Background:  Occurrence of HIV-1 superinfection offer a unique opportunity to investigate the correlates of immune protection. Here we describe the neutralizing antibody responses of a cohort of recently infected individuals who were screened for HIV superinfection.

Methods:  We performed a case-control study, matched for primary HIV infection (< 6 months) and ongoing male homosexual HIV risk exposures, within a cohort previously screened for superinfection. Neutralizing antibody, CD4, and viral load measurements, and HIV env sequences (gp120) were obtained for the first 11 matched individuals within the cohort who screened negative for intra-clade superinfection (controls) and the 3 individuals who became superinfected (cases). Responses were measured against autologous and clade B laboratory virus strains (NL4-3 and JRCSF) with the first available blood sample and 6 months later, which was before and after superinfection. Significance was assessed by a Fisher’s exact test for categorical comparisons and the Mann-Whitney test in all others. Glycosylation patterns, co-receptor usage, and genetic distance were computed from the gp120 nucleotide sequences. Phylogenetic reconstruction was performed using PHYLIP software of the C2-V3 env sequences.

Results:  All superinfected patients lacked detectable neutralizing antibody to heterologous laboratory strains at baseline in contrast to the non-superinfected group (NL4-3, p = 0.02; JRCSF, p = 0.05). A weak response to autologous virus could be detected in only 1 of the 3 superinfected patients, suggesting a weaker response to autologous HIV-1 in these patients than in the 11 control patients (p = 0.09). In the superinfected patients, neutralizing antibody responses to the baseline autologous and lab strain viruses were stronger after superinfection, which were not different between the 2 groups 6 months later. However, a trend for less neutralizing antibody response remained in the superinfected group to baseline autologous virus (p = 0.12) and JRCSF (p = 0.08). No significant differences in env glycosylation or genetic distances between viruses were observed in either group or laboratory strains, NL4-3 (R² = 0.012) or JRCSF (R² = 0.10).

Conclusions:  All 3 individuals identified with HIV superinfection had less cross-protective and autologous neutralizing antibody response than their non-superinfected case-controls. These data identify cross-protective neutralizing antibody in the prevention of superinfection and elucidate important goals for protective vaccine design.