Immune response to hepatitis A vaccination in HIV-infected patients

The natural history of HIV-infection has been altered due to the use of Highly Active Antiretroviral Therapy [HAART]. Survival and quality of life of HIV-infected patients have increased. However HIV-patients are still at great risk of some vaccine-preventable diseases especially these diseases which have sexual transmission. Hepatitis A remains a public health problem and is of special concern in HIV-infected patients, especially MSM and intravenous drug users. Hepatitis A is considered to be a self-limited disease but immunocompromised individuals may experience serious complications. The most effective intervention in preventing disease is vaccination Success of hepatitis A vaccination in HIV-infected patients is an important issue for good clinical care.The immune system dysfunction in HIV-infection iw extensive and multifactorial. The immune response upon vaccination is generally impaired in HIV-infected patients. . The aim of this study was to evaluate the immune response to hepatitis A vaccine, the factors that may affect the response and vaccination’s effect to HIV-infection parameters. Eligibility criteria included CD4 T-cell counts more than 200cells/mm3 at the time of vaccination.351 HIV-infected MSM men were recruited to the study. Anti-HAV antibody titers were determined with a commercial enzyme-linked fluorescent assay method [VIDAS Anti-HAV Total, Biomerieux, France] at month 1, 6, 12 and 18 after the second dose of vaccine. CD4, CD8 T-, NK-, B-cells counts and HIV RNA level were determined 1 month after second dose of vaccine . Seroconversion occurred 1 month after the second dose of HAV vaccine in74.4% [260/351] of the cases. Seroprotective titers of anti-HAV antibodies were measured in 68.4%, 61.2 % and 56.1% at months 6, 12 and 18 respectively. Those who responded had significantly higher CD4 T-cell counts at the time of vaccination than those who didn’t respond [580 cells/mm3 vs. 528 cells/mm3] .There was no significant difference to response rate between patients with plasma HIV RNA500 cells/mm3] are supposed to have sufficient immune system, our study demonstrates that a number of HIV-patients, even those with high CD4 counts, do not respond to the hepatitis A vaccine. It is then confirmed that immune dysfunction in HIV-infection is multifactorial and the determination of the number of CD4 T cells helps quantify immune status but it is not an accurate predictor of immune response to vaccines Furthermore, new challenges arise, concerning guidelines for administration strategies for non-responders and those with no detectable antibodies should be evaluatedH πορεία της HIV-λοίμωξης έχει αλλάξει θεαματικά με τη χορήγηση της υψηλής αποτελεσματικότητας αντιρετροϊκής θεραπείας [Highly Activated Antiretroviral Therapy, HAART] Η φροντίδα των ασθενών στοχεύει όχι απλώς στην επιβίωση αλλά στη μείωση επιπλοκών και συλλοιμώξεων και βελτίωση της ποιότητας ζωής. Παρ’ όλα αυτά οι ασθενείς εξακολουθούν να βρίσκονται σε υψηλό κίνδυνο προσβολής από νοσήματα που μπορούν να προληφθούν με τα εμβόλια, ιδίως αν έχουν και σεξουαλική μετάδοση. Η ηπατίτιδα Α αποτελεί πρόβλημα της δημόσιας υγείας και έχει ιδιαίτερη σημασία για τους ασθενείς με ΗIV-λοίμωξη, κυρίως τους ομοφυλόφυλους και τους τοξικομανείς. Αν και αποτελεί συνήθως ήπιο αυτοπεριοριζόμενο νόσημα, στους ανοσοκατασταλμένους μπορεί να εμφανίσει σοβαρές επιπλοκές. Ο πιο αποτελεσματικός τρόπος πρόληψής της είναι ο εμβολιασμός των ομάδων κινδύνου. Η ολοκληρωμένη φροντίδα των ασθενών με ΗIV-λοίμωξη πρέπει να περιλαμβάνει και επιτυχή εμβολιασμό έναντι της ηπατίτιδας Α.Η ανεπάρκεια του ανοσοποιητικού συστήματος που παρατηρείται στη HIV-λοίμωξη είναι εκτεταμένη και πολυπαραγοντική. Ετσι, η ανοσολογική ανταπόκριση των ασθενών στα εμβόλια είναι γενικά μειωμένη. Σκοπός της παρούσας εργασίας ήταν να καταγράψει το εύρος της αντισωματικής απάντησης στο εμβόλιο της ηπατίτιδας Α, τους παράγοντες που επηρεάζουν την ανταπόκριση και την επίδραση του εμβολίου σε ανοσολογικές παραμέτρους της ΗIV-λοίμωξης. Κριτήριο ένταξης αποτελούσε ο αριθμός των CD4 T-λεμφοκυττάρων> 200cells/mm3.Στη μελέτη εντάχθηκαν 351 άνδρες ομοφυλόφυλοι με ΗIV-λοίμωξη. Τα αντισώματα έναντι της ηπατίτιδας Α [anti-HAV]. υπολογίσθηκαν με ποσοτική μέθοδο μέτρησης ολικών anti-HAV [VIDAS Anti-HAV Total, Biomerieux, France] 1,6,12 και 18 μήνες μετά τη χορήγηση της δεύτερης δόσης του εμβολίου. Παρομοίως ένα μήνα μετά τη δεύτερη δόση μετρήθηκαν τα CD4, CD8 T-λεμφοκύτταρα, NK- και B-κύτταρα καθώς και το HIV RNA.Το ποσοστό ανταπόκρισης στον εμβολιασμό, 1 μήνα μετά την χορήγηση της 2ης δόσης, υπολογίσθηκε σε 74% [216/351]. Τον 6ο, 12ο και 18ο μήνα τα ποσοστά ανταπόκρισης στο σύνολο των συμμετεχόντων ήταν 68,4% [95% CI, 64-73] , 61,2 % [95% CI, 56-66] και 56,1% [95% CI, 51-61] αντίστοιχα. Οι ασθενείς που ανταποκρίθηκαν στον εμβολιασμό είχαν σημαντικά υψηλότερα CD4 T-λεμφοκύτταρα σε σύγκριση με όσους δεν ανταποκρίθηκαν [580 cells/mm3 έναντι 528 cells/mm3]. Αντίθετα δεν υπήρχε διαφορά στην ανταπόκριση μεταξύ των ασθενών με μη ανιχνεύσιμο ιικό φορτίο [HIV RNA50copies/ml]: ποσοστό ανταπόκρισης 71% και 70% αντίστοιχα.Ο μέσος γεωμετρικός τίτλος των αντισωμάτων [geometric mean titer -GMT] παρουσίασε μείωση στις επαναληπτικές μετρήσεις [τιμή p500 cells/mm3 είχαν υψηλότερους τίτλους αντισωμάτων, από τους εμβολιασμένους με CD4 T-λεμφοκύτταρα 200-499 cells/mm3 .Μετά τον εμβολιασμό [μήνας 1] δεν καταγράφηκε στατιστικά σημαντική διαφορά στο ιικό φορτίο ή ανοσολογικές παραμέτρους της ΗIV-λοίμωξης. Μελετήθηκαν διάφοροι παράγοντες για τυχόν επίδρασή τους στην ανοσολογική ανταπόκριση, όπως: τα CD4 T-λεμφοκύτταρα, το ιικό φορτίο HIV RNA, τα nadir CD4, η λήψη HAART, το ιστορικό καθοριστικών για το AIDS καταστάσεων, η ηλικία, το κάπνισμα και ο δείκτης μάζας σώματος. Με τη λογιστική παλινδρόμηση διαπιστώθηκε ότι μόνο τα CD4 T-λεμφοκύτταρα κατά τον εμβολιασμό σχετίζονται με την ανταπόκριση.Οι ασθενείς με υψηλά CD4 T-λεμφοκύτταρα [>500 cells/mm3 ] αντιμετωπίζονται ως έχοντες επαρκές ανοσοποιητικό σύστημα. Στην παρούσα μελέτη ένα ποσοστό των ασθενών αυτών δεν ανταποκρίθηκε στο εμβόλιο της ηπατίτιδας Α. Επιβεβαιώνεται έτσι ότι στην ανοσολογική δυσλειτουργία της ΗIV-λοίμωξης εμπλέκονται πολλοί μηχανισμοί. Η παρακολούθηση των CD4 T-λεμφοκυττάρων αποτελεί αδρό μόνο δείκτη της κατάστασης του ανοσοποιητικού συστήματος και δεν προδικάζει την ανοσολογική απάντηση στα εμβόλια. Περαιτέρω ανακύπτουν νέες επιστημονικές προκλήσεις όπως η σύσταση οδηγιών για την αντιμετώπιση όσων δεν ανταποκρίνονται στο εμβόλιο ή εμφανίζουν απώλεια των ανιχνεύσιμων αντισωμάτων

Evaluation of a convenient vaccination schedule against hepatitis B in HIV-patients with undetectable HIV viral load

Vaccination against hepatitis B virus (HBV) is recommended for all HIV-positive individuals but the standard schedule is not satisfactory. High or more doses have also been studied with variable results. We compared a vaccination schedule with a higher dose but fewer shots to the standard scheme (HBVaxPro 40 mu g versus Engerix 20 mu g at 0, 1, and 6 months). Of the 63 patients vaccinated with HBVaxPro 79%, 65% and 47% seroconverted at month 1, 12 and 24 after vaccination, respectively. A total of 137 patients received Engerix and showed lower response rates (68%, 53% and 38%, respectively). AntiHBs titers in the Engerix group were also lower with a statistically significant difference. In patients younger than 55 years HBVaxPro was 3 times more likely to provoke a response compared with Engerix (OR = 3, p = 0.006). In conclusion, HBVaxPro 40 g at 3 doses could be proposed as a more robust and acceptable alternative. (C) 2018 Elsevier Ltd. All rights reserved

Effects of first antiretroviral regimen on lipid levels in HIV (+) individuals

Objective: To evaluate the long-term effects of different boosted protease inhibitors (bPIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs)-based antiretroviral regimens on lipid levels in HIV seropositive individuals who have not received lipid-lowering agents. Methods: Data consisted of 595 patients participating in the population-based Athens Multicenter Cohort Study who were consistently followed up during 1996-2008. Results: In naive patients, lipid parameters increased sharply during the first 3 months of antiretroviral therapy and reached a plateau level approximately 6-9 months after therapy initiation. The plateau levels remained almost stable for up to 3.5 years. In general, bPIs exerted a more pronounced effect compared to NNRTIs. Conclusions: The administration of PI-or NNRTI-based regimens especially in naive but also in unboosted PI experienced patients provoked a sharp increase in lipid levels that remained stable in higher levels for more than 3 years

The HIV patient profile in 2013 and 2003: Results from the Greek AMACS cohort.

Combined Antiretroviral therapy (cART) has improved life-expectancy of people living with HIV (PLHIV) but as they age, prevalence of chronic non-AIDS related comorbidities may increase. We study the evolution of HIV-disease markers and comorbidities' prevalence in PLHIV in Greece. Two cross-sectional analyses (2003 and 2013) on data from the AMACS cohort were performed. Comparisons were based on population average models and were repeated for subjects under follow-up at both 2003 and 2013. 2,403 PLHIV were identified in 2003 and 4,910 in 2013 (1,730 contributing for both cross-sections). Individuals in 2013 were on average older, diagnosed/treated for HIV for longer, more likely to be on cART, virologically suppressed, and with higher CD4 counts. Chronic kidney disease, dyslipidemia and hypertension prevalence increased over time. There was an increase in prescription of lipid-lowering treatment (3.5% in 2003 vs. 7.7% 2013, p20%) increased from 18.2% to 22.2% (p = 0.002). Increase in the prevalence of comorbidities was more pronounced in the subset of patients who were followed in both 2003 and 2013. The increased availability and uptake of cART led to significant improvements in the immuno-virological status of PLHIV in Greece, but they aged alongside an increase in prevalence of non-AIDS related comorbidities. These results highlight the need for appropriate monitoring, optimal cART selection and long-term management and prevention strategies for such comorbidities

The HIV patient profile in 2013 and 2003: Results from the Greek AMACS cohort

Combined Antiretroviral therapy (cART) has improved life-expectancy of people living with HIV (PLHIV) but as they age, prevalence of chronic non-AIDS related comorbidities may increase. We study the evolution of HIV-disease markers and comorbidities’ prevalence in PLHIV in Greece. Two cross-sectional analyses (2003 and 2013) on data from the AMACS cohort were performed. Comparisons were based on population average models and were repeated for subjects under follow-up at both 2003 and 2013. 2,403 PLHIV were identified in 2003 and 4,910 in 2013 (1,730 contributing for both cross-sections). Individuals in 2013 were on average older, diagnosed/treated for HIV for longer, more likely to be on cART, viro-logically suppressed, and with higher CD4 counts. Chronic kidney disease, dyslipidemia and hypertension prevalence increased over time. There was an increase in prescription of lipid-lowering treatment (3.5% in 2003 vs. 7.7% 2013, p<0.001). Among 220 and 879 individuals eligible for Framingham 10-year Event Risk calculation, the proportion of patients in the high-risk group (>20%) increased from 18.2% to 22.2% (p = 0.002). Increase in the prevalence of comorbidities was more pronounced in the subset of patients who were followed in both 2003 and 2013. The increased availability and uptake of cART led to significant improvements in the immuno-virological status of PLHIV in Greece, but they aged alongside an increase in prevalence of non-AIDS related comorbidities. These results highlight the need for appropriate monitoring, optimal cART selection and long-term management and prevention strategies for such comorbidities. © 2018 Pantazis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Inequalities by educational level in response to combination antiretroviral treatment and survival in HIV-positive men and women in Europe

Background: Socioeconomic inequality challenges population-level implementation of health interventions. We investigated differences by educational level in clinical, virological, and immunological responses to combined antiretroviral treatment (cART) in HIV-positive men and women in Collaboration of Observational HIV Epidemiological Research in Europe, a European collaboration. Methods: Data were pooled from 15 cohorts in eight countries of patients initiating cART in 1996-2013 with data on educational level categorized in UNESCO/ISCED classifications. Kaplan-Meier curves, Cox and piecewise linear mixed models were used. Results: Of 24 069 HIV-positive patients, 9% had not completed primary education, 32% had completed primary, 44% secondary, and 15% tertiary education. Overall, 21% were women, who were overrepresented in lower educational strata. During 132 507 person-years of follow-up, 1081 individuals died; cumulative mortality decreased with higher educational level (P< 0.001). Over 122 765 person-years, new AIDS events or death occurred in 2598 individuals; differences by education were more marked than for death alone (P< 0.001). Virological response was achieved by 67% of patients without completed basic education, 85% with completed primary education, 82% with secondary, and 87% with tertiary (P< 0.001). Patients with higher education had higher CD4(+) cell count at cART initiation and at each time after cART but rate of CD4(+) cell count recovery did not differ. Differences in mortality and clinical responses were similar for men and women and were not entirely explained by delayed HIV diagnosis and late cART initiation. Conclusion: HIV-positive patients with lower educational level had worse responses to cART and survival in European countries with universal healthcare. To maximize the population impact of cART, Europe needs to decrease the socioeconomic divide. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved