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Christian Prebensen, Marius Trøseid, Thor Ueland, Anders Dahm, Per Morten Sandset, Ingeborg Aaberge, Kristian Waalen, Anne Ma Dyrhol-Riise, Kjetil Taskén, Dag Kvale
Immune activation and HIV-specific T cell responses are modulated by a cyclooxygenase-2 inhibitor in untreated HIV-infected individuals: An exploratory clinical trial
www.plosone.org
www.plosone.org
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(University)Tj
4.405 0 Td
(Hospital,)Tj
3.8438 0 Td
(from)Tj
2.2053 0 Td
(January)Tj
3.3165 0 Td
(2011)Tj
2.126 0 Td
(through)Tj
3.4412 0 Td
(May)Tj
2.0013 0 Td
(2014,)Tj
2.347 0 Td
(in)Tj
1.0375 0 Td
(one)Tj
1.7008 0 Td
(of)Tj
-36.5213 -1.2982 Td
(two)Tj
1.7064 0 Td
(study)Tj
2.3924 0 Td
(groups.)Tj
3.1918 0 Td
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1.9389 0 Td
(group)Tj
2.6079 0 Td
(consisted)Tj
3.9401 0 Td
(of)Tj
1.0148 0 Td
(ART-na)Tj
/F12 1 Tf
[()]TJ
/F8 1 Tf
(ve)Tj
4.6034 0 Td
(patients,)Tj
3.5943 0 Td
(with)Tj
1.9956 0 Td
(CD4)Tj
2.0976 0 Td
(counts)Tj
2.8857 0 Td
(above)Tj
2.5455 0 Td
(350)Tj
-34.5144 -1.2983 Td
(cells/)Tj
/F12 1 Tf
[()]TJ
/F8 1 Tf
(L)Tj
3.2938 0 Td
(and)Tj
1.7291 0 Td
(plasma)Tj
3.0331 0 Td
(HIV)Tj
2.0239 0 Td
(RNA)Tj
2.262 0 Td
(above)Tj
2.5455 0 Td
(2000)Tj
2.1203 0 Td
(copies/mL,)Tj
4.6318 0 Td
(a)Tj
0.6576 0 Td
(confirmed)Tj
4.3937 0 Td
(diagnosis)Tj
3.9571 0 Td
(of)Tj
1.0148 0 Td
(HIV)Tj
2.024 0 Td
(infection)Tj
-33.6867 -1.3039 Td
(less)Tj
1.61 0 Td
(than)Tj
2.0296 0 Td
(8)Tj
0.6973 0 Td
(years)Tj
2.2621 0 Td
(pre-inclusion)Tj
5.5785 0 Td
(and)Tj
1.7291 0 Td
(no)Tj
1.2756 0 Td
(current)Tj
3.1861 0 Td
(indication)Tj
4.3087 0 Td
(for)Tj
1.3889 0 Td
(ART)Tj
2.1373 0 Td
(according)Tj
4.184 0 Td
(to)Tj
1.0261 0 Td
(European)Tj
-31.4133 -1.2983 Td
(guidelines)Tj
4.2746 0 Td
(at)Tj
0.9524 0 Td
(the)Tj
1.474 0 Td
(time)Tj
2.0239 0 Td
([)Tj
0.83 0.64 0.02 0 k
(33)Tj
0 g
(].)Tj
2.0807 0 Td
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1.7801 0 Td
(other)Tj
2.3471 0 Td
(study)Tj
2.3924 0 Td
(group)Tj
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(consisted)Tj
3.9344 0 Td
(of)Tj
1.0148 0 Td
(patients)Tj
3.3676 0 Td
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1.2755 0 Td
(ART,)Tj
2.3641 0 Td
(with)Tj
1.9956 0 Td
(CD4)Tj
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(counts)Tj
2.8856 0 Td
(below)Tj
2.5852 0 Td
(500)Tj
1.6497 0 Td
(cells/)Tj
/F12 1 Tf
[()]TJ
/F8 1 Tf
(L)Tj
3.2939 0 Td
(and)Tj
1.7291 0 Td
(HIV)Tj
2.0239 0 Td
(RNA)Tj
2.2621 0 Td
(below)Tj
2.5851 0 Td
(50)Tj
1.1736 0 Td
(copies/mL)Tj
4.405 0 Td
(for)Tj
1.3889 0 Td
(at)Tj
0.9525 0 Td
(least)Tj
1.9786 0 Td
(6)Tj
0.6973 0 Td
(months)Tj
3.2825 0 Td
(prior)Tj
2.2563 0 Td
(to)Tj
-35.1493 -1.304 Td
(inclusion.)Tj
4.1385 0 Td
(All)Tj
1.4003 0 Td
(included)Tj
3.7134 0 Td
(patients)Tj
3.3675 0 Td
(were)Tj
2.1203 0 Td
(between)Tj
3.5263 0 Td
(18)Tj
1.1735 0 Td
(and)Tj
1.7292 0 Td
(65)Tj
1.1735 0 Td
(years)Tj
2.262 0 Td
(of)Tj
1.0148 0 Td
(age)Tj
1.5421 0 Td
(and)Tj
1.7347 0 Td
(had)Tj
1.7065 0 Td
(no)Tj
1.2756 0 Td
(history)Tj
3.0047 0 Td
(of)Tj
-34.8829 -1.2982 Td
(symptomatic)Tj
5.4198 0 Td
(acute)Tj
2.3244 0 Td
(HIV)Tj
2.0239 0 Td
(infection)Tj
3.7927 0 Td
(within)Tj
2.812 0 Td
(the)Tj
1.4683 0 Td
(last)Tj
1.559 0 Td
(12)Tj
1.1736 0 Td
(months.)Tj
-19.3775 -1.2983 Td
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4.1385 0 Td
(criteria)Tj
3.0784 0 Td
(for)Tj
1.3833 0 Td
(all)Tj
1.1452 0 Td
(study)Tj
2.3924 0 Td
(participants)Tj
4.955 0 Td
(were)Tj
2.1259 0 Td
(concomitant)Tj
5.2951 0 Td
(use)Tj
1.5307 0 Td
(of)Tj
1.0148 0 Td
(non-steroidal)Tj
5.6126 0 Td
(anti-)Tj
-33.8681 -1.2983 Td
(inflammatory)Tj
5.7089 0 Td
(drugs,)Tj
2.6986 0 Td
(corticosteroids)Tj
6.1341 0 Td
(or)Tj
1.0942 0 Td
(interferon-alpha,)Tj
7.0072 0 Td
(total)Tj
2.0012 0 Td
(cholesterol)Tj
/F13 1 Tf
0 Tc
4.5524 0 Td
(>)Tj
/F8 1 Tf
-0.004 Tc
(7)Tj
1.4684 0 Td
(mM,)Tj
2.1599 0 Td
(elevated)Tj
-32.8249 -1.3039 Td
(serum)Tj
2.7212 0 Td
(creatinine,)Tj
4.4504 0 Td
(creatinine)Tj
4.2292 0 Td
(clearance)Tj
/F13 1 Tf
0 Tc
3.9458 0 Td
(<)Tj
/F8 1 Tf
-0.004 Tc
(30ml/min,)Tj
5.1987 0 Td
(hypertension,)Tj
5.692 0 Td
(heart)Tj
2.279 0 Td
(failure,)Tj
2.999 0 Td
(diabetes,)Tj
3.6907 0 Td
(ische-)Tj
-35.206 -1.2982 Td
(mic)Tj
1.7291 0 Td
(heart)Tj
2.2733 0 Td
(disease,)Tj
3.2429 0 Td
(peripheral)Tj
4.3199 0 Td
(arteriosclerosis)Tj
6.2135 0 Td
(and/or)Tj
2.9367 0 Td
(cerebrovascular)Tj
6.5026 0 Td
(disease,)Tj
3.2429 0 Td
(cardiovascular)Tj
-30.4609 -1.2983 Td
(events)Tj
2.7269 0 Td
(or)Tj
1.0998 0 Td
(stroke)Tj
2.6759 0 Td
(in)Tj
1.0375 0 Td
(parents,)Tj
3.4015 0 Td
(siblings)Tj
3.2428 0 Td
(or)Tj
1.0942 0 Td
(offspring)Tj
3.8324 0 Td
(of)Tj
/F13 1 Tf
0 Tc
1.0148 0 Td
(<)Tj
/F8 1 Tf
-0.004 Tc
(55)Tj
1.9446 0 Td
(years)Tj
2.2677 0 Td
(of)Tj
1.0148 0 Td
(age,)Tj
1.7631 0 Td
(pregnancy)Tj
4.4107 0 Td
(or)Tj
1.0941 0 Td
(insufficient)Tj
-32.6208 -1.3039 Td
(birth-control,)Tj
5.6692 0 Td
(breast-feeding,)Tj
6.1341 0 Td
(deranged)Tj
3.9402 0 Td
(liver)Tj
1.9842 0 Td
(function,)Tj
3.8551 0 Td
(inflammatory)Tj
5.7089 0 Td
(bowel)Tj
2.5852 0 Td
(disease,)Tj
3.2428 0 Td
(active)Tj
2.5229 0 Td
(pep-)Tj
-35.6426 -1.2983 Td
(tic)Tj
1.2075 0 Td
(ulcer,)Tj
2.4378 0 Td
(or)Tj
1.0998 0 Td
(gastrointestinal)Tj
6.3496 0 Td
(haemorrhage.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 460.7433 cm
BT
/F0 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Study)Tj
2.7543 0 Td
(design)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 443.7354 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(ART-na)Tj
/F12 1 Tf
[()]TJ
/F8 1 Tf
(ve)Tj
4.6034 0 Td
(and)Tj
1.7291 0 Td
(ART-treated)Tj
5.2667 0 Td
(patients)Tj
3.3676 0 Td
(were)Tj
2.1203 0 Td
(separately)Tj
4.1839 0 Td
(randomized)Tj
5.0626 0 Td
(to)Tj
1.0262 0 Td
(one)Tj
1.6951 0 Td
(of)Tj
1.0148 0 Td
(three)Tj
2.2677 0 Td
(arms)Tj
2.2053 0 Td
(in)Tj
1.0318 0 Td
(a)Tj
-35.5745 -1.2982 Td
(2:1:1)Tj
2.0919 0 Td
(fashion)Tj
3.1464 0 Td
(and)Tj
1.7292 0 Td
(in)Tj
1.0261 0 Td
(blocks)Tj
2.7553 0 Td
(of)Tj
1.0148 0 Td
(20,)Tj
1.3889 0 Td
(by)Tj
1.1792 0 Td
(drawing)Tj
3.5093 0 Td
(allocation)Tj
4.1272 0 Td
(numbers)Tj
3.7757 0 Td
(from)Tj
2.1997 0 Td
(a)Tj
0.6463 0 Td
(pre-generated)Tj
5.794 0 Td
(random)Tj
-34.384 -1.2983 Td
(sequence)Tj
3.855 0 Td
(to)Tj
1.0262 0 Td
(which)Tj
2.6532 0 Td
(the)Tj
1.4683 0 Td
(investigators)Tj
5.2781 0 Td
(were)Tj
2.1203 0 Td
(blinded)Tj
3.2655 0 Td
(beforehand.)Tj
5.006 0 Td
(Arm)Tj
2.0976 0 Td
(1)Tj
0.6916 0 Td
(received)Tj
3.5376 0 Td
(oral)Tj
1.7802 0 Td
(etoricoxib)Tj
-32.7796 -1.3039 Td
(90)Tj
1.1678 0 Td
(mg)Tj
1.508 0 Td
(once)Tj
2.1203 0 Td
(daily)Tj
2.1487 0 Td
(for)Tj
1.389 0 Td
(six)Tj
1.3152 0 Td
(months,)Tj
3.5036 0 Td
(arm)Tj
1.8482 0 Td
(2)Tj
0.6916 0 Td
(received)Tj
3.5377 0 Td
(oral)Tj
1.7801 0 Td
(etoricoxib)Tj
4.252 0 Td
(90)Tj
1.1735 0 Td
(mg)Tj
1.5023 0 Td
(once)Tj
2.126 0 Td
(daily)Tj
2.1487 0 Td
(for)Tj
1.3889 0 Td
(two)Tj
-33.6016 -1.2983 Td
(weeks)Tj
2.6078 0 Td
(whereas)Tj
3.4469 0 Td
(arm)Tj
1.8425 0 Td
(3)Tj
0.6973 0 Td
(received)Tj
3.532 0 Td
(no)Tj
1.2756 0 Td
(drug.)Tj
2.3414 0 Td
(The)Tj
1.7801 0 Td
(study)Tj
2.3868 0 Td
(was)Tj
1.7008 0 Td
(open)Tj
2.2166 0 Td
(label.)Tj
2.3017 0 Td
(Patients)Tj
3.4129 0 Td
(were)Tj
2.1203 0 Td
(examined)Tj
4.1273 0 Td
(and)Tj
-35.79 -1.2982 Td
(blood)Tj
2.5114 0 Td
(samples)Tj
3.3846 0 Td
(were)Tj
2.1203 0 Td
(drawn)Tj
2.7893 0 Td
(at)Tj
0.9524 0 Td
(screening,)Tj
4.2746 0 Td
(inclusion)Tj
3.9175 0 Td
(\(week)Tj
2.5908 0 Td
(0\),)Tj
1.2586 0 Td
(study)Tj
2.3924 0 Td
(week)Tj
2.245 0 Td
(5)Tj
0.6974 0 Td
(in)Tj
1.0318 0 Td
(arms)Tj
2.2053 0 Td
(2/3,)Tj
1.7291 0 Td
(study)Tj
-34.1005 -1.2983 Td
(week)Tj
2.245 0 Td
(9)Tj
0.6973 0 Td
(in)Tj
1.0375 0 Td
(arm)Tj
1.8425 0 Td
(1,)Tj
0.9241 0 Td
(four)Tj
1.9105 0 Td
(months)Tj
3.2825 0 Td
(and)Tj
1.7291 0 Td
(six)Tj
1.3153 0 Td
(months.)Tj
-13.7876 -1.3039 Td
(Final)Tj
2.245 0 Td
(analysis)Tj
3.3278 0 Td
(of)Tj
1.0148 0 Td
(immunological)Tj
6.2986 0 Td
(endpoints)Tj
4.2179 0 Td
(was)Tj
1.7008 0 Td
(performed)Tj
4.4674 0 Td
(at)Tj
0.9524 0 Td
(four)Tj
1.9162 0 Td
(months)Tj
3.2825 0 Td
(as)Tj
1.0148 0 Td
(opposed)Tj
3.5773 0 Td
(to)Tj
1.0261 0 Td
(the)Tj
-36.2378 -1.2983 Td
(protocol-ascribed)Tj
7.2623 0 Td
(six)Tj
1.3152 0 Td
(months.)Tj
3.5036 0 Td
(This)Tj
1.9899 0 Td
(was)Tj
1.6951 0 Td
(due)Tj
1.7008 0 Td
(to)Tj
1.0262 0 Td
(illness)Tj
2.6702 0 Td
(of)Tj
1.0204 0 Td
(key)Tj
1.5931 0 Td
(study)Tj
2.3868 0 Td
(personnel,)Tj
4.3936 0 Td
(leading)Tj
3.1351 0 Td
(to)Tj
-33.6923 -1.2982 Td
(delayed)Tj
3.2541 0 Td
(sampling)Tj
3.8834 0 Td
(at)Tj
0.9525 0 Td
(six)Tj
1.3096 0 Td
(months)Tj
3.2825 0 Td
(of)Tj
1.0148 0 Td
(a)Tj
0.6519 0 Td
(significant)Tj
4.3937 0 Td
(proportion)Tj
4.6318 0 Td
(of)Tj
1.0148 0 Td
(patients,)Tj
3.5886 0 Td
(after)Tj
2.0353 0 Td
(cessation)Tj
3.8437 0 Td
(of)Tj
1.0148 0 Td
(study)Tj
-34.8715 -1.304 Td
(drug.)Tj
2.3357 0 Td
(Thus,)Tj
2.4718 0 Td
(endpoint)Tj
3.8607 0 Td
(data)Tj
1.9106 0 Td
(related)Tj
2.948 0 Td
(to)Tj
1.0261 0 Td
(COX-2i)Tj
3.3732 0 Td
(effects)Tj
2.7269 0 Td
(beyond)Tj
3.1862 0 Td
(four)Tj
1.9162 0 Td
(months)Tj
3.2825 0 Td
(of)Tj
1.0148 0 Td
(follow-up)Tj
4.0932 0 Td
(were)Tj
-34.1459 -1.2982 Td
(incomplete.)Tj
4.9209 0 Td
(Notably,)Tj
3.6283 0 Td
(no)Tj
1.2756 0 Td
(patients)Tj
3.3675 0 Td
(discontinued)Tj
5.4482 0 Td
(the)Tj
1.4683 0 Td
(study)Tj
2.3868 0 Td
(due)Tj
1.7007 0 Td
(to)Tj
1.0262 0 Td
(adverse)Tj
3.2144 0 Td
(events)Tj
2.7326 0 Td
(or)Tj
1.0942 0 Td
(commence-)Tj
-32.2637 -1.2983 Td
(ment)Tj
2.3073 0 Td
(of)Tj
1.0148 0 Td
(ART)Tj
2.1373 0 Td
(after)Tj
2.0353 0 Td
(four)Tj
1.9162 0 Td
(months)Tj
3.2825 0 Td
(of)Tj
1.0148 0 Td
(follow-up)Tj
4.0932 0 Td
(\(see)Tj
0.83 0.64 0.02 0 k
1.7688 0 Td
(Fig)Tj
1.4797 0 Td
(1)Tj
0 g
0.6916 0 Td
(for)Tj
1.389 0 Td
(patient)Tj
3.0047 0 Td
(flow)Tj
1.9502 0 Td
(and)Tj
0.83 0.64 0.02 0 k
1.7292 0 Td
(Fig)Tj
1.4796 0 Td
(2)Tj
0 g
0.6917 0 Td
(for)Tj
1.389 0 Td
(overview)Tj
-33.3749 -1.3039 Td
(study)Tj
2.3867 0 Td
(design\).)Tj
-1.1905 -1.2983 Td
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3.6226 0 Td
(informed)Tj
3.9685 0 Td
(consent)Tj
3.3335 0 Td
(was)Tj
1.7008 0 Td
(obtained)Tj
3.7304 0 Td
(from)Tj
2.2053 0 Td
(all)Tj
1.1452 0 Td
(study)Tj
2.3924 0 Td
(participants.)Tj
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1.7858 0 Td
(study)Tj
2.3868 0 Td
(was)Tj
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(approved)Tj
3.9741 0 Td
(by)Tj
1.1792 0 Td
(the)Tj
1.4683 0 Td
(Norwegian)Tj
4.6602 0 Td
(Medicines)Tj
4.354 0 Td
(Agency)Tj
3.2201 0 Td
(\(EudraCT)Tj
4.2633 0 Td
(No:)Tj
1.6894 0 Td
(2010-020382-25\))Tj
6.9675 0 Td
(and)Tj
1.7292 0 Td
(the)Tj
1.4683 0 Td
(Nor-)Tj
-34.9736 -1.3039 Td
(wegian)Tj
3.0387 0 Td
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3.736 0 Td
(Committee)Tj
4.7395 0 Td
(for)Tj
1.389 0 Td
(Medical)Tj
3.4299 0 Td
(and)Tj
1.7348 0 Td
(Health)Tj
2.914 0 Td
(Research)Tj
3.8097 0 Td
(Ethics)Tj
2.6646 0 Td
(South)Tj
2.5568 0 Td
(East)Tj
1.8822 0 Td
(\(application)Tj
-31.8952 -1.2983 Td
(#2010/1593\).)Tj
5.3971 0 Td
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1.7801 0 Td
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2.3868 0 Td
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1.7008 0 Td
(registered)Tj
4.1555 0 Td
(at)Tj
0.9525 0 Td
(Clinicaltrials.gov)Tj
6.9448 0 Td
(\(Identifier:)Tj
4.5411 0 Td
(NCT01269515\).)Tj
6.599 0 Td
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-34.4577 -1.2983 Td
(study)Tj
2.3867 0 Td
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1.7008 0 Td
(independently)Tj
5.9754 0 Td
(monitored)Tj
4.49 0 Td
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1.389 0 Td
(safety)Tj
2.4775 0 Td
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1.1792 0 Td
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q
1 j
1 J
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BT
/F0 1 Tf
1 TL
-0.0033 Tc
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Q
q
1 j
1 J
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BT
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1 TL
-0.004 Tc
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3.4979 0 Td
(endpoints)Tj
4.2179 0 Td
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2.1203 0 Td
(changes)Tj
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2.5739 0 Td
(density)Tj
3.1011 0 Td
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1.2755 0 Td
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Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 430.9795 163.8992 cm
BT
/F8 1 Tf
1 TL
-0.0053 Tc
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(+)Tj
ET
Q
q
1 j
1 J
0 w
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BT
/F8 1 Tf
1 TL
-0.004 Tc
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(T)Tj
0.8277 0 Td
(cells)Tj
1.9218 0 Td
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(four)Tj
1.9162 0 Td
(months)Tj
3.2825 0 Td
(of)Tj
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