%PDF-1.6
%
1 0 obj
<>
endobj
2 0 obj
<>stream
Davide De Francesco, Ferdinand W. Wit, James H. Cole, Neeltje A. Kootstra, Alan Winston, Caroline A. Sabin, Jonathan Underwood, Rosan A. van Zoest, Judith Schouten, Katherine W. Kooij, Maria Prins, Giovanni Guaraldi, Matthan W. A. Caan, David Burger, Claudio Franceschi, Claude Libert, Alexander Bürkle, Peter Reiss, on behalf of the COmorBidity in Relation to AIDS (COBRA) collaboration
The ‘COmorBidity in Relation to AIDS’ (COBRA) cohort: Design, methods and participant characteristics
www.plosone.org
www.plosone.org
endstream
endobj
3 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 12 0 R/Annots 13 0 R/Contents 14 0 R/TrimBox[0 0 612 792]>>
endobj
13 0 obj
[15 0 R 16 0 R 17 0 R 18 0 R 19 0 R 20 0 R 21 0 R 22 0 R 23 0 R 24 0 R 25 0 R 26 0 R 27 0 R 28 0 R 29 0 R 30 0 R 31 0 R]
endobj
15 0 obj
<>/Border[0 0 0]/Dest(Rpone.0191791.ref001)>>
endobj
16 0 obj
<>/Border[0 0 0]/Dest(Rpone.0191791.ref002)>>
endobj
17 0 obj
<>/Border[0 0 0]/Dest(Rpone.0191791.ref003)>>
endobj
18 0 obj
<>/Border[0 0 0]/Dest(Rpone.0191791.ref005)>>
endobj
19 0 obj
<>/Border[0 0 0]/Dest(Rpone.0191791.ref006)>>
endobj
20 0 obj
<>/Border[0 0 0]/Dest(Rpone.0191791.ref007)>>
endobj
21 0 obj
<>/Border[0 0 0]/Dest(Rpone.0191791.ref008)>>
endobj
22 0 obj
<>/Border[0 0 0]/Dest(Rpone.0191791.ref009)>>
endobj
23 0 obj
<>/Border[0 0 0]/Dest(Rpone.0191791.ref010)>>
endobj
24 0 obj
<>/Border[0 0 0]/Dest(Rpone.0191791.ref012)>>
endobj
25 0 obj
<>/Border[0 0 0]/Dest(Rpone.0191791.ref013)>>
endobj
26 0 obj
<>/Border[0 0 0]/Dest(Rpone.0191791.ref014)>>
endobj
27 0 obj
<>/Border[0 0 0]/Dest(Rpone.0191791.ref015)>>
endobj
28 0 obj
<>/Border[0 0 0]/Dest(Rpone.0191791.ref016)>>
endobj
29 0 obj
<>/Border[0 0 0]/Dest(Rpone.0191791.ref017)>>
endobj
30 0 obj
<>/Border[0 0 0]/Dest(Rpone.0191791.ref018)>>
endobj
31 0 obj
<>/Border[0 0 0]/A 32 0 R>>
endobj
32 0 obj
<>
endobj
14 0 obj
[33 0 R 34 0 R 35 0 R 36 0 R 37 0 R 38 0 R 39 0 R 40 0 R 41 0 R 42 0 R 43 0 R 44 0 R 45 0 R 46 0 R 47 0 R 48 0 R 49 0 R 50 0 R]
endobj
33 0 obj
<>stream
q
0.45 0.36 0.35 0.01 k
0 w
575.9997 587.6144 m
199.9998 587.6144 l
199.9998 588.1144 l
575.9997 588.1144 l
f*
0.83 0.64 0.02 0 k
268.2709 484.8945 m
273.0331 484.8945 l
h
f*
277.5118 484.8945 m
282.274 484.8945 l
h
f*
455.9811 432.9071 m
460.7433 432.9071 l
h
f*
465.9591 432.9071 m
470.6646 432.9071 l
h
f*
290.4378 367.937 m
295.1433 367.937 l
h
f*
304.1575 367.937 m
308.9197 367.937 l
h
f*
317.9339 367.937 m
322.6961 367.937 l
h
f*
534.2173 315.9496 m
538.9795 315.9496 l
h
f*
485.7449 289.9276 m
495.2693 289.9276 l
h
f*
500.4283 289.9276 m
509.9528 289.9276 l
h
f*
485.8016 224.9008 m
495.2693 224.9008 l
h
f*
499.748 224.9008 m
509.2724 224.9008 l
h
f*
503.4331 133.9087 m
512.9575 133.9087 l
h
f*
517.4362 133.9087 m
526.9606 133.9087 l
h
f*
292.0252 107.9433 m
301.5496 107.9433 l
h
f*
305.9717 107.9433 m
315.4961 107.9433 l
h
f*
0 g
1 j
1 J
9.5 0 0 9.5 200.0125 707.7543 cm
BT
/F0 1 Tf
1 TL
-0.0042 Tc
0 0 Td
(Similarly,)Tj
4.225 0 Td
(the)Tj
1.5934 0 Td
(79)Tj
1.3189 0 Td
(HIV-negative)Tj
5.9378 0 Td
(subjects)Tj
3.8491 0 Td
(had)Tj
1.8679 0 Td
(a)Tj
0.7639 0 Td
(median)Tj
3.4612 0 Td
(\(IQR\))Tj
2.6496 0 Td
(age)Tj
1.8679 0 Td
(of)Tj
1.0444 0 Td
(57)Tj
1.3188 0 Td
(\(52,)Tj
1.9276 0 Td
(64\))Tj
1.647 0 Td
(and)Tj
1.8619 0 Td
(92%)Tj
-35.3344 -1.474 Td
(were)Tj
2.3631 0 Td
(male,)Tj
2.6377 0 Td
(97%)Tj
2.2021 0 Td
(of)Tj
1.0443 0 Td
(white)Tj
2.5244 0 Td
(ethnicity)Tj
3.8431 0 Td
(and)Tj
1.8679 0 Td
(80%)Tj
2.2021 0 Td
(were)Tj
2.3632 0 Td
(MSM.)Tj
ET
Q
q
1 j
1 J
0 w
11.4998 0 0 11.4998 200.0125 660.1322 cm
BT
/F2 1 Tf
1 TL
-0.0035 Tc
0 0 Td
(Conclusions)Tj
ET
Q
q
1 j
1 J
0 w
9.5 0 0 9.5 200.0125 643.1244 cm
BT
/F0 1 Tf
1 TL
-0.0042 Tc
0 0 Td
(The)Tj
1.9275 0 Td
(results)Tj
3.133 0 Td
(from)Tj
2.2081 0 Td
(the)Tj
1.5933 0 Td
(COBRA)Tj
3.7537 0 Td
(study)Tj
2.5899 0 Td
(will)Tj
1.5815 0 Td
(be)Tj
1.3188 0 Td
(a)Tj
0.7639 0 Td
(significant)Tj
4.607 0 Td
(resource)Tj
4.0699 0 Td
(to)Tj
1.0444 0 Td
(understand)Tj
5.168 0 Td
(the)Tj
1.5933 0 Td
(link)Tj
-35.3523 -1.474 Td
(between)Tj
3.9565 0 Td
(HIV)Tj
1.8738 0 Td
(and)Tj
1.8679 0 Td
(AANCC)Tj
3.694 0 Td
(and)Tj
1.8679 0 Td
(the)Tj
1.5933 0 Td
(pathogenic)Tj
5.0487 0 Td
(mechanisms)Tj
5.7826 0 Td
(underlying)Tj
4.7682 0 Td
(this)Tj
1.7545 0 Td
(link.)Tj
1.9753 0 Td
(COBRA)Tj
3.7536 0 Td
(will)Tj
-37.9363 -1.474 Td
(inform)Tj
2.9659 0 Td
(future)Tj
2.7511 0 Td
(development)Tj
5.8841 0 Td
(of)Tj
1.0443 0 Td
(novel)Tj
2.578 0 Td
(prognostic)Tj
4.7801 0 Td
(tools)Tj
2.3035 0 Td
(for)Tj
1.3786 0 Td
(earlier)Tj
2.954 0 Td
(diagnosis)Tj
4.3862 0 Td
(of)Tj
1.0443 0 Td
(AANCC)Tj
3.694 0 Td
(and)Tj
1.8679 0 Td
(of)Tj
-37.632 -1.474 Td
(novel)Tj
2.578 0 Td
(interventions)Tj
5.8184 0 Td
(which,)Tj
3.0197 0 Td
(as)Tj
1.2651 0 Td
(an)Tj
1.3189 0 Td
(adjunct)Tj
3.4015 0 Td
(to)Tj
1.0503 0 Td
(cART,)Tj
2.9839 0 Td
(may)Tj
2.0946 0 Td
(prevent)Tj
3.5209 0 Td
(AANCC.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 529.0015 cm
BT
/F2 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Introduction)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 511.9937 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Combination)Tj
5.5842 0 Td
(antiretroviral)Tj
5.5162 0 Td
(therapy)Tj
3.2428 0 Td
(\(cART\))Tj
3.2428 0 Td
(has)Tj
1.542 0 Td
(reduced)Tj
3.4469 0 Td
(the)Tj
1.4684 0 Td
(risk)Tj
1.7177 0 Td
(of)Tj
1.0148 0 Td
(AIDS-defining)Tj
6.1398 0 Td
(illnesses)Tj
-32.9156 -1.2982 Td
(and)Tj
1.7291 0 Td
(their)Tj
2.1089 0 Td
(associated)Tj
4.2576 0 Td
(mortality,)Tj
4.1386 0 Td
(and)Tj
1.7348 0 Td
(has)Tj
1.542 0 Td
(markedly)Tj
3.9912 0 Td
(and)Tj
1.7291 0 Td
(sustainably)Tj
4.6601 0 Td
(improved)Tj
4.1103 0 Td
(survival)Tj
3.3335 0 Td
(for)Tj
1.3889 0 Td
(people)Tj
-34.7241 -1.3039 Td
(living)Tj
2.4661 0 Td
(with)Tj
2.0012 0 Td
(HIV)Tj
2.0183 0 Td
([)Tj
0.83 0.64 0.02 0 k
(1)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.2642 0 Td
(2)Tj
0 g
(].)Tj
1.2586 0 Td
(As)Tj
1.2642 0 Td
(a)Tj
0.6577 0 Td
(consequence)Tj
5.3347 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(rising)Tj
2.5001 0 Td
(average)Tj
3.2258 0 Td
(age)Tj
1.5421 0 Td
(of)Tj
1.0148 0 Td
(those)Tj
2.3414 0 Td
(living)Tj
2.4661 0 Td
(with)Tj
2.0012 0 Td
(HIV,)Tj
-33.8397 -1.2983 Td
(morbidity)Tj
4.2406 0 Td
(and)Tj
1.7291 0 Td
(mortality)Tj
3.9174 0 Td
(in)Tj
1.0318 0 Td
(these)Tj
2.2564 0 Td
(individuals)Tj
4.6488 0 Td
(is)Tj
0.8504 0 Td
(increasingly)Tj
5.0286 0 Td
(a)Tj
0.652 0 Td
(result)Tj
2.4491 0 Td
(of)Tj
1.0148 0 Td
(age-associated)Tj
5.93 0 Td
(non-)Tj
-33.749 -1.2983 Td
(communicable)Tj
6.1681 0 Td
(co-morbidities)Tj
6.1171 0 Td
(\(AANCC\))Tj
4.3313 0 Td
(such)Tj
2.058 0 Td
(as)Tj
1.0148 0 Td
(cardiovascular)Tj
6.0037 0 Td
(disease,)Tj
3.2428 0 Td
(diabetes)Tj
3.4639 0 Td
(mellitus,)Tj
-32.3997 -1.2982 Td
(chronic)Tj
3.2881 0 Td
(kidney)Tj
2.9367 0 Td
(and)Tj
1.7291 0 Td
(liver)Tj
1.9843 0 Td
(disease,)Tj
3.2428 0 Td
(osteoporosis,)Tj
5.4368 0 Td
(non-AIDS)Tj
4.4107 0 Td
(associated)Tj
4.2519 0 Td
(malignancies,)Tj
5.6863 0 Td
(chronic)Tj
-32.9667 -1.3039 Td
(obstructive)Tj
4.6601 0 Td
(pulmonary)Tj
4.6431 0 Td
(disease,)Tj
3.2428 0 Td
(as)Tj
1.0148 0 Td
(well)Tj
1.8198 0 Td
(as)Tj
1.0148 0 Td
(cognitive)Tj
3.8778 0 Td
(impairment)Tj
4.9833 0 Td
([)Tj
0.83 0.64 0.02 0 k
(3)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(5)Tj
0 g
(].)Tj
-24.0603 -1.2983 Td
(As)Tj
1.2699 0 Td
(treated)Tj
2.9933 0 Td
(HIV-positive)Tj
5.4709 0 Td
(individuals)Tj
4.6488 0 Td
(age,)Tj
1.7688 0 Td
(their)Tj
2.1089 0 Td
(care)Tj
1.8709 0 Td
(becomes)Tj
3.685 0 Td
(increasingly)Tj
5.0286 0 Td
(complex)Tj
3.6227 0 Td
(and)Tj
1.7291 0 Td
(chal-)Tj
-35.3931 -1.2983 Td
(lenging)Tj
3.1804 0 Td
(because)Tj
3.3222 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(need)Tj
2.143 0 Td
(to)Tj
1.0261 0 Td
(prevent)Tj
3.2599 0 Td
(and)Tj
1.7291 0 Td
(manage)Tj
3.3448 0 Td
(multiple)Tj
3.566 0 Td
(concomitant)Tj
5.2951 0 Td
(AANCC.)Tj
3.8778 0 Td
(The)Tj
1.7801 0 Td
(result-)Tj
-35.0076 -1.3039 Td
(ing)Tj
1.5023 0 Td
(requirement)Tj
5.1987 0 Td
(for)Tj
1.389 0 Td
(integrated)Tj
4.2746 0 Td
(multidisciplinary)Tj
7.0639 0 Td
(care)Tj
1.8708 0 Td
(\(including)Tj
4.3824 0 Td
(disciplines)Tj
4.4333 0 Td
(not)Tj
1.5704 0 Td
(traditionally)Tj
-31.6854 -1.2983 Td
(heavily)Tj
3.0273 0 Td
(involved)Tj
3.651 0 Td
(in)Tj
1.0318 0 Td
(the)Tj
1.474 0 Td
(management)Tj
5.4312 0 Td
(of)Tj
1.0148 0 Td
(HIV-positive)Tj
5.4708 0 Td
(patients\))Tj
3.7077 0 Td
(will)Tj
1.6611 0 Td
(present)Tj
3.1634 0 Td
(new)Tj
1.8766 0 Td
(challenges)Tj
4.3199 0 Td
(for)Tj
-35.8296 -1.2982 Td
(health-care)Tj
4.6771 0 Td
(providers)Tj
4.0252 0 Td
([)Tj
0.83 0.64 0.02 0 k
(6)Tj
0 g
(])Tj
1.3719 0 Td
([)Tj
0.83 0.64 0.02 0 k
(7)Tj
0 g
(])Tj
1.3776 0 Td
([)Tj
0.83 0.64 0.02 0 k
(8)Tj
0 g
(].)Tj
-10.2556 -1.3039 Td
(Moreover,)Tj
4.3993 0 Td
(AANCC,)Tj
3.8778 0 Td
(and)Tj
1.7291 0 Td
(possibly)Tj
3.4412 0 Td
(their)Tj
2.109 0 Td
(treatment,)Tj
4.3597 0 Td
(may)Tj
1.9275 0 Td
(undermine)Tj
4.6771 0 Td
(sustained)Tj
3.9685 0 Td
(adherence)Tj
4.3257 0 Td
(to)Tj
-36.0111 -1.2983 Td
(lifelong)Tj
3.2087 0 Td
(cART)Tj
2.5626 0 Td
(with)Tj
1.9955 0 Td
(the)Tj
1.4684 0 Td
(resulting)Tj
3.7303 0 Td
(polypharmacy)Tj
5.9301 0 Td
(leading)Tj
3.1294 0 Td
(to)Tj
1.0261 0 Td
(an)Tj
1.2019 0 Td
(increased)Tj
4.0025 0 Td
(potential)Tj
3.7587 0 Td
(for)Tj
1.389 0 Td
(drug-drug)Tj
-33.4032 -1.2983 Td
(interactions,)Tj
5.193 0 Td
(thereby)Tj
3.2258 0 Td
(potentially)Tj
4.4617 0 Td
(jeopardizing)Tj
5.2157 0 Td
(both)Tj
2.0636 0 Td
(the)Tj
1.4684 0 Td
(long-term)Tj
4.2519 0 Td
(effectiveness)Tj
5.2044 0 Td
(of)Tj
1.0148 0 Td
(cART)Tj
2.5568 0 Td
(for)Tj
1.389 0 Td
(the)Tj
-36.0451 -1.2982 Td
(individual,)Tj
4.5127 0 Td
(as)Tj
1.0148 0 Td
(well)Tj
1.8198 0 Td
(as)Tj
1.0148 0 Td
(its)Tj
1.1452 0 Td
(benefits)Tj
3.3392 0 Td
(to)Tj
1.0261 0 Td
(society)Tj
2.9537 0 Td
(in)Tj
1.0375 0 Td
(preventing)Tj
4.5354 0 Td
(onward)Tj
3.2938 0 Td
(HIV)Tj
2.0239 0 Td
(transmission)Tj
5.3632 0 Td
([)Tj
0.83 0.64 0.02 0 k
(9)Tj
0 g
(].)Tj
-31.8839 -1.3039 Td
(Recent)Tj
2.9593 0 Td
(studies)Tj
2.9877 0 Td
(have)Tj
2.058 0 Td
(suggested)Tj
4.0761 0 Td
(that)Tj
1.7802 0 Td
(in)Tj
1.0318 0 Td
(people)Tj
2.8573 0 Td
(living)Tj
2.4661 0 Td
(with)Tj
2.0013 0 Td
(HIV)Tj
2.0182 0 Td
(several)Tj
2.9367 0 Td
(AANCC)Tj
3.651 0 Td
(may)Tj
1.9276 0 Td
(occur)Tj
-33.9475 -1.2983 Td
(more)Tj
2.3414 0 Td
(frequently)Tj
4.3086 0 Td
(and)Tj
1.7291 0 Td
(at)Tj
0.9524 0 Td
(an)Tj
1.2019 0 Td
(earlier)Tj
2.7553 0 Td
(age)Tj
1.5477 0 Td
(than)Tj
2.0239 0 Td
(in)Tj
1.0375 0 Td
(HIV-negative)Tj
5.6863 0 Td
(individuals)Tj
4.6487 0 Td
([)Tj
0.83 0.64 0.02 0 k
(10)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(12)Tj
0 g
(].)Tj
3.549 0 Td
(Whilst)Tj
2.8856 0 Td
(these)Tj
-34.6674 -1.2983 Td
(findings)Tj
3.4922 0 Td
(should)Tj
2.9197 0 Td
(be)Tj
1.1452 0 Td
(interpreted)Tj
4.6941 0 Td
(with)Tj
1.9956 0 Td
(caution,)Tj
3.4526 0 Td
(these)Tj
2.2563 0 Td
(observations)Tj
5.2554 0 Td
(may)Tj
1.9332 0 Td
(partly)Tj
2.5399 0 Td
(explain)Tj
3.1237 0 Td
(the)Tj
1.4684 0 Td
(finding)Tj
-34.2763 -1.3039 Td
(that,)Tj
2.0012 0 Td
(despite)Tj
3.0387 0 Td
(the)Tj
1.4684 0 Td
(use)Tj
1.5363 0 Td
(of)Tj
1.0148 0 Td
(cART,)Tj
2.7836 0 Td
(the)Tj
1.4684 0 Td
(estimated)Tj
4.0762 0 Td
(average)Tj
3.2258 0 Td
(life)Tj
1.4456 0 Td
(expectancy)Tj
4.6318 0 Td
(of)Tj
1.0148 0 Td
(people)Tj
2.8516 0 Td
(living)Tj
2.4718 0 Td
(with)Tj
1.9956 0 Td
(HIV)Tj
-35.0246 -1.2983 Td
(remains)Tj
3.4412 0 Td
(shorter)Tj
3.0841 0 Td
(than)Tj
2.0296 0 Td
(that)Tj
1.7744 0 Td
(of)Tj
1.0148 0 Td
(HIV-negative)Tj
5.692 0 Td
(persons)Tj
3.3051 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.474 0 Td
(same)Tj
2.2564 0 Td
(age,)Tj
1.7688 0 Td
(particularly)Tj
4.8075 0 Td
(when)Tj
2.4038 0 Td
(diagno-)Tj
-34.0665 -1.2982 Td
(sis)Tj
1.2075 0 Td
(and)Tj
1.7291 0 Td
(treatment)Tj
4.1386 0 Td
(of)Tj
1.0148 0 Td
(HIV)Tj
2.0182 0 Td
(infection)Tj
3.7928 0 Td
(is)Tj
0.8504 0 Td
(delayed)Tj
3.2541 0 Td
(to)Tj
1.0261 0 Td
(an)Tj
1.2019 0 Td
(advanced)Tj
3.9968 0 Td
(disease)Tj
3.0161 0 Td
(stage)Tj
2.1997 0 Td
(\(i.e.,)Tj
1.9275 0 Td
(AIDS)Tj
2.4605 0 Td
(and/or)Tj
-33.8341 -1.3039 Td
(severe)Tj
2.6758 0 Td
(immunodeficiency)Tj
7.7556 0 Td
(with)Tj
2.0012 0 Td
(CD4)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 343.0488 230.4566 cm
BT
/F7 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(+)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 349.6251 225.9779 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(T-cell)Tj
2.5171 0 Td
(counts)Tj
2.8857 0 Td
(below)Tj
2.5908 0 Td
(200)Tj
1.6441 0 Td
(cells/)Tj
/F11 1 Tf
[()]TJ
/F7 1 Tf
(L\))Tj
3.6396 0 Td
([)Tj
0.83 0.64 0.02 0 k
(13)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7348 0 Td
(14)Tj
0 g
(].)Tj
1.7348 0 Td
(As)Tj
1.2643 0 Td
(a)Tj
0.6576 0 Td
(conse-)Tj
-33.6299 -1.2982 Td
(quence,)Tj
3.2938 0 Td
(there)Tj
2.2621 0 Td
(continues)Tj
4.1215 0 Td
(to)Tj
1.0261 0 Td
(be)Tj
1.1452 0 Td
(a)Tj
0.652 0 Td
(reduced)Tj
3.4411 0 Td
(probability)Tj
4.5978 0 Td
(that)Tj
1.7745 0 Td
(people)Tj
2.8516 0 Td
(living)Tj
2.4661 0 Td
(with)Tj
1.9956 0 Td
(HIV)Tj
2.0183 0 Td
(will)Tj
1.6611 0 Td
(experience)Tj
-33.3068 -1.2983 Td
(healthy)Tj
3.1294 0 Td
(aging)Tj
2.4038 0 Td
(with)Tj
1.9956 0 Td
(good)Tj
2.228 0 Td
(quality)Tj
2.9537 0 Td
(of)Tj
1.0148 0 Td
(life)Tj
1.4455 0 Td
(while)Tj
2.3698 0 Td
(remaining)Tj
4.3653 0 Td
(able)Tj
1.8255 0 Td
(to)Tj
1.0261 0 Td
(work)Tj
2.2791 0 Td
(and)Tj
1.7291 0 Td
(contribute)Tj
4.3937 0 Td
(economi-)Tj
-33.1594 -1.3039 Td
(cally)Tj
2.0239 0 Td
(and)Tj
1.7291 0 Td
(in)Tj
1.0375 0 Td
(other)Tj
2.3471 0 Td
(ways)Tj
2.1543 0 Td
(to)Tj
1.0261 0 Td
(society.)Tj
-9.1218 -1.2983 Td
(In)Tj
1.1112 0 Td
(studies)Tj
2.9877 0 Td
(conducted)Tj
4.4277 0 Td
(thus)Tj
1.9332 0 Td
(far,)Tj
1.5363 0 Td
(early)Tj
2.1543 0 Td
(onset)Tj
2.3584 0 Td
(and)Tj
1.7291 0 Td
(occurrence)Tj
4.6601 0 Td
(of)Tj
1.0148 0 Td
(AANCC)Tj
3.651 0 Td
(were)Tj
2.126 0 Td
(common)Tj
3.8437 0 Td
(in)Tj
-34.7297 -1.2982 Td
(HIV-positive)Tj
5.4651 0 Td
(people)Tj
2.8574 0 Td
(with)Tj
1.9955 0 Td
(traditional)Tj
4.422 0 Td
(modifiable)Tj
4.507 0 Td
(or)Tj
1.0998 0 Td
(unmodifiable)Tj
5.5786 0 Td
(demographic,)Tj
5.7316 0 Td
(lifestyle-)Tj
-31.657 -1.2983 Td
(related)Tj
2.9423 0 Td
(and)Tj
1.7292 0 Td
(behavioural)Tj
4.9209 0 Td
(risk)Tj
1.7177 0 Td
(factors)Tj
2.9027 0 Td
(for)Tj
1.3832 0 Td
(AANCC.)Tj
3.8778 0 Td
(Among)Tj
3.2485 0 Td
(these)Tj
2.2507 0 Td
(AANCC,)Tj
3.8777 0 Td
(clinically)Tj
3.7758 0 Td
(significant)Tj
-32.6265 -1.3039 Td
(cognitive)Tj
3.8721 0 Td
(impairment)Tj
4.9889 0 Td
(is)Tj
0.8448 0 Td
(often)Tj
2.2903 0 Td
(observed)Tj
3.7927 0 Td
(in)Tj
1.0374 0 Td
(people)Tj
2.8517 0 Td
(living)Tj
2.4718 0 Td
(with)Tj
1.9955 0 Td
(HIV)Tj
2.024 0 Td
(on)Tj
1.2756 0 Td
(cART)Tj
2.5568 0 Td
([)Tj
0.83 0.64 0.02 0 k
(15)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7404 0 Td
(16)Tj
0 g
(].)Tj
1.7348 0 Td
(Neuro-)Tj
-33.4768 -1.2983 Td
(imaging)Tj
3.4866 0 Td
(is)Tj
0.8447 0 Td
(beginning)Tj
4.2633 0 Td
(to)Tj
1.0261 0 Td
(provide)Tj
3.2882 0 Td
(important)Tj
4.2802 0 Td
(insights)Tj
3.3165 0 Td
(into)Tj
1.8425 0 Td
(the)Tj
1.4683 0 Td
(pathogenesis)Tj
5.3518 0 Td
(of)Tj
1.0148 0 Td
(HIV-associated)Tj
-30.183 -1.2982 Td
(cognitive)Tj
3.8721 0 Td
(impairment)Tj
4.9889 0 Td
([)Tj
0.83 0.64 0.02 0 k
(17)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7348 0 Td
(18)Tj
0 g
(])Tj
1.5137 0 Td
(and)Tj
1.7291 0 Td
(recent)Tj
2.7098 0 Td
(advances)Tj
3.8268 0 Td
(in)Tj
1.0375 0 Td
(magnetic)Tj
3.8947 0 Td
(resonance)Tj
4.2633 0 Td
(imaging)Tj
3.4866 0 Td
(\(MRI\))Tj
-33.0573 -1.304 Td
(allow)Tj
2.3357 0 Td
(further)Tj
3.0274 0 Td
(study)Tj
2.3924 0 Td
(of)Tj
1.0148 0 Td
(brain)Tj
2.3471 0 Td
(structure)Tj
3.8211 0 Td
(and)Tj
1.729 0 Td
(function)Tj
3.6283 0 Td
(in)Tj
1.0375 0 Td
(greater)Tj
3.0104 0 Td
(detail)Tj
2.4151 0 Td
(and)Tj
1.7291 0 Td
(thus)Tj
1.9332 0 Td
(increase)Tj
3.4753 0 Td
(our)Tj
-33.8964 -1.2982 Td
(understanding)Tj
6.0661 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.474 0 Td
(pathogenesis)Tj
5.3518 0 Td
(of)Tj
1.0148 0 Td
(HIV-associated)Tj
6.4118 0 Td
(cognitive)Tj
3.8721 0 Td
(impairment.)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 107.1496 23.6976 re
W* n
q
107.0929 0 0 23.6409 36 741.3165 cm
q
/I0 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 508.8755 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(The)Tj
1.9204 0 Td
(COBRA)Tj
3.7347 0 Td
(cohort)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
81.5811 34.9228 m
237.8835 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(ONE)Tj
2.3669 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.137)Tj
3.8198 0 Td
(1/journal.po)Tj
5.1236 0 Td
(ne.01917)Tj
4.089 0 Td
(91)Tj
0 g
2.0906 0 Td
(March)Tj
2.9622 0 Td
(29,)Tj
1.5874 0 Td
(2018)Tj
34.3562 0 Td
(2)Tj
0.7654 0 Td
(/)Tj
0.496 0 Td
(16)Tj
/F9 1 Tf
-0.025 Tc
-66.402 84.0904 Td
(the)Tj
1.3677 0 Td
(study,)Tj
2.4945 0 Td
(design)Tj
2.6717 0 Td
(and)Tj
1.5874 0 Td
(feasibility,)Tj
3.8906 0 Td
(statistical)Tj
3.6709 0 Td
(power)Tj
-15.6828 -1.3748 Td
(and)Tj
1.5874 0 Td
(overlap)Tj
2.9338 0 Td
(with)Tj
1.7788 0 Td
(existing)Tj
3.0756 0 Td
(projects)Tj
2.9622 0 Td
(.)Tj
0.4465 0 Td
(If)Tj
0.7299 0 Td
(the)Tj
1.3748 0 Td
(proposed)Tj
-14.889 -1.3749 Td
(analysis)Tj
3.189 0 Td
(is)Tj
0.8291 0 Td
(for)Tj
1.2614 0 Td
(verifica)Tj
2.6292 0 Td
(tion/replicat)Tj
4.337 0 Td
(ion,)Tj
1.5874 0 Td
(data)Tj
1.793 0 Td
(will)Tj
1.4386 0 Td
(then)Tj
-17.0647 -1.3748 Td
(be)Tj
1.1126 0 Td
(made)Tj
2.289 0 Td
(available.)Tj
3.6071 0 Td
(If)Tj
0.7299 0 Td
(the)Tj
1.3748 0 Td
(proposed)Tj
3.7347 0 Td
(research)Tj
3.4158 0 Td
(is)Tj
0.8362 0 Td
(for)Tj
-17.1001 -1.3748 Td
(novel)Tj
2.2039 0 Td
(science,)Tj
3.2174 0 Td
(upon)Tj
2.1118 0 Td
(completion)Tj
4.3512 0 Td
(of)Tj
0.9496 0 Td
(the)Tj
1.3748 0 Td
(review,)Tj
-14.2087 -1.3748 Td
(feedback)Tj
3.5291 0 Td
(will)Tj
1.4386 0 Td
(be)Tj
1.1126 0 Td
(provided)Tj
3.4583 0 Td
(to)Tj
0.9496 0 Td
(the)Tj
1.3677 0 Td
(proposer\(s\).)Tj
4.8332 0 Td
(In)Tj
-16.6891 -1.3748 Td
(some)Tj
2.2889 0 Td
(circumstanc)Tj
4.5639 0 Td
(es,)Tj
1.2897 0 Td
(a)Tj
0.6378 0 Td
(revision)Tj
3.1253 0 Td
(of)Tj
0.9496 0 Td
(the)Tj
1.3677 0 Td
(concept)Tj
-14.2229 -1.3748 Td
(may)Tj
1.8141 0 Td
(be)Tj
1.1197 0 Td
(requested)Tj
3.6638 0 Td
(.)Tj
0.4465 0 Td
(If)Tj
0.7299 0 Td
(the)Tj
1.3748 0 Td
(concep)Tj
2.6788 0 Td
(t)Tj
0.4748 0 Td
(is)Tj
0.8362 0 Td
(approved)Tj
3.6851 0 Td
(for)Tj
-16.8237 -1.3748 Td
(implementa)Tj
4.3583 0 Td
(tion,)Tj
1.8425 0 Td
(a)Tj
0.6378 0 Td
(writing)Tj
2.7567 0 Td
(group)Tj
2.4236 0 Td
(will)Tj
1.4386 0 Td
(be)Tj
1.1126 0 Td
(established)Tj
-14.5701 -1.3748 Td
(consisting)Tj
4.0181 0 Td
(of)Tj
0.9496 0 Td
(the)Tj
1.3677 0 Td
(proposers)Tj
3.9969 0 Td
(\(up)Tj
1.474 0 Td
(to)Tj
0.9497 0 Td
(3)Tj
0.6944 0 Td
(persons)Tj
3.2103 0 Td
(that)Tj
-16.6607 -1.3749 Td
(were)Tj
2.0126 0 Td
(central)Tj
2.4874 0 Td
(ly)Tj
0.8362 0 Td
(involved)Tj
3.2953 0 Td
(in)Tj
0.8858 0 Td
(the)Tj
1.3678 0 Td
(developm)Tj
3.6284 0 Td
(ent)Tj
1.3748 0 Td
(of)Tj
0.9496 0 Td
(the)Tj
-16.8379 -1.3748 Td
(concept\))Tj
3.4653 0 Td
(and)Tj
1.5874 0 Td
(members)Tj
3.7772 0 Td
(of)Tj
0.9497 0 Td
(the)Tj
1.3677 0 Td
(COBRA)Tj
2.9693 0 Td
(group)Tj
2.4236 0 Td
(\(or)Tj
-16.5402 -1.3748 Td
(other)Tj
2.1543 0 Td
(appoin)Tj
2.5016 0 Td
(ted)Tj
1.3748 0 Td
(cohort)Tj
2.6221 0 Td
(representati)Tj
4.3724 0 Td
(ves\).)Tj
2.0198 0 Td
(All)Tj
-15.045 -1.3748 Td
(persons)Tj
3.2102 0 Td
(involved)Tj
3.2953 0 Td
(in)Tj
0.8858 0 Td
(the)Tj
1.3678 0 Td
(process)Tj
3.1606 0 Td
(of)Tj
0.9496 0 Td
(reviewing)Tj
3.7631 0 Td
(these)Tj
-16.6324 -1.3748 Td
(research)Tj
3.4157 0 Td
(concepts)Tj
3.5788 0 Td
(are)Tj
1.3748 0 Td
(bound)Tj
2.5866 0 Td
(by)Tj
1.1126 0 Td
(confidentia)Tj
4.0536 0 Td
(lity.)Tj
-16.1221 -1.3748 Td
(Medisch)Tj
3.3803 0 Td
(Ethische)Tj
3.352 0 Td
(Toetsingsc)Tj
4.0252 0 Td
(ommissie,)Tj
-10.7575 -1.3748 Td
(Academis)Tj
3.6283 0 Td
(ch)Tj
1.1197 0 Td
(Medisch)Tj
3.3733 0 Td
(Centrum,)Tj
3.6567 0 Td
(Universiteit)Tj
4.3654 0 Td
(van)Tj
-16.1434 -1.3749 Td
(Amsterdam)Tj
4.5567 0 Td
(Academ)Tj
3.0118 0 Td
(isch)Tj
1.7292 0 Td
(Medisch)Tj
3.3803 0 Td
(Centrum,)Tj
3.6567 0 Td
(XT4-)Tj
-16.3347 -1.3819 Td
(140)Tj
1.637 0 Td
(Meibergdreef)Tj
5.1449 0 Td
(9,)Tj
0.9213 0 Td
(1105)Tj
2.1118 0 Td
(AZ)Tj
1.2189 0 Td
(Amsterdam)Tj
4.33 0 Td
(,)Tj
0.4464 0 Td
(The)Tj
-15.8103 -1.3748 Td
(Netherland)Tj
4.0252 0 Td
(s.)Tj
0.8716 0 Td
(UK)Tj
1.3323 0 Td
(Nationa)Tj
2.8205 0 Td
(l)Tj
0.4181 0 Td
(Researc)Tj
2.9977 0 Td
(h)Tj
0.6945 0 Td
(Ethics)Tj
2.4591 0 Td
(Service)Tj
-15.619 -1.3748 Td
(\(NRES\),)Tj
3.2315 0 Td
(Charing)Tj
3.0898 0 Td
(Cross)Tj
2.3669 0 Td
(Hospital,)Tj
3.4654 0 Td
(Fulham)Tj
2.9551 0 Td
(W6)Tj
1.5024 0 Td
(8RF,)Tj
-16.6111 -1.3748 Td
(London,)Tj
3.2882 0 Td
(UK.)Tj
/F8 1 Tf
-3.2882 -2.1189 Td
(Funding:)Tj
/F9 1 Tf
3.5716 0 Td
(This)Tj
1.7788 0 Td
(study)Tj
2.2677 0 Td
(was)Tj
1.7008 0 Td
(supported)Tj
3.9969 0 Td
(by)Tj
1.1126 0 Td
(a)Tj
0.6378 0 Td
(European)Tj
-15.0662 -1.3748 Td
(Union)Tj
2.4236 0 Td
(Seventh)Tj
3.2103 0 Td
(Framewor)Tj
3.7417 0 Td
(k)Tj
0.6449 0 Td
(Programme)Tj
4.6559 0 Td
(grant)Tj
2.1544 0 Td
(to)Tj
0.9425 0 Td
(the)Tj
-17.7733 -1.3819 Td
(Comorbid)Tj
3.6708 0 Td
(ity)Tj
1.0914 0 Td
(in)Tj
0.8858 0 Td
(Relation)Tj
3.2386 0 Td
(to)Tj
0.9496 0 Td
(AIDS)Tj
2.1119 0 Td
(\(COBRA\))Tj
3.5858 0 Td
(project)Tj
-15.5339 -1.3748 Td
(\(FP-7-HEA)Tj
3.926 0 Td
(LTH)Tj
1.7575 0 Td
(305522,)Tj
3.2811 0 Td
(all)Tj
1.0276 0 Td
(authors\),)Tj
3.5787 0 Td
(National)Tj
-13.5709 -1.3749 Td
(Institute)Tj
3.2244 0 Td
(for)Tj
1.2543 0 Td
(Health)Tj
2.5725 0 Td
(Research)Tj
3.6992 0 Td
(\(NIHR\))Tj
2.8489 0 Td
(Professorsh)Tj
4.5 0 Td
(ip)Tj
-18.0993 -1.3748 Td
(\(NIHR-RP-011)Tj
5.4709 0 Td
(-048\),)Tj
2.4803 0 Td
(NIHR)Tj
2.2394 0 Td
(Imperial)Tj
3.2386 0 Td
(Biomedical)Tj
-13.4292 -1.3748 Td
(Research)Tj
3.6992 0 Td
(Centre,)Tj
2.8417 0 Td
(the)Tj
1.3749 0 Td
(Netherlan)Tj
3.5504 0 Td
(ds)Tj
1.1197 0 Td
(Organisa)Tj
3.2953 0 Td
(tion)Tj
1.6157 0 Td
(for)Tj
-17.4969 -1.3748 Td
(Health)Tj
2.5724 0 Td
(Research)Tj
3.6922 0 Td
(and)Tj
1.5945 0 Td
(Developm)Tj
3.7417 0 Td
(ent)Tj
1.3748 0 Td
(\(grant)Tj
2.452 0 Td
(number)Tj
-15.4276 -1.3748 Td
(30002000)Tj
3.7842 0 Td
(7\))Tj
1.0063 0 Td
(&)Tj
0.8575 0 Td
(Stichting)Tj
3.4867 0 Td
(AIDS)Tj
2.1118 0 Td
(Fonds)Tj
2.4803 0 Td
(\(grant)Tj
-13.7268 -1.3748 Td
(number)Tj
3.1252 0 Td
(200906)Tj
2.8346 0 Td
(3\),)Tj
1.226 0 Td
(Nuts-Ohra)Tj
4.0607 0 Td
(Foundation)Tj
4.3512 0 Td
(\(grant)Tj
-15.5977 -1.3748 Td
(number)Tj
3.1252 0 Td
(1003-026\))Tj
4.1457 0 Td
(and)Tj
1.5874 0 Td
(unrestricted)Tj
4.6488 0 Td
(scientif)Tj
2.6292 0 Td
(ic)Tj
-16.1363 -1.3749 Td
(grants)Tj
2.5724 0 Td
(from:)Tj
2.2323 0 Td
(Gilead)Tj
2.5087 0 Td
(Sciences,)Tj
3.7488 0 Td
(ViiV)Tj
1.6512 0 Td
(Healthcare,)Tj
-12.7134 -1.3748 Td
(Janssen)Tj
3.274 0 Td
(Pharmaceu)Tj
4.2166 0 Td
(tica)Tj
1.5165 0 Td
(N.V.)Tj
1.7788 0 Td
(Bristol-My)Tj
3.848 0 Td
(ers)Tj
1.3748 0 Td
(Squibb)Tj
-16.0087 -1.3748 Td
(\(BMS\),)Tj
2.863 0 Td
(and)Tj
1.5874 0 Td
(Merck)Tj
2.5441 0 Td
(&)Tj
0.8646 0 Td
(Co)Tj
1.2189 0 Td
(to)Tj
0.9425 0 Td
(the)Tj
1.3748 0 Td
(AGEhIV)Tj
3.0615 0 Td
(cohort)Tj
-14.4568 -1.3748 Td
(study,)Tj
2.4874 0 Td
(as)Tj
1.063 0 Td
(well)Tj
1.6653 0 Td
(as)Tj
1.063 0 Td
(investigator)Tj
4.5355 0 Td
(initiated)Tj
3.0969 0 Td
(grants)Tj
2.5724 0 Td
(from)Tj
-16.4835 -1.3748 Td
(BMS,)Tj
2.2464 0 Td
(Gilead)Tj
2.5087 0 Td
(Sciences,)Tj
3.7489 0 Td
(Janssen,)Tj
3.4937 0 Td
(Merck)Tj
2.5512 0 Td
(and)Tj
1.5874 0 Td
(ViiV)Tj
-16.1363 -1.3748 Td
(Healthcare)Tj
4.1457 0 Td
(to)Tj
0.9496 0 Td
(the)Tj
1.3677 0 Td
(POPPY)Tj
2.9055 0 Td
(cohort)Tj
2.6292 0 Td
(study.)Tj
2.4874 0 Td
(The)Tj
1.5874 0 Td
(funders)Tj
-16.0725 -1.3748 Td
(had)Tj
1.5874 0 Td
(no)Tj
1.1693 0 Td
(role)Tj
1.6157 0 Td
(in)Tj
0.8859 0 Td
(study)Tj
2.2606 0 Td
(design,)Tj
2.9055 0 Td
(data)Tj
1.793 0 Td
(collecti)Tj
2.5653 0 Td
(on)Tj
1.1693 0 Td
(and)Tj
-15.952 -1.3749 Td
(analysis,)Tj
3.4086 0 Td
(decision)Tj
3.2953 0 Td
(to)Tj
0.9497 0 Td
(publish,)Tj
3.1393 0 Td
(or)Tj
1.0064 0 Td
(prepara)Tj
2.8205 0 Td
(tion)Tj
1.6157 0 Td
(of)Tj
0.9496 0 Td
(the)Tj
-17.1851 -1.3748 Td
(manuscript.)Tj
/F8 1 Tf
0 -2.126 Td
(Competing)Tj
4.3795 0 Td
(interests)Tj
3.3307 0 Td
(:)Tj
/F9 1 Tf
0.4819 0 Td
(PR)Tj
1.3323 0 Td
(through)Tj
3.1465 0 Td
(his)Tj
1.311 0 Td
(institutio)Tj
3.182 0 Td
(n)Tj
-17.1639 -1.3748 Td
(has)Tj
1.5378 0 Td
(received)Tj
3.3023 0 Td
(independe)Tj
3.8198 0 Td
(nt)Tj
0.9496 0 Td
(scientific)Tj
3.4724 0 Td
(grant)Tj
2.1473 0 Td
(support)Tj
-15.2292 -1.3748 Td
(from)Tj
2.0126 0 Td
(Gilead)Tj
2.5086 0 Td
(Sciences)Tj
3.2953 0 Td
(,)Tj
0.4465 0 Td
(Janssen)Tj
3.274 0 Td
(Pharmaceu)Tj
4.2166 0 Td
(ticals)Tj
-15.7536 -1.3748 Td
(Inc,)Tj
1.5945 0 Td
(Merck)Tj
2.5441 0 Td
(&)Tj
0.8575 0 Td
(Co,)Tj
1.4456 0 Td
(Bristol-Myer)Tj
4.578 0 Td
(s)Tj
0.6449 0 Td
(Squibb)Tj
2.8347 0 Td
(and)Tj
1.5874 0 Td
(ViiV)Tj
-16.0867 -1.3748 Td
(Healthcare;)Tj
4.3653 0 Td
(he)Tj
1.1197 0 Td
(has)Tj
1.5378 0 Td
(served)Tj
2.6859 0 Td
(on)Tj
1.1622 0 Td
(a)Tj
0.6449 0 Td
(scientific)Tj
3.4654 0 Td
(advisory)Tj
-14.9812 -1.3748 Td
(board)Tj
2.3669 0 Td
(for)Tj
1.2614 0 Td
(Gilead)Tj
2.5087 0 Td
(Sciences)Tj
3.515 0 Td
(and)Tj
1.5874 0 Td
(on)Tj
1.1693 0 Td
(a)Tj
0.6449 0 Td
(data)Tj
1.7858 0 Td
(safety)Tj
-14.8394 -1.3749 Td
(monitorin)Tj
3.5929 0 Td
(g)Tj
0.6945 0 Td
(committee)Tj
4.174 0 Td
(for)Tj
1.2544 0 Td
(Janssen)Tj
-9.7158 -1.3748 Td
(Pharmaceu)Tj
4.2165 0 Td
(ticals)Tj
2.126 0 Td
(Inc)Tj
1.3748 0 Td
(for)Tj
1.2544 0 Td
(which)Tj
2.4236 0 Td
(his)Tj
1.304 0 Td
(institution)Tj
3.8835 0 Td
(has)Tj
-16.5828 -1.3748 Td
(received)Tj
3.3023 0 Td
(remuner)Tj
3.1536 0 Td
(ation;)Tj
2.2607 0 Td
(he)Tj
1.1196 0 Td
(has)Tj
1.5379 0 Td
(chaired)Tj
2.9268 0 Td
(a)Tj
0.6448 0 Td
(scientific)Tj
-14.9457 -1.3748 Td
(symposiu)Tj
3.6283 0 Td
(m)Tj
0.978 0 Td
(by)Tj
1.1126 0 Td
(ViiV)Tj
1.6583 0 Td
(Healthcare,)Tj
4.3654 0 Td
(for)Tj
1.2614 0 Td
(which)Tj
2.4165 0 Td
(his)Tj
-15.4205 -1.3748 Td
(institution)Tj
3.8834 0 Td
(has)Tj
1.5308 0 Td
(received)Tj
3.3024 0 Td
(remuneratio)Tj
4.5 0 Td
(n.)Tj
0.9213 0 Td
(RZ)Tj
1.2826 0 Td
(has)Tj
-15.4205 -1.3748 Td
(received)Tj
3.3023 0 Td
(travel)Tj
2.2394 0 Td
(grants)Tj
2.5725 0 Td
(from)Tj
2.0126 0 Td
(Gilead)Tj
2.5087 0 Td
(Sciences)Tj
3.2953 0 Td
(,)Tj
0.4464 0 Td
(and)Tj
-16.3772 -1.3748 Td
(was)Tj
1.7008 0 Td
(a)Tj
0.6448 0 Td
(speaker)Tj
3.104 0 Td
(at)Tj
0.9 0 Td
(an)Tj
1.1126 0 Td
(event)Tj
2.2111 0 Td
(sponsored)Tj
4.1598 0 Td
(by)Tj
1.1197 0 Td
(Gilead)Tj
-14.9528 -1.3749 Td
(Sciences)Tj
3.522 0 Td
(for)Tj
1.2544 0 Td
(which)Tj
2.4165 0 Td
(her)Tj
1.4244 0 Td
(institution)Tj
ET
endstream
endobj
34 0 obj
<>stream
endstream
endobj
35 0 obj
<>stream
endstream
endobj
36 0 obj
<>stream
endstream
endobj
37 0 obj
<>stream
endstream
endobj
38 0 obj
<>stream
endstream
endobj
39 0 obj
<>stream
endstream
endobj
40 0 obj
<>stream
endstream
endobj
41 0 obj
<>stream
endstream
endobj
42 0 obj
<>stream
endstream
endobj
43 0 obj
<>stream
endstream
endobj
44 0 obj
<>stream
endstream
endobj
45 0 obj
<>stream
endstream
endobj
46 0 obj
<>stream
endstream
endobj
47 0 obj
<>stream
endstream
endobj
48 0 obj
<>stream
endstream
endobj
49 0 obj
<>stream
endstream
endobj
50 0 obj
<>stream
BT
12.5008 6.9661 Td
(received)Tj
ET
Q
endstream
endobj
51 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 12 0 R/Annots 53 0 R/Contents 54 0 R/TrimBox[0 0 612 792]>>
endobj
53 0 obj
[55 0 R 56 0 R 57 0 R 58 0 R 59 0 R 60 0 R]
endobj
55 0 obj
<>/Border[0 0 0]/Dest(Rpone.0191791.ref019)>>
endobj
56 0 obj
<>/Border[0 0 0]/Dest(Rpone.0191791.ref020)>>
endobj
57 0 obj
<>/Border[0 0 0]/Dest(Rpone.0191791.ref021)>>
endobj
58 0 obj
<>/Border[0 0 0]/Dest(Rpone.0191791.ref022)>>
endobj
59 0 obj
<>/Border[0 0 0]/Dest(Rpone.0191791.ref023)>>
endobj
60 0 obj
<>/Border[0 0 0]/A 61 0 R>>
endobj
61 0 obj
<>
endobj
54 0 obj
[62 0 R 63 0 R 64 0 R 65 0 R 66 0 R 67 0 R 68 0 R 69 0 R]
endobj
62 0 obj
<>stream
q
0.83 0.64 0.02 0 k
393.5622 680.315 m
403.0299 680.315 l
h
f*
424.9701 654.3496 m
434.4378 654.3496 l
h
f*
488.0693 615.3449 m
497.5937 615.3449 l
h
f*
502.0157 615.3449 m
511.5402 615.3449 l
h
f*
486.3118 524.2961 m
495.8362 524.2961 l
h
f*
0 g
1 j
1 J
0 w
10 0 0 10 211.9748 707.4141 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Other)Tj
2.5908 0 Td
(factors)Tj
2.9027 0 Td
(related)Tj
2.9423 0 Td
(to)Tj
1.0261 0 Td
(HIV,)Tj
2.2507 0 Td
(including)Tj
4.0422 0 Td
(activation)Tj
4.1499 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(innate)Tj
2.744 0 Td
(and)Tj
1.7291 0 Td
(adaptive)Tj
3.5773 0 Td
(immune)Tj
3.6226 0 Td
(sys-)Tj
-35.257 -1.3039 Td
(tem,)Tj
1.9842 0 Td
(immune)Tj
3.6283 0 Td
(exhaustion)Tj
4.5808 0 Td
(and)Tj
1.7291 0 Td
(senescence)Tj
4.5807 0 Td
(and)Tj
1.7292 0 Td
(chronic)Tj
3.2881 0 Td
(inflammation,)Tj
5.9244 0 Td
(likely)Tj
2.3527 0 Td
(causally)Tj
3.3506 0 Td
(contribute)Tj
-33.1481 -1.2982 Td
(to)Tj
1.0262 0 Td
(the)Tj
1.4682 0 Td
(increased)Tj
3.9968 0 Td
(and)Tj
1.7348 0 Td
(premature)Tj
4.405 0 Td
(risk)Tj
1.7178 0 Td
(of)Tj
1.0148 0 Td
(AANCC)Tj
3.651 0 Td
([)Tj
0.83 0.64 0.02 0 k
(19)Tj
0 g
(].)Tj
2.075 0 Td
(These)Tj
2.5681 0 Td
(immune)Tj
3.6227 0 Td
(pathologies)Tj
4.7735 0 Td
(may)Tj
1.9332 0 Td
(lead)Tj
1.8482 0 Td
(to)Tj
1.0261 0 Td
(a)Tj
-36.8614 -1.2983 Td
(process)Tj
3.1804 0 Td
(of)Tj
1.0148 0 Td
(accentuated)Tj
4.9833 0 Td
(and/or)Tj
2.9423 0 Td
(accelerated)Tj
4.6488 0 Td
(aging,)Tj
2.6249 0 Td
(given)Tj
2.3754 0 Td
(that)Tj
1.7801 0 Td
(they)Tj
1.9276 0 Td
(are)Tj
1.4456 0 Td
(features)Tj
3.3506 0 Td
(of)Tj
1.0148 0 Td
(chronic)Tj
3.2881 0 Td
(HIV)Tj
-34.5767 -1.2983 Td
(infection)Tj
3.7927 0 Td
(and)Tj
1.7291 0 Td
(have)Tj
2.0579 0 Td
(each)Tj
2.0296 0 Td
(also)Tj
1.7688 0 Td
(been)Tj
2.1203 0 Td
(associated)Tj
4.2576 0 Td
(with)Tj
1.9956 0 Td
(aging)Tj
2.4038 0 Td
([)Tj
0.83 0.64 0.02 0 k
(20)Tj
0 g
(].)Tj
2.0749 0 Td
(A)Tj
0.9071 0 Td
(number)Tj
3.4129 0 Td
(of)Tj
1.0148 0 Td
(biomarkers,)Tj
5.006 0 Td
(indica-)Tj
-34.5711 -1.3039 Td
(tive)Tj
1.6554 0 Td
(of)Tj
1.0148 0 Td
(persistent)Tj
4.0818 0 Td
(immune)Tj
3.6227 0 Td
(activation,)Tj
4.3766 0 Td
(inflammation,)Tj
5.9187 0 Td
(coagulation)Tj
4.8699 0 Td
(activation,)Tj
4.3767 0 Td
(and)Tj
1.7235 0 Td
(neuronal)Tj
3.821 0 Td
(dam-)Tj
-35.4611 -1.2982 Td
(age,)Tj
1.7687 0 Td
(have)Tj
2.058 0 Td
(been)Tj
2.1203 0 Td
(studied)Tj
3.1578 0 Td
(in)Tj
1.0318 0 Td
(HIV-positive)Tj
5.4708 0 Td
(subjects,)Tj
3.6056 0 Td
(and)Tj
1.7292 0 Td
(a)Tj
0.6519 0 Td
(strong)Tj
2.7723 0 Td
(association)Tj
4.6261 0 Td
(has)Tj
1.542 0 Td
(been)Tj
-30.5345 -1.2983 Td
(documented)Tj
5.244 0 Td
(between)Tj
3.5319 0 Td
(some)Tj
2.3301 0 Td
(of)Tj
1.0148 0 Td
(these)Tj
2.2507 0 Td
(biomarkers)Tj
4.7792 0 Td
(and)Tj
1.7348 0 Td
(all-cause)Tj
3.6623 0 Td
(mortality)Tj
3.9175 0 Td
([)Tj
0.83 0.64 0.02 0 k
(21)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7348 0 Td
(22)Tj
0 g
(].)Tj
1.7404 0 Td
(However,)Tj
-31.9405 -1.3039 Td
(their)Tj
2.1089 0 Td
(relation)Tj
3.3165 0 Td
(to)Tj
1.0205 0 Td
(the)Tj
1.474 0 Td
(development)Tj
5.4085 0 Td
(of)Tj
1.0148 0 Td
(specific)Tj
3.1917 0 Td
(comorbidities)Tj
5.7657 0 Td
(has)Tj
1.542 0 Td
(not)Tj
1.5761 0 Td
(been)Tj
2.1203 0 Td
(as)Tj
1.0148 0 Td
(extensively)Tj
4.5864 0 Td
(studied.)Tj
-34.1402 -1.2983 Td
(HIV)Tj
2.0182 0 Td
(infection)Tj
3.7927 0 Td
(and)Tj
1.7291 0 Td
(the)Tj
1.4741 0 Td
(presence/absence)Tj
7.1602 0 Td
(of)Tj
1.0148 0 Td
(cART)Tj
2.5625 0 Td
(may)Tj
1.9276 0 Td
(affect)Tj
2.3754 0 Td
(the)Tj
1.4683 0 Td
(complex)Tj
3.6227 0 Td
(interplay)Tj
3.7814 0 Td
(between)Tj
-32.927 -1.2983 Td
(the)Tj
1.4683 0 Td
(innate)Tj
2.7382 0 Td
(and)Tj
1.7348 0 Td
(adaptive)Tj
3.5716 0 Td
(immune)Tj
3.6284 0 Td
(system,)Tj
3.1634 0 Td
(inflammation,)Tj
5.9244 0 Td
(the)Tj
1.4683 0 Td
(central)Tj
2.965 0 Td
(and)Tj
1.7292 0 Td
(autonomic)Tj
4.5524 0 Td
(nervous)Tj
-32.944 -1.3039 Td
(system.)Tj
3.1634 0 Td
(These)Tj
2.5682 0 Td
(interrelated)Tj
4.8528 0 Td
(mechanisms)Tj
5.2044 0 Td
(are)Tj
1.4457 0 Td
(thought)Tj
3.3732 0 Td
(to)Tj
1.0261 0 Td
(jointly)Tj
2.8006 0 Td
(enhance)Tj
3.549 0 Td
(the)Tj
1.4683 0 Td
(pathogenesis)Tj
5.3518 0 Td
(of)Tj
-34.8035 -1.2982 Td
(AANCC)Tj
3.6509 0 Td
(\(including)Tj
4.3824 0 Td
(cognitive)Tj
3.8721 0 Td
(impairment\),)Tj
5.5558 0 Td
(and)Tj
1.7292 0 Td
(thereby)Tj
3.2258 0 Td
(may)Tj
1.9275 0 Td
(explain)Tj
3.1238 0 Td
(the)Tj
1.4683 0 Td
(increased)Tj
3.9968 0 Td
(risk)Tj
1.7178 0 Td
(and)Tj
-34.6504 -1.2983 Td
(possible)Tj
3.4072 0 Td
(premature)Tj
4.4106 0 Td
(onset)Tj
2.3585 0 Td
(of)Tj
1.0147 0 Td
(these)Tj
2.2507 0 Td
(conditions)Tj
4.4788 0 Td
(in)Tj
1.0318 0 Td
(persons)Tj
3.3108 0 Td
(living)Tj
2.4718 0 Td
(with)Tj
1.9956 0 Td
(HIV)Tj
2.0239 0 Td
(on)Tj
1.2756 0 Td
(cART.)Tj
2.7836 0 Td
(Novel)Tj
-32.8136 -1.3039 Td
(promising)Tj
4.3426 0 Td
(candidate)Tj
4.1045 0 Td
(biomarkers)Tj
4.7792 0 Td
(of)Tj
1.0148 0 Td
(aging)Tj
2.3981 0 Td
(have)Tj
2.0636 0 Td
(recently)Tj
3.4072 0 Td
(been)Tj
2.1203 0 Td
(identified)Tj
4.0592 0 Td
([)Tj
0.83 0.64 0.02 0 k
(23)Tj
0 g
(],)Tj
2.0806 0 Td
(but)Tj
1.5534 0 Td
(have)Tj
2.058 0 Td
(not)Tj
1.5703 0 Td
(yet)Tj
-35.5518 -1.2983 Td
(been)Tj
2.1202 0 Td
(validated)Tj
3.8325 0 Td
(in)Tj
1.0374 0 Td
(the)Tj
1.4684 0 Td
(setting)Tj
2.8856 0 Td
(of)Tj
1.0148 0 Td
(HIV)Tj
2.0183 0 Td
(infection.)Tj
4.0195 0 Td
(The)Tj
1.7801 0 Td
(simultaneous)Tj
5.5445 0 Td
(analysis)Tj
3.3222 0 Td
(of)Tj
1.0148 0 Td
(both)Tj
2.0636 0 Td
(these)Tj
2.2507 0 Td
(novel)Tj
-34.3726 -1.2982 Td
(aging)Tj
2.398 0 Td
(biomarkers)Tj
4.7792 0 Td
(as)Tj
1.0148 0 Td
(well)Tj
1.8198 0 Td
(as)Tj
1.0148 0 Td
(those)Tj
2.3358 0 Td
(of)Tj
1.0148 0 Td
(altered)Tj
2.948 0 Td
(metabolism,)Tj
5.125 0 Td
(residual)Tj
3.3789 0 Td
(HIV)Tj
2.0239 0 Td
(replication)Tj
4.5241 0 Td
(and)Tj
1.7291 0 Td
(produc-)Tj
-34.1062 -1.2983 Td
(tion,)Tj
2.0635 0 Td
(immune)Tj
3.6284 0 Td
(activation)Tj
4.1499 0 Td
(and)Tj
1.7348 0 Td
(senescence,)Tj
4.8018 0 Td
(inflammation,)Tj
5.9244 0 Td
(coagulation)Tj
4.8812 0 Td
(activation,)Tj
4.3767 0 Td
(antiretroviral)Tj
-31.5607 -1.3039 Td
(pharmacology,)Tj
6.1511 0 Td
(and)Tj
1.7291 0 Td
(neuronal)Tj
3.8267 0 Td
(damage)Tj
3.3279 0 Td
(is)Tj
0.8447 0 Td
(therefore)Tj
3.8551 0 Td
(important)Tj
4.2803 0 Td
(to)Tj
1.0261 0 Td
(clarify)Tj
2.7043 0 Td
(the)Tj
1.4683 0 Td
(potential)Tj
3.7644 0 Td
(pathogenic)Tj
-32.978 -1.2983 Td
(mechanisms)Tj
5.2043 0 Td
(underlying)Tj
4.6034 0 Td
(the)Tj
1.4684 0 Td
(links)Tj
2.1373 0 Td
(between)Tj
3.5319 0 Td
(HIV)Tj
2.0183 0 Td
(and)Tj
1.7291 0 Td
(AANCC.)Tj
-19.4965 -1.2983 Td
(In)Tj
1.1111 0 Td
(this)Tj
1.6725 0 Td
(context,)Tj
3.4128 0 Td
(the)Tj
1.4684 0 Td
(COmorBidity)Tj
5.7203 0 Td
(in)Tj
1.0374 0 Td
(Relation)Tj
3.566 0 Td
(to)Tj
1.0261 0 Td
(AIDS)Tj
2.4548 0 Td
(\(COBRA\))Tj
4.1953 0 Td
(cohort)Tj
2.8573 0 Td
(study)Tj
2.3867 0 Td
(was)Tj
1.7008 0 Td
(designed)Tj
-33.8057 -1.3039 Td
(to)Tj
1.0262 0 Td
(investigate)Tj
4.4616 0 Td
(the)Tj
1.4683 0 Td
(potential)Tj
3.7587 0 Td
(causal)Tj
2.6476 0 Td
(link)Tj
1.7801 0 Td
(between)Tj
3.5263 0 Td
(HIV)Tj
2.0239 0 Td
(and)Tj
1.7291 0 Td
(AANCC,)Tj
3.8778 0 Td
(amongst)Tj
3.651 0 Td
(others,)Tj
2.9367 0 Td
(in)Tj
1.0318 0 Td
(a)Tj
0.6576 0 Td
(cohort)Tj
-34.5767 -1.2982 Td
(of)Tj
1.0148 0 Td
(middle-aged)Tj
5.2327 0 Td
(individuals)Tj
4.6487 0 Td
(with)Tj
1.9956 0 Td
(HIV)Tj
2.0239 0 Td
(on)Tj
1.2756 0 Td
(suppressive)Tj
4.8019 0 Td
(cART)Tj
2.5625 0 Td
(and)Tj
1.7291 0 Td
(otherwise)Tj
4.0876 0 Td
(comparable)Tj
4.8982 0 Td
(HIV-)Tj
-34.2706 -1.2983 Td
(negative)Tj
3.5319 0 Td
(controls.)Tj
3.7077 0 Td
(The)Tj
1.7858 0 Td
(objectives)Tj
4.1385 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4741 0 Td
(COBRA)Tj
3.5149 0 Td
(study)Tj
2.3867 0 Td
(are:)Tj
-21.5544 -1.8992 Td
(i.)Tj
0.9922 0 Td
(to)Tj
1.026 0 Td
(investigate)Tj
4.4617 0 Td
(the)Tj
1.4683 0 Td
(association)Tj
4.6261 0 Td
(between)Tj
3.532 0 Td
(HIV)Tj
2.0182 0 Td
(infection)Tj
3.7928 0 Td
(and)Tj
1.7291 0 Td
(AANCC)Tj
3.651 0 Td
(\(including)Tj
4.3823 0 Td
(cognitive)Tj
-30.6875 -1.3039 Td
(function\);)Tj
-0.9922 -1.8992 Td
(ii.)Tj
1.2585 0 Td
(to)Tj
1.0261 0 Td
(further)Tj
3.0274 0 Td
(elucidate)Tj
3.7928 0 Td
(possible)Tj
3.4072 0 Td
(causative)Tj
3.8437 0 Td
(links)Tj
2.143 0 Td
(between)Tj
3.5263 0 Td
(HIV)Tj
2.0239 0 Td
(and)Tj
1.7291 0 Td
(AANCC;)Tj
-25.778 -1.8992 Td
(iii.)Tj
1.525 0 Td
(to)Tj
1.0261 0 Td
(clarify)Tj
2.7042 0 Td
(the)Tj
1.4684 0 Td
(potential)Tj
3.7644 0 Td
(pathogenic)Tj
4.6317 0 Td
(mechanisms)Tj
5.2044 0 Td
(underlying)Tj
4.5978 0 Td
(any)Tj
1.6611 0 Td
(links)Tj
2.1373 0 Td
(identified,)Tj
4.2859 0 Td
(including)Tj
-31.4813 -1.2983 Td
(the)Tj
1.4683 0 Td
(possible)Tj
3.4129 0 Td
(induction)Tj
4.1329 0 Td
(of)Tj
1.0148 0 Td
(an)Tj
1.2019 0 Td
(inflammation-associ)Tj
8.1864 0 Td
(ated)Tj
1.8992 0 Td
(accelerated)Tj
4.6488 0 Td
(aging)Tj
2.4037 0 Td
(phenotype;)Tj
-29.8939 -1.8992 Td
(iv.)Tj
1.4456 0 Td
(to)Tj
1.0261 0 Td
(identify)Tj
3.2939 0 Td
(biomarkers)Tj
4.7792 0 Td
(\(or)Tj
1.4399 0 Td
(combinations)Tj
5.709 0 Td
(of)Tj
1.0148 0 Td
(biomarkers\))Tj
5.1136 0 Td
(that)Tj
1.7802 0 Td
(may)Tj
1.9275 0 Td
(be)Tj
1.1509 0 Td
(used)Tj
2.0579 0 Td
(for)Tj
1.389 0 Td
(better)Tj
2.5398 0 Td
(pre-)Tj
-33.2218 -1.3039 Td
(vention,)Tj
3.4923 0 Td
(treatment)Tj
4.1385 0 Td
(and)Tj
1.7291 0 Td
(management)Tj
5.4369 0 Td
(of)Tj
1.0148 0 Td
(AANCC.)Tj
-16.061 -1.8992 Td
(Cohort)Tj
3.0954 0 Td
(studies)Tj
2.9877 0 Td
(like)Tj
1.6554 0 Td
(COBRA,)Tj
3.7417 0 Td
(can)Tj
1.6214 0 Td
(only)Tj
1.9786 0 Td
(establish)Tj
3.6453 0 Td
(associations.)Tj
5.2157 0 Td
(In)Tj
1.1055 0 Td
(order)Tj
2.4208 0 Td
(to)Tj
1.0261 0 Td
(fulfil)Tj
2.0863 0 Td
(objective)Tj
3.7814 0 Td
(ii.)Tj
0.9751 0 Td
(a)Tj
-36.5326 -1.2983 Td
(Human)Tj
3.7076 0 Td
(Immune)Tj
3.7021 0 Td
(System)Tj
3.4412 0 Td
(mouse)Tj
2.863 0 Td
(model)Tj
2.7439 0 Td
(has)Tj
1.542 0 Td
(been)Tj
2.1203 0 Td
(developed)Tj
4.269 0 Td
(allowing)Tj
3.6226 0 Td
(to)Tj
1.0262 0 Td
(distinguish)Tj
4.6374 0 Td
(the)Tj
1.4684 0 Td
(effect)Tj
-35.1437 -1.2982 Td
(of)Tj
1.0148 0 Td
(exposure)Tj
3.8153 0 Td
(to)Tj
1.0262 0 Td
(HIV)Tj
2.0239 0 Td
(and)Tj
1.7291 0 Td
(cART)Tj
2.5569 0 Td
(on)Tj
1.2755 0 Td
(various)Tj
3.1465 0 Td
(metabolic)Tj
4.1442 0 Td
(outcomes)Tj
4.0875 0 Td
(as)Tj
1.0148 0 Td
(well)Tj
1.8199 0 Td
(as)Tj
1.0148 0 Td
(immune)Tj
3.6283 0 Td
(and)Tj
1.7291 0 Td
(aging)Tj
-34.0268 -1.304 Td
(biomarkers,)Tj
5.0002 0 Td
(when)Tj
2.4038 0 Td
(applied)Tj
3.1578 0 Td
(under)Tj
2.6192 0 Td
(controlled)Tj
4.3143 0 Td
(conditions.)Tj
4.7054 0 Td
(The)Tj
1.7802 0 Td
(methods)Tj
3.685 0 Td
(and)Tj
1.7291 0 Td
(results)Tj
2.812 0 Td
(of)Tj
1.0148 0 Td
(this)Tj
1.6724 0 Td
(mouse)Tj
-34.8942 -1.2982 Td
(model)Tj
2.7439 0 Td
(are)Tj
1.4456 0 Td
(beyond)Tj
3.1918 0 Td
(the)Tj
1.4683 0 Td
(scope)Tj
2.4548 0 Td
(of)Tj
1.0148 0 Td
(this)Tj
1.6725 0 Td
(paper)Tj
2.4831 0 Td
(and)Tj
1.7291 0 Td
(will)Tj
1.6668 0 Td
(be)Tj
1.1452 0 Td
(reported)Tj
3.6623 0 Td
(elsewhere.)Tj
-23.482 -1.2983 Td
(The)Tj
1.7858 0 Td
(COBRA)Tj
3.5149 0 Td
(study)Tj
2.3868 0 Td
(was)Tj
1.7007 0 Td
(funded)Tj
3.0614 0 Td
(through)Tj
3.4469 0 Td
(the)Tj
1.4684 0 Td
(European)Tj
4.1215 0 Td
(Union)Tj
2.829 0 Td
(Seventh)Tj
3.3675 0 Td
(Framework)Tj
4.8586 0 Td
(Pro-)Tj
-33.7377 -1.3039 Td
(gramme)Tj
3.5546 0 Td
(in)Tj
1.0318 0 Td
(2013)Tj
2.1259 0 Td
(following)Tj
3.9799 0 Td
(independent)Tj
5.2724 0 Td
(peer)Tj
1.9559 0 Td
(review)Tj
2.8459 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(planned)Tj
3.4639 0 Td
(study)Tj
2.3924 0 Td
(design.)Tj
3.0387 0 Td
(The)Tj
1.7802 0 Td
(current)Tj
-33.9248 -1.2983 Td
(paper)Tj
2.4831 0 Td
(sets)Tj
1.6611 0 Td
(out)Tj
1.5533 0 Td
(the)Tj
1.4684 0 Td
(key)Tj
1.5987 0 Td
(aspects)Tj
3.0387 0 Td
(underlying)Tj
4.5978 0 Td
(the)Tj
1.4683 0 Td
(COBRA)Tj
3.5206 0 Td
(cohort)Tj
2.8517 0 Td
(study,)Tj
2.6135 0 Td
(including)Tj
4.0422 0 Td
(its)Tj
1.1508 0 Td
(design,)Tj
3.0331 0 Td
(meth-)Tj
-35.0813 -1.2982 Td
(ods,)Tj
1.8368 0 Td
(demographic)Tj
5.5048 0 Td
(characteristics)Tj
5.9017 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(participants)Tj
4.9549 0 Td
(at)Tj
0.9524 0 Td
(study)Tj
2.3868 0 Td
(entry)Tj
2.313 0 Td
(and)Tj
1.7292 0 Td
(their)Tj
2.1089 0 Td
(overall)Tj
2.9027 0 Td
(representa-)Tj
-33.0744 -1.304 Td
(tiveness)Tj
3.3561 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(two)Tj
1.7121 0 Td
(larger)Tj
2.5285 0 Td
(European)Tj
4.1215 0 Td
(aging)Tj
2.3981 0 Td
(cohorts)Tj
3.2145 0 Td
(of)Tj
1.0148 0 Td
(people)Tj
2.8573 0 Td
(living)Tj
2.4661 0 Td
(with)Tj
2.0013 0 Td
(HIV.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 131.0173 cm
BT
/F2 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Methods)Tj
/F12 1 Tf
0 -1.5023 Td
(Study)Tj
2.6173 0 Td
(design)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 95.9811 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(The)Tj
1.7801 0 Td
(COBRA)Tj
3.5149 0 Td
(clinical)Tj
3.0784 0 Td
(cohort)Tj
2.8517 0 Td
(is)Tj
0.8504 0 Td
(a)Tj
0.6519 0 Td
(longitudinal)Tj
5.108 0 Td
(cohort)Tj
2.8517 0 Td
(study)Tj
2.3924 0 Td
(of)Tj
1.0148 0 Td
(middle-aged)Tj
5.2327 0 Td
(HIV-positive)Tj
5.4652 0 Td
(sub-)Tj
-34.7922 -1.2982 Td
(jects)Tj
1.9842 0 Td
(with)Tj
1.9956 0 Td
(sustained)Tj
3.9684 0 Td
(HIV)Tj
2.024 0 Td
(suppression)Tj
4.9832 0 Td
(on)Tj
1.27 0 Td
(cART)Tj
2.5625 0 Td
(recruited)Tj
3.8551 0 Td
(from)Tj
2.2053 0 Td
(two)Tj
1.7121 0 Td
(large)Tj
2.16 0 Td
(European)Tj
4.1159 0 Td
(HIV)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 107.1496 23.6976 re
W* n
q
107.0929 0 0 23.6409 36 741.3165 cm
q
/I0 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 508.8755 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(The)Tj
1.9204 0 Td
(COBRA)Tj
3.7347 0 Td
(cohort)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
81.5811 34.9228 m
237.8835 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(ONE)Tj
2.3669 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.137)Tj
3.8198 0 Td
(1/journal.po)Tj
5.1236 0 Td
(ne.01917)Tj
4.089 0 Td
(91)Tj
0 g
2.0906 0 Td
(March)Tj
2.9622 0 Td
(29,)Tj
1.5874 0 Td
(2018)Tj
34.3562 0 Td
(3)Tj
0.7654 0 Td
(/)Tj
0.496 0 Td
(16)Tj
/F9 1 Tf
-0.025 Tc
-66.402 84.0904 Td
(remunerati)Tj
4.0252 0 Td
(on.)Tj
1.3961 0 Td
(KK)Tj
1.2685 0 Td
(has)Tj
1.5378 0 Td
(received)Tj
3.3024 0 Td
(travel)Tj
2.2393 0 Td
(grants)Tj
2.5725 0 Td
(from)Tj
-16.3418 -1.3748 Td
(Gilead)Tj
2.5086 0 Td
(Sciences)Tj
3.5221 0 Td
(and)Tj
1.5874 0 Td
(ViiV)Tj
1.6583 0 Td
(Healthcare)Tj
3.9189 0 Td
(,)Tj
0.4465 0 Td
(was)Tj
1.7008 0 Td
(a)Tj
0.6449 0 Td
(speaker)Tj
-15.9875 -1.3749 Td
(at)Tj
0.9 0 Td
(an)Tj
1.1126 0 Td
(event)Tj
2.211 0 Td
(sponsored)Tj
4.1599 0 Td
(by)Tj
1.1126 0 Td
(Gilead)Tj
2.5158 0 Td
(Sciences)Tj
3.5149 0 Td
(and)Tj
-15.5268 -1.3748 Td
(served)Tj
2.6858 0 Td
(on)Tj
1.1693 0 Td
(a)Tj
0.6378 0 Td
(scientific)Tj
3.4725 0 Td
(advisory)Tj
3.352 0 Td
(board)Tj
2.3669 0 Td
(for)Tj
1.2544 0 Td
(Gilead)Tj
-14.9387 -1.3748 Td
(Sciences.)Tj
3.7417 0 Td
(There)Tj
2.3174 0 Td
(are)Tj
1.3748 0 Td
(no)Tj
1.1622 0 Td
(patents,)Tj
3.1677 0 Td
(products)Tj
3.5221 0 Td
(in)Tj
-15.2859 -1.3748 Td
(developm)Tj
3.6283 0 Td
(ent,)Tj
1.5945 0 Td
(or)Tj
1.0063 0 Td
(markete)Tj
2.9977 0 Td
(d)Tj
0.6945 0 Td
(products)Tj
3.5221 0 Td
(to)Tj
0.9496 0 Td
(declare.)Tj
-14.393 -1.3748 Td
(This)Tj
1.7787 0 Td
(does)Tj
2.0126 0 Td
(not)Tj
1.4244 0 Td
(alter)Tj
1.8142 0 Td
(our)Tj
1.4741 0 Td
(adherence)Tj
4.0535 0 Td
(to)Tj
0.9496 0 Td
(PLOS)Tj
2.3316 0 Td
(ONE)Tj
-15.8387 -1.3748 Td
(policies)Tj
3.0118 0 Td
(on)Tj
1.1622 0 Td
(sharing)Tj
2.9835 0 Td
(data)Tj
1.7929 0 Td
(and)Tj
ET
endstream
endobj
63 0 obj
<>stream
endstream
endobj
64 0 obj
<>stream
endstream
endobj
65 0 obj
<>stream
endstream
endobj
66 0 obj
<>stream
endstream
endobj
67 0 obj
<>stream
endstream
endobj
68 0 obj
<>stream
endstream
endobj
69 0 obj
<>stream
BT
10.5378 74.4667 Td
(materials.)Tj
ET
Q
endstream
endobj
70 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 12 0 R/Annots 71 0 R/Contents 72 0 R/TrimBox[0 0 612 792]>>
endobj
71 0 obj
[73 0 R 74 0 R 75 0 R 76 0 R 77 0 R 78 0 R 79 0 R 80 0 R 81 0 R 82 0 R 83 0 R 84 0 R 85 0 R]
endobj
73 0 obj
<>/Border[0 0 0]/Dest(Rpone.0191791.s002)>>
endobj
74 0 obj
<>/Border[0 0 0]/Dest(Rpone.0191791.ref024)>>
endobj
75 0 obj
<>/Border[0 0 0]/Dest(Rpone.0191791.ref025)>>
endobj
76 0 obj
<>/Border[0 0 0]/Dest(Rpone.0191791.s001)>>
endobj
77 0 obj
<>/Border[0 0 0]/A 86 0 R>>
endobj
86 0 obj
<>
endobj
78 0 obj
<>/Border[0 0 0]/A 87 0 R>>
endobj
87 0 obj
<>
endobj
79 0 obj
<>/Border[0 0 0]/A 88 0 R>>
endobj
88 0 obj
<>
endobj
80 0 obj
<>/Border[0 0 0]/A 89 0 R>>
endobj
89 0 obj
<>
endobj
81 0 obj
<>/Border[0 0 0]/Dest(Rpone.0191791.s003)>>
endobj
82 0 obj
<>/Border[0 0 0]/Dest(Rpone.0191791.ref026)>>
endobj
83 0 obj
<>/Border[0 0 0]/Dest(Rpone.0191791.ref027)>>
endobj
84 0 obj
<>/Border[0 0 0]/Dest(Rpone.0191791.ref028)>>
endobj
85 0 obj
<>/Border[0 0 0]/A 90 0 R>>
endobj
90 0 obj
<>
endobj
72 0 obj
[91 0 R 92 0 R 93 0 R 94 0 R 95 0 R 96 0 R 97 0 R 98 0 R 99 0 R]
endobj
91 0 obj
<>stream
q
0.83 0.64 0.02 0 k
314.8724 433.3039 m
341.2346 433.3039 l
h
f*
559.6724 433.3039 m
569.1969 433.3039 l
h
f*
288.5102 420.3213 m
298.0346 420.3213 l
h
f*
246.3874 368.3339 m
280.2898 368.3339 l
h
f*
539.6031 251.3197 m
568.5165 251.3197 l
h
f*
200.0126 238.337 m
330.0094 238.337 l
h
f*
349.4551 238.337 m
559.8425 238.337 l
h
f*
200.0126 225.2976 m
213.1087 225.2976 l
h
f*
238.5638 173.3102 m
264.926 173.3102 l
h
f*
470.2677 173.3102 m
479.7921 173.3102 l
h
f*
203.4142 160.3276 m
212.9386 160.3276 l
h
f*
308.9764 160.3276 m
318.5008 160.3276 l
h
f*
0 g
1 j
1 J
0 w
10 0 0 10 200.0125 707.4141 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(treatment)Tj
4.1328 0 Td
(centres)Tj
3.0728 0 Td
(and)Tj
1.7291 0 Td
(similarly-aged)Tj
5.8904 0 Td
(HIV-negative)Tj
5.6862 0 Td
(controls)Tj
3.4809 0 Td
(recruited)Tj
3.8551 0 Td
(from)Tj
2.2054 0 Td
(sexual)Tj
2.6759 0 Td
(health)Tj
2.6815 0 Td
(cen-)Tj
-35.4101 -1.3039 Td
(tres)Tj
1.661 0 Td
(and)Tj
1.7235 0 Td
(targeted)Tj
3.4469 0 Td
(community)Tj
4.8812 0 Td
(groups.)Tj
3.1805 0 Td
(Both)Tj
2.126 0 Td
(HIV-positive)Tj
5.4538 0 Td
(and)Tj
1.7234 0 Td
(HIV-negative)Tj
5.675 0 Td
(subjects)Tj
3.3675 0 Td
(underwent)Tj
-33.2388 -1.2982 Td
(a)Tj
0.6519 0 Td
(first)Tj
1.8085 0 Td
(study)Tj
2.3868 0 Td
(visit)Tj
1.8708 0 Td
(at)Tj
0.9525 0 Td
(study)Tj
2.3867 0 Td
(entry)Tj
2.3187 0 Td
(with)Tj
1.9956 0 Td
(a)Tj
0.652 0 Td
(comprehensive)Tj
6.2929 0 Td
(assessment)Tj
4.6091 0 Td
(for)Tj
1.3889 0 Td
(AANCC,)Tj
3.8721 0 Td
(cognitive)Tj
3.8778 0 Td
(test-)Tj
-35.0643 -1.2983 Td
(ing,)Tj
1.7234 0 Td
(biomarker)Tj
4.4164 0 Td
(measurements)Tj
6.032 0 Td
(and)Tj
1.7348 0 Td
(MRI)Tj
2.0693 0 Td
(scanning.)Tj
4.0422 0 Td
(All)Tj
1.4003 0 Td
(subjects)Tj
3.3789 0 Td
(underwent)Tj
4.5694 0 Td
(a)Tj
0.6576 0 Td
(repeat)Tj
2.6873 0 Td
(assessment)Tj
-32.7116 -1.2983 Td
(at)Tj
0.9524 0 Td
(approximately)Tj
5.9754 0 Td
(two)Tj
1.7064 0 Td
(years)Tj
2.2677 0 Td
(later;)Tj
2.2167 0 Td
(a)Tj
0.652 0 Td
(two-year)Tj
3.7473 0 Td
(follow)Tj
2.6986 0 Td
(up)Tj
1.2643 0 Td
(period)Tj
2.8346 0 Td
(was)Tj
1.6951 0 Td
(considered)Tj
4.6034 0 Td
(sufficient)Tj
3.9118 0 Td
(to)Tj
-34.5257 -1.3039 Td
(detect)Tj
2.6135 0 Td
(meaningful)Tj
4.7905 0 Td
(changes)Tj
3.4016 0 Td
(in)Tj
1.0374 0 Td
(biomarkers)Tj
4.7792 0 Td
(and)Tj
1.7291 0 Td
(neuroimaging)Tj
5.862 0 Td
(outcomes)Tj
4.0876 0 Td
(based)Tj
2.4718 0 Td
(on)Tj
1.2756 0 Td
(previously)Tj
-32.0483 -1.2982 Td
(reported)Tj
3.6566 0 Td
(results.)Tj
-2.4604 -1.2983 Td
(At)Tj
1.2075 0 Td
(baseline,)Tj
3.651 0 Td
(details)Tj
2.778 0 Td
(captured)Tj
3.7473 0 Td
(included)Tj
3.7134 0 Td
(participant)Tj
4.5921 0 Td
(demographics,)Tj
6.0944 0 Td
(socioeconomic)Tj
6.2022 0 Td
(status,)Tj
-33.1821 -1.3039 Td
(detailed)Tj
3.3675 0 Td
(medical)Tj
3.3619 0 Td
(history)Tj
3.0047 0 Td
(including)Tj
4.0421 0 Td
(details)Tj
2.778 0 Td
(of)Tj
1.0148 0 Td
(lifestyle,)Tj
3.4525 0 Td
(use)Tj
1.5364 0 Td
(of)Tj
1.0148 0 Td
(\(non-antiretroviral\))Tj
8.1467 0 Td
(medication,)Tj
-31.7194 -1.2983 Td
(anthropometric)Tj
6.5309 0 Td
(assessments,)Tj
5.1987 0 Td
(questionnaires)Tj
6.0661 0 Td
(on)Tj
1.2756 0 Td
(quality)Tj
2.9537 0 Td
(of)Tj
1.0148 0 Td
(life,)Tj
1.6724 0 Td
(work)Tj
2.2791 0 Td
(participation)Tj
5.3688 0 Td
(and)Tj
1.7291 0 Td
(depres-)Tj
-34.0892 -1.2983 Td
(sion,)Tj
2.1259 0 Td
(detailed)Tj
3.3676 0 Td
(cognitive)Tj
3.8777 0 Td
(function)Tj
3.6284 0 Td
(assessment,)Tj
4.8358 0 Td
(respiratory)Tj
4.5978 0 Td
(function)Tj
3.6283 0 Td
(\(spirometry\),)Tj
5.5162 0 Td
(cardiovascular)Tj
-31.5777 -1.3039 Td
(function)Tj
3.6283 0 Td
(assessment)Tj
4.6091 0 Td
(\(ECG)Tj
2.5115 0 Td
(and)Tj
1.7291 0 Td
(arterial)Tj
3.067 0 Td
(stiffness)Tj
3.4129 0 Td
(assessment\),)Tj
5.1761 0 Td
(spine,)Tj
2.5625 0 Td
(hip)Tj
1.5363 0 Td
(and)Tj
1.7292 0 Td
(femoral)Tj
3.3108 0 Td
(neck)Tj
2.109 0 Td
(dual)Tj
-35.3818 -1.2982 Td
(energy)Tj
2.9083 0 Td
(X-ray)Tj
2.4831 0 Td
(absorptiometry)Tj
6.3552 0 Td
(\(DXA\))Tj
2.9707 0 Td
(scan)Tj
1.9899 0 Td
(for)Tj
1.3833 0 Td
(bone)Tj
2.2111 0 Td
(mineral)Tj
3.3278 0 Td
(density,)Tj
3.3279 0 Td
(assessment)Tj
4.6091 0 Td
(of)Tj
1.0148 0 Td
(falls)Tj
1.7971 0 Td
(risk)Tj
-34.3783 -1.2983 Td
(and)Tj
1.7291 0 Td
(fracture)Tj
3.3562 0 Td
(risk)Tj
1.7178 0 Td
(and)Tj
1.7291 0 Td
(frailty)Tj
2.5795 0 Td
(assessment.)Tj
-9.9155 -1.3039 Td
(Different)Tj
3.8664 0 Td
(types)Tj
2.2734 0 Td
(of)Tj
1.0148 0 Td
(biological)Tj
4.0932 0 Td
(material)Tj
3.5149 0 Td
(were)Tj
2.1203 0 Td
(sampled)Tj
3.549 0 Td
(at)Tj
0.9524 0 Td
(both)Tj
2.0579 0 Td
(baseline)Tj
3.4356 0 Td
(and)Tj
1.7291 0 Td
(follow)Tj
2.6986 0 Td
(up)Tj
1.2642 0 Td
(visit)Tj
1.8652 0 Td
(for)Tj
-35.6312 -1.2983 Td
(biomarker)Tj
4.4163 0 Td
(analysis)Tj
3.3279 0 Td
(\(blood)Tj
2.8516 0 Td
(cells)Tj
1.9219 0 Td
(and)Tj
1.7291 0 Td
(serum/plasma,)Tj
6.0888 0 Td
(peripheral)Tj
4.3199 0 Td
(blood)Tj
2.5172 0 Td
(mononuclear)Tj
5.5785 0 Td
(cells)Tj
-32.7512 -1.2982 Td
(\(PBMC\),)Tj
3.821 0 Td
(DNA,)Tj
2.6022 0 Td
(cerebrospinal)Tj
5.6182 0 Td
(fluid)Tj
2.075 0 Td
(\(CSF\),)Tj
2.7949 0 Td
(urine)Tj
2.3584 0 Td
(and)Tj
1.7292 0 Td
(stool\).)Tj
2.7042 0 Td
(Different)Tj
3.8664 0 Td
(sets)Tj
1.6611 0 Td
(of)Tj
1.0148 0 Td
(biomarkers)Tj
4.7792 0 Td
(were)Tj
-35.0246 -1.2983 Td
(measured,)Tj
4.3313 0 Td
(including)Tj
4.0421 0 Td
(markers)Tj
3.498 0 Td
(of)Tj
1.0148 0 Td
(residual)Tj
3.3788 0 Td
(HIV)Tj
2.024 0 Td
(replication)Tj
4.524 0 Td
(and)Tj
1.7292 0 Td
(production,)Tj
4.9379 0 Td
(immune)Tj
3.6283 0 Td
(activation)Tj
-33.1084 -1.3039 Td
(and)Tj
1.7291 0 Td
(senescence,)Tj
4.8075 0 Td
(inflammation,)Tj
5.9187 0 Td
(coagulation)Tj
4.8812 0 Td
(activation,)Tj
4.3767 0 Td
(antiretroviral)Tj
5.5162 0 Td
(pharmacokinetics,)Tj
7.5628 0 Td
(neuro-)Tj
-34.7922 -1.2983 Td
(nal)Tj
1.4456 0 Td
(damage)Tj
3.3279 0 Td
(and)Tj
1.7291 0 Td
(ageing)Tj
2.8233 0 Td
(\(glycan)Tj
3.1294 0 Td
(profiles,)Tj
3.4299 0 Td
(genetic,)Tj
3.2938 0 Td
(epigenetic,)Tj
4.5014 0 Td
(mRNA)Tj
3.0841 0 Td
(and)Tj
1.7291 0 Td
(microRNA)Tj
4.6488 0 Td
(ratio)Tj
-33.1424 -1.2983 Td
(sequencing\).)Tj
5.278 0 Td
(Complete)Tj
4.1216 0 Td
(details,)Tj
3.0047 0 Td
(including)Tj
4.0365 0 Td
(sampling)Tj
3.8834 0 Td
(methods)Tj
3.685 0 Td
(and)Tj
1.7292 0 Td
(procedures,)Tj
4.8982 0 Td
(are)Tj
1.4513 0 Td
(reported)Tj
3.6567 0 Td
(in)Tj
-35.7446 -1.3039 Td
(the)Tj
1.4683 0 Td
(supplementary)Tj
6.1625 0 Td
(material)Tj
3.5149 0 Td
(\()Tj
0.83 0.64 0.02 0 k
(S1)Tj
1.5137 0 Td
(File)Tj
0 g
(\))Tj
2.0239 0 Td
(and,)Tj
1.9559 0 Td
(for)Tj
1.3833 0 Td
(some)Tj
2.3301 0 Td
(sets)Tj
1.6667 0 Td
(of)Tj
1.0148 0 Td
(biomarkers)Tj
4.7792 0 Td
(in)Tj
1.0318 0 Td
(Booiman)Tj
3.8835 0 Td
(T.)Tj
1.0601 0 Td
(et)Tj
0.9411 0 Td
(al)Tj
0.8958 0 Td
([)Tj
0.83 0.64 0.02 0 k
(24)Tj
0 g
(])Tj
-35.6256 -1.2982 Td
(and)Tj
1.7291 0 Td
(Booiman)Tj
3.8834 0 Td
(T.)Tj
1.0545 0 Td
(et)Tj
0.9411 0 Td
(al)Tj
0.9014 0 Td
([)Tj
0.83 0.64 0.02 0 k
(25)Tj
0 g
(].)Tj
-7.3133 -1.2983 Td
(Detailed)Tj
3.5773 0 Td
(cognitive)Tj
3.8777 0 Td
(function)Tj
3.6284 0 Td
(assessment)Tj
4.6091 0 Td
(was)Tj
1.7007 0 Td
(carried)Tj
3.0388 0 Td
(out)Tj
1.5533 0 Td
(at)Tj
0.9525 0 Td
(both)Tj
2.0579 0 Td
(baseline)Tj
3.4299 0 Td
(and)Tj
1.7348 0 Td
(follow)Tj
2.6929 0 Td
(up)Tj
1.2699 0 Td
(and)Tj
-35.3194 -1.3039 Td
(included)Tj
3.7133 0 Td
(all)Tj
1.1452 0 Td
(major)Tj
2.6079 0 Td
(cognitive)Tj
3.8721 0 Td
(domains:)Tj
3.9117 0 Td
(attention)Tj
3.8438 0 Td
(and)Tj
1.7291 0 Td
(working)Tj
3.5603 0 Td
(memory,)Tj
3.8438 0 Td
(speed)Tj
2.4718 0 Td
(of)Tj
1.0148 0 Td
(information)Tj
-31.7138 -1.2983 Td
(processing,)Tj
4.6884 0 Td
(memory)Tj
3.617 0 Td
(and)Tj
1.7291 0 Td
(learning,)Tj
3.7531 0 Td
(language,)Tj
3.9855 0 Td
(executive)Tj
3.9288 0 Td
(function)Tj
3.6283 0 Td
(and)Tj
1.7291 0 Td
(psychomotor)Tj
5.5162 0 Td
(perfor-)Tj
-32.5755 -1.2983 Td
(mance)Tj
2.8686 0 Td
(\(see)Tj
0.83 0.64 0.02 0 k
1.7688 0 Td
(S1)Tj
1.1679 0 Td
(Table)Tj
0 g
(\).)Tj
3.0103 0 Td
(In)Tj
1.1055 0 Td
(addition,)Tj
3.8268 0 Td
(acquired)Tj
3.702 0 Td
(impairment)Tj
4.9833 0 Td
(of)Tj
1.0148 0 Td
(everyday)Tj
3.7644 0 Td
(functioning)Tj
4.9096 0 Td
(was)Tj
1.7007 0 Td
(assessed)Tj
-33.8227 -1.2982 Td
(by)Tj
1.1792 0 Td
(self-report)Tj
4.3766 0 Td
(questionnaires)Tj
6.0661 0 Td
(of)Tj
1.0148 0 Td
(cognitively)Tj
4.5751 0 Td
(related)Tj
2.948 0 Td
(aspects,)Tj
3.2655 0 Td
(activities)Tj
3.7134 0 Td
(of)Tj
1.0148 0 Td
(daily)Tj
2.1486 0 Td
(living)Tj
2.4661 0 Td
(\(Lawton)Tj
-32.7682 -1.3039 Td
(Instrumental)Tj
5.4368 0 Td
(Activities)Tj
3.9628 0 Td
(of)Tj
1.0148 0 Td
(Daily)Tj
2.3584 0 Td
(Living)Tj
2.7609 0 Td
(Scale\))Tj
2.5625 0 Td
(and)Tj
1.7291 0 Td
(depressive)Tj
4.354 0 Td
(symptoms)Tj
4.3597 0 Td
(\(Beck's)Tj
3.0557 0 Td
(Depression)Tj
-31.5947 -1.2983 Td
(Inventory\).)Tj
4.7338 0 Td
(These)Tj
2.5625 0 Td
(tests)Tj
1.9615 0 Td
(were)Tj
2.126 0 Td
(selected)Tj
3.3449 0 Td
(to)Tj
1.0261 0 Td
(accurately)Tj
4.2576 0 Td
(assess)Tj
2.5228 0 Td
(cognitive)Tj
3.8721 0 Td
(function)Tj
3.6284 0 Td
(based)Tj
2.4718 0 Td
(on)Tj
1.2755 0 Td
(the)Tj
1.4741 0 Td
(cur-)Tj
-35.2571 -1.2983 Td
(rent)Tj
1.8595 0 Td
(literature,)Tj
4.1102 0 Td
(with)Tj
1.9956 0 Td
(the)Tj
1.4683 0 Td
(total)Tj
2.0069 0 Td
(testing)Tj
2.88 0 Td
(time)Tj
2.0296 0 Td
(estimated)Tj
4.0705 0 Td
(to)Tj
1.0261 0 Td
(be)Tj
1.1509 0 Td
(approximately)Tj
5.9754 0 Td
(120)Tj
1.6498 0 Td
(minutes)Tj
3.4639 0 Td
(per)Tj
1.5307 0 Td
(sub-)Tj
-35.2174 -1.3039 Td
(ject,)Tj
1.8481 0 Td
(including)Tj
4.0422 0 Td
(resting)Tj
2.9537 0 Td
(time)Tj
2.0296 0 Td
(between)Tj
3.5263 0 Td
(tests.)Tj
2.1883 0 Td
(Designated)Tj
4.7055 0 Td
(trained)Tj
3.0897 0 Td
(clinical)Tj
3.0784 0 Td
(research)Tj
3.5546 0 Td
(staff)Tj
1.8879 0 Td
(undertook)Tj
-32.9043 -1.2982 Td
(the)Tj
1.4569 0 Td
(assessment)Tj
4.6035 0 Td
(of)Tj
1.0034 0 Td
(cognitive)Tj
3.8665 0 Td
(function)Tj
3.6226 0 Td
(at)Tj
0.9411 0 Td
(each)Tj
2.0183 0 Td
(clinical)Tj
3.067 0 Td
(site,)Tj
1.7859 0 Td
(adhering)Tj
3.7757 0 Td
(to)Tj
1.0148 0 Td
(the)Tj
1.4627 0 Td
(study)Tj
2.381 0 Td
(operations)Tj
4.4447 0 Td
(man-)Tj
-35.4441 -1.2983 Td
(ual)Tj
1.4286 0 Td
(for)Tj
1.3833 0 Td
(completing)Tj
4.7395 0 Td
(this)Tj
1.6724 0 Td
(battery)Tj
3.0047 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4683 0 Td
(same)Tj
2.2621 0 Td
(fashion)Tj
3.1521 0 Td
(in)Tj
1.0318 0 Td
(each)Tj
2.0296 0 Td
(study)Tj
2.3924 0 Td
(participant.)Tj
-24.4061 -1.3039 Td
(Historical)Tj
4.1669 0 Td
(information)Tj
5.0739 0 Td
(on)Tj
1.2756 0 Td
(HIV)Tj
2.024 0 Td
(treatment,)Tj
4.3596 0 Td
(CD4+)Tj
2.6759 0 Td
(T)Tj
0.8334 0 Td
(cell)Tj
1.559 0 Td
(count)Tj
2.5228 0 Td
(and)Tj
1.7292 0 Td
(HIV)Tj
2.0239 0 Td
(viral)Tj
1.9956 0 Td
(load)Tj
1.9332 0 Td
(were)Tj
-33.3692 -1.2983 Td
(obtained)Tj
3.7303 0 Td
(for)Tj
1.389 0 Td
(all)Tj
1.1452 0 Td
(HIV-positive)Tj
5.4708 0 Td
(subjects)Tj
3.3789 0 Td
(from)Tj
2.2053 0 Td
(national)Tj
3.5036 0 Td
(\(Dutch)Tj
3.0728 0 Td
(and)Tj
1.7291 0 Td
(UK\))Tj
1.9672 0 Td
(HIV)Tj
2.0239 0 Td
(databases)Tj
4.0025 0 Td
(\()Tj
0.83 0.64 0.02 0 k
(https://)Tj
-33.6186 -1.2983 Td
(www.hiv-monitoring.nl/english/)Tj
0 g
13.215 0 Td
(and)Tj
0.83 0.64 0.02 0 k
1.7291 0 Td
(http://www.ctu.mrc.ac)Tj
8.9801 0 Td
(.uk/UKCHIC/indexUKCHIC.)Tj
-23.9242 -1.3039 Td
(asp)Tj
0 g
(\).)Tj
1.1962 -1.2982 Td
(In)Tj
1.1111 0 Td
(addition,)Tj
3.8211 0 Td
(multiple)Tj
3.566 0 Td
(MRI)Tj
2.0749 0 Td
(modalities)Tj
4.371 0 Td
(were)Tj
2.126 0 Td
(used)Tj
2.0579 0 Td
(to)Tj
1.0262 0 Td
(acquire)Tj
3.1747 0 Td
(a)Tj
0.652 0 Td
(wide)Tj
2.1203 0 Td
(range)Tj
2.4661 0 Td
(of)Tj
1.0148 0 Td
(complementary)Tj
-30.7783 -1.2983 Td
(measures)Tj
3.9401 0 Td
(of)Tj
1.0148 0 Td
(brain)Tj
2.3471 0 Td
(structure)Tj
3.821 0 Td
(and)Tj
1.7348 0 Td
(function)Tj
3.6283 0 Td
(of)Tj
1.0148 0 Td
(all)Tj
1.1452 0 Td
(subjects)Tj
3.3789 0 Td
(at)Tj
0.9524 0 Td
(both)Tj
2.058 0 Td
(baseline)Tj
3.4299 0 Td
(and)Tj
1.7348 0 Td
(follow)Tj
2.6985 0 Td
(up.)Tj
1.4854 0 Td
(Details)Tj
-34.384 -1.2983 Td
(concerning)Tj
4.7451 0 Td
(the)Tj
1.4684 0 Td
(modalities)Tj
4.371 0 Td
(and)Tj
1.7347 0 Td
(the)Tj
1.4684 0 Td
(data)Tj
1.9105 0 Td
(acquisition)Tj
4.6318 0 Td
(methods)Tj
3.685 0 Td
(are)Tj
1.4457 0 Td
(reported)Tj
3.6623 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4683 0 Td
(supplementary)Tj
-31.6287 -1.3039 Td
(material)Tj
3.5149 0 Td
(\()Tj
0.83 0.64 0.02 0 k
(S2)Tj
1.508 0 Td
(File)Tj
0 g
(\))Tj
2.0239 0 Td
(and)Tj
1.7348 0 Td
(have)Tj
2.058 0 Td
(been)Tj
2.1203 0 Td
(previously)Tj
4.354 0 Td
(reported)Tj
3.6566 0 Td
(in)Tj
1.0375 0 Td
(Cole)Tj
2.0579 0 Td
(J.)Tj
0.7767 0 Td
(et)Tj
0.9411 0 Td
(al)Tj
0.9014 0 Td
([)Tj
0.83 0.64 0.02 0 k
(26)Tj
0 g
(],)Tj
2.075 0 Td
(Underwood)Tj
5.057 0 Td
(J.)Tj
0.771 0 Td
(et)Tj
0.9411 0 Td
(al)Tj
-35.5292 -1.2983 Td
([)Tj
0.83 0.64 0.02 0 k
(27)Tj
0 g
(])Tj
1.8481 0 Td
(and)Tj
1.7348 0 Td
(van)Tj
1.6554 0 Td
(Zoest)Tj
2.4095 0 Td
(R.)Tj
1.0658 0 Td
(et)Tj
0.9411 0 Td
(al)Tj
0.9014 0 Td
([)Tj
0.83 0.64 0.02 0 k
(28)Tj
0 g
(].)Tj
-9.3599 -1.2982 Td
(A)Tj
0.907 0 Td
(detailed)Tj
3.3676 0 Td
(data)Tj
1.9162 0 Td
(exchange)Tj
3.9288 0 Td
(platform)Tj
3.702 0 Td
(was)Tj
1.7008 0 Td
(established)Tj
4.5978 0 Td
(prior)Tj
2.2506 0 Td
(to)Tj
1.0262 0 Td
(recruitment.)Tj
5.2157 0 Td
(This)Tj
1.9899 0 Td
(included)Tj
-31.7988 -1.3039 Td
(information)Tj
5.0739 0 Td
(on)Tj
1.2756 0 Td
(the)Tj
1.4684 0 Td
(standardisation)Tj
6.4062 0 Td
(of)Tj
1.0148 0 Td
(data)Tj
1.9162 0 Td
(across)Tj
2.6759 0 Td
(the)Tj
1.4683 0 Td
(two)Tj
1.7122 0 Td
(clinical)Tj
3.0784 0 Td
(cohorts)Tj
3.2144 0 Td
(\(i.e.)Tj
1.7008 0 Td
(variable)Tj
3.3562 0 Td
(names,)Tj
-34.3613 -1.2983 Td
(formats,)Tj
3.5206 0 Td
(ranges)Tj
2.8289 0 Td
(of)Tj
1.0148 0 Td
(values)Tj
2.6646 0 Td
(and)Tj
1.7291 0 Td
(units)Tj
2.2223 0 Td
(of)Tj
1.0148 0 Td
(measurements\),)Tj
6.599 0 Td
(data)Tj
1.9163 0 Td
(quality)Tj
2.9536 0 Td
(assurance)Tj
4.1046 0 Td
(checks,)Tj
3.1011 0 Td
(data)Tj
1.9105 0 Td
(pro-)Tj
-35.5802 -1.2983 Td
(tection,)Tj
3.2087 0 Td
(data)Tj
1.9163 0 Td
(preservation)Tj
5.1987 0 Td
(and)Tj
1.7291 0 Td
(sharing.)Tj
3.4185 0 Td
(All)Tj
1.4004 0 Td
(data)Tj
1.9105 0 Td
(were)Tj
2.126 0 Td
(transferred)Tj
4.6374 0 Td
(electronically)Tj
5.5332 0 Td
(from)Tj
2.2053 0 Td
(the)Tj
1.4684 0 Td
(clinics)Tj
-34.7525 -1.3039 Td
(and)Tj
1.7291 0 Td
(laboratories)Tj
4.9492 0 Td
(to)Tj
1.0205 0 Td
(the)Tj
1.474 0 Td
(data)Tj
1.9105 0 Td
(co-ordinating)Tj
5.7373 0 Td
(centre)Tj
2.7099 0 Td
(in)Tj
1.0375 0 Td
(London.)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 107.1496 23.6976 re
W* n
q
107.0929 0 0 23.6409 36 741.3165 cm
q
/I0 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 508.8755 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(The)Tj
1.9204 0 Td
(COBRA)Tj
3.7347 0 Td
(cohort)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
81.5811 34.9228 m
237.8835 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(ONE)Tj
2.3669 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.137)Tj
3.8198 0 Td
(1/journal.po)Tj
5.1236 0 Td
(ne.01917)Tj
4.089 0 Td
(91)Tj
0 g
2.0906 0 Td
(March)Tj
2.9622 0 Td
(29,)Tj
1.5874 0 Td
(2018)Tj
34.3562 0 Td
(4)Tj
0.7654 0 Td
(/)Tj
ET
endstream
endobj
92 0 obj
<>stream
endstream
endobj
93 0 obj
<>stream
endstream
endobj
94 0 obj
<>stream
endstream
endobj
95 0 obj
<>stream
endstream
endobj
96 0 obj
<>stream
endstream
endobj
97 0 obj
<>stream
endstream
endobj
98 0 obj
<>stream
endstream
endobj
99 0 obj
<>stream
BT
66.402 0 Td
(16)Tj
ET
Q
endstream
endobj
100 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 12 0 R/Annots 103 0 R/Contents 104 0 R/TrimBox[0 0 612 792]>>
endobj
103 0 obj
[105 0 R 106 0 R 107 0 R]
endobj
105 0 obj
<>/Border[0 0 0]/Dest(Rpone.0191791.ref012)>>
endobj
106 0 obj
<>/Border[0 0 0]/Dest(Rpone.0191791.ref029)>>
endobj
107 0 obj
<>/Border[0 0 0]/A 108 0 R>>
endobj
108 0 obj
<>
endobj
104 0 obj
[109 0 R 110 0 R 111 0 R 112 0 R 113 0 R]
endobj
109 0 obj
<>stream
q
0.83 0.64 0.02 0 k
373.6063 635.9811 m
383.1307 635.9811 l
h
f*
525.0898 635.9811 m
534.6142 635.9811 l
h
f*
0 g
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 706.0535 cm
BT
/F12 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Population)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 689.1023 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(COBRA)Tj
3.5035 0 Td
(was)Tj
1.6895 0 Td
(conducted)Tj
4.422 0 Td
(among)Tj
2.982 0 Td
(individuals)Tj
4.6432 0 Td
(recruited)Tj
3.8437 0 Td
(at)Tj
0.9411 0 Td
(two)Tj
1.7008 0 Td
(clinical)Tj
3.0671 0 Td
(sites,)Tj
2.1486 0 Td
(in)Tj
1.0261 0 Td
(Amsterdam)Tj
4.9493 0 Td
(\(Neth-)Tj
-34.9169 -1.3039 Td
(erlands\))Tj
3.4639 0 Td
(and)Tj
1.7234 0 Td
(London)Tj
3.3902 0 Td
(\(UK\))Tj
2.3074 0 Td
(in)Tj
1.0262 0 Td
(order)Tj
2.4151 0 Td
(to)Tj
1.0204 0 Td
(obtain)Tj
2.7723 0 Td
(a)Tj
0.652 0 Td
(sample)Tj
3.0103 0 Td
(representative)Tj
5.8337 0 Td
(of)Tj
1.0091 0 Td
(the)Tj
1.4627 0 Td
(aging)Tj
2.3924 0 Td
(HIV)Tj
2.0126 0 Td
(popula-)Tj
-34.4917 -1.2982 Td
(tion)Tj
1.8425 0 Td
(in)Tj
1.0318 0 Td
(Western)Tj
3.6113 0 Td
(and)Tj
1.7348 0 Td
(Northern)Tj
4.0025 0 Td
(Europe)Tj
3.1351 0 Td
(and)Tj
1.7291 0 Td
(to)Tj
1.0261 0 Td
(secure)Tj
2.7496 0 Td
(an)Tj
1.2019 0 Td
(adequate)Tj
3.7984 0 Td
(sample)Tj
3.0217 0 Td
(size.)Tj
1.9105 0 Td
(Participants)Tj
-30.7953 -1.2983 Td
(were)Tj
2.1203 0 Td
(recruited)Tj
3.855 0 Td
(from)Tj
2.2054 0 Td
(ongoing)Tj
3.5263 0 Td
(prospective)Tj
4.7848 0 Td
(cohort)Tj
2.8573 0 Td
(studies)Tj
2.9877 0 Td
(on)Tj
1.2756 0 Td
(co-morbidity)Tj
5.5219 0 Td
(and)Tj
1.7291 0 Td
(aging)Tj
2.3981 0 Td
(in)Tj
1.0374 0 Td
(HIV)Tj
-34.2989 -1.3039 Td
(\(the)Tj
1.8084 0 Td
(AGE)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 237.77 635.4141 cm
BT
/F7 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(h)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 241.7385 637.0582 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(IV)Tj
1.2529 0 Td
(Cohort)Tj
3.0954 0 Td
(Study)Tj
2.5058 0 Td
(in)Tj
1.0375 0 Td
(Amsterdam)Tj
4.9549 0 Td
([)Tj
0.83 0.64 0.02 0 k
(12)Tj
0 g
(])Tj
1.8538 0 Td
(and)Tj
1.7292 0 Td
(the)Tj
1.4683 0 Td
(POPPY)Tj
3.2768 0 Td
(study)Tj
2.3924 0 Td
(in)Tj
1.0319 0 Td
(London)Tj
3.3958 0 Td
([)Tj
0.83 0.64 0.02 0 k
(29)Tj
0 g
(]\).)Tj
2.4208 0 Td
(Both)Tj
-34.588 -1.2982 Td
(studies)Tj
2.9877 0 Td
(were)Tj
2.1202 0 Td
(set)Tj
1.3039 0 Td
(up)Tj
1.2642 0 Td
(with)Tj
1.9956 0 Td
(the)Tj
1.4684 0 Td
(objective)Tj
3.7814 0 Td
(of)Tj
1.0148 0 Td
(investigating)Tj
5.3234 0 Td
(the)Tj
1.4683 0 Td
(effects)Tj
2.7269 0 Td
(of)Tj
1.0148 0 Td
(ageing)Tj
2.8233 0 Td
(and)Tj
1.7291 0 Td
(comorbidities)Tj
-31.022 -1.2983 Td
(in)Tj
1.0318 0 Td
(people)Tj
2.8573 0 Td
(living)Tj
2.4717 0 Td
(with)Tj
1.9956 0 Td
(HIV)Tj
2.0239 0 Td
(and)Tj
1.7291 0 Td
(recruited)Tj
3.8551 0 Td
(middle-aged)Tj
5.2327 0 Td
(HIV-positive)Tj
5.4652 0 Td
(subjects)Tj
3.3789 0 Td
(and)Tj
1.7291 0 Td
(HIV-negative)Tj
-31.7704 -1.3039 Td
(controls)Tj
3.4809 0 Td
(with)Tj
1.9955 0 Td
(similar)Tj
2.9877 0 Td
(demographics)Tj
5.8677 0 Td
(and)Tj
1.7291 0 Td
(lifestyles.)Tj
3.8154 0 Td
(Both)Tj
2.1316 0 Td
(studies)Tj
2.9877 0 Td
(adopted)Tj
3.4526 0 Td
(enrolment)Tj
4.4107 0 Td
(criteria)Tj
3.0727 0 Td
(for)Tj
-35.9316 -1.2983 Td
(HIV-positive)Tj
5.465 0 Td
(participants)Tj
4.9606 0 Td
(to)Tj
1.0262 0 Td
(ensure)Tj
2.8743 0 Td
(these)Tj
2.2564 0 Td
(were)Tj
2.1203 0 Td
(representative)Tj
5.8336 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.474 0 Td
(population)Tj
4.5864 0 Td
(of)Tj
1.0148 0 Td
(people)Tj
2.8573 0 Td
(liv-)Tj
-35.4837 -1.2982 Td
(ing)Tj
1.5023 0 Td
(with)Tj
1.9956 0 Td
(HIV)Tj
2.0238 0 Td
(commonly)Tj
4.5411 0 Td
(seen)Tj
1.9786 0 Td
(in)Tj
1.0375 0 Td
(clinics)Tj
2.7552 0 Td
(in)Tj
1.0375 0 Td
(Amsterdam)Tj
4.9606 0 Td
(and)Tj
1.7291 0 Td
(in)Tj
1.0318 0 Td
(London.)Tj
3.6227 0 Td
(In)Tj
1.1111 0 Td
(order)Tj
2.4208 0 Td
(to)Tj
1.0261 0 Td
(best)Tj
1.8085 0 Td
(take)Tj
-34.5823 -1.2983 Td
(into)Tj
1.8425 0 Td
(account)Tj
3.3788 0 Td
(the)Tj
1.4683 0 Td
(effects)Tj
2.7269 0 Td
(of)Tj
1.0148 0 Td
(age,)Tj
1.7688 0 Td
(sex,)Tj
1.6951 0 Td
(other)Tj
2.3471 0 Td
(demographics)Tj
5.8677 0 Td
(as)Tj
1.0148 0 Td
(well)Tj
1.8198 0 Td
(as)Tj
1.0148 0 Td
(behavioural)Tj
4.9209 0 Td
(factors)Tj
2.9027 0 Td
(\(includ-)Tj
-33.783 -1.3039 Td
(ing)Tj
1.5023 0 Td
(sexual)Tj
2.6758 0 Td
(risk-taking)Tj
4.5751 0 Td
(behaviours\))Tj
4.9379 0 Td
(HIV-negative)Tj
5.692 0 Td
(individuals)Tj
4.6488 0 Td
(were)Tj
2.1203 0 Td
(recruited)Tj
3.855 0 Td
(into)Tj
1.8426 0 Td
(the)Tj
1.4683 0 Td
(two)Tj
1.7064 0 Td
(stud-)Tj
-35.0245 -1.2983 Td
(ies)Tj
1.2699 0 Td
(from)Tj
2.2053 0 Td
(sexual)Tj
2.6758 0 Td
(health)Tj
2.6816 0 Td
(clinics)Tj
2.7552 0 Td
(and)Tj
1.7292 0 Td
(targeted)Tj
3.4639 0 Td
(community)Tj
4.8869 0 Td
(groups.)Tj
3.1918 0 Td
(Moreover)Tj
4.1725 0 Td
(age,)Tj
1.7688 0 Td
(sex,)Tj
1.6952 0 Td
(and)Tj
-32.4961 -1.2982 Td
(ethnicity)Tj
3.7303 0 Td
(were)Tj
2.1202 0 Td
(regularly)Tj
3.7588 0 Td
(monitored,)Tj
4.7168 0 Td
(and)Tj
1.7291 0 Td
(enrolment)Tj
4.405 0 Td
(was)Tj
1.7008 0 Td
(adjusted)Tj
3.5773 0 Td
(accordingly)Tj
4.8869 0 Td
(to)Tj
1.0261 0 Td
(ensure)Tj
2.8743 0 Td
(compa-)Tj
-34.5256 -1.304 Td
(rability)Tj
3.067 0 Td
(of)Tj
1.0148 0 Td
(HIV-positive)Tj
5.4651 0 Td
(and)Tj
1.7291 0 Td
(HIV-negative)Tj
5.692 0 Td
(participants.)Tj
-15.7718 -1.2982 Td
(While)Tj
2.6532 0 Td
(these)Tj
2.2563 0 Td
(two)Tj
1.7064 0 Td
(studies)Tj
2.9877 0 Td
(comprehensively)Tj
6.9902 0 Td
(assessed)Tj
3.4696 0 Td
(a)Tj
0.652 0 Td
(wide)Tj
2.1259 0 Td
(range)Tj
2.4605 0 Td
(of)Tj
1.0148 0 Td
(AANCC)Tj
3.651 0 Td
(and)Tj
1.7291 0 Td
(associated)Tj
-32.8929 -1.2983 Td
(outcomes,)Tj
4.3142 0 Td
(patients)Tj
3.3675 0 Td
(enrolled)Tj
3.5093 0 Td
(within)Tj
2.8176 0 Td
(COBRA)Tj
3.5149 0 Td
(underwent)Tj
4.5751 0 Td
(further)Tj
3.0274 0 Td
(detailed)Tj
3.3676 0 Td
(assessments)Tj
4.9719 0 Td
(and)Tj
1.7291 0 Td
(test-)Tj
-35.1946 -1.3039 Td
(ing)Tj
1.5023 0 Td
(\(cognitive)Tj
4.2122 0 Td
(testing,)Tj
3.1067 0 Td
(biomarker)Tj
4.4164 0 Td
(measurements)Tj
6.0321 0 Td
(and)Tj
1.7291 0 Td
(MRI)Tj
2.0749 0 Td
(scanning\))Tj
4.1556 0 Td
(as)Tj
1.0148 0 Td
(described)Tj
4.0535 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4683 0 Td
(previ-)Tj
-34.8034 -1.2983 Td
(ous)Tj
1.6157 0 Td
(section.)Tj
-0.4195 -1.2982 Td
(All)Tj
1.389 0 Td
(COBRA)Tj
3.5035 0 Td
(participants)Tj
4.9492 0 Td
(were)Tj
2.1147 0 Td
(required)Tj
3.6283 0 Td
(to)Tj
1.0148 0 Td
(be)Tj
1.1395 0 Td
(aged)Tj
2.0636 0 Td
(45)Tj
1.1622 0 Td
(years)Tj
2.2507 0 Td
(or)Tj
1.0885 0 Td
(over)Tj
1.9672 0 Td
(and)Tj
1.7235 0 Td
(to)Tj
1.0148 0 Td
(be)Tj
1.1395 0 Td
(able)Tj
1.8198 0 Td
(to)Tj
1.0148 0 Td
(compre-)Tj
-34.1798 -1.2983 Td
(hend)Tj
2.245 0 Td
(the)Tj
1.4683 0 Td
(study)Tj
2.3924 0 Td
(information)Tj
5.0739 0 Td
(leaflet.)Tj
2.8063 0 Td
(HIV-positive)Tj
5.4709 0 Td
(subjects)Tj
3.3788 0 Td
(were)Tj
2.1203 0 Td
(required)Tj
3.6397 0 Td
(to)Tj
1.0261 0 Td
(have)Tj
2.058 0 Td
(a)Tj
0.6576 0 Td
(documented)Tj
-32.3373 -1.3039 Td
(HIV)Tj
2.0182 0 Td
(infection,)Tj
4.0194 0 Td
(to)Tj
1.0262 0 Td
(be)Tj
1.1508 0 Td
(on)Tj
1.2756 0 Td
(cART)Tj
2.5568 0 Td
(and)Tj
1.7348 0 Td
(to)Tj
1.0205 0 Td
(have)Tj
2.0636 0 Td
(had)Tj
1.7065 0 Td
(undetectable)Tj
5.3064 0 Td
(plasma)Tj
3.0274 0 Td
(HIV)Tj
2.0239 0 Td
(RNA)Tj
2.262 0 Td
(\()Tj
/F13 1 Tf
0 Tc
(<)Tj
/F7 1 Tf
-0.004 Tc
(50)Tj
2.2847 0 Td
(copies/)Tj
-33.4768 -1.2983 Td
(mL\))Tj
1.9162 0 Td
(for)Tj
/F6 1 Tf
0 Tc
1.389 0 Td
()Tj
/F7 1 Tf
-0.004 Tc
(12)Tj
1.9387 0 Td
(months)Tj
3.2825 0 Td
(prior)Tj
2.2564 0 Td
(to)Tj
1.0261 0 Td
(enrolment.)Tj
4.6318 0 Td
(A)Tj
0.9014 0 Td
(confirmed)Tj
4.3994 0 Td
(negative)Tj
3.5319 0 Td
(HIV)Tj
2.0239 0 Td
(test)Tj
1.5988 0 Td
(was)Tj
1.7008 0 Td
(required)Tj
3.6396 0 Td
(for)Tj
-34.2365 -1.2982 Td
(HIV-negative)Tj
5.6861 0 Td
(subjects.)Tj
3.6057 0 Td
(Exclusion)Tj
4.1329 0 Td
(criteria)Tj
3.0784 0 Td
(were)Tj
2.1203 0 Td
(as)Tj
1.0148 0 Td
(follows:)Tj
3.2881 0 Td
(current)Tj
3.1805 0 Td
(major)Tj
2.6079 0 Td
(depression)Tj
4.5297 0 Td
(\(as)Tj
1.3549 0 Td
(indi-)Tj
-34.5993 -1.304 Td
(cated)Tj
2.3244 0 Td
(by)Tj
1.1848 0 Td
(a)Tj
0.652 0 Td
(PHQ-9)Tj
3.118 0 Td
(questionnaire)Tj
5.7033 0 Td
(score)Tj
/F6 1 Tf
0 Tc
2.3074 0 Td
()Tj
/F7 1 Tf
-0.004 Tc
(15)Tj
1.9445 0 Td
(at)Tj
0.9524 0 Td
(screening\),)Tj
4.6148 0 Td
(confounding)Tj
5.3801 0 Td
(neurological)Tj
5.1874 0 Td
(diseases,)Tj
-33.3691 -1.2982 Td
(previous)Tj
3.651 0 Td
(severe)Tj
2.6758 0 Td
(head)Tj
2.1316 0 Td
(injury)Tj
2.6475 0 Td
(\(with)Tj
2.3358 0 Td
(loss)Tj
1.6951 0 Td
(of)Tj
1.0148 0 Td
(consciousness)Tj
/F6 1 Tf
0 Tc
5.8393 0 Td
()Tj
/F7 1 Tf
-0.004 Tc
(30)Tj
1.9446 0 Td
(minutes\),)Tj
4.0308 0 Td
(a)Tj
0.652 0 Td
(history)Tj
3.0104 0 Td
(of)Tj
1.0148 0 Td
(cerebral)Tj
-32.6435 -1.2983 Td
(infections)Tj
4.1499 0 Td
(\(including)Tj
4.3822 0 Td
(AIDS-defining)Tj
6.1455 0 Td
(diseases)Tj
3.3789 0 Td
(involving)Tj
3.9741 0 Td
(the)Tj
1.474 0 Td
(central)Tj
2.965 0 Td
(nervous)Tj
3.4129 0 Td
(system\),)Tj
3.5036 0 Td
(current)Tj
-33.3861 -1.3039 Td
(intravenous)Tj
4.9605 0 Td
(drug)Tj
2.1146 0 Td
(use)Tj
1.5307 0 Td
(\(in)Tj
1.372 0 Td
(the)Tj
1.474 0 Td
(past)Tj
1.8311 0 Td
(six)Tj
1.3096 0 Td
(months,)Tj
3.5093 0 Td
(based)Tj
2.4718 0 Td
(on)Tj
1.2756 0 Td
(self-report\),)Tj
4.9436 0 Td
(daily)Tj
2.1486 0 Td
(use)Tj
1.5364 0 Td
(of)Tj
1.0148 0 Td
(recreational)Tj
-31.4926 -1.2983 Td
(drugs)Tj
2.4718 0 Td
(\(with)Tj
2.3356 0 Td
(the)Tj
1.474 0 Td
(exception)Tj
4.0932 0 Td
(of)Tj
1.0148 0 Td
(cannabis\),)Tj
4.3086 0 Td
(excess)Tj
2.6759 0 Td
(alcohol)Tj
3.1125 0 Td
(intake)Tj
2.6872 0 Td
(\()Tj
/F13 1 Tf
0 Tc
(>)Tj
/F7 1 Tf
-0.004 Tc
(48)Tj
2.2847 0 Td
(units)Tj
2.2223 0 Td
(per)Tj
1.5307 0 Td
(week\),)Tj
2.812 0 Td
(severe)Tj
2.6759 0 Td
(psy-)Tj
-35.6992 -1.2982 Td
(chiatric)Tj
3.2315 0 Td
(disease)Tj
3.0159 0 Td
(or)Tj
1.0998 0 Td
(contraindication)Tj
6.8938 0 Td
(to)Tj
1.0205 0 Td
(MRI)Tj
2.075 0 Td
(or)Tj
1.0998 0 Td
(lumbar)Tj
3.1238 0 Td
(puncture.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 281.9905 cm
BT
/F12 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Sample)Tj
3.2787 0 Td
(size)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 264.9826 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(The)Tj
1.7801 0 Td
(study)Tj
2.3924 0 Td
(was)Tj
1.6951 0 Td
(not)Tj
1.5761 0 Td
(designed)Tj
3.7644 0 Td
(to)Tj
1.0261 0 Td
(be)Tj
1.1509 0 Td
(powered)Tj
3.6736 0 Td
(to)Tj
1.0262 0 Td
(detect)Tj
2.6135 0 Td
(associations)Tj
4.9889 0 Td
(with)Tj
1.9956 0 Td
(clinical)Tj
3.0784 0 Td
(AANCC.)Tj
3.8778 0 Td
(Such)Tj
2.1713 0 Td
(a)Tj
-36.8104 -1.2982 Td
(study)Tj
2.3867 0 Td
(would)Tj
2.7156 0 Td
(be)Tj
1.1508 0 Td
(infeasible)Tj
3.9855 0 Td
(within)Tj
2.812 0 Td
(most)Tj
2.2053 0 Td
(standard)Tj
3.7247 0 Td
(funding)Tj
3.3902 0 Td
(schemes)Tj
3.5603 0 Td
(given)Tj
2.3811 0 Td
(the)Tj
1.4683 0 Td
(high)Tj
2.007 0 Td
(costs)Tj
2.1713 0 Td
(and)Tj
-33.9588 -1.2983 Td
(complexity)Tj
4.6431 0 Td
(of)Tj
1.0148 0 Td
(capturing)Tj
4.0705 0 Td
(the)Tj
1.4683 0 Td
(detailed)Tj
3.3676 0 Td
(neuro-imaging)Tj
6.2191 0 Td
(and)Tj
1.7292 0 Td
(biomarker)Tj
4.4163 0 Td
(\(including)Tj
4.3823 0 Td
(cerebrospinal)Tj
-31.3112 -1.3039 Td
(fluid)Tj
2.0749 0 Td
(markers\))Tj
3.8381 0 Td
(data)Tj
1.9162 0 Td
(that)Tj
1.7745 0 Td
(were)Tj
2.1259 0 Td
(required.)Tj
3.8608 0 Td
(Rather,)Tj
3.1238 0 Td
(the)Tj
1.4683 0 Td
(target)Tj
2.5115 0 Td
(sample)Tj
3.0217 0 Td
(size)Tj
1.6838 0 Td
(was)Tj
1.7007 0 Td
(pragmatically)Tj
5.6296 0 Td
(set)Tj
1.3039 0 Td
(at)Tj
-36.0337 -1.2983 Td
(150)Tj
1.644 0 Td
(HIV-positive)Tj
5.4709 0 Td
(subjects)Tj
3.3788 0 Td
(\(75)Tj
1.5081 0 Td
(at)Tj
0.9524 0 Td
(each)Tj
2.0296 0 Td
(site\))Tj
1.9105 0 Td
(and)Tj
1.7292 0 Td
(100)Tj
1.6497 0 Td
(HIV-negative)Tj
5.6863 0 Td
(controls)Tj
3.4809 0 Td
(\(50)Tj
1.5137 0 Td
(at)Tj
0.9524 0 Td
(each)Tj
2.0296 0 Td
(site\).)Tj
-33.9361 -1.2982 Td
(These)Tj
2.5681 0 Td
(numbers)Tj
3.7757 0 Td
(and)Tj
1.7292 0 Td
(the)Tj
1.474 0 Td
(HIV-positive)Tj
5.4651 0 Td
(to)Tj
1.0262 0 Td
(HIV-negative)Tj
5.6862 0 Td
(ratio)Tj
2.0977 0 Td
(were)Tj
2.1259 0 Td
(considered,)Tj
4.8246 0 Td
(at)Tj
0.9524 0 Td
(the)Tj
1.4683 0 Td
(time,)Tj
2.2564 0 Td
(to)Tj
1.0261 0 Td
(be)Tj
-36.4759 -1.3039 Td
(feasible)Tj
3.1691 0 Td
(based)Tj
2.4718 0 Td
(on)Tj
1.2755 0 Td
(the)Tj
1.4684 0 Td
(size)Tj
1.6837 0 Td
(and)Tj
1.7348 0 Td
(design)Tj
2.812 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(two)Tj
1.7121 0 Td
(ongoing)Tj
3.5263 0 Td
(larger)Tj
2.5342 0 Td
(cohort)Tj
2.8516 0 Td
(studies)Tj
2.9877 0 Td
(on)Tj
1.2756 0 Td
(co-morbidity)Tj
-31.9859 -1.2983 Td
(and)Tj
1.7291 0 Td
(aging)Tj
2.3981 0 Td
(in)Tj
1.0374 0 Td
(HIV)Tj
2.024 0 Td
(in)Tj
1.0318 0 Td
(the)Tj
1.474 0 Td
(Netherlands)Tj
5.1136 0 Td
(and)Tj
1.7348 0 Td
(in)Tj
1.0318 0 Td
(the)Tj
1.474 0 Td
(UK,)Tj
1.8539 0 Td
(and)Tj
1.7291 0 Td
(based)Tj
2.4718 0 Td
(on)Tj
1.2756 0 Td
(the)Tj
1.4683 0 Td
(demand)Tj
3.5036 0 Td
(of)Tj
1.0148 0 Td
(time)Tj
2.0296 0 Td
(and)Tj
-34.3953 -1.2983 Td
(commitment)Tj
5.4424 0 Td
(from)Tj
2.2054 0 Td
(study)Tj
2.3924 0 Td
(participants)Tj
4.9549 0 Td
(required)Tj
3.6397 0 Td
(to)Tj
1.0261 0 Td
(complete)Tj
3.8778 0 Td
(all)Tj
1.1509 0 Td
(the)Tj
1.4683 0 Td
(planned)Tj
3.4639 0 Td
(assessments)Tj
4.9719 0 Td
(and)Tj
-34.5937 -1.2982 Td
(tests.)Tj
2.1883 0 Td
(Several)Tj
3.0444 0 Td
(members)Tj
3.9458 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.474 0 Td
(HIV)Tj
2.0182 0 Td
(community)Tj
4.8869 0 Td
(\(as)Tj
1.355 0 Td
(part)Tj
1.8425 0 Td
(of)Tj
1.0148 0 Td
(a)Tj
0.652 0 Td
(wider)Tj
2.4944 0 Td
(scientific)Tj
3.7871 0 Td
(advisory)Tj
3.6 0 Td
(board)Tj
-33.3182 -1.304 Td
(nominated)Tj
4.592 0 Td
(by)Tj
1.1849 0 Td
(the)Tj
1.4684 0 Td
(COBRA)Tj
3.5149 0 Td
(steering)Tj
3.3789 0 Td
(committee\))Tj
4.8415 0 Td
(were)Tj
2.1203 0 Td
(also)Tj
1.7688 0 Td
(involved)Tj
3.651 0 Td
(in)Tj
1.0318 0 Td
(discussions)Tj
4.7339 0 Td
(around)Tj
3.1351 0 Td
(study)Tj
-35.4215 -1.2982 Td
(design,)Tj
3.0387 0 Td
(to)Tj
1.0261 0 Td
(ensure)Tj
2.8743 0 Td
(that)Tj
1.7802 0 Td
(recruitment)Tj
4.9889 0 Td
(methods)Tj
3.685 0 Td
(and)Tj
1.7291 0 Td
(procedures)Tj
4.6772 0 Td
(would)Tj
2.7099 0 Td
(be)Tj
1.1508 0 Td
(acceptable)Tj
4.354 0 Td
(to)Tj
1.0262 0 Td
(partici-)Tj
-33.0404 -1.2983 Td
(pants.)Tj
2.6021 0 Td
(Whilst)Tj
2.8857 0 Td
(no)Tj
1.2756 0 Td
(formal)Tj
2.8856 0 Td
(sample)Tj
3.0217 0 Td
(size)Tj
1.6838 0 Td
(calculation)Tj
4.5808 0 Td
(was)Tj
1.6951 0 Td
(performed)Tj
4.473 0 Td
(\(there)Tj
2.6022 0 Td
(was)Tj
1.7008 0 Td
(no)Tj
1.2756 0 Td
(primary)Tj
3.4525 0 Td
(end-)Tj
-34.1345 -1.3039 Td
(point)Tj
2.3584 0 Td
(and)Tj
1.7291 0 Td
(the)Tj
1.4683 0 Td
(distribution)Tj
4.972 0 Td
(of)Tj
1.0148 0 Td
(many)Tj
2.4717 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4741 0 Td
(proposed)Tj
3.9514 0 Td
(biomarker)Tj
4.4164 0 Td
(outcomes)Tj
4.0875 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4683 0 Td
(HIV-positive)Tj
-31.4643 -1.2983 Td
(population)Tj
4.5864 0 Td
(had)Tj
1.7121 0 Td
(not)Tj
1.576 0 Td
(been)Tj
2.1203 0 Td
(previously)Tj
4.3484 0 Td
(documented\),)Tj
5.8166 0 Td
(it)Tj
0.7824 0 Td
(was)Tj
1.7008 0 Td
(recognised)Tj
4.5354 0 Td
(that)Tj
1.7801 0 Td
(a)Tj
0.652 0 Td
(cohort)Tj
2.8573 0 Td
(of)Tj
1.0148 0 Td
(this)Tj
1.6724 0 Td
(size)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 107.1496 23.6976 re
W* n
q
107.0929 0 0 23.6409 36 741.3165 cm
q
/I0 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 508.8755 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(The)Tj
1.9204 0 Td
(COBRA)Tj
3.7347 0 Td
(cohort)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
81.5811 34.9228 m
237.8835 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(ONE)Tj
2.3669 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.137)Tj
3.8198 0 Td
(1/journal.po)Tj
5.1236 0 Td
(ne.01917)Tj
4.089 0 Td
(91)Tj
0 g
2.0906 0 Td
(March)Tj
2.9622 0 Td
(29,)Tj
1.5874 0 Td
(2018)Tj
34.3562 0 Td
(5)Tj
0.7654 0 Td
(/)Tj
ET
endstream
endobj
110 0 obj
<>stream
endstream
endobj
111 0 obj
<>stream
endstream
endobj
112 0 obj
<>stream
endstream
endobj
113 0 obj
<>stream
BT
66.402 0 Td
(16)Tj
ET
Q
endstream
endobj
114 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 12 0 R/Annots 116 0 R/Contents 117 0 R/TrimBox[0 0 612 792]>>
endobj
116 0 obj
[118 0 R 119 0 R]
endobj
118 0 obj
<>/Border[0 0 0]/Dest(Rpone.0191791.ref030)>>
endobj
119 0 obj
<>/Border[0 0 0]/A 120 0 R>>
endobj
120 0 obj
<>
endobj
117 0 obj
[121 0 R 122 0 R 123 0 R 124 0 R 125 0 R]
endobj
121 0 obj
<>stream
q
0.83 0.64 0.02 0 k
469.8142 94.9039 m
479.3386 94.9039 l
h
f*
0 g
1 j
1 J
0 w
10 0 0 10 200.0125 707.4141 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(would)Tj
2.7099 0 Td
(be)Tj
1.1508 0 Td
(substantially)Tj
5.2044 0 Td
(larger)Tj
2.5341 0 Td
(that)Tj
1.7745 0 Td
(most)Tj
2.2054 0 Td
(ongoing)Tj
3.5319 0 Td
(neuroimaging)Tj
5.862 0 Td
(studies.)Tj
3.2145 0 Td
(In)Tj
1.1055 0 Td
(addition,)Tj
3.8267 0 Td
(given)Tj
2.3755 0 Td
(the)Tj
-35.4952 -1.3039 Td
(continuous)Tj
4.7338 0 Td
(nature)Tj
2.8233 0 Td
(of)Tj
1.0148 0 Td
(many)Tj
2.4774 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(biomarker)Tj
4.422 0 Td
(and)Tj
1.7291 0 Td
(neuroimaging)Tj
5.862 0 Td
(outcomes,)Tj
4.3143 0 Td
(this)Tj
1.6724 0 Td
(sample)Tj
3.0218 0 Td
(size)Tj
-34.5541 -1.2982 Td
(was)Tj
1.6951 0 Td
(believed)Tj
3.4979 0 Td
(to)Tj
1.0205 0 Td
(be)Tj
1.1508 0 Td
(sufficient)Tj
3.9175 0 Td
(to)Tj
1.0204 0 Td
(allow)Tj
2.3414 0 Td
(estimation)Tj
4.4447 0 Td
(of)Tj
1.0148 0 Td
(key)Tj
1.5931 0 Td
(parameters)Tj
4.6715 0 Td
(with)Tj
2.0012 0 Td
(sufficient)Tj
3.9118 0 Td
(precision)Tj
3.9061 0 Td
(to)Tj
-36.1868 -1.2983 Td
(allow)Tj
2.3357 0 Td
(meaningful)Tj
4.7905 0 Td
(comparisons)Tj
5.3348 0 Td
(of)Tj
1.0148 0 Td
(most)Tj
2.2053 0 Td
(outcomes,)Tj
4.3143 0 Td
(based)Tj
2.4718 0 Td
(on)Tj
1.2756 0 Td
(previously)Tj
4.354 0 Td
(reported)Tj
3.6567 0 Td
(results)Tj
2.8119 0 Td
(from)Tj
-34.5654 -1.2983 Td
(similar)Tj
2.9876 0 Td
(studies.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 628.9511 cm
BT
/F12 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Recruitment)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 611.9433 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Recruitment)Tj
5.2327 0 Td
(to)Tj
1.0148 0 Td
(the)Tj
1.4626 0 Td
(study)Tj
2.3755 0 Td
(took)Tj
2.0182 0 Td
(place)Tj
2.2564 0 Td
(between)Tj
3.5206 0 Td
(January)Tj
3.3108 0 Td
(2013)Tj
2.109 0 Td
(and)Tj
1.7234 0 Td
(October)Tj
3.4866 0 Td
(2014)Tj
2.1147 0 Td
(with)Tj
1.9842 0 Td
(some)Tj
2.3244 0 Td
(partic-)Tj
-34.9339 -1.2982 Td
(ipants)Tj
2.6475 0 Td
(already)Tj
3.1067 0 Td
(enrolled)Tj
3.515 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4683 0 Td
(AGE)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 337.4362 597.2598 cm
BT
/F7 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(h)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 341.4047 598.9606 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(IV)Tj
1.2529 0 Td
(study,)Tj
2.6192 0 Td
(who)Tj
1.9388 0 Td
(had)Tj
1.7065 0 Td
(been)Tj
2.126 0 Td
(enrolled)Tj
3.5092 0 Td
(between)Tj
3.532 0 Td
(December)Tj
4.3483 0 Td
(2011)Tj
-35.172 -1.3039 Td
(and)Tj
1.7291 0 Td
(December)Tj
4.3484 0 Td
(2012,)Tj
2.347 0 Td
(were)Tj
2.1203 0 Td
(also)Tj
1.7688 0 Td
(retrospectively)Tj
6.0661 0 Td
(recruited)Tj
3.8494 0 Td
(into)Tj
1.8425 0 Td
(the)Tj
1.4683 0 Td
(COBRA)Tj
3.515 0 Td
(cohort.)Tj
3.084 0 Td
(A)Tj
0.9014 0 Td
(follow-up)Tj
-33.0403 -1.2982 Td
(visit)Tj
1.8652 0 Td
(was)Tj
1.7008 0 Td
(planned)Tj
3.4639 0 Td
(for)Tj
1.389 0 Td
(all)Tj
1.1452 0 Td
(recruited)Tj
3.8551 0 Td
(participants)Tj
4.9548 0 Td
(at)Tj
0.9524 0 Td
(approximately)Tj
5.9754 0 Td
(two)Tj
1.7121 0 Td
(years)Tj
2.2621 0 Td
(from)Tj
2.2053 0 Td
(the)Tj
1.474 0 Td
(baseline)Tj
-32.9553 -1.2983 Td
(visit.)Tj
2.092 0 Td
(Due)Tj
1.9105 0 Td
(to)Tj
1.0205 0 Td
(the)Tj
1.474 0 Td
(difficulties)Tj
4.405 0 Td
(of)Tj
1.0148 0 Td
(recruiting)Tj
4.1838 0 Td
(participants)Tj
4.9549 0 Td
(in)Tj
1.0375 0 Td
(one)Tj
1.6951 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.474 0 Td
(two)Tj
1.7065 0 Td
(sites,)Tj
2.16 0 Td
(the)Tj
1.4683 0 Td
(Programme)Tj
-31.6117 -1.3039 Td
(Steering)Tj
3.4923 0 Td
(Committee)Tj
4.7395 0 Td
(made)Tj
2.4264 0 Td
(the)Tj
1.4684 0 Td
(decision)Tj
3.5431 0 Td
(to)Tj
1.0262 0 Td
(stop)Tj
1.9049 0 Td
(recruitment)Tj
4.9946 0 Td
(at)Tj
0.9524 0 Td
(the)Tj
1.4683 0 Td
(end)Tj
1.7178 0 Td
(of)Tj
1.0148 0 Td
(October)Tj
3.498 0 Td
(2014)Tj
2.1259 0 Td
(in)Tj
-34.3726 -1.2983 Td
(order)Tj
2.4208 0 Td
(to)Tj
1.0261 0 Td
(ensure)Tj
2.8743 0 Td
(a)Tj
0.652 0 Td
(comparable)Tj
4.9039 0 Td
(follow-up)Tj
4.0931 0 Td
(time)Tj
2.0296 0 Td
(of)Tj
1.0148 0 Td
(approximately)Tj
5.9754 0 Td
(two)Tj
1.7121 0 Td
(years)Tj
2.2621 0 Td
(for)Tj
1.3889 0 Td
(all)Tj
1.1452 0 Td
(participants.)Tj
-31.4983 -1.2982 Td
(When)Tj
2.6816 0 Td
(recruitment)Tj
4.9946 0 Td
(was)Tj
1.7008 0 Td
(stopped,)Tj
3.5943 0 Td
(134)Tj
1.6496 0 Td
(HIV-positive)Tj
5.4709 0 Td
(and)Tj
1.7291 0 Td
(79)Tj
1.1679 0 Td
(HIV-negative)Tj
5.6919 0 Td
(individuals)Tj
4.6488 0 Td
(had)Tj
1.7064 0 Td
(been)Tj
-35.0359 -1.304 Td
(recruited.)Tj
4.0762 0 Td
(Whilst)Tj
2.8857 0 Td
(short)Tj
2.279 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4627 0 Td
(original)Tj
3.3277 0 Td
(targeted)Tj
3.4583 0 Td
(sample)Tj
3.016 0 Td
(size,)Tj
1.9106 0 Td
(these)Tj
2.2507 0 Td
(numbers)Tj
3.7757 0 Td
(were)Tj
2.1203 0 Td
(still)Tj
1.6384 0 Td
(considered)Tj
-33.2161 -1.2982 Td
(sufficient)Tj
3.9118 0 Td
(to)Tj
1.0261 0 Td
(achieve)Tj
3.1748 0 Td
(the)Tj
1.4684 0 Td
(cohort)Tj
2.8516 0 Td
(objectives.)Tj
4.3709 0 Td
(Follow-up)Tj
4.3313 0 Td
(visits)Tj
2.228 0 Td
(took)Tj
2.0296 0 Td
(place)Tj
2.2677 0 Td
(approximately)Tj
5.9754 0 Td
(two)Tj
1.7065 0 Td
(years)Tj
-35.3421 -1.2983 Td
(after)Tj
2.0353 0 Td
(the)Tj
1.4683 0 Td
(first)Tj
1.8028 0 Td
(visit)Tj
1.8709 0 Td
(and)Tj
1.7291 0 Td
(were)Tj
2.126 0 Td
(completed)Tj
4.4049 0 Td
(in)Tj
1.0375 0 Td
(June)Tj
2.0466 0 Td
(2016.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 455.4708 cm
BT
/F12 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Funding,)Tj
4.0016 0 Td
(consent)Tj
3.4346 0 Td
(and)Tj
1.7906 0 Td
(ethical)Tj
2.9953 0 Td
(approval)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 438.4629 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(This)Tj
1.9842 0 Td
(study)Tj
2.3924 0 Td
(was)Tj
1.6951 0 Td
(supported)Tj
4.2746 0 Td
(by)Tj
1.1792 0 Td
(a)Tj
0.6577 0 Td
(European)Tj
4.1159 0 Td
(Union)Tj
2.8289 0 Td
(Seventh)Tj
3.3732 0 Td
(Framework)Tj
4.8529 0 Td
(Programme)Tj
4.989 0 Td
(grant)Tj
2.3414 0 Td
(to)Tj
1.0204 0 Td
(the)Tj
-35.7049 -1.2982 Td
(Comorbidity)Tj
5.4084 0 Td
(in)Tj
1.0375 0 Td
(Relation)Tj
3.566 0 Td
(to)Tj
1.0261 0 Td
(AIDS)Tj
2.4548 0 Td
(\(COBRA\))Tj
4.1952 0 Td
(project)Tj
3.0161 0 Td
(\(FP-7-HEALTH)Tj
6.7634 0 Td
(305522,)Tj
3.2995 0 Td
(all)Tj
1.1452 0 Td
(authors\),)Tj
-31.9122 -1.3039 Td
(National)Tj
3.6906 0 Td
(Institute)Tj
3.583 0 Td
(for)Tj
1.3833 0 Td
(Health)Tj
2.9197 0 Td
(Research)Tj
3.804 0 Td
(\(NIHR\))Tj
3.3676 0 Td
(Professorship)Tj
5.6409 0 Td
(\(NIHR-RP-011-048\),)Tj
8.6796 0 Td
(NIHR)Tj
-33.0687 -1.2983 Td
(Imperial)Tj
3.6396 0 Td
(Biomedical)Tj
4.7112 0 Td
(Research)Tj
3.8097 0 Td
(Centre,)Tj
3.1748 0 Td
(the)Tj
1.4683 0 Td
(Netherlands)Tj
5.1194 0 Td
(Organisation)Tj
5.4651 0 Td
(for)Tj
1.389 0 Td
(Health)Tj
2.914 0 Td
(Research)Tj
3.8097 0 Td
(and)Tj
-35.5008 -1.2983 Td
(Development)Tj
5.6182 0 Td
(\(grant)Tj
2.6759 0 Td
(number)Tj
3.4185 0 Td
(300020007\))Tj
4.8416 0 Td
(&)Tj
0.9241 0 Td
(Stichting)Tj
3.7927 0 Td
(AIDS)Tj
2.4548 0 Td
(Fonds)Tj
2.6929 0 Td
(\(grant)Tj
2.6759 0 Td
(number)Tj
3.4185 0 Td
(2009063\),)Tj
-32.5131 -1.2982 Td
(Nuts-Ohra)Tj
4.575 0 Td
(Foundation)Tj
4.9096 0 Td
(\(grant)Tj
2.6816 0 Td
(number)Tj
3.4129 0 Td
(1003026\))Tj
4.4106 0 Td
(and)Tj
1.7292 0 Td
(unrestricted)Tj
5.0626 0 Td
(scientific)Tj
3.7871 0 Td
(grants)Tj
2.6985 0 Td
(from:)Tj
2.4322 0 Td
(Gil-)Tj
-35.6993 -1.3039 Td
(ead)Tj
1.6043 0 Td
(Sciences,)Tj
3.7928 0 Td
(ViiV)Tj
2.143 0 Td
(Healthcare,)Tj
4.7962 0 Td
(Janssen)Tj
3.2258 0 Td
(Pharmaceutica)Tj
6.1624 0 Td
(N.V.)Tj
2.0977 0 Td
(Bristol-Myers)Tj
5.7089 0 Td
(Squibb)Tj
3.0104 0 Td
(\(BMS\),)Tj
3.0727 0 Td
(and)Tj
-35.6142 -1.2983 Td
(Merck)Tj
2.8289 0 Td
(&)Tj
0.9241 0 Td
(Co)Tj
1.389 0 Td
(to)Tj
1.0261 0 Td
(the)Tj
1.4683 0 Td
(AGE)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 296.0503 345.8267 cm
BT
/F7 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(h)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 300.0188 347.4708 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(IV)Tj
1.2529 0 Td
(cohort)Tj
2.8573 0 Td
(study,)Tj
2.6135 0 Td
(as)Tj
1.0148 0 Td
(well)Tj
1.8198 0 Td
(as)Tj
1.0148 0 Td
(investigator)Tj
4.9153 0 Td
(initiated)Tj
3.5546 0 Td
(grants)Tj
2.6985 0 Td
(from)Tj
2.2054 0 Td
(BMS,)Tj
-33.9474 -1.2982 Td
(Gilead)Tj
2.8346 0 Td
(Sciences,)Tj
3.7871 0 Td
(Janssen,)Tj
3.4525 0 Td
(Merck)Tj
2.8289 0 Td
(and)Tj
1.7291 0 Td
(ViiV)Tj
2.143 0 Td
(Healthcare)Tj
4.5694 0 Td
(to)Tj
1.0262 0 Td
(the)Tj
1.4683 0 Td
(POPPY)Tj
3.2768 0 Td
(cohort)Tj
2.8573 0 Td
(study.)Tj
2.6136 0 Td
(The)Tj
1.7801 0 Td
(funders)Tj
-34.3669 -1.3039 Td
(had)Tj
1.7064 0 Td
(no)Tj
1.2756 0 Td
(role)Tj
1.7688 0 Td
(in)Tj
1.0375 0 Td
(study)Tj
2.3867 0 Td
(design,)Tj
3.0387 0 Td
(data)Tj
1.9162 0 Td
(collection)Tj
4.1102 0 Td
(and)Tj
1.7291 0 Td
(analysis,)Tj
3.5546 0 Td
(decision)Tj
3.5433 0 Td
(to)Tj
1.0262 0 Td
(publish,)Tj
3.4015 0 Td
(or)Tj
1.0942 0 Td
(preparation)Tj
4.9096 0 Td
(of)Tj
-36.4986 -1.2983 Td
(the)Tj
1.4683 0 Td
(manuscript.)Tj
-0.2721 -1.2983 Td
(This)Tj
1.9899 0 Td
(study)Tj
2.3868 0 Td
(was)Tj
1.7007 0 Td
(approved)Tj
3.9741 0 Td
(by)Tj
1.1792 0 Td
(the)Tj
1.474 0 Td
(institutional)Tj
5.0853 0 Td
(review)Tj
2.846 0 Td
(board)Tj
2.5682 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(Academic)Tj
4.2236 0 Td
(Medical)Tj
3.4356 0 Td
(Center)Tj
-34.5427 -1.3039 Td
(\(AMC\))Tj
3.1408 0 Td
(\(reference)Tj
4.2576 0 Td
(number)Tj
3.4128 0 Td
(NL)Tj
1.4966 0 Td
(30802.018.09\))Tj
5.7657 0 Td
(and)Tj
1.7291 0 Td
(a)Tj
0.6576 0 Td
(UK)Tj
1.6271 0 Td
(Research)Tj
3.8097 0 Td
(Ethics)Tj
2.6646 0 Td
(Committee)Tj
4.7395 0 Td
(\(REC\))Tj
-33.3011 -1.2982 Td
(\(reference)Tj
4.2576 0 Td
(number)Tj
3.4186 0 Td
(13/LO/0584)Tj
5.0171 0 Td
(Stanmore,)Tj
4.32 0 Td
(London\).)Tj
3.9628 0 Td
(All)Tj
1.3947 0 Td
(participants)Tj
4.9606 0 Td
(gave)Tj
1.9955 0 Td
(written)Tj
3.1125 0 Td
(informed)Tj
-32.4394 -1.2983 Td
(consent.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 230.0031 cm
BT
/F12 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Definitions)Tj
4.9606 0 Td
(of)Tj
1.0677 0 Td
(AANCC)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 212.9952 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(In)Tj
1.1055 0 Td
(addition)Tj
3.5999 0 Td
(to)Tj
1.0262 0 Td
(the)Tj
1.4683 0 Td
(consideration)Tj
5.7033 0 Td
(of)Tj
1.0148 0 Td
(changes)Tj
3.4072 0 Td
(in)Tj
1.0318 0 Td
(the)Tj
1.4683 0 Td
(distribution)Tj
4.972 0 Td
(of)Tj
1.0148 0 Td
(most)Tj
2.2053 0 Td
(markers)Tj
3.4979 0 Td
(of)Tj
1.0148 0 Td
(AANCC)Tj
-32.5301 -1.2982 Td
(\(e.g.)Tj
1.8992 0 Td
(renal,)Tj
2.4661 0 Td
(liver)Tj
1.9842 0 Td
(and)Tj
1.7291 0 Td
(lipid)Tj
2.0466 0 Td
(profiles,)Tj
3.4299 0 Td
(glucose)Tj
3.1692 0 Td
(and)Tj
1.7347 0 Td
(haemoglobin)Tj
5.4709 0 Td
(A1c,)Tj
2.0296 0 Td
(thyroid,)Tj
3.3959 0 Td
(respiratory)Tj
4.5977 0 Td
(and)Tj
1.7291 0 Td
(car-)Tj
-35.6822 -1.3039 Td
(diovascular)Tj
4.7735 0 Td
(function)Tj
3.6283 0 Td
(assessment,)Tj
4.8359 0 Td
(and)Tj
1.7291 0 Td
(bone)Tj
2.2053 0 Td
(mineral)Tj
3.3335 0 Td
(density\))Tj
3.4413 0 Td
(several)Tj
2.931 0 Td
(clinical)Tj
3.0784 0 Td
(definitions)Tj
4.5241 0 Td
(of)Tj
-34.4804 -1.2983 Td
(AANCC)Tj
3.651 0 Td
(were)Tj
2.1203 0 Td
(pre-defined.)Tj
/F14 1 Tf
5.1136 0 Td
[()-4()4()22()4()8()11()8()]TJ
3.5546 0 Td
[()6()15( )4( )12()14()7(\n)-4()]TJ
/F7 1 Tf
3.2882 0 Td
(was)Tj
1.7008 0 Td
(considered)Tj
4.5978 0 Td
(to)Tj
1.0261 0 Td
(be)Tj
1.1508 0 Td
(present)Tj
3.1635 0 Td
(where)Tj
2.6475 0 Td
(at)Tj
0.9525 0 Td
(least)Tj
1.9842 0 Td
(one)Tj
1.7008 0 Td
(of)Tj
-36.6517 -1.2983 Td
(the)Tj
1.4683 0 Td
(following)Tj
3.9798 0 Td
(was)Tj
1.7008 0 Td
(present:)Tj
3.3845 0 Td
(self-report)Tj
4.3824 0 Td
(history)Tj
3.0047 0 Td
(of)Tj
1.0148 0 Td
(diabetes)Tj
3.4639 0 Td
(mellitus,)Tj
3.634 0 Td
(use)Tj
1.5307 0 Td
(of)Tj
1.0148 0 Td
(blood)Tj
2.5171 0 Td
(glucose)Tj
3.1748 0 Td
(lower-)Tj
-34.2706 -1.2982 Td
(ing)Tj
1.5023 0 Td
(medication,)Tj
4.9606 0 Td
(fasting)Tj
2.88 0 Td
(blood)Tj
2.5171 0 Td
(glucose)Tj
/F6 1 Tf
0 Tc
3.1748 0 Td
()Tj
/F7 1 Tf
-0.004 Tc
(7)Tj
1.4627 0 Td
(mmol/L)Tj
3.4809 0 Td
(or)Tj
1.0998 0 Td
(non-fasting)Tj
4.8359 0 Td
(blood)Tj
2.5172 0 Td
(glucose)Tj
/F6 1 Tf
0 Tc
3.1691 0 Td
()Tj
/F7 1 Tf
-0.004 Tc
(11.1)Tj
2.6475 0 Td
(mmol/)Tj
-34.2479 -1.3039 Td
(L,)Tj
0.9807 0 Td
(HbA)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 229.4362 133.3417 cm
BT
/F7 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(1c)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 238.337 134.9858 cm
BT
/F6 1 Tf
1 TL
0 0 Td
()Tj
/F7 1 Tf
-0.004 Tc
(48)Tj
1.9445 0 Td
(mmol/mol.)Tj
/F14 1 Tf
4.7395 0 Td
[()41()-13(\r)4()2()-19()11()2()10()4()11()]TJ
/F7 1 Tf
5.4255 0 Td
(was)Tj
1.7008 0 Td
(defined)Tj
3.2258 0 Td
(as)Tj
1.0148 0 Td
(use)Tj
1.5307 0 Td
(of)Tj
1.0148 0 Td
(antihypertensive)Tj
6.8427 0 Td
(drugs,)Tj
2.6986 0 Td
(all)Tj
1.1452 0 Td
(avail-)Tj
-35.1153 -1.2982 Td
(able)Tj
1.8312 0 Td
(systolic)Tj
3.135 0 Td
(blood)Tj
2.5172 0 Td
(pressure)Tj
3.5773 0 Td
(measurements)Tj
/F6 1 Tf
0 Tc
6.032 0 Td
()Tj
/F7 1 Tf
-0.004 Tc
(140)Tj
2.4151 0 Td
(mmHg,)Tj
3.3166 0 Td
(and/or)Tj
2.9423 0 Td
(all)Tj
1.1452 0 Td
(available)Tj
3.668 0 Td
(diastolic)Tj
3.549 0 Td
(blood)Tj
-34.1289 -1.2983 Td
(pressure)Tj
3.5773 0 Td
(measurements)Tj
/F6 1 Tf
0 Tc
6.032 0 Td
()Tj
/F7 1 Tf
-0.004 Tc
(90)Tj
1.9389 0 Td
(mmHg.)Tj
/F14 1 Tf
3.3165 0 Td
[()-12()2()12( )12()10(\r)11()4()4()6()2()18()4()]TJ
/F7 1 Tf
5.8337 0 Td
(was)Tj
1.6951 0 Td
(defined)Tj
3.2258 0 Td
(on)Tj
1.2756 0 Td
(the)Tj
1.474 0 Td
(basis)Tj
2.1486 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(European)Tj
-33.0007 -1.3039 Td
(guidelines)Tj
4.2746 0 Td
(on)Tj
1.2755 0 Td
(cardiovascular)Tj
6.0038 0 Td
(disease)Tj
3.016 0 Td
(prevention)Tj
4.5808 0 Td
(in)Tj
1.0375 0 Td
(clinical)Tj
3.0784 0 Td
(practice)Tj
3.3788 0 Td
([)Tj
0.83 0.64 0.02 0 k
(30)Tj
0 g
(])Tj
1.8482 0 Td
(as)Tj
1.0148 0 Td
(total)Tj
2.0069 0 Td
(cholesterol)Tj
/F13 1 Tf
0 Tc
4.5524 0 Td
(>)Tj
/F7 1 Tf
-0.004 Tc
(5)Tj
-36.0677 -1.2983 Td
(mmol/L)Tj
3.481 0 Td
(or)Tj
1.094 0 Td
(low-density)Tj
4.8926 0 Td
(lipoprotein)Tj
/F13 1 Tf
0 Tc
4.6885 0 Td
(>)Tj
/F7 1 Tf
-0.004 Tc
(3)Tj
1.4683 0 Td
(mmol/L)Tj
3.4809 0 Td
(\(in)Tj
1.372 0 Td
(individuals)Tj
4.6488 0 Td
(with)Tj
2.0012 0 Td
(history)Tj
3.0047 0 Td
(of)Tj
1.0148 0 Td
(myocardial)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 107.1496 23.6976 re
W* n
q
107.0929 0 0 23.6409 36 741.3165 cm
q
/I0 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 508.8755 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(The)Tj
1.9204 0 Td
(COBRA)Tj
3.7347 0 Td
(cohort)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
81.5811 34.9228 m
237.8835 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(ONE)Tj
2.3669 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.137)Tj
3.8198 0 Td
(1/journal.po)Tj
5.1236 0 Td
(ne.01917)Tj
4.089 0 Td
(91)Tj
0 g
2.0906 0 Td
(March)Tj
2.9622 0 Td
(29,)Tj
1.5874 0 Td
(2018)Tj
34.3562 0 Td
(6)Tj
0.7654 0 Td
(/)Tj
ET
endstream
endobj
122 0 obj
<>stream
endstream
endobj
123 0 obj
<>stream
endstream
endobj
124 0 obj
<>stream
endstream
endobj
125 0 obj
<>stream
BT
66.402 0 Td
(16)Tj
ET
Q
endstream
endobj
126 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 12 0 R/Annots 128 0 R/Contents 129 0 R/TrimBox[0 0 612 792]>>
endobj
127 0 obj
<>stream
xyV}
PBRd$rɐ2h2E"
n!i!T$*!{K(BD;~ֻN`oVquG H@$ H@$ d$K,yGß_tE\p֦UVs7jSN9餓Nܰ& dn'|zgy͚5ky
[˖-۴isW2dFdNK@$ H@$ H@N eßyؙC9FGu{߱cǞ={0&g18?I{ɓ'?OlئI@iOXϖxɁ6q &;vĈM7]s5(ںuVRjժrɗ_~7pv_$ H@$ H@@[vm&Qc瞋!楗^Zx1}ÆG7 H /W_}ϛ7RVcƌڵkwem6l*U jSeݎJ@$ H@$ H@KB6_5ytB|Ͷna͖p*\>}G֭{g;. c~
f駟FԒr%JmPlYrQX4u[@ nڵ/u]Wn]*^'t*`beސ$ H@$ H@$ t"Я^>C^z.]O,4'NlѢnN;*o}c H@$ H@$ H ;mڴSdB
:uz7)caM&Ϫ}@OSNmРp7ڵ{ɵX7u H@$ H@$ H@E K˗/袋Xw%N2e$[nРAUTg߾}WXA-v$ H@$ H@$Pz7lMjا8en* l,XyyPfܸqU̓O^& H@$ H@$ c?}ݷܺ{\z/YH\}Mp_H!'8~{
4i҄[|u$ H@$ H@$ \PfsJ*հaɓ'WF-v$P P ?gΜ_5$QD#Xؽ%J*us%gz$ H@$ H@$ bNUVu_CMjrʔ(bNK@y'@fEuy=y'NނgJ@$ H@$ H@(~G*4k֬L2*UjݬYSIQK@[_=a
b!bϞ=ϟou-F$ H@$ H@$ J?_ti>}>ۯqÇ
9ӊ$/o
7p>M6%fռsݽ$ H@$ H@$ L$>˂jժUԩCٳg
8YC ;_RΫ\r͚5wywNtҞH@$ H@$ H@H+~Qe˞r)Æ
U'$~y)\T>{ԩ֭ıg H@$ H@$ H@[ 'nrʕ(Q6?ڵk}$P :mݖh1c|E~P$ H@$ H@@Pf[n_֭[r#U@V[[wr֠AV\4H@$ H@$ H@ >.]ksRuB,}Μ9d_$ov#[˷T# H@$ H@$ HXj5\e]hѢ"6@# .w}6;oOdҥK?]$ H@$ H@@tk6\}.L1 d(>.(Y$i;uxݖ$ H@$ H@$PȐ
U'wlٲK@Ŋ /dMҥ6;v\pa$ H@$ H@$wڐo%'3% Xf
vqGM>\9$ H@$ H@!hmYbE1% #_n ֆYZCm$ H@$ H@@3xP+GZLP/t#7n +XhQH@$ H@$ H@HXkӳgOM̋ݐ@!vkC%K9 H@$ H@$ H@[f5 H k
6W]u&_% H@$ H@$ DZ H P&ZΝ;/] b$ H@$ H@ MD t&!
cG}νo$ H@$ H@
֦{k IkCͲeˊè$ H@$ H@$ |H@y';+ϔ$ H@$ H@9M1
֦ ۾$ H@$ H@$PdhmT: 'Mz$ H@$ H@Ґ&
'.I(t,$ H@$ H@@(^6>$ H@$ H@H@kGP& 䏀&ܼJ$ H@$ H@(6p&֤$ H@$ H@$ &HZ#{( H@$ H@$ MLݐ@Q%)3$ H@$ H@$ -N@kőڠ$$Ip_$ H@$ H@@.6Gl>C[$ H@$ H@ M1h)"),W$ H@$ H@8Z2;,"ɬ$ H@$ H@@!"|o-@@kSf1J@$ H@$ H@[f` H 'Zx\$ H@$ H@@
M
J@[f5 H@$ H@$ HuhHZt H@$ H@$ dMFL@ds H@$ H@$ H`+leNō֦㕀$ H@$ H@M@kot^( 䅀&/