title: Persistence of VRC01-resistant HIV-1 during antiretroviral therapy.
abstract: VRC01, a broadly neutralizing monoclonal antibody (bnmAb), can neutralize a diverse array of HIV-1 isolates by mimicking CD4 binding to the envelope glycoprotein gp120. 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.
authors.affiliation: Beijing Tropical Medicine Research Institute, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
authors.forename: Dongxing
authors.initials: D
authors.lastname: Guo
authors.forename: Xuanling
authors.initials: X
authors.lastname: Shi
authors.forename: Dingka
authors.initials: D
authors.lastname: Song
authors.forename: Linqi
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D000080908:Broadly Neutralizing Antibodies; D015483:HIV Antibodies; D019302:HIV Envelope Protein gp160 / Q000235:genetics; D015658:HIV Infections / Q000628:therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D010802:Phylogeny
chemical_list: D000911:Antibodies, Monoclonal; D000080908:Broadly Neutralizing Antibodies; D015483:HIV Antibodies; D019302:HIV Envelope Protein gp160; C578595:VRC01 monoclonal antibody