Background:  Sequential expression of dual infections (SEDI) has been reported more often in recently infected persons and is often attributed to HIV-1 superinfection. The frequency, risk factors, and consequences of superinfection are unknown. Few cases have been linked to a source partner, so primary dual infection cannot be ruled out. Screening for SEDI incidence in the OPTIONS Study, a natural history study of acute HIV-1 infection, was begun with the aim of investigating incidence and seroadaptative behavior contributing to the risk of superinfection.

Methods:  Acute and recent infection was diagnosed by serological evolution. Population sequencing of the pol gene was performed at enrollment and 3 subsequent query intervals. Phylogenetic analysis of baseline and follow-up time points was conducted. We analyzed occurrence of SEDI using time-to-event methods.

Results:  We analyzed 220 recently infected persons at 2 or more time points, representing 563.7 person-years of observation. The mean age was 36.6 and the cohort had been infected on average 107 days before their baseline genotype. Divergent viruses appeared in 7 cases, an overall incidence density of 1.24/100 person-years. No source partners have been identified. Our model estimated a 16-fold reduction in the risk of SEDI at times more than 1 year post-infection compared to times within 1 year of infection. The estimated rate of SEDI was 4.1/100 person-years (95% CI, 1.8 to 9.2) in the first year following infection and was 0.2 per 100 person-years beyond 1 year post-infection (95% CI, 0.03 to 1.8).

Conclusions: The incidence of SEDI cases early in infection suggests that mechanisms partially blocking superinfection may develop over the first few years of infection. These mechanisms may include viral interference, depletion of target cells, or immune responses. Additional analysis is required to evaluate whether limited or localized superinfection has occurred in the absence of systemic overgrowth. The 16-fold reduction in risk of SEDI beyond 1 year post-infection could be due to factors discussed above, by frailty selection, or a combination of both. In particular, mechanisms that govern susceptibility to superinfection may be acquired over time, or may be present at primary infection. We are gathering additional data which may permit better assessment of the causes of decreasing SEDI risk over time.