time. The proportion of subtype CRF01_AE decreased from 55.4% to 43.5% during 2009-2014 (P=0.044),while at the same time, the proportion of subtype CRF07_BC increased from 25.6%to 40.1% (P=0.016). We identified 7 clusters which most spread among the 13 provinces. The distinct cluster of CRF07 BC is quite different from the stains that spread among the IDUs in protein tertiary structure. The TDR is 3.2%, mainly be PI related drug resistance mutations.Conclusions:The infection of HIV among MSM in China is highly. The HIV-1 subtypes among MSM are changing and diversify; The use of nitrite inhalants was alarmingly prevalent among MSM which were associated with high-risks of HIV infection;Complex new recombinant strains been found among MSM; A distinct cluster of CRF07 BC is fast spread among MSM; The TDR is lower, mainly be PI related drug resistance mutations.