Quantitative HIV-1-specific antibodies as predictors of peripheral blood cell-associated HIV-1 DNA concentrations
Program in Molecular Medicine; UMass Center for Clinical and Translational Science
Immunology of Infectious Disease | Immunoprophylaxis and Therapy | Immunotherapy | Infectious Disease | Pediatrics | Translational Medical Research | Virus Diseases | Viruses
OBJECTIVE: This study evaluated HIV-1 antibody levels as predictors of cell-associated HIV-1 DNA levels in perinatally infected (PHIV) children with long-term viral suppression on antiretroviral therapy (ART).
DESIGN: HIV-1 antibody and HIV-1 DNA levels were measured in blood specimens from 61 children and adolescents from the Pediatric HIV/AIDS Cohort Study: Adolescent Master Protocol. Twenty perinatally HIV-1-exposed, uninfected children studied through 2 years served as controls.
METHODS: HIV-1 IgG antibodies to six HIV-1 proteins were measured by quantitative ELISA; HIV-1 DNA levels were measured by droplet digital PCR.
RESULTS: Among 13 children with viral suppression at less than 1 year, antibodies to gp160 and gp41 were low but stable longitudinally; antibodies to p17, p24, and RT decreased, and antibodies to p31 were low or undetectable. Among 48 children with viral suppression between 1 and 5 years, antibody levels to all six HIV-1 proteins were higher than in children with earlier viral suppression and remained high over time. A receiver operator curve approach identified gp41 and gp160 as useful predictors of HIV-1 DNA less than 10 or less than 100 copies per million PBMC (cpm); C-statistics including all antibodies ranged from 0.75 to 0.77. An ensemble learning approach also identified gp41 and gp160 as important predictors of HIV-1 DNA less than 10 or less than 100 cpm; area under the curve estimates utilizing all HIV-1 antibodies ranged from 0.70 to 0.81.
CONCLUSION: Quantitative HIV-1 gp41 and gp160 antibody levels may serve as rapid, inexpensive screening tools for low PBMC HIV-1 DNA levels in children with viral suppression on ART, facilitating inclusion into remission protocols.
UMCCTS funding, antiretroviral therapy, ART, HIV-1, children
DOI of Published Version
McManus M, Karalius B, Patel K, Persaud D, Luzuriaga K; Pediatric HIV/AIDS Cohort Study. Quantitative HIV-1-specific antibodies as predictors of peripheral blood cell-associated HIV-1 DNA concentrations. AIDS. 2020 Jul 1;34(8):1117-1126. doi: 10.1097/QAD.0000000000002525. PMID: 32287055; PMCID: PMC7573836. Link to article on publisher's site
AIDS (London, England)
McManus MM, Karalius B, Patel K, Persaud D, Luzuriaga K, Pediatric HIV/AIDS Cohort Study. (2020). Quantitative HIV-1-specific antibodies as predictors of peripheral blood cell-associated HIV-1 DNA concentrations. University of Massachusetts Medical School Faculty Publications. https://doi.org/10.1097/QAD.0000000000002525. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/1946