Development and Validation of the San Diego Early Test Score to Predict Acute and Early HIV Infection Risk in Men Who Have Sex With Men

Men who have sex with men (MSM) bear the greatest burden of human immunodeficiency virus (HIV) infection in the United States and many other nations [1, 2]. MSM represent a dominant risk group for HIV; however, the risk of HIV infection within this population is not uniform [3–5]. Characterizing and identifying the MSM at greatest risk for incident HIV infection might permit more focused delivery of both prevention resources and selection of appropriate interventions, such as intensive counseling, regular HIV screening with methods that detect acute infection (ie, nucleic acid amplification test [NAAT]), and antiretroviral preexposure prophylaxis (PrEP) [6]. Although there are a number of symptom-based scores correlated with risk of acute and early HIV infection (AEH), few of these scores actually predict HIV acquisition risk [7, 8]. One of these, the Denver HIV risk score, focuses on the overall population at risk for HIV infection [9, 10]. Demographic characteristics such as male sex, younger age, and being an MSM are the main drivers of this score [9]; therefore, it would be difficult to discern the relative risk of incident HIV infection in populations that share some or all of these characteristics (ie, MSM). To date, 2 scores have been developed based on data from MSM repeat HIV testers: the Menza score [5] and the Smith score [11]. Both of these risk scores focus mainly on risk behavior during the 6 months before HIV diagnosis. Each of these scores has issues, however, that may contribute to suboptimal performance in real-world settings. First, there are issues with the derivation and validation cohorts used to estimate these scores. The Menza score focused on HIV acquisition in general (ie, acute and chronic infection at the time of diagnosis) in sexually transmitted infection (STI) clinic patients. Because the population used for development of the score sought HIV testing at a median of every 1.6 years (range, 30 days–6.7 years) [5] the behavior reported for the 6 months before diagnosis may not have included the risk behavior at the time of HIV acquisition. The Smith score was derived using a clinical vaccine trial population (enrolled 1998–1999) [11]. Both of the scores were validated using subjects of Project Explore (a HIV prevention trial conducted between 1999 and 2001 [12]). Thus, both scoring methods relied on behavioral risk data collected more than a decade ago in a clinical trial population that may not accurately represent the behavioral risks associated with HIV acquisition risk in a real-world setting today. Finally, the use of methamphetamine or inhaled nitrites in the prior 6 months is weighted in both scores, whereas other drugs are not [5, 11]. The Menza score weighted the use of methamphetamine or inhaled nitrites as the most important variable (11 points), whereas all other risk variables together accounted for a maximum total of 8 points [5]. The fact that behaviors directly associated with HIV acquisition, such as condomless anal intercourse (1 point), have been weighted as significantly less important restricts the use of the score to settings where methamphetamines and inhaled nitrites are the primary drivers of the HIV epidemic (ie, the score may not be applicable to settings where other drugs such as ketamine, γ-hydroxybutyric acid [GHB], cocaine, or ecstasy are significant drivers of HIV risk). An abbreviated version of the Smith score—with similar limitations (ie, data were collected more than a decade ago in a clinical trial population using behavior reported for the 6 months before diagnosis, with inclusion of methamphetamine but exclusion of other drugs)—is currently recommended as a tool to target PrEP among MSM by the US Public Health Service [13]. It may be possible to derive a more robust model that predicts incident HIV acquisition risk by assessing contemporary risk behaviors reported in the period prior to diagnosis with AEH, not chronic infection. Here we aimed (1) to estimate the risk of AEH among MSM, designated the San Diego Early Test (SDET) score, and (2) to validate the SDET score and compare to the 2 previously published risk scores in a real-world population of MSM who underwent HIV testing between 2008 and 2014.