A Simplified Formula for Inferring HIV Incidence from Cross-Sectional Surveys Using a Test for Recent Infection

The paper of McDougal et al., previously published in this journal, 1 is becoming a standard reference used for the estimation of HIV incidence from applications of the BED IgG-capture enzyme immunoassay (BED assay) to crosssectional blood samples. 2,3Their approach provides an estimate for an annual risk of infection in a hypothetical cohort, using an estimate for the true proportion, P t , of ''recent infections'' among HIV-seropositive individuals.The estimate P t is in turn derived from the proportion, P o , of seropositive individuals in a survey who test below a threshold value for normalized BED optical density (OD-n). 4The condition of being below the OD-n threshold is declared to be an imperfect test for recent infection.True ''recent infection'' is defined as having been infected for less than a period o, where o is the mean time individuals spend below the OD-n threshold.Since it is well known that not all individuals progress to a given threshold, even after arbitrarily long times, o needs to be carefully defined as the mean threshold crossing time among those who do progress.It is also known that during late stage illness, or under the influence of antiretroviral therapy, individuals may regress to OD-n values below the recency threshold.It is further plausible, and indeed appears to be the case, 5,6 that the parameters characterizing progression through the BED-defined states of infection vary regionally.These complications have caused doubt about the prospects for using the BED assay as a robustly characterizable test for recent infection for the purposes of estimating HIV incidence, as reflected in a UNAIDS statement in 2006 7 recommending it not be used for this purpose.Hence, new assays, or combinations of assays (such as a BED and an antibody avidity test), are being developed to provide more robust tests for recent infection.The fraction of individuals that progresses atypically through an assaydefined class of ''recently infected'' may thus be reduced, but is unlikely to be zero.Therefore, the methodology developed to deal with this problem for the BED assay appears, at face value, to be immediately transferable, requiring only minor modification (namely in the values of its parameters) to be applicable to other imperfect tests for recent infection.We argue that several subtle points need to be addressed to ensure that incidence inferences based on imperfect tests for recent infection are not unnecessarily limited, or even in error, and we do this by a critique of the original application.The interindividual variability of BED OD-n progression is captured in the McDougal model by three parameters: