Evaluation of the Predictive Potential of the Short Acute Retroviral Syndrome Severity Score for HIV-1 Disease Progression in Individuals With Acute HIV Infection

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To the Editors:
Expert guidelines now recommend immediate antiretroviral therapy (ART) for all HIV-infected persons regardless of CD4 cell count, to reduce the risk of disease progression and prevent HIV transmission.1,2 There is also increasing evidence that very early ART benefits the individual infected with HIV by leading to more rapid and robust immunologic recovery, lower inflammation, and reduced viral reservoir size compared with a later start.3–12 However, in low-income and middle-income countries, universal immediate ART is rarely available. To assist clinicians in regions where universal ART is not available in prioritizing provision of immediate ART to patients who benefit most, Braun et al recently developed the Acute Retroviral Syndrome (ARS) Severity Score (ARSSS). Following the hypothesis that severity of primary HIV infection correlates with disease progression,13–17 the score includes mostly clinical variables that reflect the intensity of the clinical presentation of primary HIV infection.18 The score was evaluated retrospectively among 290 individuals of the Zurich primary HIV infection study and correlated well with validated surrogate markers associated with HIV-1 disease progression, that is, baseline CD4+ cell count, baseline viral load, and set-point viral load.18 External validation of the ARSSS is still missing, however. Furthermore, it remains unclear if the score has predictive validity also in individuals at the earliest stage of HIV infection, as only 3 of these 290 individuals fulfilled the earliest criteria of acute HIV infection (AHI; ie, Fiebig I or II).18,19
In this retrospective analysis of a prospective observational cohort study, we evaluated the performance of the ARSSS18 in patients diagnosed with AHI between 2007 and 2014 by the San Diego Primary HIV Infection Consortium.20 A total of 90 persons were identified with AHI and provided questionnaire responses on signs and symptoms of ARS at the time of AHI diagnosis, although only the subset of 48 individuals who provided information on whether they had sought medical attention for signs or symptoms of ARS (ie, a substantial 3-point component of the ARSSS) were included in this analysis (the question was not included in the questionnaire used between 2010 and 2012). All individuals were diagnosed with AHI with the “Early Test” that included routine individual donation (ID), HIV nucleic acid amplification testing (ID-NAT) to all rapid antibody-negative participants.21–26 AHI was defined as having a negative or indeterminate HIV antibody test result with a positive ID-NAT, corresponding to Fiebig stages I–II, and a mean estimated duration of infection of 10 days.19 At each participant's first visit after documentation of AHI diagnosis (median 4 days, interquartile range , 3–6 days after AHI testing), blood samples were collected for CD4 and viral load testing. Detailed information related to occurrence, duration, and start and stop dates for signs and symptoms associated with AHI were also collected.27,28 Participants were asked if they had sought medical attention for any of these signs or any symptoms. In persons who reported symptoms that were ongoing, the date on which symptoms resolved as well as additional signs or symptoms occurring within 4 weeks after the AHI test were collected during follow-up.20 The viral set point was defined as the first HIV-RNA measurement ≥90 days after the estimated date of infection in treatment-naive patients.18
We evaluated 2 versions of the ARSSS, the complete 6 variable27 ARSSS assessment (ARSSS-full) in a subset of 19 participants and a shorted version (ARSSS-short) consisting of 4 variables in all 48 participants (Table 1).
For this evaluation, one of the originally proposed variables, “inpatient treatment” (ie, 3 points in ARSSS), was replaced by “seeking medical attention because of signs and symptoms of ARS,” as inpatient treatment was not assessed in our cohort undergoing community-based testing.

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