Salvatore Rocca1,2, Paola Zangari2, Nicola Cotugno1,2, Anita De Rossi3, Bridget Ferns4, Davide Petricone1, Stefano Rinaldi5, Carlo Giaquinto6, Stefania Bernardi7, Pablo Rojo8, Paolo Rossi1,2,7, Savita Pahwa5,9, Eleni Nastouli4, Paolo Palma2. 1. Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy. 2. Research Unit in Congenital and Perinatal Infection, Immune and Infectious Diseases Division, Academic Department of Pediatrics (DPUO), Bambino Gesù Children's Hospital, Rome, Italy. 3. Section of Oncology and Immunology, DiSCOG, University of Padova, Italy; 3bis Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto (IOV)-IRCCS, Padova, Italy. 4. Virology Laboratory, Clinical Microbiology and Virology, University College London Hospital NHS Foundation Trust, London, United Kingdom. 5. Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Florida. 6. Department of Women's and Children's Health, University of Padova, Italy. 7. Academic Department of Pediatrics (DPUO), Bambino Gesù Children's Hospital-University of Rome Tor Vergata, Italy. 8. Department of Pediatrics, Pediatric Infectious Diseases Unit, Hospital 12 de Octubre, Universidad Complutense, Madrid, Spain. 9. Miami Center for AIDS Research, Miller School of Medicine, University of Miami, Florida.
Abstract
BACKGROUND: Assays to estimate human immunodeficiency virus (HIV) reservoir size require large amounts of blood, which represents a drawback especially in pediatric settings. We investigated whether HIV-antibody repertoire could estimate the viral reservoir size. Moreover, we assessed the magnitude of HIV-antibody response as a predictor of time of antiretroviral therapy (ART) initiation. METHODS: Human immunodeficiency virus-antibody responses to 10 different viral proteins were evaluated by HIV Western blot (WB) kit and a WB score was assigned to each patient. Patients were classified in 2 subgroups based on the timing of ART initiation (early treated [ET], 0-24 weeks and late treated [LT], >24 weeks). Human immunodeficiency virus-deoxyribonucleic acid (DNA) was quantified using real-time quantitative polymerase chain reaction on total peripheral blood mononuclear cells. Logistic regression and principal component analysis were built on these data to test the ability of WB score to predict the expected value of HIV-DNA and the timing of ART initiation. RESULTS: Sixty-nine perinatally HIV-infected children were evaluated. Reduced HIV-specific antibody responses and lower size of HIV-DNA were observed in ET compared with LT patients (P < .001 and P = .02, respectively). We found that WB score correlates with HIV-DNA (P = .032) and timing of ART initiation (P < .001). Based on the logistic regression analysis, we found that WB score can predict the HIV-DNA size and the timing of ART initiation with an Akaike information criterion of -118.13 and -151.51, respectively. CONCLUSIONS: Western blot score can estimate HIV-DNA size and timing of ART initiation in long-term virally suppressed children. This rapid, inexpensive, and easily reproducible tool can provide useful information to identify potential candidates for HIV remission studies.
BACKGROUND: Assays to estimate human immunodeficiency virus (HIV) reservoir size require large amounts of blood, which represents a drawback especially in pediatric settings. We investigated whether HIV-antibody repertoire could estimate the viral reservoir size. Moreover, we assessed the magnitude of HIV-antibody response as a predictor of time of antiretroviral therapy (ART) initiation. METHODS: Human immunodeficiency virus-antibody responses to 10 different viral proteins were evaluated by HIV Western blot (WB) kit and a WB score was assigned to each patient. Patients were classified in 2 subgroups based on the timing of ART initiation (early treated [ET], 0-24 weeks and late treated [LT], >24 weeks). Human immunodeficiency virus-deoxyribonucleic acid (DNA) was quantified using real-time quantitative polymerase chain reaction on total peripheral blood mononuclear cells. Logistic regression and principal component analysis were built on these data to test the ability of WB score to predict the expected value of HIV-DNA and the timing of ART initiation. RESULTS: Sixty-nine perinatally HIV-infected children were evaluated. Reduced HIV-specific antibody responses and lower size of HIV-DNA were observed in ET compared with LT patients (P < .001 and P = .02, respectively). We found that WB score correlates with HIV-DNA (P = .032) and timing of ART initiation (P < .001). Based on the logistic regression analysis, we found that WB score can predict the HIV-DNA size and the timing of ART initiation with an Akaike information criterion of -118.13 and -151.51, respectively. CONCLUSIONS: Western blot score can estimate HIV-DNA size and timing of ART initiation in long-term virally suppressed children. This rapid, inexpensive, and easily reproducible tool can provide useful information to identify potential candidates for HIV remission studies.
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