HIV-1 superinfection can occur in the presence of broadly neutralizing antibodies
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Date
2018
Journal Title
Journal ISSN
Volume Title
Publisher
Vaccine
Abstract
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.
Description
Keywords
HIV-1, Superinfection, Clade A, Clade D, Broadly neutralizing antibodies
Citation
Serwanga, J., Ssemwanga, D., Muganga, M., Nakiboneka, R., Nakubulwa, S., Kiwuwa-Muyingo, S., ... & Porcella, S. F. (2018). HIV-1 superinfection can occur in the presence of broadly neutralizing antibodies. Vaccine, 36(4), 578-586. https://doi.org/10.1016/j.vaccine.2017.11.075