Jennifer Serwanga1, Deogratius Ssemwanga2, Michael Muganga2, Ritah Nakiboneka2, Susan Nakubulwa2, Sylvia Kiwuwa-Muyingo2, Lynn Morris3, Andrew D Redd4, Thomas C Quinn4, Pontiano Kaleebu5. 1. MRC/UVRI Uganda Research Unit on AIDS, c/o Uganda Virus Research Institute, Entebbe, Uganda. Electronic address: Jennifer.Serwanga@mrcuganda.org. 2. MRC/UVRI Uganda Research Unit on AIDS, c/o Uganda Virus Research Institute, Entebbe, Uganda. 3. National Institute for Communicable Diseases, Johannesburg, South Africa; Center for the AIDS Program of Research in South Africa (CAPRISA), South Africa; University of the Witwatersrand, Johannesburg, South Africa. 4. Laboratory of Immunoregulation, Division of Intramural Research, NIAID, NIH, Bethesda, USA; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 5. MRC/UVRI Uganda Research Unit on AIDS, c/o Uganda Virus Research Institute, Entebbe, Uganda; London School of Hygiene and Tropical Medicine, Department of Clinical Research, London, UK.
Abstract
BACKGROUND: Superinfection 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. METHODS: Six 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. RESULTS: Preexisting 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. CONCLUSION: These data demonstrate that HIV-1 superinfection can occur both in the presence, and in the absence of broadly neutralizing antibodies.
BACKGROUND: Superinfection 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. METHODS: Six 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. RESULTS: Preexisting 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. CONCLUSION: These data demonstrate that HIV-1 superinfection can occur both in the presence, and in the absence of broadly neutralizing antibodies.
Authors: Daniel B Reeves; Amalia S Magaret; Alex L Greninger; Christine Johnston; Joshua T Schiffer Journal: J R Soc Interface Date: 2018-02 Impact factor: 4.118