OBJECTIVE: Our objective was to define early virologic and immunologic determinants of human immunodeficiency virus (HIV) type 1 disease progression among 22 case subjects with acute infection from the Trinidad Seroconvertor Cohort. METHODS: A linear segmented regression model was fitted to sequential quantitative virus load measurements. Parameters of virus kinetics during different phases of primary infection were correlated with clinical and immunologic end points, by use of Kaplan-Meier estimates and Cox regression. RESULTS: Ten individuals developed acquired immunodeficiency syndrome (AIDS)-defining events. In univariate analysis, progression to AIDS was associated with rate of initial HIV clearance (P=.002), virus load during set point (P=.008), and CD4(+) cell count during steady state (P=.04). In the multivariate analysis, a rapid rate of initial clearance was the sole independent predictor of subsequent progression to AIDS and was associated with a 92% reduction in the risk of AIDS. The rate of initial clearance is inversely correlated with the number of early symptoms (r=-0.66; P=.0008). However, symptoms did not predict subsequent risk of AIDS. CONCLUSION: Among a subset of patients, rapid clearance of plasma HIV-1 after peak viremia is associated with lower viral set point, prolonged virus suppression before loss of virologic control, and decreased risk of AIDS. These findings are consistent with the hypothesis that effective immune responses during the earliest phase of infection are important determinants of the subsequent natural history.
OBJECTIVE: Our objective was to define early virologic and immunologic determinants of human immunodeficiency virus (HIV) type 1 disease progression among 22 case subjects with acute infection from the Trinidad Seroconvertor Cohort. METHODS: A linear segmented regression model was fitted to sequential quantitative virus load measurements. Parameters of virus kinetics during different phases of primary infection were correlated with clinical and immunologic end points, by use of Kaplan-Meier estimates and Cox regression. RESULTS: Ten individuals developed acquired immunodeficiency syndrome (AIDS)-defining events. In univariate analysis, progression to AIDS was associated with rate of initial HIV clearance (P=.002), virus load during set point (P=.008), and CD4(+) cell count during steady state (P=.04). In the multivariate analysis, a rapid rate of initial clearance was the sole independent predictor of subsequent progression to AIDS and was associated with a 92% reduction in the risk of AIDS. The rate of initial clearance is inversely correlated with the number of early symptoms (r=-0.66; P=.0008). However, symptoms did not predict subsequent risk of AIDS. CONCLUSION: Among a subset of patients, rapid clearance of plasma HIV-1 after peak viremia is associated with lower viral set point, prolonged virus suppression before loss of virologic control, and decreased risk of AIDS. These findings are consistent with the hypothesis that effective immune responses during the earliest phase of infection are important determinants of the subsequent natural history.
Authors: Frederick M Hecht; Robert Wellman; Michael P Busch; Christopher D Pilcher; Philip J Norris; Joseph B Margolick; Ann C Collier; Susan J Little; Martin Markowitz; Jean-Pierre Routy; Sarah Holte Journal: J Infect Dis Date: 2011-08-15 Impact factor: 5.226
Authors: Sumathi Sankaran; Michael D George; Elizabeth Reay; Moraima Guadalupe; Jason Flamm; Thomas Prindiville; Satya Dandekar Journal: J Virol Date: 2007-10-24 Impact factor: 5.103
Authors: Vladimir Novitsky; Rui Wang; Hermann Bussmann; Shahin Lockman; Marianna Baum; Roger Shapiro; Ibou Thior; Carolyn Wester; C William Wester; Anthony Ogwu; Aida Asmelash; Rosemary Musonda; Adriana Campa; Sikhulile Moyo; Erik van Widenfelt; Madisa Mine; Claire Moffat; Mompati Mmalane; Joseph Makhema; Richard Marlink; Peter Gilbert; George R Seage; Victor DeGruttola; M Essex Journal: PLoS One Date: 2010-04-12 Impact factor: 3.240
Authors: Xiaoying Shen; Robert J Parks; David C Montefiori; Jennifer L Kirchherr; Brandon F Keele; Julie M Decker; William A Blattner; Feng Gao; Kent J Weinhold; Charles B Hicks; Michael L Greenberg; Beatrice H Hahn; George M Shaw; Barton F Haynes; Georgia D Tomaras Journal: J Virol Date: 2009-02-04 Impact factor: 5.103
Authors: C Koegl; E Wolf; N Hanhoff; H Jessen; K Schewe; M Rausch; J Goelz; A Goetzenich; H Knechten; H Jaeger; W Becker; I Becker-Boost; D Berzow; B Beiniek; J Brust; D Shcuster; S Dupke; S Fenske; H J Gellermann; R Gippert; P Hartmann; B Hintsche; H Jaeger; E Jaegel-Guedes; H Jessen; J Gölz; J Koelzsch; E B Helm; G Knecht; H Knechten; I Lochet; P Gute; S Mauruschat; S Mauss; V Miasnikov; F A Mosthaf; M Rausch; M Freiwald; B Reuter; H M Schalk; B Schappert; E Schnaitmann; I Schneider; W Schüler-Maué; C Schuler; T Seidel; W Starke; A Ulmer; M Müller; I Weitner; K Schewe; C Zamani; A Hanmond; K Ross; A Bottlaender; C Hoffmann; A Dix; A Schneidewind; M Lademann Journal: Eur J Med Res Date: 2009-07-22 Impact factor: 2.175
Authors: N L Yates; A R Stacey; T L Nolen; N A Vandergrift; M A Moody; D C Montefiori; K J Weinhold; W A Blattner; P Borrow; R Shattock; M S Cohen; B F Haynes; G D Tomaras Journal: Mucosal Immunol Date: 2013-01-09 Impact factor: 7.313