-
AIDSAIDSH e l l e n i c A r c h i v e s
22, Supplement 1, 2014 Volume 22, Supplement 1, November
2014
AIDS
EDITION OF THE HELLENIC ASSOCIATION FOR THE STUDY AND CONTROL OF
AIDS
http: //www.aids.org.gre-mail: [email protected]
1105-8900
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Turnhoutseweg 30, B-2340 Beerse, B. () : EU/1/06/380/002. : 20
2014. - http://www.ema.europa.eu. : , . .
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PREZISTA 600 mg F.C.TAB, BT x 60 TABS 478,32
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ADV_SPECIALTY_21X28_11-14_Layout 1 11/17/14 5:56 PM Page 1
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AIDS
AIDS
: AIDS 6, 11527 . Fax: 210-6983945 e-mail: [email protected]
Website: www.aids.org.gr
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ISSN 1105-8900
: . .
: AIDS . .. 14085 11521
e-mail : [email protected]
:
P.O BOX 14085 GR-11521 Athens
: 15.00 ..... 6.00 50.00 110.00
: Focus on Health .: 210-7223046 Fax: 210-7223220
AIDS 1/543/99, 2 . 122 18/02/1999
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viii
HELLENIC ARCHIVES of AIDSQUARTERLY SCIENTIFIC EDITION OF THE
HELLENIC ASSOCIATION
FOR THE STUDY AND CONTROL OF AIDS
Edited by the: Hellenic Association For the Study and Control of
AIDS 6, Erythrou Stavrou Str., 115 27 Athens Tel. & Fax: (+30)
210-6983945 e-mail: [email protected] Website: www.aids.org.gr
ADVISORY BOARD
President: M. K. Lazanas
Vice-President: C. Gogos
Secretary: G. Chrysos
Special Secretary: V. Papastamopoulos
Treasurer: K. Thomatou
Members: P. Gargalianos-Kakolyris, P. Kollaras, A. Papadopoulos,
V. Paparizos
EDITORIAL BOARD
Chairman: M. K. Lazanas
Editor in Chief: M. Chini
Asst. Editor in Chief: Ch. Loupa, G. Tsekes
Members: D. Agrafiotis, E. Choremi-Papadopoulou, G. Chrysos, G.
Xylomenos, N. Magkafas, M. Maragkos, Z. Matsou, S. Metallidis, A.
Papadopoulos, V. Paparizos, V. Papastamopoulos, D. Paraskevis, A.
Psarra, N. Sipsas, . Tsalimalma, E. Vogiatzakis
ISSN 1105-8900
Scientific Correspondence: HELLENIC ARCHIVES of AIDS M. Chini,
P.O Box 14085 11521 Athens Greece
e-mail Magazine: [email protected]
Subscriptions: P.O. BOX 14085 GR 11521 Athens
Annual Subscriptions: Doctors 15,00 Members of H.A.S.C.A 6,00
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Published By: Focus on Health Tel.: (+30) 210-7223046 Fax:
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AIDS 1408511521
*
: 15.00 ....AIDS 6.00 , 50.00 110.00
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9. .10. .
: , - , , -, , , -, , , , , , . .
: : , ( ), . - .
- 150 . , .
3-10 ( ) , - -. (Index Medicus).
- , .
- - . -, . , -
(1975). - , .
- . - , .
.
, - .. , (. . - 1, 2, 1 ..).
- . - .
, . - - ( Vancouver, 4 , 1991).
- - ( 2) - ., - 2, . - , .. , , . .
Index Medicus - .
. , -, , , - .
6 , - . 6 6 et al.
-
xii
.. Watkins J.A., Carman P.S., Melling W.S.: In vitro inhibition
of CL. difficile. Amer. J. Clin. Path. 1985, 3: 125-131.
- ( - ) Anonymous.
.. Anonymous. Carcinoid tumors and syn-drome (Editorial). JAMA
1986, 83-85.
, (supple-ments) , , - . .. AIDS, 28 (suppl. 2): 35.
- . - - , , , , , -, . - :
., .: . : . 1 . As-cent, 1992, 132-137.
- , : Carman J.A. : Bacillus antracis. In (), Collins C.H. ed (
.) Medical Microbiology. London, Aca-demic Press 1985, 71-78.
: , - . -
350-500 , 200-300 . , , . - - .
-. - . .
(, ..) -. , - .
() ( ).
-, . . .
: - .
: , - .
-
xiii
: Focus on Health 16, 11521 , .: 210 7223046, Fax: 210
7223220
E-mail: [email protected], [email protected], Website:
www.aids2012.gr.
-
xiv
AIDS
: .. : . . : . . : . : . : . - . . .
26 AIDS
: . : . : . . . . . . . . . . .
26 AIDS
: . : . : . . . . . . . . . . . . .
-
xv
M .....
, ,
.. ..... 26 AIDS 28 30 2014.
. , .
, HIV , , .
, , , , , , .
HIV , , , , .
.
.. .....
.
-
xvi
26 aIDs
28 2014
9:00-10:30 : . , .
01 CD4 . , . , . , .. , . -, . , . , . , . , . , . , . , .
02 HIV-1 : . , . , . , . -, . , .. , . , . , . , . , . , . , . ,
.
03 . , . , . , . , . , . , .
04 (linkage) (retention to care) () HIV : . , . , . , . , . , .
, . , . , . , .
05HIV : 20 . M, . , . , . , . , . -
06 (PAF) HIV : . , .. , . , . , . , . -, .. , . , ..
07 HIV . , . , . , . , . , .-. , .
08 / HIV+ . , . , . , . , . , . , . , .
09 atazanavir/ritonavir HIV . , . , . , . , . , . , . , . -,
..
-
xvii
26 aIDs
10:30-12:30 ( )- HIV HIV/AIDS
: . , . HIV/AIDS
... : . , .. , . , . : .
HIV/AIDS. HIV/AIDS . HIV/AIDS . HIV/AIDS &
... : . , . , .. , . , . , . , . : .
: . 12:30-13:00 13:00-13:30 : HIV :
: . : .
13:30-15:30 ( ): . , . , . : . , .
- . HIV . HIV . ..
15:30-16:00 : HIV: ;: . : .
16:00-16:30 16:30-18:00 : HIV
: . , . : . . HIV . : .
18:00-19:30 : 2014: : . -, .
NNRTIs . . .
19:30 AbbVie: . Cocktail
( )11:30-13:30
: . , . 14:00-16:00
: . , .
-
xviii
26 aIDs
29 2014
9:00-10:00 : . , .
10 -. , . , . , . , . , . , . , .
11 HIV CD4+ - . , . , . , . , . , . , . , . , . , . , .
12 HIV(+) . , . , . , . , . , . , . , . , . , . , .
13 HIV . . , . , . , . , . , .
14 Eviplera HIV+ 103. , . , . , . , . , . , . , . , . , . , . ,
.
15 Eviplera HIV . , . , . , . , . , . , . , . , . , . , . , . ,
.
10:00-11:30 : : . , .
, , .
.
. .
11:30-12:00 : HPV HIV 2014 : . : .
12:00-12:30
-
xix
26 aIDs
12:30-14:00 : HIV : . , .
. Kaposi . .
14:00-16:30 -
16:30-18:30 : C HIV : : . , .
. C . C . HIV/HCV .
18:30-19:00 : . : .
19:00-19:30 : HIV : . : .
( )
10:00-12:00 : . , . , .
HIV . , HAART . HIV : , .
-
xx
26 aIDs
30 2014
9:30-11:00 : . -, .
& . . : ; . HIV AIDS . -
11:00-11:30
11:30-12:00 : : ;: . : .
12:00-14:00 ...: ... , , : . , .
HIV, , : ..
() .
- HIV/AIDS .
14:00-14:30
14:30-16:30 : HIV : 2014: . , .
HIV . . . .
16:30-17:00
17:00-18:30 : : . , . : . : . , . , . , .
18:30-19:30 AIDS: . , ..
. .
-
xxi
1 hIV
3 2014:
4
24 hIV
25 c hIV :
26 ...: ... , ,
27 hIV : 2014
29
33
35
39
51
71
-
1
hIV
: .
HIV ( ). 5 32 (CCR5-32). , . 5 (ART) HIV , , , HIV HIV DNA , -
ART.
, HIV(+), ART 30 . 18 , , ART 23 . HIV-1 RNA , HIV-1 , CD4+ .
DNA CD4+ , HIV-1 CD4+ . HIV HIV-1. 36 HIV ART . [International
Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Group]
71 .
, , 27 ART, - HIV-1 RNA , HIV-1 CD4+ . , 27 , , ART .
HIV, ART, . ART, elite controllers. , - , .
HIV , - . HIV , ART .
ART , . ART.
, , ....
-
HELLENIC ARCHIVES of AIDS, 2014; 22(Suppl 1):1-70
2
. , , CCR5-32 . , Hodkgin ART 12 32 . - CCR5, anti-sense RNA ,
1.
:
1. .
2. , HIV .
3. .
, , , .
, HIV , .
.
HIV . , 13-32% 25-48% , . PACTG 076, 1993. - 1-2%. , HIV HIV+
.
1 (uman Immunodeficiency Virus, HIV-1) , - , CD4 T-, , , - .
UNAIDS, 2013 35 HIV 16,0 3,2
-
AIDS, 2014; 22(Suppl 1):1-70
3
, , V , .., . , - HIV .
: .
HIV - zidovudine. , , NNRTIs PIs .
AIDS 86 HIV(+) zidovudine 200 .
ART . - . . , , , , . .
- .
2014:
. .
. . -, , . -, - . Atazanavir Darunavir, Lopinavir - Atazanavir.
, , CYP3A4 P450 - ( - ). , Atazanavir , . , - NNRTIs.
, , ,
-, ,
-
HELLENIC ARCHIVES of AIDS, 2014; 22(Suppl 1):1-70
4
Cobicistat P450 .
, , .
- (International Organiza-tion for Standardization) ISO, . ,
1946 : - - -. - (...).
-. , -, , - -, -.1
, - , , . , , .2
, - , , :
(Licensing): .
(certification): - .
(accreditation): - .
, , .. - , / . .
, . .. ( ) ... ... ( )
MSc, PhD, EurClinChem, - , ... ,
-
AIDS, 2014; 22(Suppl 1):1-70
5
(....). .. , , EA (European co-operation for Accreditation) ILAC
(International Laboratory Accreditation Cooperation). .
ISO 15189, 2003 TC 212 2007 2012.3,4 - ISO 9001:2000 2009 - -
.
ISO 15189 , :
: , -
(marketing)
:
: .
ISO 15189 - (Total Qual-ity Management, TQM) 1950 W.E. Deming
J.M. Juran 5Q:
1. (Quality planning, QP), 2. (Quality laboratory process, QLP),
3. (Quality control, QC),4. (Quality assessment, QA) 5. (Quality
improvement, QI).
, PDCA Deming (Plan, Do, Check, Act) .2,5,6 - , - , -, , , . ISO
15189:2012 -:1,4
- , (non conformities)
-
HELLENIC ARCHIVES of AIDS, 2014; 22(Suppl 1):1-70
6
(internal audits) (quality indicators) (management review).
, , ISO15189 :7-9
. : . ( - ). . HIV pre-PCR post-PCR - (.. , vortex) - . . , , ,
vortex, .
. (scope of accreditation) (.. , ) (application
characteristics): , , (.. Screening test), -, , , -, (QC controls),
- ..8-10
HIV ( - ), Western blot , , (CD4+ ..).
- (SOPs, Standard Operating Procedures) - . (GLP, Good
Laboratory Practice) - (internal audits).
- , () () - (specimen timing), , , , - , ..11 [11]. RNA, -80C
(.. RNAlater).12,13 , (.. ) DNA/RNA ( PCR).
- : (.. Laboratory Information System), - , DNA/RNA - ,
(report).14 - (Laboratory Information System, LIS)
-
AIDS, 2014; 22(Suppl 1):1-70
7
( , , , ).
. (in house) (kit, CE-IVD) :
1) (analytical characteristics):i. (methodology characteristics)
:
(analytical sensitivity and specificity)ii. (performance
characteristics) :
(precision), (trueness, bias), (accuracy), - (limit of detection
and quantification), (linearity) - (range), (recovery),
(interference), (uncer-tainty), (robustness) (ruggedness) ,
(reference values).15-17
2) : - (clinical validation) ( , ). , (clinical utility),
.18
(traceability) (CRM, certified reference materials).19
, - .20-22
(verification) (.. FDA IVD/CE ), , , , .
in-house - (.. RUO), (optimiza-tion) (documentation) :
1. (analytical validation) , ,
2. (fit for purpose),
3. (reference method) 4. ,
, .
(method comparison) , ( 40), . , - . .8 , 40 (, , ) -
(concordance) , (McNemars test).
-
HELLENIC ARCHIVES of AIDS, 2014; 22(Suppl 1):1-70
8
(assay modification): , .
. (internal QC controls). JRC-IRMM, WHO, CDC, ATCC/Coriell,
NIBSC, NGRL, LGC, Ac-rometrix, Advanced Biotechnologies, MMQCI .. -
Westgard Levey-Jennings.6
. (EQA, external quality assessment PT, proficiency testing). ,
HV, HIV , CD4+ .. UK-NEQAS, EMQN, CAP, QCMD, UNIQ, INSTAND, EHEQAS
.. ISO 17043. SDI (Standard Deviation Index) : 3 .
(non conformity) , , .
1. . . 1 , - -
. - , 2006:7-11.2. . . 2007;24:58-78.3. Huisman W. European
medical laboratory accreditation. Present situation and steps to
harmonisation. Clin Chem Lab Med
2012;50:1147-52.4. International Standards Organisation. ISO
15189: Medical Laboratories-particular requirements for quality and
competence. 2012.5. . . 1 ,
. - , 2003:99-111.6. Westgard JO, Klee GG. Quallity Management.
In: Burtis CA, Ashwood ER, Bruns DE, editors. Tietz textbook of
Clinical
Chemisty and Molecular Diagnostics.: Elsevier, 2005:485-529.7. -
, , , , . -
. 1 , - . - - , 2006:53-6.
8. . ISO 15189: . 5o - , , 2008:19-30.
9. . ISO 15189. 8o , - , 2009:17-24.
10. . . 1 , - . - , 2003:52-85.
11. Davis BH, Dasgupta A, Kussick S, Han JY, Estrellado A.
Validation of cell-based fluorescence assays: practice guidelines
from the ICSH and ICCS-Part II-Preanalytical issues. Cytometry B
Clin Cytom 2013;84:286-90.
12. Neumaier M, Braun A, Wagener C. Fundamentals of quality
assessment of molecular amplification methods in clinical
diagnostics. International Federation of Clinical Chemistry
Scientific Division Committee on Molecular Biology Techniques. Clin
Chem 1998;44:12-26.
13. . ( ). 18 , . - , 2005:127-41.
14. Barnett D, Louzao R, Gambell P, De J, Oldaker T, Hanson CA.
Validation of cell-based fluorescence assays: practice guidelines
from the ICSH and ICCS-Part IV-Postanalytical considerations.
Cytometry B Clin Cytom 2013;84:309-14.
-
AIDS, 2014; 22(Suppl 1):1-70
9
15. . . , 2008.16. National Pathology Accreditation Advisory
Council. Requirements for the validation of in-house in vitro
diagnostic devices
(IVDs). Australia 2003.17. Tanqri S, Vall H, Kaplan D, Hoffman
B, Purvis N, Porwit A, et al. Validation of cell-based fluorescence
assays: practice guidelines
from the ICSH and ICCS-Part III-Analytical Issues. Cytometry B
Clin Cytom 2013;84:291-308.18. OECD. Guidelines for quality
assurance in molecular genetic testing. 2007.19. Panteghini M.
Traceability as a unique tool to improve standardization in
laboratory medicine. Clin Biochem 2009;42:236-40.20. Kessler HH,
Raggam RB. Quality assurance and quality control in the routine
molecular diagnostic laboratory for infectious
diseases. Clin Chem Lab Med 2012;50:1153-9.21. Wood B,
Jevremovic D, Bene MC, Yan M, Jacobs P, Litwin V. Validation of
cell-based fluorescence assays: practice guidelines
from the ICSH and ICSS-Part V-Assay Performance Criteria.
Cytometry B Clin Cytom 2013;84:315-23.22. Sack U, Barnett D,
Demirel GY, Fossat C, Fricke S, Kafassi N, et al. Accreditation of
flow cytometry in Europe. Cytometry B Clin
Cytom 2013;84:135-42.
hIV.
1.
1,2 , 20% . 50.000 , 30%-50% - .1
HIV , . - HIV, , , , .
HIV, .
2. HIV-1
p9 gag
p7 gag
p24 core antigen
integrace
host cell proteins
reverse transcriptase
gp41gp120
lipid layer
p17 matrix antigen
HIV-RNA
1. IV-1 () :
http://biology.kenyon.edu/slonc/gene-web/Lentiviral/Lentivi2.html2
() : http://hivbook.com/tag/viral-genome/.3
HIV-1 (Majority), (-, -) (Outlier).4,5 . , . ,
, MSc. PhD, N.Y. , ..
-
HELLENIC ARCHIVES of AIDS, 2014; 22(Suppl 1):1-70
10
. 9 , - , . , . , D, C, .
3. HIV-2
2 (HIV-2), HIV-1 , , , .
HIV-1, . , HIV-2, - HIV-1, .., , .6
HIV-1Polymerase
Gene Products(p66/51; p31)
PolymeraseGene Products
ReverseTrascriptase
LipidMembrane
GagProteins
GagProteins
EnvelopeProteins
EnvelopeProteins
p17
p16
p24
p26
gp41
gp36
p66gp120
gp105
p34
RNA
HIV-2
2. HIV-1 HIV-2.
4. HIV-
o HIV-RNA , 10 , (peak) 30 40 , (plateau). p-24 HIV 14 , peak 30
45 .
HIV . - , . - .
, , p24 gp41 gp120 .
. IgM IgG. IgM -
22 , peak 35 38 , IgG .7,8
-
AIDS, 2014; 22(Suppl 1):1-70
11
5. HIV-
(eclipse), HIV- - .
(seroconversion) HIV- . - .
(acute) HIV- HIV RNA . , - -.
(established) HIV- - IgG , Western-blot.
HIV RNA (plasma)
HIV-1 p24 Antigen
HIV Antibody
0
HIV Infection
Days
Established HIV InfectionAcute HIV Infection
Seroconversion window
Viral Detection Nucleic acid
text
Antibody Detection 3rd generation Immuneassay
Antibody Detection 2nd generation Immuneassay
Antibody Detection 1st generation Immuneassay
Viral Detection 4th generation Immuneassay
EclipsePeriod
10 20 30 40 50 60 70 80 180 360 540 720
3. HIV- . Laboratory Testing for the Diagnosis of HIV Infection:
Up-dated Recommendations http://stacks.cdc.gov/view/cdc/23447.7
6. H HIV
1985 test HIV. - , , . test, . 1985 HIV, .
ELISA ELISA . o -
(1985) HIV I , , , - .
-
HELLENIC ARCHIVES of AIDS, 2014; 22(Suppl 1):1-70
12
-, (HRP), -, . IgG-, HIV I, 30-40 .
(1987), , -
(cor, env) HIV I group O, HIV I. IgG-.
(1990)
(cor, env) HIV I HIV I. .
IgG Ig 22 , , , , ( ) .
, (2010) : 24 HIV I
IgG Ig HIV I ( ) HIV I. -
, . , HIV. . , HIV-1 HIV-2 - , - .
P24 , - P24.7,9,10
7.
ELISA, , , , .. HRP, .. 4-MUP MU, (), , (CHLIA) ..
H ELISA . -
, . ,
, - HIV ( ).
() ,
1 sec. ,
.
-
AIDS, 2014; 22(Suppl 1):1-70
13
(background) /. .
8.
99,5% 100%.10
9. ELISA
, - Micro Enzyme Immuno Assay (), , - , .
, , , , -, .
10. HIV (CDC & APHL1989)
CDC (Center for Disease Control and Prevention) APHL
(Association of Public Heath Laboratories), - :
a. WB (Western Blot) b. IFA (Indirect Immunofluorescence
Assay).
, , :
c. ,d. HIV-Ag e. HIV-RNA.
11. HIV (CDC & APHL 2014)
2004, CDC APHL . , :
(3 4 ) .
, WB IFA - .
.
. HIV-2 WB HIV-1 .
-
HELLENIC ARCHIVES of AIDS, 2014; 22(Suppl 1):1-70
14
4. HIV . (Test) HIV 1 HIV 2, BioRad Multi-spot HIV1/HIV2
differentiation immunoassay.7
12. ELISA HIV
ELISA HIV ELISA, , , Western Blot HIV-RNA.
cut-off , .
ELISA : , , , -
, , , , , , , , , .13,14
13. HIV (Rapid test)
HIV - ( ), . tests EIA, HIV, , - HIV EIA.
FDA 2002. . , -, , .. - -HIV IgG IgM , , . o - 30.
2012 self test (OraQuick In-Home HIV Test) , - . 2013 -HIV 1/2
24 (Alere HIV 1/2 Ag/Ab Combo test) .15,16,17,18
14.
HIV 1985, ELISA 1 , HIV I. , HIV 4 ,
-
AIDS, 2014; 22(Suppl 1):1-70
15
HIV HIV I, .
, , -, , - , .
(NAT, Nucleic Acid Techniques), , - .
, - 2008, 9 2014 4 .
PCR Roche TMA Chiron . DNA RNA C HIV.19
15. HIV
, - , .
HIV ISO 15189 2012.20,21 - .. . .. , - , ISO 9001 2008. , - -
.
2002/98 , , , -, . , -, .
, - . , , :
..
2002/98 .. 138/2005, 3402/17-10-2005.22,23
, - . R(95)15 , , , . , ISO-9000.
:
. . .
-
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., . ., , , ., .
, ( 9, 2, 17 2013) : - .
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Methods http://cid.oxfordjournals.org/content/early/2013/06/13/
cid.cit281.full2.
http://biology.kenyon.edu/slonc/gene-web/Lentiviral/Lentivi2.html
3. http://hivbook.com/tag/viral-genome 4. Leitner T. Genetic
subtypes of HIV-1 in Myers G. Korber BT, Foley BT et al Hyman
Retroviruses and AIDS (Available on line at
http://hiv-web.lanl.gov).5. Robertson DL, Anderson JP, Bradac
JA, et al. HIV-1 nomenclature proposal: a reference guide to HIV-1
classification. In: Kuiken
CL, Foley B, Hahn B, et al, eds. Human Retroviruses and AIDS
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(Available on line at http://hiv-web.lanl.gov)
6. Clavel F. HIV-2, the West African AIDS virus. AIDS
1987;1:135-140.7. Laboratory Testing for the Diagnosis of HIV
Infection: Updated Recommendations
http://stacks.cdc.gov/view/cdc/23447.8. Immunoassays for the
Diagnosis of HIV: Meeting Future Needs by Enhancing the Quality of
Testing. Roderick J Chappel, Kim
M Wilson, Elizabeth M Dax Future. Microbiol.
2009;4(8):963-982.9. Abbott Diagnostics, .
HIV 1986-2005.10. Abbott Diagnostics, HIV Ag/Ab Combo,
ARCHITECT, Assay insert Instructions 2013.
www.abbottdiagnostics.com11. Enhanced immunoassay sensitivity using
chemiluminescer acridinium esters with increased light output Anand
Natrajan et
al. Analytical Biochemistry 406 (2010); 204-213.12.
Chemiluminescence www.invitron.com13. HIV & AIDS Factors Known
to Cause False-Positive HIV Antibody By Cristine Johnson
http://www.virusmyth.com/aids/hiv/
cjtestfp.htm14. False-Positive Rate of a Fourth-Generation HIV
Antigen/Antibody Combination Assay in an Area of Low HIV
Prevalence.
Sinyoung Kim et al. Clin Vaccine Immunol October 2010 vol. 17
no. 10 1642-1644.15. HIV ... 2013.16. HIV
Testing/hivbook.com/2011/10/29.17. FDA Approves First Rapid
Diagnostic Test to Detect Both HIV-1 Antigen and HIV-1/2 Antibodies
http://www.idsociety.org/FD
AApprovesFirstRapidDiagnosticTest.aspx18. First Rapid Home-Use
HIV Kit Approved for Self-Testing.19.
http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm310545.htm20. .
, O , 9 -
- , 2009.21. Quality control in Infectious Disease Serology NRL
QC.22. Implementing SO 15189 in Kisumu, Kenya. Am J Clin Pathol
2010;134:410-418.23. 138/2005, . 3402/17-10-2005: .24. , : (14
2008,16
2010 17 2013).
-
AIDS, 2014; 22(Suppl 1):1-70
17
hIV .
HIV - HIV : - , - HIV Western Blot, HIV .
, -, , .
Western Blot AIDS .
, - . , , - .
, . - HIV . HIV HIV , EIA - ( , - HIV ) Western Blot. , - .
, HIV - . HIV . CDC 38,3% AIDS 1-3 HIV .
, - 26% 53%. HIV .
HIV , HIV - , .
, anti-HIV , - .
.
HIV - - .
, HIV - - (EIA 4 ), - .
, , AIDS , ....
-
HELLENIC ARCHIVES of AIDS, 2014; 22(Suppl 1):1-70
18
HIV , Western Blot , HIV , HIV-1 RNA ().
HIV - , - (HIV RNA).
AIDS .... 28- HIV . ( anti-HIV - Western Blot) HIV RNA p24 Ag
HIV.
3.073 anti-HIV , .
94,83% HIV (1.743 1.838 ) - HIV RNA HIV . , HIV 93 , - HIV .
, AIDS , CDC HIV .
CDC - Western Blot HIV . - - - (EIA 4 ). - HIV . HIV1 HIV2. ,
HIV1 RNA HIV2 RNA.
-.
, (HIV RNA) HIV .
. cD4 .
CD4 (CD4) (HIV). CD4 , HIV -.1 HIV, CD4 - ( ) . , -
-, ...
-
AIDS, 2014; 22(Suppl 1):1-70
19
CD4 .1 CD4
-
HELLENIC ARCHIVES of AIDS, 2014; 22(Suppl 1):1-70
20
. , .
. , , , . , - .
, . 1 - CD4.
1. CD4, .
/ /
EPICS XL, FC 500 (Beckmann Coulter)
FACSCalibur, Canto (BD)
PanLeukogating CD4
Tritest Multitest
30-300
30-300
EDTA 5
EDTA 48
FACSCount(BD)
Guava PCA (Millipore)
CyFlow SL and Counter (Partec)
FACSCount reagent CD4 reagent
Easy CD4, Easy CD4% Auto CD4
Partec Easy Count CD4 CD4%
-
AIDS, 2014; 22(Suppl 1):1-70
21
.
CD4 EDTA. ! - , . -, 48 , .
, , - 30C.5 , .
o -
. , , , , .
. . .
. , . CD4 , . , . 2 .
- Levey-Jennings . - 2SD ( 1). Levey-Jennings - ( Westgard).
2. .
*/
(C)
Beckmann Coulter
BD
BD
Immuno-Trol/low normal
Multi-Check/low normal
True count Control/ low, medium, high
FACSCalibur
6-9 (90 )
1
1
2-8
2-8
2-8
-
HELLENIC ARCHIVES of AIDS, 2014; 22(Suppl 1):1-70
22
*/
(C)
Streck, Omaha
Streck
Streck
Synexa, Bellvile, South Africa
CD4 count/low, normal
CD4 Chex Plus/low, normal
CD4 Chex Plus BC/low, normal
LymphoSure/normal
Beckman Coulter
3
3
3
1
2-10
2-10
2-10
2-8
* .
Westgard . :12s 2S 3S13s 3S22s 2S 3SR4s 4S41s 1S10
, - . -. .
1. Levey-Jennings CD4.
CD4
/
l
3 SD 2 SD 1 SD
225
200
175
150
125
100
04/1
2/13
10/1
2/13
11/1
2/13
17/1
2/13
18/1
2/13
19/1
2/13
23/1
2/13
24/1
2/13
27/1
2/13
29/1
2/13
30/1
2/13
-
( ). . , 48 (, /) .
-
AIDS, 2014; 22(Suppl 1):1-70
23
CD4 CD4 (SOPs)
, . (SOPs) .
(, ). - . - - . .
. - CD4 . - .
. , () , - . .
.
.
. : , . CD4 ().
- CD4 .6 .
.
1. World Health Organization Consolidated guidelines on the use
of antiretroviral drugs for treating and preventing HIV infec-tion
Recommendations for a public health approach. 30 June 2013 ISBN:
978 92 4 150572 7.
2. Centers for Disease Control and Prevention. Guidelines for
performing single-platform absolute CD4+ T-cell determinations with
CD45 gating for persons infected with human immunodeficiency virus.
MMWR Recomm Rep. 2003;52(RR-2):1-13.
3. Stevens W, Gelman R, Glencross DK, et al. Evaluating new CD4
enumeration technologies for resource-constrainedcountries. Nat Rev
Microbiol. 2008;6(suppl):S29-S38.
4. Glencross DK, Janossy G, Coetzee LM, et al. Large-scale
affordable PanLeucogated CD4 testing with proactive internal and
external quality assessment: in support of the South African
National Comprehensive Care, Treatment and Management Programme for
HIV and AIDS. Cytometry B Clin Cytom. 2008;74B(suppl 1):S40-S51
5. Ruiz AR, Perez Fernandez I, Perea Baena JM, et al. Influence
of sample storage time and temperature on lymphocyte subset counts
using a FACSCount system [letter]. Haematologica.
2000;85:550-551.
6. Peter TF, Shimada Y, Freeman RR, et al. The need for
standardization in laboratory networks. Am J Clin Pathol.
2009;131:867-874.
-
HELLENIC ARCHIVES of AIDS, 2014; 22(Suppl 1):1-70
24
hIV
Kaposi.
Kaposi 1872, - 80 AIDS. -8 (HHV-8) 1994, .
Kaposi 4 : , , AIDS - . AIDS - HIV . , HIV .
, HHV-8, , tat HIV. - , - spindle-cells,
Kaposi , , / . - AIDS , - . HIV .
Kaposi AIDS (R). (PIs), - (NNRTIs). HAART HIV . Kaposi -. AIDS
aposi, - . .
HIV - .
.
HIV AIDS (AIDS defining malignancies-ADM, Kaposi, non-Hodgkin -
) (non-AIDS defining malignancies-NADM).
, ADM NADM HAART . DAD, - , 58% NADM.
, ...,
-, ...., , ... .
-
AIDS, 2014; 22(Suppl 1):1-70
25
, , , - HIV 9 , . HAART CD4 . HIV HPV - . , - . - , HPV HIV
.
NADM, HIV 12 - . HIV - , , Hodgkin, . HIV ADM.
, - , , , - CD4 . NADM , HPV, EBV, HBV HCV.
, , HPV, 16 18, . - - . . screening MSM , HPV, .
EACS - HIV , . , , HAART , - . , - , , .
NADM, - HAART -, . - , .
c hIV :
c.
C 2014 - - - telaprevir boceprevir ( ). sofosbuvir ( ),
simeprevir ( )
-
-
HELLENIC ARCHIVES of AIDS, 2014; 22(Suppl 1):1-70
26
daclatasvir ( ) 2013 - 2014, 2014 (EASL, 2014) (AASLD, - 2014)
(WHO, 2014). , .... ( - 2013).
: 1. C , - (Metavir score F3-4), - HCV, HBV. 2. - sofosbuvir. 3.
12 1 . 4. - 24 48 . 5. C per os, , - ( , , ).
...:
... , ,
hIV. , : ...
. , - . - .
HIV, , , .
, : ) , ) , ) , - .
, , , , , , , -, .
, , - HIV, , , , , - .
, , .
-
-
AIDS, 2014; 22(Suppl 1):1-70
27
, , .
HIV - . -. .
- , : - , - HIV, , , , .
- hIV/aIDs - PraKsIs.
PRAKSIS , , , , . , PRAKSIS 2014, - - PRAKSIS - , HIV.
hIV : 2014
.
2011-2013, HIV - (). HIV - -. - HIV 2014. , , HIV XEN , - .
PRAKSIS
,
-
29
hIV : .
HIV . . . , - - .
microbicides (-) , HIV , - .
, - . , , .. . , , -9, HIV .
-. , , 2010, - Tenofovir gel 39% (CAPRISA 004). o , (VOICE
study). Tenofovir gel (FACTS 001). - Dapivirine ( ) -. 4.500 2015.
, (Raltegravir, Dapivirine/Darunavir, Tenofovir/Efavirenz,
Darunavir/Maraviroc, UC871 ..). , 70 - .
HIV , . , , .
: -, , , - , , . , . . HIV.
hPV hIV.
HPV (Human papilloma virus, ), DNA - . 120 , 40 . ( 6 11) - , (
16 18) - .
-, ..., & .
, , , ....
-
HELLENIC ARCHIVES of AIDS, 2014; 22(Suppl 1):1-70
30
HPV 80% .
HPV HIV .
HPV HIV, , HIV - HPV, .
HAART PV . HAART - HPV , . , ART .
HPV (HPV 6, 11, 16 18) (HPV 16 18) . - HPV . - . . . HIV+ HIV-,
.
, - HIV+ - . , / .
: ;.
- HIV . , , , . , . HIV /AIDS, - , libido, , - , . HAART, - . ,
, HIV .
, , . ( , , ..), , / -
MD, PhD, - , , & (....), , , ...
-
AIDS, 2014; 22(Suppl 1):1-70
31
( , , , ). HDL-. . / .
, , , . D - HIV , . , , OH-25- D.
In vitro HIV . HIV /AIDS, , . , - . - . - HIV -, .
- , , . .
- , . . , - , , - (St Johns wort), .
, - , . - .
-
33
.
HIV . : , -. - [MSM ( ), - (), ]. MSM - , .
- (--, -), - , , , . , , ( ), . - , , , . , (0,1%, , , - . , ,
MSM/ . , , , AIDS. - .
,
-
HELLENIC ARCHIVES of AIDS, 2014; 22(Suppl 1):1-70
34
hIV .
HIV , . , , - . , - , - (.. ). - - .
, , CDC (late presenters) ( , - , , - HIV HAART-indicator
diseases).
, - ( HIV ), -, , .
hIV ..
HIV HIV, .
, 1984 - 344 . , 124 - .
, - . , ! - . -, - .
HIV. 6 . 1 - , . 2 , . 3 , , - . .
,
-
AIDS, 2014; 22(Suppl 1):1-70
35
, ) , ) , ) , . , - . , , . 4 - - ( 3). 5 4 -, . , HIV , , test
. , - 6 6 .
, - HIV , , .
.
, HIV , . 2012 35,3 - HIV, 3,3 2002 2,3 2012. AIDS , 2,3 2005
1,6 2012. , 5, - 34% WHO 2013.
, ...., 31/12/2013 13.622 (82,2% ) HIV ( AIDS). HIV . 2013 8,3
HIV 100.000 , 2010 5,5 100.000 . - HIV 2011 2012 (8,7 10,7 100.000
, ), (). 2013 2014 , - HIV . - HIV , , - , , .
HIV , HIV .
, ..., & , ... - ...
-
HELLENIC ARCHIVES of AIDS, 2014; 22(Suppl 1):1-70
36
HIV (post-exposure prophylaxis, PEP) 80% -, (pre-exposure
prophylaxis, PrEP) 44-92% HIV . - gel . - , HIV .
- .
- , - , , .
- .
DNA , , , , - .
:
1. 2. 3. 4. , pH 5. 6. 7. ,8. .
, , , - , .
, - , , , , - .
, , , .
, , .
, , , , -, , - , .
- - - , -. , , 60%. - , .
-
AIDS, 2014; 22(Suppl 1):1-70
37
72% .
, - , , , - . , , , - , , - .
, , - , 6-10 , , , , , - .
, , - , - (VOCs/Volatile Organic Compounds). . - , - , OPA, - -
.
. - , , , . -, , , . , - .
, -. , , , -, .
Gram+ , . , , . Gram-. -, .
, , -, . - . , . , , , .
- , , ,
-
HELLENIC ARCHIVES of AIDS, 2014; 22(Suppl 1):1-70
38
. - , , , .
- .
hIV .
HIV , 50%-90% . . , HIV .
HIV .
2011-24/10/2014 32 HIV , . .
32 , 31 , 39,5 ( 22 73 ). , 10 2 . , 10 17 . 17 , 6 : (1 ), (1),
(1), Fordyce (1) (2). (34,4%) HIV Kaposi (1 ), (3), - (2), / (2),
(1) (2) 11. CD4 9 75 /mm3 (200 /mm3.
, HIV- , - .
-, , , ,
-
39
01
cD4 . ,1 . ,2 . ,3 .. ,4 . -,5 . ,6 . ,7 . ,8 . ,9 . ,10 . ,11 .
,12 . 1
: (combined antiretroviral treatment - cART) HIV+ -, cART CD4
(CD4) HIV . - CD4 cART - , , CD4, cART / .
: AMACS (Athens Multi-center Cohort Study). 15 cART - -, 2002 ,
. CD4 .
: 1.525 . (85,4%) ( - ) 35,6 (30,2-43,7) . (56,9%) () - cART 2,7
(1,2-5,1) . CD4 . cART 100 CD4 /L, CD4 600 /L 5 cART. 250 CD4 /L -
cART CD4 600 /L , 3 , . , , CD4 (800 /L) >350 CD4 /L. 5 , CD4 ,
.
: CD4 CD4 5 cART. cART , CD4 - CD4 350 /L. HIV .
1 , , ,
2 , .
3 , ...
4 , ... - ..
5... . 6 ,
7 , ,
8 , ...
9 , ..
10 , , ...
11 , ...
12 , 1 ...
-
HELLENIC ARCHIVES of AIDS, 2014; 22(Suppl 1):1-70
40
02
hIV-1 : . ,1 . ,1 . ,2 . -,3 . ,4 .. ,5 . ,6 . ,7 . ,8 . ,9 .
,10 . ,11 . ,12 . 1
: (cART) - . - cART.
: AMACS (Athens Multi-center Cohort Study). 15 , - cART
(Boosted-PIs) - (NNRTIs) 2002 . >90% . - .
: AMACS, 66,7% (n=3.733) - . 83,4% (n=3.115) 83,1% (n=3.102) .
(50,2%) , 194 (5,2%) . 6.491 cART , 3.720 (57,3%) Boosted-PIs 2.771
(42,7%) NNRTIs. , 59,9% -. , 2002 2006 - 2006 2013. 2002-2004, -
NNRTIs (85,3%) Boosted-PIs (80,5%). (IDUs) (OR=0,288, p-value3/,
(p-value=0,009).
: . - IDUs . cART. - cART , - .
1 , , ,
2 , .
3... . 4 , ...
5 , ... - ..
6 , ,
7 ,
8 , ..
9 , ...
10 , ...
11 , 1 ...
12 , , ...
-
AIDS, 2014; 22(Suppl 1):1-70
41
03
. , . , . , . , . , . , .
: , , .
: -
: ... ( ), 2002, .
: 01/01/2007-01/01/2013 - 304 . 111 (36,5%) , 91 (29,4%) , 22
(7,5%) 15 (4,9%) - . , 65 (21,6%). 50,98%, (155 ) - 21-35 , 35,52%
(108 ) 36-45 13,5% (41 ) 46-65. 91,1% . 66,77% (203 ) - , 10,85%
(33 ) , 7,56% (23 ) 14,82 % (35 ) . 52,2% , 39,9% - , 7,9% . 78% -
HBV. - , HBV, HCV HIV. 82,3% / HBV, HCV HIV, 9% (25 ) HbsAg(+),
6,8% (19 ) anti-HCV(+), 0,7% (2 ) HbsAg(+) anti-HCV(+) 1% (3 )
HIV(+).
: . . .
, ...
-
HELLENIC ARCHIVES of AIDS, 2014; 22(Suppl 1):1-70
42
04
(linkage) (retention to care) () hIV : . ,1 . ,1 . ,1 . ,1 . ,2
. ,3 . ,3 . ,2 . ,2 . 1
: , 2011, V (). , - , HAART , - HIV . - HIV XEN.
: HIV : ) 3-6 HIV , ) - 3-6 , ) HAART, ) (HIV RNA
-
AIDS, 2014; 22(Suppl 1):1-70
43
: 11 (10 , 27 ) 18 . 10 , 7 3 , - 34 ( 28-46) HIV 7,6 . - A, B C
. (IVF). IVF. - 2 6 - . HIV , 5 (4 -), 5 1 . , 2 , 3 2 C 3 , 2 .
HIV 3, . 5 2 IVF. ART 4 , 2 5. 6/7 ART. - ART HIV . 4 ART , -, . ,
HIV (8 ). HIV 7 , ART 1-2 (1 status ). 1 - .
: HIV . - . , , - , .
06
(PaF) hIV : . , .. ,2 . ,3 . ,4 . ,2 . -,5 .. ,2 . ,4 .. 3
: (PAF) - . - PAF HIV .
: 21 - ... 1, 3, 6, 9 12 . tenofovir-DF/emtricitabine/
atazanavir-r (7 , 33%), abacavir/lamivudine/atazanavir-r (5 ,
23,8%), abacavir/lamivudine/ efavirenz (4 , 19%),
tenofovir-DF/emtricitabine/darunavir-r (4 , 19%)
tenofovir-DF/emtricitabine/efavirenz (1 , 4,8%). , (MedDietScore)
(FRAP). (RM ANOVA)
, ... - ...
, ,
3 - , ... - ...
4 -,
5 , ... .
-
HELLENIC ARCHIVES of AIDS, 2014; 22(Suppl 1):1-70
44
PAF, PAF-CPT, lyso-PAF-AT, PAF-AH, Lp-PLA2 - , , - .
: PAF 1 (=-0,134, P=0,04). , PAF-CPT 9 (B= -0,37, P=0,06
B=0,018, P=0,04, ). - PAF-AH 3 Lp-PLA2 6 (=0,52, P=0,05 =0,542,
P=0,06, ).
: A - PAF, . - PAF HIV .
07
hIV . ,1,2 . ,3 . ,3 . ,3 . ,3 .. ,3 . 2
: HIV (HAART). - HIV .
: 57 HIV (52 , 42 HAART), 42,711,4 , 24,74, -- .... - . , , -
(MedDietScore).
: 27 kcal/kg/ (23, 42 kcal/kg/) 1,15 gr/kg/ (0,75, 1.46 gr/kg/).
- 420 . (270, 660 .), 210 . (60, 450 .) 2,5 (0,5, 2,5 ). / 0,33
(0,13, 1 ), 20 . (8,5, 30 .), 0,33 (0, 1 ), 2 (1, 3 ), 1,5 (1, 2 ).
1 (1, 3 ). MedDietScore 286 . , 35% .
: , , , . , -. .
1 , ... - ...
2 -,
3 , , ... - ...
-
AIDS, 2014; 22(Suppl 1):1-70
45
08
/ hIV+ . ,1 . ,1 . ,1 . ,2 . ,1 . ,1 . ,2 . 1
: () / HIV .
: (cross-sectional) HIV+ .. ( ) (DEXA) WHO . - . , , (), , 25()
D, HIV-RNA, CD4 , HAART, .
: 143 (117 , 96 MSM, 25,5, 77%, 116 -81%, 45 7,7, ). CD4 285 /L
VL 68.851 /mL ( 28882-186881). DEXA CD4 403/L VL
-
HELLENIC ARCHIVES of AIDS, 2014; 22(Suppl 1):1-70
46
: 60 (52 , 8 ) 3 . 45 , 96 , 15 . HAART 48 96 .
: (..) 39 . HAART, .. CD4+ 261 /l, .. 132.183 copies/ml. .. 166
mg/dl, HDL 36 mg/dl, LDL 101 mg/dl, 128 mg/dl 90 mg/dl, . , 17/53
LDL 130 mg/dL 19/53 HDL 160 mg/dL. 46/60 tenofovir DF/emtricitabine
14/60 abacavir/lamivudine. . 48 - (59/60 ), .. CD4 598 /l 58/60
(96,6%)
-
AIDS, 2014; 22(Suppl 1):1-70
47
: , Atripla. ( , - SPREAD) .
11
hIV cD4+ -. ,1 . ,2 . ,3 . ,3 . ,3 . ,3 . ,3 . ,4 . ,1,3 . ,1,3
. 1
: HIV , - CD4+ .
: ( 2001 2013) 919 HIV - AIDS . CD4+ , . , , (, , -) CD4+ CD4+ .
, cut off ROC CD4+
-
HELLENIC ARCHIVES of AIDS, 2014; 22(Suppl 1):1-70
48
12
hIV(+) . ,1 . ,2 . ,2 . ,1 . ,1 . ,1 . ,1 . ,1 . ,3 . ,2 . 2
: , Neisseria gonorrhoeae. , / , -. , , , , , , .
: HIV(+) ( 2013- 2014).
: - ( Gram ), .
: N. gonorrhoeae 6 , 3 (50%) HIV(+) . HIV(+) - N. gonorrhoeae 3
(42,9%) 7 HIV(+) . HIV(+) . - , . . . .
: N. gonorrhoeae - 125 mg .., 1 gr P.O. vibramycin ( 30% C.
trachomatis). N. gonorrhoeae , - . Gram . . 40 , ( ). N.
gonorrhoeae - N. gonorrhoeae . , , .
13
hIV . . , . , . , . , . , .
: HIV , - ,
1 , ...
2 ... & , ...
3
.
-
AIDS, 2014; 22(Suppl 1):1-70
49
. - (), , , , .
: 291 , - . , . , , . , - . 150 , , , - HIV . : 291 158 (54,3%)
, , -, . , 73 , - . , 60 - . , - 133 (45,7%). 150 , 98 (65,3%), 28
24 , 52 (34,7%). - (p=0,032).
: HIV , - . , , , . - , .
14
Eviplera hIV+ 103. ,4 . ,1 . ,3 . ,2 . ,1 . ,3 . ,5 . ,1 . ,5 .
,4 . ,2 . 1
: 103 . , - . EVP 103 - .
: ( ) HIV+ , EVP 2013- 2014. EVP . 103 EVP . (on-treatment
analysis, missing=excluded).
: 211 10 103 (9 , 6 , 8 MSM, 7/10 ) ( 34,9 - 2,2- ).
1 , ...
2 , ...
3 .
4 B , , ...
5 , ...
-
HELLENIC ARCHIVES of AIDS, 2014; 22(Suppl 1):1-70
50
1 . , EVP (IQR1-3) 17 (11-24). CD4 330 /L (2/10 - VL>100.000
/mL). CD4 EVP 330/L VL 9506 /mL ( VL98%) EVP.
: EVP 103 . (Rokx C et al. HIV Med 2014;15:611), EVP STR ,
K103N.
15
Eviplera hIV . ,2 . ,1 . ,5 . ,1 . ,3 . ,4 . ,5 . ,2 . ,1 . ,3 .
,4 . ,2 . 1
: Eviplera (EVP) 2012 - / HIV+ . EVP HIV , .
: ( ) -HIV+ , EVP 2012- 2014. -, , . . (on-treatment analysis,
missing=excluded).
: 104 (90 , 81 MSM, 81,6%) ( 33,9 - 2,2, ). 37/104 anti-HCV+
2/104 HBsAg+. CD4 324 /L - VL EVP 29.439 /mL (14 VL>100.000).
CD4 EVP 336/L VL 14.613 /mL (4 >100.000). H EVP (IQR1-3) 18
(13-22). VL 3 77,8% (42/54, - CD4 483/L), 94,7% 6 (54/57, CD4
527/L), 98% 12 (49/50, CD4 606/L) 100% 18 (20/20, CD4 559/L).
>100.000 - 6 12 . , ALT 6 12 . >98% 85-93% 18 . EVP ( ).
>2 WHO.
: EVP HIV+ . EVP -, .
1 , ...
2 , ...
3 .
4 B , , ...
5 , ...
-
51
01
dolutegravir , hIV(+) . , . , . , .
: H 3 (RTIs, NNRTIs PIs) . dolutegravir 2013, raltegravir. ,
dolutegravir .
: 53 HIV Kaposi 1995 (CD4 187, VL 54550 copies)*. ZDV (1995)
DDI/3TC/saquinavir (1996) d4T/3TC/efavirenz/ritonavir 2000, . 2003
(VL 78073) tenofovir/tipranavir/ritonavir/stavudine 2007 . To 2008
(CD4 115, VL 109536) tenofovir/darunavir/ritonavir/raltegravir, .
2010 maraviroc (CR5 , CD4 214, VL 25662) 20 - . 2012 (CD4 94, VL
1.075.000) ** - rilpivirine tenofovir/3TC raltegravir maraviroc.
2013 (CD4 52, VL 460.757) . - - darunavir. tenofovir/3TC/maraviroc
PI (saquinavir+lopinavir) - , , ( -, , ). 2014 (CD4 22, VL
1.049.000) dolutegravir 50 mg , saquinavir. , - CD4 (183, 213 276
1, 3 5 ), VL (695, 192 1 3 ) .
: , dolutegravir .
*CD4 /mm, VL=Viral load cop/ml, ** RT: M41L, E44D, D67N, L74V,
V118I, M184V, T215C, T215Y, K219R, K103N, V179F, Y181C, PI: L10F,
V11I, V32I, M46I, I54T, Q58E, A71V, G73S, T74P, I84V, L89V, L90M,
L33V, K55R, K20I, .
02
Mycobacterium avium complex (MAC) . , . , . , . , . , .
: - MAC. . IV(+) MAC .
: 30 IV(+) CD4 17/mm3 - , . -
, , ...
, , ...
-
HELLENIC ARCHIVES of AIDS, 2014; 22(Suppl 1):1-70
52
Pneumocystis jiroveci . - , . . -, tenofovir, emtricitabine
efavirenz, . MAC iehl-Nielsen . . avium , , -, , . , -, efavirenz
darunavir/ritonavir. H 5 . , - . 16 CD4 130/mm ( 2014).
: MAC , - - . . MAC - .
03
hIV(+) . ,1 . ,1 . ,1 . ,1 . ,3 . ,2 . 1,2
: HIV - .
: , 28 HIV - (CD4:39) tenofovir/emtricitabine, darunavir,
ritonavir /. , ( ) . 15 (ART) , - . , -, , , - , , . - . , , , -ALA
. . darunavir - - raltegravir atovaquone tenofovir/emtricitabine.
human hemin (5 - 3 ). : , , ,
1 , ...
2 , ...
3 , ...
-
AIDS, 2014; 22(Suppl 1):1-70
53
(). , / . ART abacavir, lamivudine, raltegravir. - ( ), , -, , -
.
: , 1/20.000. . , , - . , HIV . HIV -, ART .
04
hIV () () . , .
: o, . - , . HIV . neofor-mans , , () - . HIV , .
: 35 , , - , , - , , - . 10 g/dl =50.000/l Coombs IgG+/++. A -
(large granular lymphocytes). . - , Kerning Bruzinski . - , , , , -
, . , . , . V bc-Total, RPR, sAg, nti-HBs, CV . 38,5C, , - .
Cryptococcus neoformans . 2
, ..
-
HELLENIC ARCHIVES of AIDS, 2014; 22(Suppl 1):1-70
54
- .
: , . HIV - , .
05
hIV . .
: HIV - ( Hodgkin , , ). HIV . - HIV .
: 67 - . 15 2 , , . 10. - . WBC=2.580/l, b=11,2 gr/dl, Ht=34,3%,
MCV=91,7 fl, MCH=29,9 pg, MCHC=32,7 g/dl, RDW=14,8%, PLT=90.000/l.
TKE=90 mm. , LDH=593 U/L, 29 g/dl (59-158), 1555 ng/dl. , - , 12 .
-. . . , , , - . , HIV.
: O HIV , - . - .
: HIV - , HIV .
06
hIV .
: - HIV . HPV.
, ..
-
AIDS, 2014; 22(Suppl 1):1-70
55
: 2011-2014 344 . 35 HIV. (high resolution anoscopy). . - .
: 7/35 ( 20%) - HPV. .
: , , , HIV - . HIV . , 20% HIV - HPV. -, ( ), . . - . .
07
aIDs . , .
3 HIV, , -- AIDS. , - AIDS , , . , AIDS . , AIDS . , 60% AIDS .
4,8 HIV. AIDS. - HIV (51%) . , (33,4%), HIV 2013 2014. , 1 3 HIV -
. HIV. 28,5% , 17,3% HIV . AIDS. , 35 AIDS, 1,6 . , 3.386 AIDS
1,547 .
,
-
HELLENIC ARCHIVES of AIDS, 2014; 22(Suppl 1):1-70
56
08
hIV(+) . , . , . , . , . , . , .
: - (ART), . - ART 2 .
: 101 350 . 2
-
AIDS, 2014; 22(Suppl 1):1-70
57
: 31 , , , 5. , - . , , -. - 24 . - , , . 4 . - 3 . - Treponema
pallidum , VDRL , IgM IgG T. pallidum EIA TPHA 1/2560. . HIV 1 2 ,
ELISA , Western Blot . 2,4 - G. , Western Blot CD4 441, CD4/CD8
0,124 140.000 copies/ml, HIV .
: HIV - - . HIV , , . HIV . - - HIV. HIV HIV . , HIV .
10
hIV 33 . , .. , . , . , . , .. , ..
: , , , HIV , 33 .
: K , , , , -, , , - (HAART) , , . - . 2013-30/9/2014 / / Excel
EPI5-Info (CDC, 2008). CD4 .
: 15, , (14 , . 37,9 ) HIV+ (5) , , - (2 ) , , . - 13/15 CD4 o
200 2/3 (10/15) 124. 4, Pneumocystis jirovecii. , , , HIV (),
, .. -
-
HELLENIC ARCHIVES of AIDS, 2014; 22(Suppl 1):1-70
58
. , . 15, 4 . HAART - - 10, 4 .
: - , , -, , HIV . , , - HIV. , , 21 .
11
hIV . , . , . , . , . , . , .
: HIV HIV .
: 59 HIV , 65 , - . . - , HIV . , - C CDC.
: 69,664,88 . - 8/59 (13,5%), (13,4%). 58/59 (). . HIV . - 29
HIV (0,49 ) 196 - (3,32 ). HIV - (6/59) Kaposi (5/59). , - (40/59,
67,8%), (22/59, 37,3%), (20/59, 33,9%), (14/59, 23,72%) (9/59,
15,25%).
: , , , HIV -. . , , , . , - , .
12
hIV(+) . ,1 . ,2, . ,1 . ,2 . ,2 . ,2 . ,2 . ,1 . 2
: HIV(+) , , . , .
.
1 , ..
2 , ..
-
AIDS, 2014; 22(Suppl 1):1-70
59
, - - 2014.
: 29 , HIV - 2012 abacavir/3TC atazanavir/ritonavir. - . . , . .
. 8 , , , 50% . . - , - . . - RPR FTA Abs . G 2 . -, , .
: , - HIV(+) - . - .
13
Eviplera (XEn) hIV . ,5 . ,1 . ,1 . ,2 . ,4 . ,5 . ,3 . ,1 . ,3
. ,4 . ,2 . 1
: EVP, (STR), HIV+ -, .
: ( ) -HIV+ , EVP 2012- 2014. , . . (on-treatment analysis,
missing=excluded).
: 38 XEN (2 , 28 ) ( 34,5 - - 2,1, , 37/38 anti-HCV+, 2/38
HBsAg+). 29/38 (, 26 /3 ). 11/38 (, , ). CD4 275 /L VL EVP 22.195
/mL (4 VL>100.000). CD4 EVP 292/L VL 1545 /mL. H EVP (IQR1-3) 16
(10-22). VL 72,2% 3 ( CD4 363/L), 88% 6 (CD4 331/L) 94,4% 12 (CD4
400/L). >98%
1 , ...
2 , ...
3 .
4 B , , ...
5 , ..
-
HELLENIC ARCHIVES of AIDS, 2014; 22(Suppl 1):1-70
60
80% 12 . 12/37 (32%) 14/37 (37%) 3 6 , -. ALT. ALT >45 IU/L
(12/38), -19, 6 +6 12 -5,6 (P>0,05). EVP (1 , 1 ). - >2
WHO.
: EVP HIV+ . EVP . , -, .
14
Eviplera : , hIV+ . ,1 . ,2 . ,1 . ,4 . ,3 . ,5 . ,1 . ,2 . ,5 .
,3 E. ,4 . ,2 . 1
: EVP , .
: ( ) HIV+ , EVP 2012- 2014. - , , - . . (on-treatment analysis,
missing=excluded).
: 107 (91 -81 MSM) ( 40,9 -- 8,6- 5,7, ). - 1 . CD4 292 /L VL
63.000 /mL. CD4 700/L 79/107 (79,4%) VL
-
AIDS, 2014; 22(Suppl 1):1-70
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15
castleman hIV 8 (V8). , . , . , . , . , . , . , . , . , .
: Castleman (C). H C HHV 8, . A - -6 .1,2
: 42 (emtricitabine, tenofovir, darunavir, ritonavir), (, - )
39C. CD4 191 /l HIV RNA. . .
: , - , . C, HHV 8 . rituximab . rituximab - , , , , . - , .
rituximab -, , - L-6 (tocilizumab). A , PCT CRP , - .
: Castleman - L-6 , TNF-, IL-1, L-4, T-reg .3 - rituximab - .
IL-6 HIV HHV-8 .
1. Sumerai JD, et al. Cancer Control. 2014 Oct;21(4):266-78.2.
Carbone A et al., Int J Cancer 2014; Ap:27.3. Borden EC. J Lab
Cllin Med 1994;123:824-29.
, ...
-
HELLENIC ARCHIVES of AIDS, 2014; 22(Suppl 1):1-70
62
16
hIV . , . , . , . , . , . , . , . , . , .
: HIV . - - , o -, - - (Natural Killler Cells). IV , .1
: 31 - . - HIV ( ) HSV I HSV II. . tenofovir, emtricitabine (
CD4 399/L, HIV RNA 100.000 copies/ml) . . , , LDH, d-Dimers , , - .
Epstein-Barr .
: - , HLH-2004 . - , ( , ), - . .
: HIV . , . .
1. Doyle T, et al. Curr Opin Infect Dis. 2009;22(1):1-6.
17
hIV, hBV hcV ... . . , . , . , . , . , . -
: - HIV, HBV HCV - .
, ...
, ... .
-
AIDS, 2014; 22(Suppl 1):1-70
63
: . 6/2011-10/2014 - HIV,HBV HCV. - -. HIV1,2 HBV/HCV - ( )
.
: 33 (33 -, 41 ). 82% , - (24%), (21%) (21%). (24%), (21%),
(21%). - (79%), - (15%) (6%). , - . HBV 36%. O - HIV 6 (18%), HCV 3
(1 HIV), HBsAg 1 -, 12 (36%) - , - . 9 (27%) . - 1 HBV 6 (18%), 2 .
24% - HBV, - 6/7 (86%) . 33 HIV, HBV HCV .
: . , - HIV, HBV HCV. HBV - , .
18
-590 IL-4 hIV-1. ,1 . ,2 . ,1 . ,2 . ,1 . ,1 . ,1 . ,2 . ,1 . ,1
. ,1 . ,2 . ,1 . 1
: IL-4 IgE - - h2. IL-4 CCR5 CD4 R5 HIV-1 - -. C -590 IL-4 IL-4.
-590 IL-4 HIV-1.
: 173 HIV-1 . 48 AIDS 125 .
1 , , , ,
2 , ...
-
HELLENIC ARCHIVES of AIDS, 2014; 22(Suppl 1):1-70
64
-590 IL-4 Cytokine Genotyping Kit DYNAL/Biotech.
: 173 HIV-1 , 76,3%, 35,5 . - IL-4 -590. , , 1998, CD4 . -590
AIDS (35 - AIDS 5 ).
IL-4 -590
CC CT TT
133 (76.9%) 36 (20,8%) 4 (2,3%) 173 0,001
103 (77,4%)30 (22,6%)
25 (69,4%)11 (30,4%)
4 (3%)0 (0%)
132 (76,3%)41 (23,7%)
0,33
35,2 10,3 37,5 11,5 27,5 2 35,5 10,5 0,25
98
52 (39,1%) 9 (25%) 4 (100%) 65 (37,6%) 0,26
MSM 86 (64,6%) 23(63,8%) 4 (100%) 113 (65,3%) 0.5
CD4 368 345 389 358 0,78
AIDS
43 (32,3%)90 (67,7%)
5 (13,8%)31 (86,2%)
0 (0%)4 (100%)
48 (27,7%)125 (72,2%)
0,04
AIDS KaplenMeier AIDS .
: -590 - IL-4 . .
19
hIV-1 . ,1 . ,1 . ,1 . ,1 . ,1 . ,1 .. ,1 . ,1 . ,1 . ,1 . 1
: 2000-2010.
: 453 -. , -, . - . - .
: - .
1 , , , , ...
-
AIDS, 2014; 22(Suppl 1):1-70
65
NNRTIs
PIs
179 (39,5%) 274 (60,5%) 453 (100%) 0,001
149 (83,2 %) 220 (80,3 %) 369 (81,5 %) 0,254
35,9 11,7 41,5 12 39,3 12,2 0,001
>50 24 (13,4%) 68 (24,8%) 92 (20,3%) 0,002
15 18,5 8 14,4 10,8 16,5 0,001
AIDS 14 (7,8%) 70 (25,5%) 84 (18,5 %) 0,001
AIDS 17 (10,4%) 45 (22,1%) 62 (16,8%) 0,002
502,7 128,6 593,8 122,8 557,8 132,7 0,001
23,4 25,8
36,2 27,5 (54)17,9 23 (110)
30,1 25,5
47,3 23,8 (106)19,3 20 (132)
27,5 25,8
43,6 25,6 (160)18,7 21,3 (242)
0,007
0,0020,56
10473,4 9855,3 17749,5 14656,3 14874,4 13441,3 0,001
606,7 117,1 (110)NNRTIs (68) 576.2
83.5PIs (42) 643.9 117.4
578 127,2 (132)NNRTIs (30) 532.7
11.5PIs (102) 591.7 129.1
590,9 122,8 (242)NNRTIs (98) 563.41
94.1PIs (144) 607.3 127.6
0,08
82 (45,8%) 186 (67,9%) 268 (59,2%) 0,001
1 (49)2 (14)
>3 (18)
1 (79)2 (62)
>3 (41)
1 (128)2 (76)
>3 (59)
2000-2010 PIs (60.5%). PI ( 41,5 ), AIDS (25,5% 7,8%), AIDS
(22,1% 10,4%). PIs. PIs (30,1 23,4) - . . NNRTIs. NNRTIs (45,8%
67,9%) - .
: NNRTIs . . PIs, NNRTIs. .
-
HELLENIC ARCHIVES of AIDS, 2014; 22(Suppl 1):1-70
66
-
AIDS, 2014; 22(Suppl 1):1-70
67
Overall Comparisonsa
Chi-Square df Sig.
Log Rank (Mantel-Cox) ,504 1 ,478
Breslow (Generalized Wilcoxon) 2,878 1 ,090
Tarone-Ware 1,797 1 ,180
Test of equality of survival distributions for the different
levels of pivsnnrtis.a. switch = switch
-
HELLENIC ARCHIVES of AIDS, 2014; 22(Suppl 1):1-70
68
20
hIV-1 2000-2010. ,1 . ,2 . ,1 . ,2 . ,2 . ,1 . ,1 . ,1 . ,1 . ,1
. ,1 . ,1 . ,1 . ,2 . ,1 . , . ,1 . 1
: HIV-1 2 NRTIs PI NNRTI - 2000-2010 .
- : 453 . , >18 , . - 6 >1000 , >14 . Kaplan-Meier.
: - . 44 . - NNRTIs (10% 9.4%) . PIs. (21.1 NNRTIs 19.3). .
NNRTIs
PIs
VF
179 (39,5%)18 (10%)
274 (60,5%)26 (9.4%)
453 (100%)44 (9.7%)
0,0010,008
VF
149 (83,2 %)14 (7.8%)
220 (80,3 %)20 (7.2%)
369 (81,5 %)34 (7.6%)
0,2540.32
VF
35,9 11,734.8 8.7
41,5 1243.1 10.4
39,3 12,239.7 10.4
0,0010.001
>50 VF
24 (13,4%)2 (1.1%)
68 (24,8%)7 (2.5%)
92 (20,3%)9 (1.9%)
0,0020.34
AIDS VF
14 (7,8%)3
70 (25,5%)2
84 (18,5 %)5
0,0010.35
17,9 23 (110)
21,1 16,4 (18)
19,3 20 (132)
19,3 16,4 (26)
18,7 21,3 (242)
20 16,2 (44)
0,56
0,45
2 NRTIs 10 (55.5%) 15 (57.6%) 25 (56.8%) 0.45
1 , , , , ...
2 , ...
-
AIDS, 2014; 22(Suppl 1):1-70
69
- . - PI .
RTIs18 VF, 3
s26 , VF, 13
RT
RT
6 K103N 4 L10I, M36I 4 M184V 7 M36I
5 M184V 3 I13V 2 D67N, K70R, K103N 4 L89M, I13V, L10I
3 Y181C 2 L63P, I62V, I93L 1 V106I, E138A, L74V, Y75I, V75T,
Y75A,
Y188L, T69N, G190A, K219Q
3 H69K, L63P
2 E44D 1 K20I, L19I, A71T, I54V,
H69K, L89M
2 L90M
1 V179D, M41L, L210W, T215Y,K101Q, G190A, G190S, P225H, D67N,
K70R, K219Q, K219E,
V118I, A62V, V75I, K101I, Y115F, G190S
1 G16E, L33V, E35G, I54M, A71T, K20M, I62V, A71I,
V77I, I93L
: PIs NNRTIs. VF . PI .
21
hIV-1 .. ,1 . ,1 . ,3 . ,3 . ,1 . ,2 . ,3 . ,3 . ,3 . ,4 . ,4 J.
Hezka,4 . ,4 . ,3 . 2
: HIV-1 DNA - , CD4 T - (Kostrikis et al., 2002, Tierney etal.,
2003,Goujard et al., 2006).
: HIV-1 DNA, . , - HIV-1 DNA CD4 - .
: 94 HIV-1 - 2009-2010. .
1 , ... ,
2 ...
3 , , ... ,
4
-
HELLENIC ARCHIVES of AIDS, 2014; 22(Suppl 1):1-70
70
HIV-1 DNA - (beacon) (real-time) PCR (Kostrikis et al 2002,
Demetriou et al 2010). HIV-1 pol - REGA HIV-1 subtyping tool v2.0
(http://www.bioafrica.net/subtypetool), HIV Drug Resistance
Database (http://hivdb.stanford.edu) Calibrated population
resistance tool v.6 (Surveillance Drug Resistance Mutation list,
2009 http://hivdb.stanford.edu)
HIV-1 DNA, Mann-Whitney Pearson, HIV-1 Kruskal-Wallis.
: HIV-1 DNA 3.309 (IQR 2.889-3.631 log10 / 106 PBMC).
HIV-1 DNA - . - HIV-1 DNA CD4 - (R2 = 0,004, P = 0,969). HIV-1
(A, B, C, CRF- AG, CRF04-cpx, CRF-01, F1 G) . DNA.
: HIV-1 DNA - HIV-1 .
-
71
J. Hezka 69. 39, 45, 49, 50, 59,
60, 61, 62, 69. 56, 58. 43. 42, 62. 48. 51. 47, 63, 64, 68. 58.
64. 53, 54. 27. 58. 41, 46. - 39, 40, 42, 43, 45,
62. 48, 56. 48. 39, 40, 51. 39, 40, 42. 47, 63, 64, 68. 48, 56,
58. 42. 41.. 43. 57.. 34. 46. 45. 63, 64, 68. 61, 62. 45, 48, 51.
48. 44. 61, 62. 58. 44. 30. 42. 52. 51. 45, 49, 50, 59, 60. 39. 33.
56. 69
. 47, 63, 64, 68, 69. 2. 44. 3. 39, 40. 52. 63. 48. 17.. 26. 40.
63, 69. 24, 39, 40, 48, 49,
50, 56, 58, 59, 60. 61, 62. 52. 57. 46. 4. 41. 69. 61, 62.. 39,
40, 43, 45. 46. 58. 56. 51. 24, 42, 49, 50, 59,
60, 62. 63, 68, 69. 41, 46, 49, 50, 59,
60. 69. 51. 68. 61. 55. 56, 58. 47, 63, 64, 68, 69E. 42, 62. 56,
58. 42. 57. 41. 47. 48. 42, 62
-
HELLENIC ARCHIVES of AIDS, 2014; 22(Suppl 1):1-70
72
. 48. 63. 47, 69. 27. 48 63, 68. 55. 43.. 64. 42, 45, 62. 45.
45. 53, 54. 3, 41, 46, 49, 50,
59, 60. 39, 40, 51. 39, 40. 68. 45, 49, 50, 59, 60,
61, 62. 38. 45. 47.. 43. 25. 29, 48, 49, 50, 56,
58, 59, 60. 45, 48, 51, 52. 56, 58. 46.. 57. 48. 69. 44. 56. 61,
62. 29, 40, 45, 49, 50,
59, 60, 61, 62.. 44. 64, 68. 48, 58. 1. 39, 40, 49, 50, 59, 60.
69
. 51. 47, 63, 68, 69. 45, 48, 51, 52. 42. 9. 43. 54. 42. 52. 50,
60.. 57.. 57. 41, 64, 68. 57. 58. 36. 39, 40. 40. 18. 63, 64, 68,
69. 35. 42. 62. 61, 62. 44, 45. 68. 34, 42, 49, 50, 59,
60. 68. 43. 56, 58. 47. 42, 46. 56, 58. 45. 63, 68. 43, 44, 45.
47, 68. 52. 47, 63, 64, 68, 69. 39, 40, 56, 58. 48 42, 49, 50, 59,
60
0
5
25
75
95
100
new_stribild_21x29
, 12 2014 2:09:06
-
05
25
75
95
100
new_stribild_21x29
, 12 2014 2:09:06