Suchergebnisse

There are very limited data on the impact of ART initiation on inflammatory and coagulation biomarkers compared to patients who remain ART naïve [1]. We designed a prospective comparative study to evaluate these changes. Prospective observational cohort study of HIV‐infected patients who start ART and a group of age‐matched controls who remain ART‐naïve. Blood levels of insulin, fibrinogen, D‐dimer, high‐sensitivity PCR, inflammatory (IL‐1β, IL‐6, MCP‐1 and sCD40) and anti‐inflammatory cytokines (IL‐4), were compared at baseline, 24 weeks and 48 weeks. Summary of results: 94 patients included (57 treated, 37 controls). Baseline characteristics were balanced except for (treated/controls): median [IQR], HIV duration (0.9 [0.4–2.4] / 2.7 [0.6–5.5]) years, CD4 nadir (262 [198–317] / 452 [367–553]) cells/µl, viral load (4.4 [4–5.1] / 3.8 [3.1–4.4]) log cop/ml, current CD4 count (283 [213–323] / 525 [449–669]) cells/µl, HDL cholesterol (38 [29–45] / 41 [36–50]) mg/dl and female gender (8.8%/35%). There were no differences between groups in baseline biomarkers levels except that those starting ART had lower median [IQR] IL‐1β (4.1 [3.5–4.7] vs. 4.6 [3.7–6.8] pg/ml; p= 0.019) and lower IL–6 levels (4 [3.4–4.6] vs. 5.2 [4.2–6.6] pg/ml; p< 0.001). No significant correlation was found between biomarkers and baseline viral load. 91% of treated patients achieved viral suppression (<50 c/ml). There were statistically significant differences between groups at week 48 with lower (mean [95% CI]) D‐dimer (−138.2 [−268.0, −8.4] mg/L; p=0.001), IL‐1β (−0.6 [−0.9, −0.4] pg/ml; p<0.001) and higher IL‐4 (0.6 [0.2, 0.9] pg/ml; p=0.004) in those starting ART. In the ART‐naïve group there were significant increases of IL‐1β (1.3 [0.9, 1.6] pg/ml; p<0.001), sCD40 (22.7 [0.8, 44.6] AU; p=0.043), IL‐6 (0.5 [0.0, 0.9] pg/ml; p= 0.049) and a significant decrease of IL‐4 (−0.7 [−1.1, −0.3] pg/ml; p=0.001) levels. After 48 weeks of ART there were statistically significant decreases in pro‐inflammatory and coagulation markers (Figure 1) while levels of anti‐inflammatory cytokines (e.g. IL‐4) were significantly increased. Opposite trends were found in controls.In conclusion, compared to untreated controls, 48 weeks of effective ART significantly reduces pro‐inflammatory (IL‐1β, IL‐6), coagulation (fibrinogen, D‐dimer), and metabolic (insulin) markers and increases levels of an anti‐inflammatory cytokines like IL‐4.Median percentage changes in bio markers from baseline to week 48.image

Purpose of the studyTo investigate if boosted protease inhibitor monotherapy is associated with a higher risk of neurocognitive impairment (NCI).MethodsHIV‐infected patients from two hospitals in Madrid (Spain) without concomitant major neurocognitive confounders, currently receiving for ≥1 year lopinavir/ritonavir (LPV) or darunavir/ritonavir (DRV) as monotherapy or with two N(t)RTIs were included if they had prolonged (≥1 year) plasma viral suppression (<50 c/mL, single blip allowed). Patients underwent full neurocognitive assessment (7 domains) by two psychologists blinded to the treatment group. NCI was defined as per 2007 Frascati criteria using demographically adjusted normative scores. Rates of NCI and the association between NCI and boosted protease inhibitor monotherapy, adjusted by significant confounders, were analyzed. Two categories of monotherapy duration were considered: short‐term (1–2 years) and long‐term (2–9 years). We evaluated as potential confounding variables: demographics, HIV risk factor, AIDS, CD4 (nadir/current), smoking, alcohol/illicit drug use, prior medical, neurological and psychiatric disease, HCV coinfection, years of ART, prior blips, time with HIV viral suppression, type of protease inhibitor, lipids and HOMA index.Summary of results191 patients (89.5% Caucasian) were included (Table 1).










Triple therapy (n=95)
Monotherapy (n=96)
p value




Male. n (%)
70 (73.7)
70 (72.9)
0.91


Former IVDU. n (%)
30 (31.6)
34 (35.4)
0.85


MSM. n (%)
29 (30.5)
30 (31.3)
0.85


Age. Median (IQR)
44.7 (40.6–48.4)
47.4 (44.8–51.4)
<0.01


Years of education. Mean (SD)
11.3 (4.1)
10.4 (4.4)
0.13


Prior neurologic disease. N (%)
12 (12.6)
10 (10.4)
0.63


Prior psychiatric disease. n (%)
19 (20.0)
24 (25.0)
0.44


Current or past use of illicit drugs. n (%)
49 (53.6)
46 (47.9)
0.66


HCV coinfection (past or active)
43 (47.3)
43 (45.3)
0.54


Years of ART. Median (IQR)
10.7 (4.8–15.7)
14.1 (10.7–15.9)
0.01


Years of monotherapy. Median (IQR)
Not applicable
2.3 (1.7–3.2)
Not applicable


Years suppressed (<50 c/mL). Median (IQR)
4.8 (2.9–8.9)
7.5 (4.5–10.0)
<0.01


No prior blip
63 (66.3)
61 (63.5)
0.17


Currently on LPV. n (%)
70 (73.7)
53 (55.2)
<0.01


Currently on DRV. n (%)
25 (26.3)
43 (44.8)
<0.01


CPE score (2010). Median (IQR)
7 (7–7)
3 (3–3)
Not applicable


CD4 cell nadir. Median (IQR)
153 (49–255)
182 (76–288)
0.11


CD4 cell current. Median (IQR)
560 (440–754)
629.5 (476–845.5)
<0.05




Proportion (95% CI) with NCI: Overall: 27.2% (20.9–33.6, all asymptomatic or mild). Triple therapy: 31.6 (22.1–41.0). 1–2 years of monotherapy (n=40): 25.0 (11.3–38.7). 2–9 years of monotherapy (n=56): 21.4 (10.5–32.3) No differences in rates of NCI were found by treatment group (p=0.38). In our regression model confounding variables for NCI were years on ART, ethnicity, years of education, transmission category and the HOMA index. Adjusted by those variables the odds ratio (95% CI) for NCI of patients receiving boosted protease inhibitor monotherapy monotherapy during 1–2 years was 0.85 (0.29–2.50) and for 2–9 years was 0.40 (0.14–1.15).ConclusionsBoosted protease inhibitor monotherapy, regardless of duration, was not associated with a higher rate of neurocognitive impairment than triple drug ART. These results call into question the ability of neuropenetrance scores to predict the neuroefficacy of antiretroviral regimens in HIV‐infected patients with adequate blood viral suppression.