April 28, 2015
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Relative infectivity of HIV-1 acute phase may be overestimated

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The relative infectivity of the HIV-1 acute phase appears to be significantly overestimated and is biased by unmodeled heterogeneity in transmission rates between couples and by study exclusion criteria, according to recent findings.

In the study, researchers evaluated previously published estimates measuring the relative hazard (RH) of transmission during the acute phase, and developed a new measure using excess hazard-months (EHM) of acute phase infection. EHM was determined using RH and acute phase duration. Measurements of trajectory viral load throughout the acute phase were used, rather than the previous practice of peak viral load.

RH and duration of acute phase infection was estimated by fitting a couples transmission model to a retrospectively selected cohort of serodiscordant heterosexual couples in Rakai, Uganda. The model accounted for factors omitted from prior studies, including individual heterogeneity in infectiousness and susceptibility, as well as the Rakai cohort’s exclusion of couples documented as serodiscordant.

Based on these data, the researchers estimated that acute phase RH was 5.3 (95% credibility interval [CrI], 0.79-57) and duration was 1.7 months (95% CrI, 0.55-6.8). These wide intervals indicate inability to differentiate a long, mildly infectious acute phase from a short, highly infectious acute phase given the 10-month observation intervals of the Rakai cohort, the researchers wrote.

“The total additional risk, measured as [acute phase EHM], can be estimated more precisely, and should be interpreted with respect to the 120 hazard-months generated by a constant untreated chronic phase infectivity over 10 years of infection,” the researchers wrote.

From the Rakai data, the researchers estimated that acute phase EHM was 8.4 (95% CrI, –0.27 to 63), nine times lower than the most frequently used estimate. This estimate also was concordant with the researchers’ independent estimate from viral load trajectories (5.6; 95% CI, 3.3-9.1).

Failure to account for risk heterogeneity and retrospective cohort study design bias were likely responsible for the prior overestimates, the investigators said. These findings are likely indicative of the relationship between the retrospective study exclusion criteria and the high rates of censorship among incident serodiscordant couples in the Rakai cohort.

“The proportion of transmission occurring immediately after infection should be re-evaluated, and may have more to do with risk heterogeneity and HIV intervention measures than with physiological differences between the acute and chronic stages of infection,” the researchers wrote. “These revised estimates should be considered when designing population-scale interventions and communicating individual-level risk in clinical or community settings.” – by Jen Byrne

Disclosure: The researchers report no relevant financial disclosures.