OBJECTIVE: HIV cure research urgently needs to identify pre-analytic treatment interruption (ATI) biomarkers of time-to-viral-rebound and viral setpoint to mitigate the risk of ATI and accelerate development of a cure. We previously reported that galactosylated IgG glycans, G2, negatively correlate with cell-associated HIV DNA and RNA during antiretroviral therapy (ART). We hypothesized that this and other plasma glycomic traits can predict time-to-viral-rebound and viral setpoint upon ART cessation. DESIGN: We profiled the circulating glycomes (plasma and bulk IgG) of two geographically distinct cohorts: Philadelphia Cohort - 24 HIV-infected, ART-suppressed individuals who had participated in an open-ended ATI study without concurrent immunomodulatory agents. Johannesburg Cohort - 23 HIV-infected, ART-suppressed individuals who had participated in a 2-week ATI. METHODS: Capillary electrophoresis and lectin microarray were used for glycomic analyses. Cox proportional-hazards model and log-rank test were used for statistical analyses. RESULTS: Higher pre-ATI levels of the IgG glycan, G2, were significantly associated with a longer time-to-viral-rebound (hazard ratio = 0.12, P = 0.05). In addition to G2, we identified several predictive glycomic traits in plasma, for example, levels of FA2BG1, a non-sialylated, core-fucosylated glycan, associated with a longer time-to-viral-rebound (hazard ratio = 0.023, P = 0.05), whereas FA2G2S1, a sialylated glycan, associated with a shorter time-to-viral-rebound (hazard ratio = 24.1, P = 0.028). Additionally, pre-ATI plasma glycomic signatures associated with a lower viral setpoint, for example, T-antigen (Galβ1-3GalNAc) (r = 0.75, P = 0.0007), or a higher viral setpoint, for example, polylactosamine (r = -0.58, P = 0.01). These results were initially validated in the Johannesburg Cohort. CONCLUSION: We describe first-in-class, non-invasive, plasma and IgG glycomic biomarkers that inform time-to-viral-rebound and viral setpoint in two geographically distinct cohorts.
OBJECTIVE: HIV cure research urgently needs to identify pre-analytic treatment interruption (ATI) biomarkers of time-to-viral-rebound and viral setpoint to mitigate the risk of ATI and accelerate development of a cure. We previously reported that galactosylated IgG glycans, G2, negatively correlate with cell-associated HIV DNA and RNA during antiretroviral therapy (ART). We hypothesized that this and other plasma glycomic traits can predict time-to-viral-rebound and viral setpoint upon ART cessation. DESIGN: We profiled the circulating glycomes (plasma and bulk IgG) of two geographically distinct cohorts: Philadelphia Cohort - 24 HIV-infected, ART-suppressed individuals who had participated in an open-ended ATI study without concurrent immunomodulatory agents. Johannesburg Cohort - 23 HIV-infected, ART-suppressed individuals who had participated in a 2-week ATI. METHODS: Capillary electrophoresis and lectin microarray were used for glycomic analyses. Cox proportional-hazards model and log-rank test were used for statistical analyses. RESULTS: Higher pre-ATI levels of the IgG glycan, G2, were significantly associated with a longer time-to-viral-rebound (hazard ratio = 0.12, P = 0.05). In addition to G2, we identified several predictive glycomic traits in plasma, for example, levels of FA2BG1, a non-sialylated, core-fucosylated glycan, associated with a longer time-to-viral-rebound (hazard ratio = 0.023, P = 0.05), whereas FA2G2S1, a sialylated glycan, associated with a shorter time-to-viral-rebound (hazard ratio = 24.1, P = 0.028). Additionally, pre-ATI plasma glycomic signatures associated with a lower viral setpoint, for example, T-antigen (Galβ1-3GalNAc) (r = 0.75, P = 0.0007), or a higher viral setpoint, for example, polylactosamine (r = -0.58, P = 0.01). These results were initially validated in the Johannesburg Cohort. CONCLUSION: We describe first-in-class, non-invasive, plasma and IgG glycomic biomarkers that inform time-to-viral-rebound and viral setpoint in two geographically distinct cohorts.
Authors: Amy W Chung; Max Crispin; Laura Pritchard; Hannah Robinson; Miroslaw K Gorny; Xiaojie Yu; Chris Bailey-Kellogg; Margaret E Ackerman; Chris Scanlan; Susan Zolla-Pazner; Galit Alter Journal: AIDS Date: 2014-11-13 Impact factor: 4.177
Authors: Jonathan Z Li; Behzad Etemad; Hayat Ahmed; Evgenia Aga; Ronald J Bosch; John W Mellors; Daniel R Kuritzkes; Michael M Lederman; Michael Para; Rajesh T Gandhi Journal: AIDS Date: 2016-01-28 Impact factor: 4.177
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: Irena Trbojević Akmačić; Nicholas T Ventham; Evropi Theodoratou; Frano Vučković; Nicholas A Kennedy; Jasminka Krištić; Elaine R Nimmo; Rahul Kalla; Hazel Drummond; Jerko Štambuk; Malcolm G Dunlop; Mislav Novokmet; Yurii Aulchenko; Olga Gornik; Harry Campbell; Maja Pučić Baković; Jack Satsangi; Gordan Lauc Journal: Inflamm Bowel Dis Date: 2015-06 Impact factor: 5.325
Authors: Frano Vučković; Jasminka Krištić; Ivan Gudelj; Maria Teruel; Toma Keser; Marija Pezer; Maja Pučić-Baković; Jerko Štambuk; Irena Trbojević-Akmačić; Clara Barrios; Tamara Pavić; Cristina Menni; Youxin Wang; Yong Zhou; Liufu Cui; Haicheng Song; Qiang Zeng; Xiuhua Guo; Bernardo A Pons-Estel; Paul McKeigue; Alan Leslie Patrick; Olga Gornik; Tim D Spector; Miroslav Harjaček; Marta Alarcon-Riquelme; Mariam Molokhia; Wei Wang; Gordan Lauc Journal: Arthritis Rheumatol Date: 2015-11 Impact factor: 10.995
Authors: James P Williams; Jacob Hurst; Wolfgang Stöhr; Nicola Robinson; Helen Brown; Martin Fisher; Sabine Kinloch; David Cooper; Mauro Schechter; Giuseppe Tambussi; Sarah Fidler; Mary Carrington; Abdel Babiker; Jonathan Weber; Kersten K Koelsch; Anthony D Kelleher; Rodney E Phillips; John Frater Journal: Elife Date: 2014-09-12 Impact factor: 8.140
Authors: Leila B Giron; Florent Colomb; Emmanouil Papasavvas; Livio Azzoni; Xiangfan Yin; Matthew Fair; Alitzel Anzurez; Mohammad Damra; Karam Mounzer; Jay R Kostman; Pablo Tebas; Una O'Doherty; Hiroaki Tateno; Qin Liu; Michael R Betts; Luis J Montaner; Mohamed Abdel-Mohsen Journal: EBioMedicine Date: 2020-08-19 Impact factor: 8.143
Authors: Michael J Corley; Alina P S Pang; Thomas A Rasmussen; Martin Tolstrup; Ole S Søgaard; Lishomwa C Ndhlovu Journal: AIDS Date: 2021-11-15 Impact factor: 4.177
Authors: Christina K Psomas; Karl Salzwedel; Mario Stevenson; Guido Poli; Jean-Pierre Routy; David Margolis; Nicolas Chomont; Alain Lafeuillade Journal: J Virus Erad Date: 2020-04-30
Authors: Yannic C Bartsch; Carolin Loos; Evan Rossignol; Jesse M Fajnzylber; Dansu Yuan; Anchalee Avihingsanon; Sasiwimol Ubolyam; Thidarat Jupimai; Bernard Hirschel; Jintanat Ananworanich; Douglas A Lauffenburger; Jonathan Z Li; Galit Alter; Boris Julg Journal: mBio Date: 2021-03-09 Impact factor: 7.867
Authors: Leila B Giron; Clovis S Palmer; Qin Liu; Xiangfan Yin; Emmanouil Papasavvas; Radwa Sharaf; Behzad Etemad; Mohammad Damra; Aaron R Goldman; Hsin-Yao Tang; Rowena Johnston; Karam Mounzer; Jay R Kostman; Pablo Tebas; Alan Landay; Luis J Montaner; Jeffrey M Jacobson; Jonathan Z Li; Mohamed Abdel-Mohsen Journal: Nat Commun Date: 2021-06-29 Impact factor: 17.694
Authors: Mohamed Abdel-Mohsen; Douglas Richman; Robert F Siliciano; Michel C Nussenzweig; Bonnie J Howell; Javier Martinez-Picado; Nicolas Chomont; Katharine J Bar; Xu G Yu; Mathias Lichterfeld; Jose Alcami; Daria Hazuda; Frederic Bushman; Janet D Siliciano; Michael R Betts; Adam M Spivak; Vicente Planelles; Beatrice H Hahn; Davey M Smith; Ya-Chi Ho; Maria J Buzon; Christian Gaebler; Mirko Paiardini; Qingsheng Li; Jacob D Estes; Thomas J Hope; Jay Kostman; Karam Mounzer; Marina Caskey; Lawrence Fox; Ian Frank; James L Riley; Pablo Tebas; Luis J Montaner Journal: Nat Med Date: 2020-09-07 Impact factor: 87.241
Authors: Florent Colomb; Leila B Giron; Leticia Kuri-Cervantes; Opeyemi S Adeniji; Tongcui Ma; Harsh Dweep; Emilie Battivelli; Eric Verdin; Clovis S Palmer; Hiroaki Tateno; Andrew V Kossenkov; Nadia R Roan; Michael R Betts; Mohamed Abdel-Mohsen Journal: Cell Rep Date: 2020-08-04 Impact factor: 9.423