title: Longitudinal study of humoral immune responses in HIV type 1 subtype CRF01_AE (E)-infected Thai patients with different rates of disease progression.
abstract: Identification of immune correlates associated with disease progression will provide information for HIV-1 vaccine design in countries such as Thailand, where the prevalent subtypes (B and CRF01_AE [E]) are characterized. In this study, plasma viral load and humoral immune responses were measured in 20 HIV-1 subtype E-infected Thai patients with different rates of disease progression, based on CD4(+) T cell decline and clinical symptoms. Nine progressors (PRs) and 11 slower progressors (SPs) were evaluated. CD4(+) T cell counts were inversely correlated with viral load (p = 0.004) and positively correlated with p24 Ab (p = 0.022). In progressors, p24 Ab showed a significant decrease (p < 0.001) over time. V3 and gp41 Ab did not change significantly in either group. Both CD4-binding site (CD4/gp120BS) and gp120 titers correlated positively with neutralizing antibody (NAb) against both a subtype E cell line-adapted virus (NP03) and a primary isolate (TH023). However, V3 Ab correlated only with NAb against NP03 (p < 0.001). Increased NAb over time was observed more frequently in SPs as compared with PRs, against both the TH023 (p = 0.004) and NPO3 (p = 0.004) viruses. Cross-clade antibody-dependent cellular cytotoxicity was demonstrated in both groups. These data suggest that in HIV-1 subtype E infection, declining p24 Ab titer is a predictive marker of disease progression, as described for subtype B. Furthermore, in subtype E-infected patients, slower progressors retain the immune competence to develop new antibody responses to Env over time; these evolving responses may contribute to prolonged survival during HIV-1 disease progression.
authors.affiliation: Armed Forces Research Institute of Medical Sciences, Bangkok 10400, Thailand.
authors.forename: Thippawan
authors.initials: T
authors.lastname: Chuenchitra
authors.forename: Chantapong
authors.initials: C
authors.lastname: Wasi
authors.forename: Suda
authors.initials: S
authors.lastname: Louisirirojchanakul
authors.forename: Sorachai
authors.initials: S
authors.lastname: Nitayaphan
authors.forename: Ruengpung
authors.initials: R
authors.lastname: Sutthent
authors.forename: Josephine H
authors.initials: JH
authors.lastname: Cox
authors.forename: Mark S
authors.initials: MS
authors.lastname: De Souza
authors.forename: Arthur E
authors.initials: AE
authors.lastname: Brown
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Birx
authors.forename: Victoria R
authors.initials: VR
authors.lastname: Polonis
mesh_terms: D000920:Antibody-Dependent Cell Cytotoxicity; D018791:CD4 Lymphocyte Count; D019742:Chemokines, CC / Q000097:blood; D004279:DNA, Viral / Q000097:blood; D018450:Disease Progression; D015686:Gene Products, env / Q000276:immunology; D015683:Gene Products, gag / Q000276:immunology; D015483:HIV Antibodies / Q000097:blood*; D015658:HIV Infections / Q000276:immunology / Q000503:physiopathology*; D015497:HIV-1 / Q000145:classification / Q000276:immunology*; D006801:Humans; D008137:Longitudinal Studies; D009500:Neutralization Tests; D013785:Thailand; D019562:Viral Load
chemical_list: D019742:Chemokines, CC; D004279:DNA, Viral; D015686:Gene Products, env; D015683:Gene Products, gag; D015483:HIV Antibodies