HIV-1 superinfection can occur in the presence of broadly neutralizing antibodies |
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| Institution: | 1. MRC/UVRI Uganda Research Unit on AIDS; c/o Uganda Virus Research Institute, Entebbe, Uganda;2. National Institute for Communicable Diseases, Johannesburg, South Africa;7. Aalto University School of Science, Department of Mathematics, and Systems Analysis, Finland;9. Genomics Unit, Research Technologies Branch, Rocky Mountain Laboratories, Division of Intramural Research, NIAID, NIH, Hamilton, MT, USA;1. MRC/UVRI Uganda Research Unit on AIDS, c/o Uganda Virus Research Institute, Entebbe, Uganda;2. National Institute for Communicable Diseases, Johannesburg, South Africa;3. Center for the AIDS Program of Research in South Africa (CAPRISA), South Africa;8. University of the Witwatersrand, Johannesburg, South Africa;4. Laboratory of Immunoregulation, Division of Intramural Research, NIAID, NIH, Bethesda, USA;5. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA;6. London School of Hygiene and Tropical Medicine, Department of Clinical Research, London, UK;1. Centre for HIV and STIs, National Institute for Communicable Diseases, National Health Laboratory Service, Johannesburg, South Africa;2. Department of Medical Virology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa;3. School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa;4. Empilweni Services and Research Unit, Rahima Moosa Mother and Child Hospital, Department of Paediatrics and Child Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa;5. Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, USA;6. Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, USA;7. ICAP, Mailman School of Public Health, Columbia University, New York, NY, USA;8. Department of Pediatrics, College of Physicians & Surgeons, Columbia University, New York, USA;1. Real-time Syndromic Surveillance Team, National Infection Service, Public Health England, 1st Floor, 5 St Philips Place, Birmingham B3 2PW, United Kingdom;2. The Phoenix Partnership (TPP), TPP House, 129 Low Lane, Horsforth, Leeds LS18 5PX, United Kingdom;3. Public Health England West Midlands, 6th Floor, 5 St Philips Place, Birmingham B3 2PW, United Kingdom;4. Immunisation, Hepatitis and Blood Safety Department, National Infection Service, Public Health England, 61 Colindale Avenue, London NW9 5EQ, United Kingdom;5. Royal College of General Practitioners Research and Surveillance Centre, University of Surrey, Section of Clinical Medicine and Ageing, Guildford, Surrey GU2 7XH, United Kingdom;1. School of Public Health and Community Medicine, UNSW Medicine, The University of New South Wales, Sydney, NSW, Australia;2. National Centre for Immunisation Research and Surveillance, Westmead, NSW, Australia;3. Centre for Infectious Diseases and Microbiology Laboratory Services, New South Wales Health Pathology—Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, NSW, Australia;1. Department of Cardiological, Thoracic, and Vascular Sciences, and Public Health, Hygiene and Public Health Unit, University of Padua, Via Loredan 18, 35128 Padova, Italy;2. Department of Preventive Health Care, South Tyrolean Health Service, Via Amba Alagi 33, 39100 Bolzano, Italy;1. Immunization Safety Office, Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, United States;2. Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention, Centers for Disease Control and Prevention, United States;3. Division of Tuberculosis Elimination, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, United States |
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| Abstract: | BackgroundSuperinfection of individuals already infected with HIV-1 suggests that pre-existing immune responses may not adequately protect against re-infection. We assessed high-risk female sex workers initially infected with HIV-1 clades A, D or A/D recombinants, to determine if HIV-1 broadly neutralizing antibodies were lacking prior to superinfection.MethodsSix superinfected female sex workers previously stratified by HIV-1 high-risk behavior, infecting virus clade and volunteer CD4 counts were evaluated at baseline (n = 5) and at 350 days post-superinfection (n = 6); one superinfected volunteer lacked pre-superinfection plasma. Retrospective plasmas were assessed for neutralization of a multi-clade panel of 12 HIV-1 viruses before superinfection, and then at quarterly intervals thereafter. Similarly stratified singly infected female sex workers were correspondingly assessed at baseline (n = 19) and 350 days after superinfection (n = 24). Neutralization of at least 50% of the 12 viruses (broad neutralization), and geometric means of the neutralization titers (IC50) were compared before and after superinfection; and were correlated with the volunteer HIV-1 superinfection status, CD4 counts, and pseudovirus clade.ResultsPreexisting broad neutralization occurred in 80% (4/5) of the superinfected subjects with no further broadening by 350 days after superinfection. In one of the five subjects, HIV-1 superinfection occurred when broad neutralization was lacking; with subsequent broadening of neutralizing antibodies occuring within 9 months and plateauing by 30 months after detection of superinfection. Clade B and C pseudoviruses were more sensitive to neutralization (13; 87%]); and (12; 80%]) than the locally circulating clades A (10; 67%]) and D (6; 40%]), respectively (p = 0.025). Low antibody titers correlated with clade D viruses and with >500 CD4 T cell counts, but not with the superinfection status.ConclusionThese data demonstrate that HIV-1 superinfection can occur both in the presence, and in the absence of broadly neutralizing antibodies. |
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| Keywords: | HIV-1 Superinfection Clade A Clade D Broadly neutralizing antibodies |
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