Andrew D Redd1,2, Marie Helleberg3, Matthew Sievers2, Stephen D Schmidt4, Nicole A Doria-Rose4, Daniel Bruno5, Shelby Traeger5, Craig Martens5, Jannik Fonager6, Gitte Kronborg7, Zoe Packman8, John R Mascola4, Stephen F Porcella5, Jan Gerstoft3, Thomas C Quinn1,2. 1. a Laboratory of Immunoregulation, Division of Intramural Research, NIAID, NIH , Bethesda , USA. 2. b Department of Medicine , Johns Hopkins University School of Medicine , Baltimore , MD , USA. 3. c Department of Infectious Diseases , Copenhagen University Hospital , Rigshospitalet , Denmark. 4. d Vaccine Research Center, NIAID, NIH , Bethesda , MD , USA. 5. e Genomics Unit, Research Technologies Branch, Rocky Mountain Laboratories, Division of Intramural Research, NIAID, NIH , Hamilton , MT , USA. 6. f Section for Virus Surveillance and Research, Department of Virus & Microbiological Special Diagnostics, Infectious Disease Preparedness , Statens Serum Institut , Copenhagen , Denmark. 7. g Department of Infectious Diseases , Copenhagen University Hospital , Hvidovre , Denmark. 8. h Department of Pathology , Johns Hopkins University School of Medicine , Baltimore , MD , USA.
Abstract
BACKGROUND: The role of the anti-HIV neutralizing antibody response in protecting against HIV superinfection, and changes in neutralizing antibody potency and breadth after HIV superinfection have not been fully elucidated. This study examined the rate of HIV superinfection in men who have sex with men (MSM) also diagnosed with syphilis in Denmark, and the anti-HIV neutralizing antibody response in men who became superinfected. MATERIALS AND METHODS: MSM enrolled in the Danish HIV cohort who acquired syphilis were examined longitudinally for HIV superinfection using a validated next-generation sequencing assay. HIV superinfection cases were matched 3:1 to controls, and neutralizing antibody responses before (cases/controls) and after (cases) HIV superinfection were determined using a 20-pseudovirus panel. RESULTS: Four cases of HIV superinfection were identified from 95 MSM screened for a rate of HIV superinfection of 1.56/100 pys (95% CI = 0.43-4.01). Prior to HIV superinfection neutralizing antibody responses were low in breadth and potency, and did not differ between cases and controls (p = 1.0). In cases, neutralizing antibody responses increased modestly after HIV superinfection. CONCLUSIONS: These data support the theory that the natural neutralizing antibody response to HIV infection may not be the controlling factor in protecting against a subsequent HIV challenge.
BACKGROUND: The role of the anti-HIV neutralizing antibody response in protecting against HIV superinfection, and changes in neutralizing antibody potency and breadth after HIV superinfection have not been fully elucidated. This study examined the rate of HIV superinfection in men who have sex with men (MSM) also diagnosed with syphilis in Denmark, and the anti-HIV neutralizing antibody response in men who became superinfected. MATERIALS AND METHODS: MSM enrolled in the Danish HIV cohort who acquired syphilis were examined longitudinally for HIV superinfection using a validated next-generation sequencing assay. HIV superinfection cases were matched 3:1 to controls, and neutralizing antibody responses before (cases/controls) and after (cases) HIV superinfection were determined using a 20-pseudovirus panel. RESULTS: Four cases of HIV superinfection were identified from 95 MSM screened for a rate of HIV superinfection of 1.56/100 pys (95% CI = 0.43-4.01). Prior to HIV superinfection neutralizing antibody responses were low in breadth and potency, and did not differ between cases and controls (p = 1.0). In cases, neutralizing antibody responses increased modestly after HIV superinfection. CONCLUSIONS: These data support the theory that the natural neutralizing antibody response to HIV infection may not be the controlling factor in protecting against a subsequent HIV challenge.
Entities:
Keywords:
Denmark; HIV superinfection; MSM; Neutralizing antibody
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