Institutes: Ukrainian Medical and Dental Academy, Regional HIV/AIDS Prevention and Control Center, Poltava Ukraine Toll-like receptor 4 polymorphism influence on the development of opportunistic diseases in HIV-infected patients The presenting author is Tetiana Kyrychenko Authors: G. Dubynska, T.Koval, I.Kaidashev, V.Korshenko
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Institutes: Ukrainian Medical and Dental Academy, Regional HIV/AIDS Prevention and Control Center, Poltava Ukraine Toll-like receptor 4 polymorphism influence.
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Institutes:Ukrainian Medical and Dental Academy,
Regional HIV/AIDS Prevention and Control Center, Poltava Ukraine
Toll-like receptor 4 polymorphism influence on the development of opportunistic diseases
in HIV-infected patients
The presenting author is Tetiana Kyrychenko
Authors: G. Dubynska, T.Koval, I.Kaidashev, V.Korshenko
The stage of the disease was recorded in accordance with the expanded European AIDS case definition.
Laboratory procedures. Routine CD-4 cell count was determined
using conventional flow cytometry with fresh blood samples from all patients.
Plasma HIV-RNA was also routinely measured by the polymerase chain reaction (PCR) (Real time HIV-1, Abbout).
TLR4 genotyping was performed by real-time PCR using oligonucleotide primers (Tercik PCR system, DNA-technology, Moscow)
Characteristic of a Cohort of 180 patients infected with HIV-1 and studied in Relation to
SNP of TLR4 Characteristic Wild type
(AA, n=165)
Asp299Gly heterozygous
(AG, n=15)
Male-to-female ratio 98:67 10:5
Ageª, mean years± standard deviation
35,21±0,51 35,13±1,33
Nadir CD-4 cell countª, mean cell/mm³± standard deviation
259,52±16,2 233,6±30,38
Maximum viral loadª, median copies/mL
249826 152671
Clinical stage(%)ABC
11 (6,6)72 (43,7)82 (49,7)
2(13,3)2(13,3)11(73,4)
History of opportunistic infections in 180 HIV-infected patients
1%
1%
1%
4%
14%
18%
20%
25%
27%
28%
33%
51%
48%
9%
0% 10% 20% 30% 40% 50% 60%
Progressive multifocal leukoencephalopathy
Kaposi sarcoma
Pneumocystis jiroveci
Cytomegalovirus disease
Toxoplasmosis of brain
TB extra pulmonary
Herpes simplex: chronic ulcers
Herpes zoster
Tuberculosis pulmonary
Wasting syndrome caused by HIV
Bacterial pneumonia
Hairy leukoplakia, oral
Candidiasis
Chronic hepatitis C
History of opportunistic infections in 180 HIV-infected patients in relation to SNP of the Toll-like receptor 4 gene
(No. (%) of patients)
Variable Wild type (AA,n=165)
Asp299Gly heterozygous
(AG, n=15)
p
Mycobacterium tuberculosis, pulmonary or extrapulm.
59 (35.7) 11 (73.3) 0.007*
Bacterial pneumonia, recurrent
42 (25.5) 8 (53.3) 0.021*
Hairy leukoplakia, oral
51 (30.9) 9 (60) 0.022*
Herpes zoster (shingles), involving two or more episodes or at least one dermatome
29 (17.6) 7 (46.7) 0.007*
*AG compared to AA, Mann-Whitney U-test
History of opportunistic infections in 180 HIV-infected patients in relation to SNP of the Toll-like receptor 4 gene
(No. (%) of patients)
Variable Wild type (AA,n=165)
Asp299Gly heterozygous
(AG, n=15)
p
Chronic hepatitis C 80 (48.5) 12 (80) 0.018*
Candidiasis, oropharyngeal or esophageal
78 (47.3) 8 (53.3) >0.05
Wasting syndrome caused by HIV (involuntary weight loss >10% of baseline body weight) associated with either chronic diarrhea or chronic weakness and documented fever for ≥1 month)
42 (25.5) 6 (40) >0.05
Herpes simplex: chronic ulcers (>1 month in duration)
28 (17) 5 (33.3) >0.05
Any 19 (11.5) 3 (20) >0.05
*AG compared to AA, Mann-Whitney U-test
Distribution of the 299 alleles of the patients when they were grouped by CD-4 T-cell counts equal to or above and below
350, 200 100
cells/mm³, respectively
*Only patients with CD4 T-cell
counts above 200cells/mm³ had the prevalence of the Asp299Gly polymorphism (12%) significantly higher than patients with CD4 T-cell counts below than 200 cells/mm³ (3.7%), p<0.05
133
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Nu
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CD4 T cell/mm
AA
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12*
0102030405060708090
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≤200 >200
CD4 T cells/mm
AA
AG
312
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CD-4 T cells/mm
AA
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Detection of opportunistic infections in HIV-infected patients with different levels of CD4
development of active tuberculosis, bacterial pneumonia, herpes zoster, hairy leukoplakia, toxoplasmosis of brain, chronic hepatitis C in patients with the Asp299Gly TLR4 polymorphism
our results demonstrate the impact of a TLR4 genetic polymorphism on development of opportunistic infections for CD4 levels more than 100.
Acknowledgments
G.Dubynska, prof., department of infectious diseases, Ukrainian Medical and Dental Academy, Poltava, Ukraine
T.Koval, prof., department of infectious diseases, Ukrainian Medical and Dental Academy, Poltava, Ukraine
I. Kajdashev, prof., chair of research department, Ukrainian Medical and Dental Academy, Poltava, Ukraine
V.Korshenko, chief doctor of Regional centre of HIV/AIDS Poltava, Ukraine