PMID- 32070681 OWN - NLM STAT- MEDLINE DCOM- 20210217 LR - 20210217 IS - 1873-2518 (Electronic) IS - 0264-410X (Linking) VI - 38 IP - 12 DP - 2020 Mar 10 TI - Effect of HIV-exposure and timing of antiretroviral treatment initiation in children living with HIV on antibody persistence and memory responses to Haemophilus influenzae type b and pneumococcal polysaccharide-protein conjugate vaccines. PG - 2651-2659 LID - S0264-410X(20)30223-1 [pii] LID - 10.1016/j.vaccine.2020.02.026 [doi] AB - BACKGROUND: We investigated the effect of in utero HIV-exposure, timing of antiretroviral treatment (ART) initiation, and ART interruption on memory responses and persistence of immunity induced by pneumococcal (PCV) and Haemophilus influenzae type b (HibCV) polysaccharide-protein conjugate vaccines. METHODS: Children were enrolled (6-12 weeks of age), and vaccinated with a three-dose primary series of 7-valent PCV (PCV7) and HibCV at 6, 10 and 14 weeks of age. Study groups included infants infected with HIV perinatally with CD4+ >/= 25% initiating ART following immunological or clinical deterioration (ART-Def), or immediately upon enrolment followed by interruption at 40 (ART-Immed/40w) or 96 weeks (ART-Immed/96w); and HIV-uninfected infants with (HEU), and without HIV (HIV-unexpsoed) exposure in utero. Within each group, children were randomized to receive either a booster dose of PCV7 or HibCV at 15 months of age. PCV serotype-specific and polyribosyl ribitol phosphate (PRP) IgG were measured pre-boost, two-weeks post-boost and at two-years of age. Opsonophagocytic activity (OPA) to serotypes 9V, 19F and 23F was measured post-booster dose. RESULTS: Persistence of IgG to PCV vaccine-serotypes and anti-PRP was similar in all groups of children living with HIV (CLWH) compared to HIV-unexposed children. Anamnestic responses to PCV and HibCV were also similar in all three groups of CLWH compared to HIV-unexposed children. CLWH, however, tended to have lower functional antibody (OPA) titers than HIV-unexposed children after the PCV booster dose for some serotypes. Immunity to PCV and HibCV was similar between the ART-Immed/40w and ART-Immed-96w groups. There were no differences in IgG kinetics between HEU and HIV-unexposed children. CONCLUSIONS: A three dose primary series, with or without PCV or HibCV booster doses in CLWH initiated on ART during infancy, would likely be similarly effective in preventing invasive bacterial disease as in HIV-unexposed children. CI - Copyright (c) 2020 Elsevier Ltd. All rights reserved. FAU - Madhi, Shabir A AU - Madhi SA AD - Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, Faculty of Health Sciences, Johannesburg, South Africa; Department of Science/National Research Foundation: Vaccine Preventable Diseases, University of the Witwatersrand, Faculty of Health Science, Johannesburg, South Africa. Electronic address: madhis@rmpru.co.za. FAU - Izu, Alane AU - Izu A AD - Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, Faculty of Health Sciences, Johannesburg, South Africa; Department of Science/National Research Foundation: Vaccine Preventable Diseases, University of the Witwatersrand, Faculty of Health Science, Johannesburg, South Africa. FAU - Violari, Avy AU - Violari A AD - Perinatal HIV Research Unit, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa. FAU - Cotton, Mark F AU - Cotton MF AD - Family Center for Clinical Research Unit, Faculty of Medicinewith Ubuntu, Department of Paediatrics and ChildMedicine and Health Sciences, Stellenbosch University, Cape Town, South Africa. FAU - Jean-Philippe, Patrick AU - Jean-Philippe P AD - Division of AIDS National Institute of Allergy and Infectious Diseases, Bethesda, MD, United States. FAU - Otwombe, Kennedy AU - Otwombe K AD - Perinatal HIV Research Unit, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa. FAU - Adrian, Peter V AU - Adrian PV AD - Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, Faculty of Health Sciences, Johannesburg, South Africa; Department of Science/National Research Foundation: Vaccine Preventable Diseases, University of the Witwatersrand, Faculty of Health Science, Johannesburg, South Africa. CN - CIPRA 4 team LA - eng PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20200215 PL - Netherlands TA - Vaccine JT - Vaccine JID - 8406899 RN - 0 (Anti-Retroviral Agents) RN - 0 (Antibodies, Bacterial) RN - 0 (Polysaccharides) RN - 0 (Vaccines, Conjugate) SB - IM MH - Anti-Retroviral Agents/*therapeutic use MH - Antibodies, Bacterial/immunology MH - Child MH - Female MH - HIV Infections/complications/drug therapy/*immunology MH - Haemophilus influenzae type b/*immunology MH - Humans MH - *Immunologic Memory MH - Male MH - Polysaccharides/chemistry/*immunology MH - Streptococcus pneumoniae/*immunology MH - Vaccines, Conjugate/*administration & dosage/immunology OTO - NOTNLM OT - Antibody persistence OT - HIV OT - HIV exposure OT - Haemophilus influenzae type b conjugate vaccine OT - Memory responses OT - Opsonophagocytic assay OT - Pneumococcal conjugate vaccine OT - Streptococcus pneumoniae COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2020/02/20 06:00 MHDA- 2021/02/18 06:00 CRDT- 2020/02/20 06:00 PHST- 2019/12/02 00:00 [received] PHST- 2020/02/06 00:00 [revised] PHST- 2020/02/07 00:00 [accepted] PHST- 2020/02/20 06:00 [pubmed] PHST- 2021/02/18 06:00 [medline] PHST- 2020/02/20 06:00 [entrez] AID - S0264-410X(20)30223-1 [pii] AID - 10.1016/j.vaccine.2020.02.026 [doi] PST - ppublish SO - Vaccine. 2020 Mar 10;38(12):2651-2659. doi: 10.1016/j.vaccine.2020.02.026. Epub 2020 Feb 15.