title: Estimating the benefit of an HIV-1 vaccine that reduces viral load set point.
abstract: Vaccines designed to induce cell-mediated immune responses against human immunodeficiency virus (HIV)-1 are being developed. Such vaccines are unlikely to provide sterilizing immunity but may be associated with reduced viral set points after infection. We modeled the potential impact of a vaccine that reduces viral set point after infection, using natural history data from 311 HIV-1 seroconverters. Log-normal parametric regression models were used to estimate the log median time to events of interest. Relative times were estimated for those with viral load set points of 30,000 copies/mL (reference group) versus those with lower viral set points. The time to key clinical events in the course of HIV-1 disease progression was significantly extended for those with viral set points 0.5-1.25 log(10) copies/mL lower than the reference group. By quantifying the anticipated clinical benefits associated with a reduction in viral set point, these findings support the use of virologic end points in HIV-1 vaccine trials.
authors.affiliation: Merck Research Laboratories, West Point, PA, USA. swati_gupta@merck.com
authors.forename: Swati B
authors.initials: SB
authors.lastname: Gupta
authors.forename: Lisa P
authors.initials: LP
authors.lastname: Jacobson
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Margolick
authors.forename: Charles R
authors.initials: CR
authors.lastname: Rinaldo
authors.forename: John P
authors.initials: JP
authors.lastname: Phair
authors.forename: Beth D
authors.initials: BD
authors.lastname: Jamieson
authors.forename: Devan V
authors.initials: DV
authors.lastname: Mehrotra
authors.forename: Michael N
authors.initials: MN
authors.lastname: Robertson
authors.forename: Walter L
authors.initials: WL
authors.lastname: Straus
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D015331:Cohort Studies; D018450:Disease Progression; D015658:HIV Infections / Q000276:immunology* / Q000628:therapy / Q000821:virology*; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology*; D006801:Humans; D008297:Male; D012044:Regression Analysis; D013997:Time Factors; D019562:Viral Load
chemical_list: D016915:AIDS Vaccines