A novel Acute Retroviral Syndrome Severity Score predicts the key surrogate markers for HIV-1 disease progression

PLoS One. 2014 Dec 9;9(12):e114111. doi: 10.1371/journal.pone.0114111. eCollection 2014.

Abstract

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/µl, 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anti-HIV Agents / pharmacology
  • Anti-HIV Agents / therapeutic use
  • Biomarkers
  • CD4 Lymphocyte Count
  • Disease Progression*
  • Female
  • Genome-Wide Association Study
  • HIV Infections* / drug therapy
  • HIV Infections* / genetics
  • HIV Infections* / immunology
  • HIV-1 / drug effects
  • HIV-1 / genetics
  • HIV-1 / physiology*
  • Humans
  • Male
  • Middle Aged
  • RNA, Viral / metabolism
  • Severity of Illness Index*
  • Viral Load / drug effects
  • Young Adult

Substances

  • Anti-HIV Agents
  • Biomarkers
  • RNA, Viral

Grants and funding

This work was supported by the Swiss National Science Foundation [grant #324730-130865 to HFG, grant #PZ00P3-142411 to RK] and by the University of Zurich's Clinical Research Priority Program (CRPP) “Viral infectious diseases: Zurich Primary HIV Infection Study” to HFG and by the matching fund program of the University Hospital of Zurich to DLB. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. For the other authors, no funding was declared.