A Novel Acute Retroviral Syndrome Severity Score Predicts the Key Surrogate Markers for HIV-1 Disease Progression

Objective: Best long-term practice in primary HIV-1 infection (PHI) remains unknown for the individual. A risk-based scoring system associated with surrogate markers of HIV-1 disease progression could be helpful to stratify patients with PHI at highest risk for HIV-1 disease progression. Methods: We prospectively enrolled 290 individuals with well-documented PHI in the Zurich Primary HIV-1 Infection Study, an open-label, non-randomized, observational, single-center study. Patients could choose to undergo early antiretroviral treatment (eART) and stop it after one year of undetectable viremia, to go on with treatment indefinitely, or to defer treatment. For each patient we calculated an a priori defined Acute Retroviral Syndrome Severity Score'' (ARSSS), consisting of clinical and basic laboratory variables, ranging from zero to ten points. We used linear regression models to assess the association between ARSSS and log baseline viral load (VL), baseline CD4(+) cell count, and log viral setpoint (sVL) (i.e. VL measured >= 90 days after infection or treatment interruption). Results: Mean ARSSS was 2.89. CD4(+) cell count at baseline was negatively correlated with ARSSS (p=0.03, n=289), whereas HIV-RNA levels at baseline showed a strong positive correlation with ARSSS (p<0.001, n=290). In the regression models, a 1-point increase in the score corresponded to a 0.10 log increase in baseline VL and a CD4(+) cell count decline of 12/mu l, respectively. In patients with PHI and not undergoing eART, higher ARSSS were significantly associated with higher sVL (p=0.029, n=64). In contrast, in patients undergoing eART with subsequent structured treatment interruption, no correlation was found between sVL and ARSSS (p=0.28, n=40). Conclusion: The ARSSS is a simple clinical score that correlates with the best-validated surrogate markers of HIV-1 disease progression. In regions where ART is not universally available and eART is not standard this score may help identifying patients who will profit the most from early antiretroviral therapy.