P34.11 LB
Background: Superinfected HIV patients provide the unique opportunity to investigate the immune response after challenge with diverse HIV antigens and remain the major source for recombinant strain production. The competition and/or coexistence of two or more viral strains drive viral evolution and diversity, eventually triggering the generation of more broad and potent neutralizing antibodies (Abs) as compared to singly infected patients. The objective of this study was to analyze the genetic evolution of the viruses found within a superinfected Cameroonian patient, and to determine the neutralization sensitivity of the recombinant viruses to both autologous and heterologous neutralizing Abs.
Methods: Longitudinal plasma samples from an HIV-1 superinfected Cameroonian patient were analyzed for their Env diversity, evolution, and recombination events. Pseudoviruses were generated from timepoints before, during, and after superinfection, and were then tested for sensitivity to homologous plasma and to heterologous neutralizing mAbs.
Results: Env sequence analysis indicated that the CRF02_AG infected subject became superinfected with an F2 strain resulting in a massive increase in viral diversity. Later, the patient's viral repertoire was narrowed to quasispecies closely clustering with the initial strain. The highest neutralization was observed with autologous plasma from timepoints after superinfection but before the intiation of ART. Of interest, the superinfecting F2 strain was resistant to neutralization with most known broadly neutralizing antibodies (bnAbs) including PG09 and VRC01 while the original infecting CRF02_AG strain was sensitive to these bnAbs.
Conclusions: The resistance of the F2 strain to known bnAbs urges the need to generate nAbs from such patients and to monitor the emerging recombinant strains. HIV-1 superinfected patients may serve for the generation of new bnAbs covering multiple subtypes and deliver important knowledge for future vaccine design.