Dataset Information

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

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.

SUBMITTER: Braun DL

PROVIDER: S-EPMC4260784 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

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

Braun Dominique L DL Kouyos Roger R Oberle Corinna C Grube Christina C Joos Beda B Fellay Jacques J McLaren Paul J PJ Kuster Herbert H Günthard Huldrych F HF

PloS one 20141209 12

<h4>Objective</h4>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.<h4>Methods</h4>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 c ...[more]

PMID: 25490090

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Project description:BackgroundIL-6 (interleukin-6) has important roles in atherosclerosis pathophysiology. To determine if anti-IL-6 therapy warrants evaluation as an adjuvant stroke prevention strategy in patients with carotid atherosclerosis, we tested whether circulating IL-6 levels predict carotid plaque severity, vulnerability, and progression in the prospective population-based CHS (Cardiovascular Health Study).MethodsDuplex carotid ultrasound was performed at baseline and 5 years. Baseline plaque severity was scored 0 to 5 based on North American Symptomatic Carotid Endarterectomy Trial grade of stenosis. Plaque vulnerability at baseline was the presence of markedly irregular, ulcerated, or echolucent plaques. Plaque progression at 5 years was a ≥1 point increase in stenosis severity. The relationship of baseline plasma IL-6 levels with plaque characteristics was modeled using multivariable linear (severity) or logistic (vulnerability and progression) regression. Risk factors of atherosclerosis were included as independent variables. Stepwise backward elimination was used with P>0.05 for variable removal. To assess model stability, we computed the E-value or minimum strength of association (odds ratio scale) that unmeasured confounders must have with log IL-6 and the outcome to suppress the association. We performed internal validation with 100 bootstrap samples.ResultsThere were 4334 participants with complete data (58.9% women, mean age: 72.7±5.1 years), including 1267 (29.2%) with vulnerable plaque and 1474 (34.0%) with plaque progression. Log IL-6 predicted plaque severity (β=0.09, P=1.3×10-3), vulnerability (OR, 1.21 [95% CI, 1.05-1.40]; P=7.4×10-3, E-value=1.71), and progression (OR, 1.44 [95% CI, 1.23-1.69], P=9.1×10-6, E-value 2.24). In participants with >50% predicted probability of progression, mean log IL-6 was 0.54 corresponding to 2.0 pg/mL. Dichotomizing IL-6 levels did not affect the performance of prediction models.ConclusionsCirculating IL-6 predicts carotid plaque severity, vulnerability, and progression. The 2.0 pg/mL cutoff could facilitate the selection of individuals that would benefit from anti-IL-6 drugs for stroke prevention.

Dataset Information

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

Objective

Methods

Results

Conclusion

Publications

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

Similar Datasets

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