Little information is available on the prevalence of drug-resistance mutations in patients harboring the human immunodeficiency virus type 1(HIV-1) circulating recombinant form(CRF)07_BC variant in Sichuan, China. Thi...Little information is available on the prevalence of drug-resistance mutations in patients harboring the human immunodeficiency virus type 1(HIV-1) circulating recombinant form(CRF)07_BC variant in Sichuan, China. This study examined 375 plasma samples from patients with HIV-1 who were infected with the CRF07_BC strain, including 104 drug-naive participants and 271 in whom antiretroviral therapy(ART) had failed. Only one participant in the drug-naive group had a drug-resistance mutation(M46L), compared with 31.73% of those in whom ART had failed. Further analysis showed that 19.56% of strains contained mutations conferring resistance to non-nucleoside reverse transcriptase inhibitors(NNRTIs) alone, 0.74% were resistant to nucleoside reverse transcriptase inhibitors(NRTIs) alone, and 11.44% were dual-resistant to both NRTIs and NNRTIs. The most common mutation in the ART-failure group was M184V(35.88%), K103N(45.01%), Y181C(17.33%), and G190S/A(15.88%). The percentages of HIV-1 strains resistant to lamivudine, emtricitabine, efavirenz, etravirine, and nevirapine were 10.70%, 10.70%, 28.04%, 7.75%, and 26.20%, respectively. To explore site variants possibly related to drug resistance, variations in the ancestor/consensus CRF07_BC sequences from the therapy-naive and ART-failure groups were compared, and seven mutations at six positions were identified as being significantly differently distributed between the two groups(p<0.05). Detailed sequence data will provide information on CRF07_BC genetic characterizations, and improve our understanding of antiretroviral susceptibility and the evolution of drug-resistance mutations. This will be valuable in developing and implementing local public-health approaches for HIV drug-resistance prevention and treatment.展开更多
VRC01, a broadly neutralizing monoclonal antibody （bnmAb）, can neutralize a diverse array of HIV-1 isolates by mimicking CD4 binding to the envelope glycoprotein gpl20. We have previously demonstrated the presence o...VRC01, a broadly neutralizing monoclonal antibody （bnmAb）, can neutralize a diverse array of HIV-1 isolates by mimicking CD4 binding to the envelope glycoprotein gpl20. We have previously demonstrated the presence of VRC01-resistant strains in an HIV-1 infected patient during antiretroviral therapy. Here, we report follow-up studies of two subsequent samples from the same patient. With genetic and phenotypic analysis of over 70 full-length molecular clones of the HIV-1 envelope, we show that VRC01-resistant HIV-1 continued to exist and change in its proportion of the infecting virus during treatment with a highly active antiretroviral therapy. Consistent with our previous observation, the resistant phenotype was associated with a single asparagine residue at position 460 （N460）, a potential N-linked glycosylation site in the V5 region. The persistence and continuing evolution of VRC01-resistant HIV-1 in vivo presents a great challenge to our future preventative and therapeutic interventions based on VRC01.展开更多
基金supported by the Chinese Government AIDS Program (grant number 2008ZX001-016)the China 4th Global Fund AIDS Program (grant number CHN-405-G05-H)a Sichuan Provincial Health Department research project (number 120154)
文摘Little information is available on the prevalence of drug-resistance mutations in patients harboring the human immunodeficiency virus type 1(HIV-1) circulating recombinant form(CRF)07_BC variant in Sichuan, China. This study examined 375 plasma samples from patients with HIV-1 who were infected with the CRF07_BC strain, including 104 drug-naive participants and 271 in whom antiretroviral therapy(ART) had failed. Only one participant in the drug-naive group had a drug-resistance mutation(M46L), compared with 31.73% of those in whom ART had failed. Further analysis showed that 19.56% of strains contained mutations conferring resistance to non-nucleoside reverse transcriptase inhibitors(NNRTIs) alone, 0.74% were resistant to nucleoside reverse transcriptase inhibitors(NRTIs) alone, and 11.44% were dual-resistant to both NRTIs and NNRTIs. The most common mutation in the ART-failure group was M184V(35.88%), K103N(45.01%), Y181C(17.33%), and G190S/A(15.88%). The percentages of HIV-1 strains resistant to lamivudine, emtricitabine, efavirenz, etravirine, and nevirapine were 10.70%, 10.70%, 28.04%, 7.75%, and 26.20%, respectively. To explore site variants possibly related to drug resistance, variations in the ancestor/consensus CRF07_BC sequences from the therapy-naive and ART-failure groups were compared, and seven mutations at six positions were identified as being significantly differently distributed between the two groups(p<0.05). Detailed sequence data will provide information on CRF07_BC genetic characterizations, and improve our understanding of antiretroviral susceptibility and the evolution of drug-resistance mutations. This will be valuable in developing and implementing local public-health approaches for HIV drug-resistance prevention and treatment.
基金supported by the National Grand Program on Key Infectious Disease Control(2012ZX10001-006,2012ZX10001-009 and 2012ZX10001-003)the National Outstanding Youth Award(30825035)+1 种基金the National Natural Science Foundation of China(81101236)the Tsinghua University Initiative Scientific Research Program
文摘VRC01, a broadly neutralizing monoclonal antibody （bnmAb）, can neutralize a diverse array of HIV-1 isolates by mimicking CD4 binding to the envelope glycoprotein gpl20. We have previously demonstrated the presence of VRC01-resistant strains in an HIV-1 infected patient during antiretroviral therapy. Here, we report follow-up studies of two subsequent samples from the same patient. With genetic and phenotypic analysis of over 70 full-length molecular clones of the HIV-1 envelope, we show that VRC01-resistant HIV-1 continued to exist and change in its proportion of the infecting virus during treatment with a highly active antiretroviral therapy. Consistent with our previous observation, the resistant phenotype was associated with a single asparagine residue at position 460 （N460）, a potential N-linked glycosylation site in the V5 region. The persistence and continuing evolution of VRC01-resistant HIV-1 in vivo presents a great challenge to our future preventative and therapeutic interventions based on VRC01.
