Značaj CD4/CD8 količnika i c-reaktivnog proteina u praćenju kardiovaskularnog rizika kod HIV pozitivnih pacijenata tokom cART terapije
Significance of CD4 / CD8 ratio and C-reactive protein in monitoring cardiovascular risk in HIV positive patients during cART therapy
Metapodaci
Prikaz svih podataka o disertacijiSažetak
Uvod: HIV-infekcija se karakteriše progresivnim manjkom CD4+ T-ćelija zbog njihove smanjene sinteze, povećanog uništavanja i izrazite aktivacije i ekspanzije CD8+ T limfocita. CD4/CD8 odnos (količnik, engl. ratio) se sve više pojavljuje kao marker različitih ishoda kod HIV-inficiranih pojedinaca. S druge strane CRP je tradicionalno
opisivan kao dobar marker akutne upale i danas je jedan od standardnih testova koji se
koriste u svakodnevnoj kliničkoj praksi, za postavljanje dijagnoze i praćenje prognoze
upale. Međutim, uloga CRP-a u različitim fiziološkim procesima, naročito kod perzistentne
infekcije i imunske aktivacije nije do kraja jasna. Efikasnom i savremenom terapijom HIVa život ovakvih pacijenta je značajno produžen. Primarni cilj antiretrovirusne terapije
(ART) je spriječiti HIV-povezane bolesti i smrtnost, a sekundarni cilj je da se smanji rizik
od prijenosa HIV-a. Ovaj cilj se najbolje postiže pomoću efikasne cART, kojom se
maksimalno inhibira HIV replikacija, tako da ...plazmatska HIV RNK (viremija) ostaje ispod
nivoa kojeg je moguće detektovati pomoću komercijalno dostupnih testova.
Cilj: Osnovni cilj ovog istraživanja je da se ispita kolika je moć CD4/CD8 odnosa i CRP-a
da predvidi razvoj rizika kardiovaskularne bolesti (KVB) kod HIV pozitivnih pacijenata
koji primaju cART terapiju.
Materijal i metode: U retrospektivno-prospektivnoj kohortnoj studiji ponovljenih mjerenja
bilo je uključeno 76 HIV pozitivnih ispitanika. Za određivanje udjela (procenta) CD4+ i
CD8+ ćelija, iz periferne krvi pacijenata, korištena je metoda protočne citometrije. U ovoj
studiji evaluirane su vrijednosti biohemijskih paremetara (CRP-a, lipidnog statusa),
parametara krvne slike (eritrociti, hemogbin, hematokrit, trombociti), leukociti i
leukocitarna formula te sedimentacija kao nespecifični parametri akutne upale, potom
imunološki parametar CD4/CD8 odnos, antropometrijska mjerenja- ITM, te vrsta cART
terapije. Za statističku analizu korišten je softver SPSS, odnosno parametrijski i
neparamterijski testovi, Spirmanova (rho) korelacija, standardna regresiona analiza i ROC
kriva.
Rezultati: U istraživanje je uključeno 76 ispitanika, 67 (88,2 %) muškaraca i 9 (11,8 %)
žena. Ispitanici su prosječne starosti 35,2±8,7 godina, najmlađi ispitanik imao je 18, a
najstariji 57 godina. Standardnom regresionom analizom, ispitivan je uticaj nezavisnih
prediktora (starosti, pola, navike pušenja, familijarne anameze za KVB, ITM, cART,5
sistolnog i dijastolnog pritiska, holesterola, triglicerda, HDL-a, ŠUK-a, CRP-a, CD4 i
CD4/CD8) na zavisno promjenljivu rizik za KVB bazično i nakon 3, 6, 12, 18 i 24 mjeseca
cART. Od 12. do 24. mjeseca osim standardnih rizikofaktora za predikciju razvoja KVB,
CD4/CD8 odnos i CRP se javljaju kao značajni prediktori. Nakon 24 mjeseca cART, CRP
se pokazao kao najbolji prediktor rizika za KVB (beta=0,224; p=0,026), veće vrijednosti
ovog parametara utiču na veći rizik za KVB, potom CD4/CD8 odnos (beta=-0,200;
p=0,025), s tim da veći odnos smanjuje vjerovatnoću za rizik KVB. Terapija (cART) u
ovom regresionom modelu prvi put je nakon 24 mjeseca pokazala statistički značajan uticaj
na rizik za KVB (beta=0,197; p=0,013). Ispitanici koji su u kombinovanoj terapiji imali
PI, imaju veći rizik za KVB. Od 18. mjeseca cART CRP može biti marker srednjeg rizika
za KVB, a nakon 24 mjeseca vrijednosti CRP-a od 5,31 mg/L ima najveću senzitivnost
78,3% i najveću specifičnost 86,8%, kao marker srednjeg u odnosu na niski rizik za KVB
(p=0,0001; AUC=0,882). Od 12 mjeseca cART CD4/CD8 odnos može biti marker niskog
rizika za KVB. Nakon 24 mjeseca terapije prosječna vrijednost CD4/CD8 odnosa od 0,53
ima najveću senzitivnost 66,0% i najveću specifičnost 73,9%, kako marker niskog u
odnosu na srednji rizik za KVB (p=0,001; AUC =0,762).
Zaključci: Količnik CD4/CD8 i CRP su se pokazali se kao značajni prediktori za rizik
KVB, i kao markeri koji mogu razlikovati nizak/srednji rizik za KVB kod HIV pacijenata
nakon 12 mjeseci cART.
Introduction: HIV infection is characterized by a progressive deficiency of CD4+ T cells due to their reduced synthesis, increased destruction and marked activation and expansion of CD8+ T lymphocytes. The CD4/CD8 ratio is increasingly emerging as a marker of different outcomes in HIV-infected individuals. On the other hand, CRP has traditionally
been described as a good marker of acute inflammation and is today one of the standard
tests used in everyday clinical practice to diagnose and monitor inflammation prognosis.
However, the role of CRP in various physiological processes, especially in persistent
infections and immune activation, is not entirely clear. The primary goal of antiretroviral
therapy (ART) is to prevent HIV-related diseases and mortality, and the secondary goal is
to reduce the risk of HIV transmission. This goal is best achieved by using efficient
combination ART (cART), which maximally inhibits HIV replication, so that plasma HIV
RNA (viral load) remains bel...ow the level that can be detected by commercially available
tests.
Aim: The main objective of this study is to examine the power of the CD4/CD8 ratio and
CRP in predicting the risk of development of cardiovascular disease (CVD) in HIV
positive patients receiving cART therapy.
Methods: In the retrospective-prospective cohort study of repeated measurements, 76 HIV
positive subjects were included. The method of flow cytometry was used to determine the
percentage of CD4+ and CD8+ cells in the peripheral blood of patients. In this study the
values of biochemical parameters (CRP, lipid status), blood parameters (erythrocytes,
hemoglobin, hematocrit, platelets), leukocytes, leukocyte formula, and sedimentation as
non-specific parameters of acute inflammation were evaluated, followed by
immunocompetent CD4/CD8 ratio, anthropometric measurements - ITM, and cART
therapy type. For statistical analysis SPSS software was used, i.e. parametric and
nonparametric tests, Spearman's (rho) correlation, standard regression analysis and ROC
curve.
Results: The study included 76 subjects, 67 (88.2%) males and 9 (11.8%) women. The
average age of subjects was 35.2 ± 8.7 years; the youngest subject was 18 and the oldest 57
years old. By standard regression analysis, the influence of independent predictors (age,
gender, smoking habits, familial anamnesis for CVD, ITM, cART, systolic and diastolic7
pressure, cholesterol, triglycerides, HDL, blood sugar, CRP, CD4 and CD4/CD8 ratio) on
the dependent variable risk of CVD, baseline and after 3, 6, 12, 18 and 24 months of cART
was examined. From 12 to 24 months apart from the standard risk factors for predicting the
development of CVD, CD4/CD8 ratio and CRP appear as significant predictors. After 24
months of cART, CRP proved to be the best risk predictor of CVD (beta = 0.224; p =
0.026), higher values of this parameter affect higher risk for CVD, then CD4/CD8 ratio
(beta -0.200, p = 0.025), with a higher ratio decreasing the likelihood of CVD risk. Therapy
(cART) in this regression model showed the first time after 24 months a statistically
significant impact on CVD risk (beta = 0.197; p = 0.013). Subjects who had PI in
combination therapy had a higher risk for CVD. From 18 months of cART CRP may be a
medium risk marker for CVD, and after 24 months the CRP value of 5.31 mg/L has the
highest sensitivity of 78.3% and the highest specificity of 86.8%, as a marker of medium
compared to low risk for CVD (p = 0.0001; AUC = 0.882). After 12 months of cART
CD4/CD8 ratio can be a low risk marker for CVD. After 24 months of therapy, the average
CD4/CD8 ratio of 0.53 had the highest sensitivity 66.0% and the highest specificity was
73.9%, as the marker of low compared to medium risk for CVD (p = 0.001, AUC = 0.762).
Conclusion: CD4/CD8 ratio and CRP counts have been shown to be significant CVD risk
predictors, and as markers that may differentiate low and intermediate risk for CVD in HIV
patients after 12 months of cART.