title: Neutralizing antibodies do not mediate suppression of human immunodeficiency virus type 1 in elite suppressors or selection of plasma virus variants in patients on highly active antiretroviral therapy.
abstract: Neutralizing antibodies (NAb) against autologous virus can reach high titers in human immunodeficiency virus type 1 (HIV-1)-infected patients with progressive disease. Less is known about the role of NAb in HIV-1-infected patients with viral loads of <50 copies/ml of plasma, including patients on effective highly active antiretroviral therapy (HAART) and elite suppressors, who control HIV-1 replication without antiretroviral therapy. In this study, we analyzed full-length env sequences from plasma viruses and proviruses in resting CD4(+) T cells of HAART-treated patients, elite suppressors, and untreated HIV-1-infected patients with progressive disease. For each patient group, we assessed plasma virus neutralization by autologous, contemporaneous plasma. The degree of env diversity, the number of N-linked glycosylation sites, and the lengths of variable loops were all lower in elite suppressors than in HAART-treated and untreated viremic patients. Both elite suppressors and HAART-treated patients had lower titers of NAb against HIV-1 lab strains than those of untreated viremic patients. Surprisingly, titers of NAb against autologous, contemporaneous plasma viruses were similarly low in chronic progressors, elite suppressors, and HAART-treated patients. In elite suppressors and HAART-treated patients, titers of NAb against autologous plasma viruses also did not differ significantly from titers against autologous proviruses from resting CD4(+) T cells. These results suggest that high-titer NAb are not required for maintenance of viral suppression in elite suppressors and that NAb do not select plasma virus variants in most HAART-treated patients. Both drug-mediated and natural suppression of HIV-1 replication to levels below 50 copies/ml may limit the stimulation and maintenance of effective NAb responses.
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Justin R
authors.initials: JR
authors.lastname: Bailey
authors.forename: Kara G
authors.initials: KG
authors.lastname: Lassen
authors.forename: Hung-Chih
authors.initials: HC
authors.lastname: Yang
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Quinn
authors.forename: Stuart C
authors.initials: SC
authors.lastname: Ray
authors.forename: Joel N
authors.initials: JN
authors.lastname: Blankson
authors.forename: Robert F
authors.initials: RF
authors.lastname: Siliciano
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D002908:Chronic Disease; D005260:Female; D015686:Gene Products, env / Q000235:genetics; D015483:HIV Antibodies / Q000494:pharmacology; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D014766:Viremia / Q000097:blood / Q000517:prevention & control / Q000821:virology
chemical_list: D015686:Gene Products, env; D015483:HIV Antibodies