BACKGROUND: Cross-sectional plasma human immunodeficiency virus (HIV) viral load (VL) measures have proven invaluable for clinical and research purposes. However, cross-sectional VL measures fail to capture cumulative plasma HIV burden longitudinally. We evaluated the cumulative effect of exposure to HIV replication on mortality following initiation of combination antiretroviral therapy (ART). METHODS: We included treatment-naive HIV-infected patients starting ART from 2000 to 2008 at 8 Center for AIDS Research Network of Integrated Clinical Systems sites. Viremia copy-years, a time-varying measure of cumulative plasma HIV exposure, were determined for each patient using the area under the VL curve. Multivariable Cox models were used to evaluate the independent association of viremia copy-years for all-cause mortality. RESULTS: Among 2027 patients contributing 6579 person-years of follow-up, the median viremia copy-years was 5.3 log₁₀ copy × y/mL (interquartile range: 4.9-6.3 log₁₀ copy × y/mL), and 85 patients (4.2%) died. When evaluated separately, viremia copy-years (hazard ratio [HR] = 1.81 per log₁₀ copy × y/mL; 95% confidence interval [CI], 1.51-2.18 per log(10) copy × y/mL), 24-week VL (1.74 per log₁₀ copies/mL; 95% CI, 1.48-2.04 per log₁₀ copies/mL), and most recent VL (HR = 1.89 per log₁₀ copies/mL; 95% CI: 1.63-2.20 per log₁₀ copies/mL) were associated with increased mortality. When simultaneously evaluating VL measures and controlling for other covariates, viremia copy-years increased mortality risk (HR = 1.44 per log₁₀ copy × y/mL; 95% CI, 1.07-1.94 per log₁₀ copy × y/mL), whereas no cross-sectional VL measure was independently associated with mortality. CONCLUSIONS: Viremia copy-years predicted all-cause mortality independent of traditional, cross-sectional VL measures and time-updated CD4+ T-lymphocyte count in ART-treated patients, suggesting cumulative HIV replication causes harm independent of its effect on the degree of immunodeficiency.
BACKGROUND: Cross-sectional plasma human immunodeficiency virus (HIV) viral load (VL) measures have proven invaluable for clinical and research purposes. However, cross-sectional VL measures fail to capture cumulative plasma HIV burden longitudinally. We evaluated the cumulative effect of exposure to HIV replication on mortality following initiation of combination antiretroviral therapy (ART). METHODS: We included treatment-naive HIV-infectedpatients starting ART from 2000 to 2008 at 8 Center for AIDS Research Network of Integrated Clinical Systems sites. Viremia copy-years, a time-varying measure of cumulative plasma HIV exposure, were determined for each patient using the area under the VL curve. Multivariable Cox models were used to evaluate the independent association of viremia copy-years for all-cause mortality. RESULTS: Among 2027 patients contributing 6579 person-years of follow-up, the median viremia copy-years was 5.3 log₁₀ copy × y/mL (interquartile range: 4.9-6.3 log₁₀ copy × y/mL), and 85 patients (4.2%) died. When evaluated separately, viremia copy-years (hazard ratio [HR] = 1.81 per log₁₀ copy × y/mL; 95% confidence interval [CI], 1.51-2.18 per log(10) copy × y/mL), 24-week VL (1.74 per log₁₀ copies/mL; 95% CI, 1.48-2.04 per log₁₀ copies/mL), and most recent VL (HR = 1.89 per log₁₀ copies/mL; 95% CI: 1.63-2.20 per log₁₀ copies/mL) were associated with increased mortality. When simultaneously evaluating VL measures and controlling for other covariates, viremia copy-years increased mortality risk (HR = 1.44 per log₁₀ copy × y/mL; 95% CI, 1.07-1.94 per log₁₀ copy × y/mL), whereas no cross-sectional VL measure was independently associated with mortality. CONCLUSIONS:Viremia copy-years predicted all-cause mortality independent of traditional, cross-sectional VL measures and time-updated CD4+ T-lymphocyte count in ART-treated patients, suggesting cumulative HIV replication causes harm independent of its effect on the degree of immunodeficiency.
Authors: S Kim; M D Hughes; S M Hammer; J B Jackson; V DeGruttola; D A Katzenstein Journal: AIDS Res Hum Retroviruses Date: 2000-05-01 Impact factor: 2.205
Authors: G Chêne; J A C Sterne; M May; D Costagliola; B Ledergerber; A N Phillips; F Dabis; J Lundgren; A D'Arminio Monforte; F de Wolf; R Hogg; P Reiss; A Justice; C Leport; S Staszewski; J Gill; G Fatkenheuer; M E Egger Journal: Lancet Date: 2003-08-30 Impact factor: 79.321
Authors: T C Quinn; M J Wawer; N Sewankambo; D Serwadda; C Li; F Wabwire-Mangen; M O Meehan; T Lutalo; R H Gray Journal: N Engl J Med Date: 2000-03-30 Impact factor: 91.245
Authors: Matthias Egger; Margaret May; Geneviève Chêne; Andrew N Phillips; Bruno Ledergerber; François Dabis; Dominique Costagliola; Antonella D'Arminio Monforte; Frank de Wolf; Peter Reiss; Jens D Lundgren; Amy C Justice; Schlomo Staszewski; Catherine Leport; Robert S Hogg; Caroline A Sabin; M John Gill; Bernd Salzberger; Jonathan A C Sterne Journal: Lancet Date: 2002-07-13 Impact factor: 79.321
Authors: Stephen R Cole; Miguel A Hernán; James M Robins; Kathryn Anastos; Joan Chmiel; Roger Detels; Carolyn Ervin; Joseph Feldman; Ruth Greenblatt; Lawrence Kingsley; Shenghan Lai; Mary Young; Mardge Cohen; Alvaro Muñoz Journal: Am J Epidemiol Date: 2003-10-01 Impact factor: 4.897
Authors: Timothy W Schacker; Phuong L Nguyen; Gregory J Beilman; Steven Wolinsky; Matthew Larson; Cavan Reilly; Ashley T Haase Journal: J Clin Invest Date: 2002-10 Impact factor: 14.808
Authors: W M El-Sadr; J D Lundgren; J D Neaton; F Gordin; D Abrams; R C Arduino; A Babiker; W Burman; N Clumeck; C J Cohen; D Cohn; D Cooper; J Darbyshire; S Emery; G Fätkenheuer; B Gazzard; B Grund; J Hoy; K Klingman; M Losso; N Markowitz; J Neuhaus; A Phillips; C Rappoport Journal: N Engl J Med Date: 2006-11-30 Impact factor: 91.245
Authors: Bruno Ledergerber; Jens D Lundgren; A Sarah Walker; Caroline Sabin; Amy Justice; Peter Reiss; Cristina Mussini; Ferdinand Wit; Antonella d'Arminio Monforte; Rainer Weber; Gregory Fusco; Schlomo Staszewski; Matthew Law; Robert Hogg; Fiona Lampe; M John Gill; Francesco Castelli; Andrew N Phillips Journal: Lancet Date: 2004 Jul 3-9 Impact factor: 79.321
Authors: Michael J Mugavero; K Rivet Amico; Andrew O Westfall; Heidi M Crane; Anne Zinski; James H Willig; Julia C Dombrowski; Wynne E Norton; James L Raper; Mari M Kitahata; Michael S Saag Journal: J Acquir Immune Defic Syndr Date: 2012-01-01 Impact factor: 3.731
Authors: Elizabeth L Yanik; Sonia Napravnik; Stephen R Cole; Chad J Achenbach; Satish Gopal; Dirk P Dittmer; Andrew F Olshan; Mari M Kitahata; Michael J Mugavero; Michael Saag; Richard D Moore; W Christopher Mathews; Peter Hunt; Joseph J Eron Journal: AIDS Date: 2014-04-24 Impact factor: 4.177
Authors: Zaza M Ndhlovu; Samuel W Kazer; Thandeka Nkosi; Funsho Ogunshola; Daniel M Muema; Gursev Anmole; Shayda A Swann; Amber Moodley; Krista Dong; Tarylee Reddy; Mark A Brockman; Alex K Shalek; Thumbi Ndung'u; Bruce D Walker Journal: Sci Transl Med Date: 2019-05-22 Impact factor: 17.956
Authors: Chad J Achenbach; Ashley L Buchanan; Stephen R Cole; Lifang Hou; Michael J Mugavero; Heidi M Crane; Richard D Moore; Richard H Haubrich; Satish Gopal; Joseph J Eron; Peter W Hunt; Benigno Rodriguez; Kenneth Mayer; Michael S Saag; Mari M Kitahata Journal: Clin Infect Dis Date: 2014-02-12 Impact factor: 9.079
Authors: Joseph A Delaney; Robin M Nance; Bridget M Whitney; Heidi M Crane; Jessica Williams-Nguyen; Mathew J Feinstein; Robert C Kaplan; David B Hanna; Matthew J Budoff; Daniel R Drozd; Greer Burkholder; Michael J Mugavero; William C Mathews; Richard D Moore; Joseph J Eron; Peter W Hunt; Elvin Geng; Michael S Saag; Mari M Kitahata; Susan R Heckbert Journal: Epidemiology Date: 2019-01 Impact factor: 4.822
Authors: Stephen T Wright; Jennifer Hoy; Brian Mulhall; Catherine C Oʼconnor; Kathy Petoumenos; Timothy Read; Don Smith; Ian Woolley; Mark A Boyd Journal: J Acquir Immune Defic Syndr Date: 2014-05-01 Impact factor: 3.731
Authors: Jessie K Edwards; Stephen R Cole; H Irene Hall; W Christopher Mathews; Richard D Moore; Michael J Mugavero; Joseph J Eron Journal: AIDS Date: 2018-01-14 Impact factor: 4.177
Authors: Sonia Napravnik; Joseph J Eron; Timothy R Sterling; Timothy Juday; Jonathan Uy; Richard D Moore Journal: AIDS Res Hum Retroviruses Date: 2012-11-12 Impact factor: 2.205