Study of HIV-1 Drug Resistance in Patients Receiving Free Antiretroviral Therapy in China

To investigate the prevalence of drug-resistance mutations,resistance to antiretroviral drugs,and the subsequent virological response to therapy in treatment-naive and antiretroviral-treated patients infected with HIV/AIDS in Henan,China,a total of 431 plasma samples were collected in Queshan county between 2003 and 2004,from patients undergoing the antiretroviral regimen Zidovudine + Didanosine + Nevirapine(Azt+Ddi+Nvp).Personal information was collected by face to face interview.Viral load and genotypic drug resistance were tested.Drug resistance mutation data were obtained by analyzing patient-derived sequences through the HIVdb Program(http://hivdb.stanford.edu).Overall,38.5% of treatment-naive patients had undetectable plasma viral load(VL),the rate significantly increased to 61.9% in 0 to 6 months treatment patients(mean 3 months)(P<0.005)but again significantly decrease to 38.6% in 6 to 12 months treatment patients(mean 9 months)(P<0.001)and 40.0% in patients receiving more than 12 months treatment(mean 16 months)(P<0.005).The prevalence of drug resistance in patients who had a detectable VL and available sequences were 7.0%,48.6%,70.8%,72.3% in treatment-na?ve,0 to 6 months treatment,6 to 12 months treatment,and treatment for greater than 12 months patients,respectively.No mutation associated with resistance to Protease inhibitor(PI)was detected in this study.Nucleoside RT inhibitor(NRTI)mutations always emerged after non-nucleoside RT inhibitor(NNRTI)mutations,and were only found in patients treated for more than 6 months,with a frequency less than 5%,with the exception of mutation T215Y(12.8%,6/47)which occurred in patients treated for more than 12 months.NNRTI mutations emerged quickly after therapy begun,and increased significantly in patients treated for more than 6 months(P<0.005),and the most frequent mutations were K103N,V106A,Y181C,G190A.There had been optimal viral suppression in patients undergoing treatment for less than 6 months in Queshan,Henan.The drug resistance strains were highly prevalent in antiretroviral-treated patients,and increased with the continuation of therapy,with many patients encountering virological failure after 6 months therapy.

Global Transmission of Human Immunodeficiency Virus 1 Subtype C and Its Impact on the Circulation of B/C Recombination Strains in China

This study aimed to reconstruct the origin and worldwide epidemic history of human immunodeficiency virus(HIV)1 subtype C and comprehend how HIV-1 subtype C was introduced into and spread throughout China in the formof B/C recombinant strains.Envelope sequences ofHIV-1 subtype C and some other subtypes deposited before December 31,2020 were downloaded from the Los Alamos HIV Database and the Chinese National Center for AIDS/STD Control and Prevention Database.The available sequences were screened for quality,and Bayesian analysis was used to build the maximum clade credibility evolutionary tree to analyze and judge the origin and spread of HIV-1 subtype C.HIV-1 subtype C originated in central Africa around 1952,then spread to southern Africa around 1969 and to eastern Africa around 1973.HIV-1 subtype C fromsouthern Africa was introduced into India in 1977.HIV-1 subtype C of eastern Africa was introduced into Brazil in 1987.Indian HIV-1 subtype C was exported to China in three migration events during the period from 1986 to 1989.The two predominant recombinants in China(CRF07_BC and CRF08_BC)emerged in 1988 and 1990,respectively.Other B/C recombinants,namely,CRF64_BC,CRF61_BC and CRF62_BC,originated in 1993,2002 and 2000,respectively.Our study has reconstructed the global origin and evolutionary history of HIV-1 subtype C.In addition,our study demonstrated that the Chinese HIV-1 subtype C originated from three related Indian lineages around the mid to late 1980s and,since then,has formed some B/C recombinants with subtype B that caused a widespread epidemic in China.

MicroRNA 31 inhibits CD8^(+) T-cell function by increasing its sensitivity to type I interferon signaling in chronic viral infection

Chronic viral infections and malignant tumors can cause T cells to become dysfunctional and exhausted through two different associated immune statuses:inflammation and immunosuppression.Inflammatory immunity is a necessary step for the establishment of the immune response to control infection and cancer.However,once a pathogen cannot be cleared in time or a tumor continues to progress,an immunosuppressive environment involving various immune cells and cytokines may form,thereby promoting the persistence of the pathogen or tumor.Among those immune factors,type I interferons play a dual role by driving inflammation and inducing a variety of suppressive factors that limit immune responses in chronic infection and cancer.