ΠΝΕΥΜΟΝΑΣ ΚΑΙ HIV ΝΟΣΟΣ

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1 ΠΝΕΥΜΟΝΑΣ ΚΑΙ HIV ΝΟΣΟΣ ΓΙΑΝΝΗΣ ΜΠΑΡΑΜΠΟΥΤΗΣ ΠΑΘΟΛΟΓΟΣ-ΛΟΙΜΩΞΙΟΛΟΓΟΣ ΛΟΙΜΩΞΙΟΛΟΓΟΣ ΜΟΝΑΔΑ ΛΟΙΜΩΞΕΩΝ Γ.Ν.Α. «Ο ΕΥΑΓΓΕΛΙΣΜΟΣ»

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14 ΜΕΙΟΥΜΕΝΗ ΘΝΗΤΟΤΗΤΑ ΜΕ ART

15 ΔΡΑΣΤΙΚΗ ΜΕΙΩΣΗ ΤΩΝ ΕΥΚΑΙΡΙΑΚΩΝ ΛΟΙΜΩΞΕΩΝ ΜΕ ΧΡΗΣΗ ART

16 ΑΝΑΠΤΥΞΗ ΑΝΤΙΡΕΤΡΟΙΪΚΩΝ ΦΑΡΜΑΚΩΝ Πρώτη αναφορά κρούσματος AIDS ZDV Νέες μορφές Σταθεροί συνδυασμοί ddi ddc d4t 3TC, SQV RTV, IDV, NVP NFV, DLV, ZDV/3TC, SQV-gc EFV, ABC APV LPV/RTV, ddi-ec, ZDV/3TC/ABC TDF EFV-600, 3TC-300, d4t-xr ENF, NFV 625, ATV, FTC, FPV ABC/3TC, TDF/FTC, ddi generic SQV 500, TPV, ZDV generic, LPV/RTV tabs DRV, TDF/FTC/EFV

17 Establishment and Maintenance of a Latent Reservoir Naive Generation of latently infected cells Ag HIV Memory Reactivation of latent HIV Ag

18 Initiating Rather than Deferring HAART at a CD4 count Between cells/mm 3 is Associated with Improved Survival North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), ACCORD), New Engl J Med Apr 2009 Timing of initiation of antiretroviral therapy in AIDS-free HIV-1-infected patients: a collaborative analysis of 18 HIV cohort studies When To Start Consortium Antiretroviral Therapy (ART) Cohort Collaboration (ACC), Lancet April 2009

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20 HIV ΛΟΙΜΩΞΗ: ΜΙΑ ΧΡΟΝΙΑ ΝΟΣΟΣ ΕΞΕΛΙΞΗ ΑΝΤΙΡΕΤΡΟΙÏΚΗΣ ΘΕΡΑΠΕΙΑΣ (ART) ΣΥΜΜΟΡΦΩΣΗ ΑΣΘΕΝΩΝ ΜΕ ART ΤΟΞΙΚΟΤΗΤΑ ART ΜΑΚΡΟΧΡΟΝΙΕΣ ΕΠΙΠΛΟΚΕΣ HIV ΛΟΙΜΩΞΗΣ ΣΥΝΥΠΑΡΧΟΝΤΑ ΝΟΣΗΜΑΤΑ ΤΟ ΓΗΡΑΣΚΟΝ ΑΤΟΜΟ ΜΕ HIV ΛΟΙΜΩΞΗ ΑΝΤΙΣΤΑΣΗ ΣΤΗΝ ART HIV ΣΕ ΑΝΑΠΤΥΣΣΟΜΕΝΕΣ ΧΩΡΕΣ ΠΡΟΛΗΨΗ ΜΕΤΑΔΟΣΗΣ HIV

21 Χαμηλά επίπεδα CD4 κατά την έναρξη χώρες 176 μονάδες 33,008 ασθενείς ART σε παγκόσμιο επίπεδο Adapted from Egger M, 14th CROI Los Angeles, CA, USA, Feb Abstract 62. ART Cohort Collaboration. Available at: Accessed March 3, 2009.

22 ΣΚΕΛΕΤΟΣ ΕΙΣΗΓΗΣΗΣ Ο ΑΣΘΕΝΗΣ ΜΕ HIV ΛΟΙΜΩΞΗ ΚΑΙ ΠΡΟΣΒΟΛΗ ΤΟΥ ΠΝΕΥΜΟΝΑ ΠΡΟ HAART ΕΠΟΧΗ (ΑΣΘΕΝΗΣ) ΜΕΤΑ HAART ΕΠΟΧΗ (ΑΣΘΕΝΗΣ) ΕΙΔΙΚΑ ΠΡΟΒΛΗΜΑΤΑ

23 Taylor IK, Thorax 1995

24 ΣΗΜΑΝΤΙΚΕΣ ΕΡΩΤΗΣΕΙΣ ΣΕ ΠΟΙΑ ΕΠΟΧΗ ΒΡΙΣΚΕΤΑΙ Ο ΑΣΘΕΝΗΣ; ΑΡΙΘΜΟΣ CD4 ΛΕΜΦΟΚΥΤΤΑΡΩΝ; ΧΡΟΝΙΩΣ ΠΑΣΧΩΝ ΕΚΤΟΣ ΑΠΌ ΤΟ ΟΞΥ ΠΡΟΒΛΗΜΑ; <100 ΚΥΤΤΑΡΑ/ΜL: > ΚΥΤΤΑΡΑ/ΜL: ΣΠΑΝΙΑ ΕΥΚΑΙΡΙΑΚΗ ΛΟΙΜΩΞΗ ΠΙΟ ΠΙΘΑΝΗ Η ΟΞΕΙΑ ΒΡΟΓΧΙΤΙΔΑ ΚΑΙ Η ΒΑΚΤΗΡΙΑΚΗ ΠΝΕΥΜΟΝΙΑ ΕΞΑΙΡΕΣΗ Η ΦΥΜΑΤΙΩΣΗ (περίπου το 50% σε CD4>200) ΠΝΕΥΜΟΝΙΚΟ ΣΑΡΚΩΜΑ KAPOSI NON-HODGKIN ΛΕΜΦΩΜΑ ΚΡΥΠΤΟΚΟΚΚΩΣΗ ΚΕΧΡΟΕΙΔΗΣ ΦΥΜΑΤΙΩΣΗ <50 ΚΥΤΤΑΡΑ/ΜL: CMV (συχνά( σε συνδυασμό με PJP) ΔΙΕΙΣΔΥΤΙΚΗ ΑΣΠΕΡΓΙΛΛΩΣΗ (συνήθως με ουδετεροπενία) ΆΛΛΕΣ ΜΥΚΗΤΙΑΣΕΙΣ ΑΤΥΠΑ ΜΥΚΟΒΑΚΤΗΡΙΔΙΑ (kansasii, άλλα, MAC σπανιότατο)

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26 ΣΗΜΑΝΤΙΚΕΣ ΕΡΩΤΗΣΕΙΣ ΠΕΡΑΙΤΕΡΩ ΙΑΤΡΙΚΟ ΙΣΤΟΡΙΚΟ Για πνευμονική νόσο (ΧΑΠ κλπ) ΦΑΡΜΑΚΑ PJP σπανιότατη (και βακτηριακή πνευμονία με μειωμένη επίπτωση) με ορθή λήψη TMP/SMX, άτυπη PJP με προφυλακτική εισπνεόμενη πενταμιδίνη ΧΡΟΝΟΣ ΕΝΑΡΞΗΣ ART ΚΑΙ ΕΙΔΟΣ ART Σύνδρομα ανοσιακής αποκατάστασης με πρόσφατη έναρξη ART (ημέρες( ημέρες-εβδομάδες) σε ήδη γνωστή φυματίωση, λοίμωξη από άτυπα μυκοβακτηρίδια, κρυπτοκόκκωση (σπανιότερα πρώτη εκδήλωση της λοίμωξης). Σπανιότατα πρώτη εκδήλωση λεμφώματος. Ειδικά σε προχωρημένο AIDS με υψηλό φορτίο ιού και χαμηλά CD4 Γαλακτική οξέωση από τους παλαιούς αναστολείς της ανάστροφης μεταγραφάσης (AZT, D4T, DDI), συνήθως στο πρώτο 3μηνο από την έναρξη. Σπανιότατη με τα νεώτερα φάρμακα. Ανεξήγητη δύσπνοια/ταχύπνοια Συνοδά ανεξήγητα γενικά συμπτώματα ή/και συμπτώματα από το γαστρεντερικό Θανατηφόρα αν δε διαγνωστεί έγκαιρα. Μόνη τεκμηριωμένα αποτελεσματική θεραπεία: διακοπη του φαρμάκου

27 ΣΗΜΑΝΤΙΚΕΣ ΕΡΩΤΗΣΕΙΣ ΚΑΠΝΙΣΜΑ???

28 Smoking Is Common Among HIV-Infected Infected Patients: D:A:D Baseline Data % of Cohort With Risk Factor Family Hx of CHD Previous Hx of CHD Current Smoking BMI > 30 mg/m 2 HTN DM Hypercholesterolemia Increased TG Friis-Moller N, et al. AIDS. 2003;17:

29 ΚΑΠΝΙΣΜΑ ΚΑΙ HIV ΝΟΣΟΣ ΣΧΕΔΟΝ ΌΛΑ ΤΑ ΝΟΣΗΜΑΤΑ ΤΟΥ ΠΝΕΥΜΟΝΑ, ΣΧΕΤΙΖΟΜΕΝΑ Η ΟΧΙ ΜΕ ΤΗ HIV ΛΟΙΜΩΞΗ, ΕΊΝΑΙ ΣΥΧΝΟΤΕΡΑ ΣΕ ΚΑΠΝΙΣΤΕΣ ΜΕ HIV ΛΟΙΜΩΞΗ ΑΠΌ Ο,ΤΙ ΣΕ ΜΗ ΚΑΠΝΙΣΤΕΣ ΜΕ HIV ΛΟΙΜΩΞΗ ΒΑΚΤΗΡΙΑΚΗ ΠΝΕΥΜΟΝΙΑ, PJP, ΧΡΟΝΙΑ ΑΠΟΦΡΑΚΤΙΚΗ ΠΝΕΥΜΟΝΟΠΑΘΕΙΑ, ΑΣΘΜΑ, ΚΑΡΚΙΝΟΣ ΤΟΥ ΠΝΕΥΜΟΝΑ (ήδη γνωστό για ΌΛΑ από την προ HAART εποχή)

30 ΣΗΜΑΝΤΙΚΕΣ ΕΡΩΤΗΣΕΙΣ ΤΑΞΙΔΙΩΤΙΚΟ ΙΣΤΟΡΙΚΟ ΕΝΔΗΜΙΚΕΣ ΜΥΚΗΤΙΑΣΕΙΣ ΦΥΜΑΤΙΩΣΗ (μετανάστες) ΤΡΟΠΟΣ ΜΕΤΑΔΟΣΗΣ HIV Σάρκωμα Κaposi αποκλειστικά σε MSM IVDA:αυξημένη πιθανότητα βακτηριακής πνευμονίας και φυματίωσης Είδος, ποιότητα και διάρκεια συμπτωμάτων Διαφοροδιάγνωση βακτηριακής πνευμονίας από PJP (μέση( διάρκεια 3-5 ημέρες και 28 ημέρες αντίστοιχα)

31 ΑΚΤΙΝΟΓΡΑΦΙΑ ΘΩΡΑΚΟΣ ΓΑΛΑΚΤΙΚΗ ΟΞΕΩΣΗ ΠΟΛΥΚΕΝΤΡΙΚΗ ΝΟΣΟΣ CASTLEMAN, ΛΕΜΦΩΜΑ ΟΡΩΔΩΝ ΚΟΙΛΟΤΗΤΩΝ, ΣΧΕΤΙΖΟΜΕΝΑ ΜΕ HHV-8

32 ΒΑΚΤΗΡΙΑΚΗ ΠΝΕΥΜΟΝΙΑ Hull MW et al, Chest 2008

33 RESPIRATORY INFECTIONS Pneumonia in HIV-infected Persons: Increased Risk with Cigarette Smoking and Treatment Interruption (SMART Study, Am J Resp Crit Care Med 2008)

34 ΒΑΚΤΗΡΙΑΚΗ ΠΝΕΥΜΟΝΙΑ ΕΚΤΟΣ ΠΝΕΥΜΟΝΙΟΚΟΚΚΟΥ ΚΑΙ ΑΙΜΟΦΙΛΟΥ ΙΝΦΛΟΥΕΝΖΑΣ ΑΥΞΗΜΕΝΗ ΕΠΙΠΤΩΣΗ ΣΕ ΑΤΟΜΑ ΜΕ HIV ΛΟΙΜΩΞΗ ΣΥΧΝΑ ΜΕ ΥΠΟΛΕΙΜΜΑΤΙΚΗ ΜΑΚΡΟΧΡΟΝΙΑ/ΜΟΝΙΜΗ ΜΟΝΙΜΗ ΒΛΑΒΗ ΤΟΥ ΠΝΕΥΜΟΝΑ (όπως PJP και KS) ΕΠΙΠΤΩΣΗ ΑΥΞΑΝΕΙ ΜΕ ΒΑΘΥΤΕΡΗ ΑΝΟΣΟΚΑΤΑΣΤΟΛΗ 2 ΕΠΕΙΣΟΔΙΑ ΣΕ 12 ΜΗΝΕΣ = AIDS (ΣΑΦΕΣΤΑΤΗ ΕΝΔΕΙΞΗ ΓΙΑ ΕΛΕΓΧΟ ΓΙΑ HIV) ΠΡΩΤΟ ΕΠΕΙΣΟΔΙΟ ΠΝΕΥΜΟΝΙΑΣ:?ΕΝΔΕΙΞΗ ΓΙΑ ΕΛΕΓΧΟ ΣΑΦΕΣΤΑΤΑ ΜΕΙΩΜΕΝΗ ΕΠΙΠΤΩΣΗ ΣΤΗ ΜΕΤΑ HAART ΕΠΟΧΗ ΣΗΜΑΝΤΙΚΑ ΠΑΘΟΓΟΝΑ : ΧΡΥΣΙΖΩΝ ΣΤΑΦΥΛΟΚΟΚΚΟΣ, BRANHAMELLA CATARRHALIS CD4<100: PSEUDOMONAS AERUGINOSA ΣΥΧΝΕΣ ΟΙ ΠΟΛΥΜΙΚΡΟΒΙΑΚΕΣ ΛΟΙΜΩΞΕΙΣ ΚΑΙ ΣΥΛΛΟΙΜΩΞΕΙΣ ΜΕ PJP ΣΕ CD4<100: ΧΑΜΗΛΟΣ ΟΥΔΟΣ ΕΙΣΑΓΩΓΗΣ ΣΤΟ ΝΟΣΟΚΟΜΕΙΟ (ΑΥΞΗΜΕΝΗ ΘΝΗΤΟΤΗΤΑ Χ6 ΣΕ ΣΧΕΣΗ ΜΕ >200) ΕΜΠΕΙΡΙΚΗ ΚΑΛΥΨΗ ΚΑΛΛΙΕΡΓΕΙΕΣ ΑΙΜΑΤΟΣ/ΠΤΥΕΛΩΝ ΠΤΥΕΛΩΝ, ΑΝΤΙΓΟΝΑ ΟΥΡΩΝ ΒΡΟΓΧΟΣΚΟΠΗΣΗ ΣΕ CD4<200

35 PNEUMOCYSTIS JIROVECI Pneumocystis Pneumonia - Los Angeles MMWR Weekly, June 5, 1981 / 30(21);250-2 Centers for Disease Control and Prevention In the period October 1980-May 1981, 5 young men, all active homosexuals, were treated for biopsy-confirmed Pneumocystis carinii pneumonia at 3 different hospitals in Los Angeles, California. Two of the patients died. All 5 patients had laboratory-confirmed previous or current cytomegalovirus (CMV) infection and candidal mucosal infection. Case reports of these patients follow. Patient 1: A previously healthy 33-year year-old man developed P. carinii pneumonia and oral mucosal candidiasis in March 1981 after a 2-2 month history of fever associated with elevated liver enzymes, leukopenia, and CMV viruria. The serum complement-fixation CMV titer in October 1980 was 256; in May 1981 it was 32.* The patient's condition deteriorated despite courses of treatment with trimethoprim- sulfamethoxazole (TMP/SMX), pentamidine, and acyclovir. He died May 3, and postmortem examination showed residual P. carinii and CMV pneumonia, but no evidence of neoplasia. Patient 2: A previously healthy 30-year year-old man developed P. carinii pneumonia in April 1981 after a 5-month 5 history of fever each day and of elevated liver-function tests,, CMV viruria, and documented seroconversion to CMV, i.e., an acute-phase titer of 16 and a convalescent-phase titer of 28* in anticomplement immunofluorescence tests. Other features of his illness included leukopenia and mucosal candidiasis. His pneumonia responded to a course of intravenous TMP/.SMX, but, as of the latest reports, he continues to have a fever each day. Patient 3: A 30-year year-old man was well until January 1981 when he developed esophageal and oral candidiasis that responded to Amphotericin B treatment. He was hospitalized in February 1981 for P. carinii pneumonia that responded to TMP/SMX. His esophageal candidiasis recurred after the pneumonia was diagnosed, and he was again given Amphotericin B. The CMV complement-fixation titer in March 1981 was 8. Material from an esophageal biopsy was positive for CMV. Patient 4: A 29-year year-old man developed P. carinii pneumonia in February He had had Hodgkins disease 3 years earlier, but had been successfully treated with radiation therapy alone. He did not improve after being given intravenous TMP/SMX and corticosteroids and died in March. Postmortem examination showed no evidence of Hodgkins disease, but P. carinii and CMV were found in lung tissue. Patient 5: A previously healthy 36-year year-old man with clinically diagnosed CMV infection in September 1980 was seen in April 1981 because of a 4-month 4 history of fever, dyspnea, and cough. On admission he was found to have P. carinii pneumonia, oral candidiasis, and CMV retinitis.. A complement-fixation CMV titer in April 1981 was 128. The patient has been treated with 2 short courses of TMP/SMX that have been limited because of a sulfa-induced neutropenia. He is being treated for candidiasis with topical nystatin. The diagnosis of Pneumocystis pneumonia was confirmed for all 5 patients antemortem by closed or open lung biopsy. The patients did not know each other and had no known common contacts or knowledge of sexual partners who had had similar illnesses. The 5 reported having frequent homosexual contacts with various partners. All 5 reported using inhalant drugs, and 1 reported parenteral drug abuse. Three patients had profoundly depressed in vitro proliferative responses to mitogens and antigens. Lymphocyte studies were not performed on the other 2 patients.

36 PNEUMOCYSTIS JIROVECI Editorial Note: Pneumocystis pneumonia in the United States is almost exclusively limited to severely immunosuppressed patients (1). The occurrence of pneumocystosis in these 5 previously healthy individuals without a clinically apparent underlying immunodeficiency is unusual. The fact that these patients were all homosexuals suggests an association between some aspect of a homosexual lifestyle or disease acquired through sexual contact and Pneumocystis pneumonia in this population. All 5 patients described in this report had laboratory-confirmed CMV disease or virus shedding within 5 months of the diagnosis of Pneumocystis pneumonia.. CMV infection has been shown to induce transient abnormalities of in vitro cellular-immune function in otherwise healthy human hosts (2,3). Although all 3 patients tested had abnormal cellular-immune function, no definitive conclusion regarding the role of CMV infection in these 5 cases can be reached because of the lack of published data on cellular-immune function in healthy homosexual males with and without CMV antibody. In 1 report,, 7 (3.6%) of 194 patients with pneumocystosis also had CMV infection' ' 40 (21%) of the same group had at least 1 other major concurrent infection (1). A high prevalence of CMV infections among homosexual males was recently reported: : 179 (94%) had CMV viruria; rates for 101 controls of similar age who were reported to be exclusively heterosexual were 54% for seropositivity and zero fro viruria (4). In another study of 64 males,, 4 (6.3%) had positive tests for CMV in semen, but none had CMV recovered from urine. Two of the 4 reported recent homosexual contacts. These findings suggest not only that virus shedding may be more readily detected in seminal fluid than urine, but also that seminal fluid may be an important vehicle of CMV transmission (5). All the above observations suggest the possibility of a cellular-immune dysfunction related to a common exposure that predisposes individuals to opportunistic infections such as pneumocystosis and candidiasis. Although the role of CMV infection in the pathogenesis of pneumocystosis remains unknown, the possibility of P. carinii infection must be carefully considered in a differential diagnosis for previously healthy homosexual males with dyspnea and pneumonia.

37 PNEUMOCYSTIS JIROVECI PNEUMONIA

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42 BACKGROUND As resource-limited countries rapidly expand their HIV/AIDS treatment and care programmes, TB/HIV is now a major public health threat for people living with HIV and the community. Among people living with HIV, TB is the most frequent lifethreatening opportunistic disease, even in those receiving antiretrovirals, and it has been shown to be a leading cause of death. Globally, there were 700,000 TB cases among people living with HIV in An estimated 230,000 people living with HIV will die as a result of TB in 2008 around 630 people every day despite the fact that TB is curable. Prevention and treatment of TB in people living with HIV is an urgent priority for both HIV/AIDS and TB programmes.

43 HIV ΚΑΙ ΦΥΜΑΤΙΩΣΗ Hull MW et al, Chest 2008

44 HIV ΚΑΙ ΦΥΜΑΤΙΩΣΗ

45 BACKGROUND Prevention and treatment of TB in people living with HIV is an urgent priority for both HIV/AIDS and TB programmes. The Three I s, Isoniazid preventive treatment (IPT), intensified case finding (ICF) for active TB, and TB Infection Control (IC), are key public health strategies to decrease the impact of TB on people living with HIV. TB preventive therapy with INH is safe and effective in people living with HIV, reducing the risk of TB by 33 62% Screening and diagnosing TB in people living with HIV can be challenging but TB is curable in people living with HIV TB infection control is essential to keep vulnerable patients, health care workers and their community safe from getting TB.

46 Policy on Collaborative TB/HIV Activities, WHO 2004

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49 Fewer Deaths With Concurrent vs Sequential ART and Tuberculosis Therapy In South African adults with HIV and TB coinfection, initiating antiretroviral therapy during TB therapy associated with 56% reduction in risk of death vs initiating antiretroviral therapy following TB therapy completion Benefit of concurrent therapy observed across CD4+ cell count strata Adverse event rates similar between strategies Integrated therapy associated with higher incidence of IRIS but no antiretroviral therapy changes required Abdool Karim SS, Naidoo K, Grobler A, et al. Timing of initiation of antiretroviral drugs during tuberculosis therapy. N Engl J Med. 2010;362:

50 WHO Guidelines for intensified tuberculosis case-finding and isoniazid preventive therapy for people living with HIV in resource-constrained settings 2011

51 WHO Guidelines for intensified tuberculosis case-finding and isoniazid preventive therapy for people living with HIV in resource-constrained settings 2011

52 ΝΕΟΠΛΑΣΜΑΤΑ ΤΟΥ AIDS ΚΑΙ ΠΝΕΥΜΟΝΑΣ ΕΠΟΧΗ ΠΡΟ HAART Autopsies in HIV Afessa B et al, Chest 1998 Bronchoscopies in HIV Taylor IK, Thorax 1995

53 AIDS-DEFINING DEFINING CANCERS IN PLWHA IN THE HAART ERA Engels et al, Int J Cancer 2008

54 ΕΠΟΧΗ HAART ΣΥΝΔΡΟΜΑ ΑΝΟΣΟΛΟΓΙΚΗΣ ΑΝΑΣΥΣΤΑΣΗΣ (IRIS)

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58 ΠΡΩΤΟΠΑΘΕΣ ΛΕΜΦΩΜΑ ΠΝΕΥΜΟΝΑ ΣΕ HIV ΝΟΣΟ

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60 ΠΝΕΥΜΟΝΙΚΗ ΥΠΕΡΤΑΣΗ ΚΑΙ HIV ΛΟΙΜΩΞΗ ΟΡΙΣΜΟΣ: μέση PAP>25 mmhg σε ηρεμία ΕΠΙΠΟΛΑΣΜΟΣ : 0.45% ΕΠΙΠΤΩΣΗ : 1/1000 ΑΤΟΜΑ/ΕΤΟΣ ΚΛΙΝΙΚΑ ΚΑΙ ΙΣΤΟΛΟΓΙΚΑ ΠΑΡΟΜΟΙΑ ΜΕ ΤΗΝ ΠΡΩΤΟΠΑΘΗ ΠΝΕΥΜΟΝΙΚΗ ΥΠΕΡΤΑΣΗ ΘΕΡΑΠΕΙΑ ΩΣ ΕΠΙ ΠΠΥ + HAART ΠΡΟΓΝΩΣΗ ΧΕΙΡΟΤΕΡΗ ΑΠΌ ΠΠΥ

61 HIGH PREVALENCE OF TOBACCO USE IN PLWHA CONSISTENTLY HIGHER PREVALENCE THAN THAT OF THE GENERAL POPULATION Significant overlap between demographic risk factors known to be associated with HIV infection and also with cigarette smoking: lower socio-economic status substance abuse belonging to ethnic minority groups MSM (tend to smoke at an early age) Pre-HAART era (pain reduction, stress relief, fear of AIDS and death relief, nothing to lose since patients faced a deadly disease) ART ERA?

62 PERSISTENTLY HIGH -AND EVEN INCREASING- PREVALENCE OF TOBACCO USE IN PLWHA IN THE HAART ERA OUTPATIENT SURVEYS IN EUROPE AND NORTH AMERICA DATA FROM LARGE COHORTS (D:A:D, ANRS, SWISS HIV COHORT, MACS) PREVALENCE AT LEAST 50-70% PREVALENCE OF HEAVY SMOKING (>20 pack-years): UP TO 30-40% OVERALL (UP TO TIMES HIGHER THAT OF THE GENERAL POPULATION)

63 PATHOGENESIS OF SMOKING-RELATED ORGAN/SYSTEM DAMAGE IN HIV PERIPHERAL BLOOD Cigarette smoking in HIV-negative individuals is known to cause increases in white blood cell counts, including all the WBC subpopulations Cigarette smoking by HIV-infected individuals has been associated with a relative increase in the peripheral blood CD4 T-lymphocyte count as compared with that of nonsmokers (Chao et al, MACS cohort data, Drug Alcohol Dep 2008)

64 PATHOGENESIS OF SMOKING-RELATED ORGAN/SYSTEM DAMAGE IN HIV LUNG Lung lymphocyte numbers are frequently increased in human immunodeficiency virus (HIV)-infected individuals in the absence of lung infection. HIV-infected smokers may have significant depressions in both the percentage and absolute numbers of CD4 and CD8 cells in their bronchoalveolar lavage fluid, decrease in CD4/CD8 cell ratios and suppression of production of both interleukin-1b (IL-1b) and tumor necrosis factora(tnfa) in comparison to HIV-infected nonsmokers (Wewers et al, Am J Resp Med Crit Care 1998). HIV-1 Infection Does Not Impair Human Alveolar Macrophage Phagocytic Function Unless Combined With Cigarette Smoking (Elssner et ak, Chest 2004)

65 SMOKING-RELATED ORGAN/SYSTEM DAMAGE IN HIV PRE-HAART ERA Association with Oral candidiasis Periodontal disease Oral hairy leukoplakia and other types of oral lesions Increased respiratory symptoms Acute bronchitis Bacterial pneumonia Pneumocystis jiroveci pneumonia (PCP) AIDS-related spontaneous pneumothorax Kaposi sarcoma Lung cancer Cervical cancer Increased risk of mother-to to-child transmission

66 SMOKING-RELATED ORGAN/SYSTEM DAMAGE IN HIV PRE-HAART ERA It is unclear as to whether cigarette smoking potentiates disease progression from HIV infection to AIDS Positive association Nieman R, Fleming J, Coker R, Harris J, Mitchell D. The effect of cigarette smoking on the development of AIDS in HIV-1 seropositive individuals. AIDS 1993; 7: Abbud R, Finegan C, Guay L, Rich E. Enhanced production of HIV type 1 by in vitro infected alveolar macrophages from otherwise healthy cigarette smokers. J Infect Dis 1995;172: No association Craib K, Schechter M, Montaner J, et al. The effect of lymphocyte subsets and progression to AIDS in a cohort of homosexual men. Clin Invest Med 1992; 15: Galai N, Park L, Wesch J, Visscher B, Riddler S, Margolick J. Effect of smoking on the clinical progression of HIV-1 infection. J Acquir Immune Defic Syndr Hum Retrovirol 1997; 14:451 8.

67 SMOKING-RELATED ORGAN/SYSTEM DAMAGE IN PLWHA IN THE HAART ERA OVERALL MORTALITY CARDIOVASCULAR PULMONARY (RESPIRATORY SYMPTOMS, INFECTIONS, CHRONIC LUNG DISEASE, CANCER) NON-LUNG LUNG CANCERS NON-LUNG INFECTIONS BONE NEUROCOGNITIVE ADHERENCE TO ANTIRETROVIRAL THERAPY (indirect health effect)

68 SMOKING AND LUNG DISEASE IN PLWHA RESPIRATORY SYMPTOMS INFECTIONS CHRONIC LUNG DISEASE CANCER

69 RESPIRATORY SYMPTOMS HIV-seropositive individuals are at increased risk for the development of respiratory symptoms even prior to the onset of AIDS-related pulmonary complications. This may reflect a heightened susceptibility to the effects of cigarette smoking (Diaz et al, Chest 2003).

70 RESPIRATORY SYMPTOMS

71 Crothers et al, Chest 2006 Increased COPD Among HIV-Positive Compared to HIV-Negative Veterans

72 ΕΜΦΥΣΗΜΑ ΣΧΕΤΙΖΟΜΕΝΟ ΜΕ ΤΗΝ HIV ΛΟΙΜΩΞΗ

73 PATHOGENESIS OF EMPHYSEMA IN HIV Petrache et al, Thorax 2008

74 ΕΜΦΥΣΗΜΑ ΣΧΕΤΙΖΟΜΕΝΟ ΜΕ HIV ΛΟΙΜΩΞΗ

75 ΕΜΦΥΣΗΜΑ ΣΧΕΤΙΖΟΜΕΝΟ ΜΕ HIV ΛΟΙΜΩΞΗ

76 ΑΣΘΜΑ ΚΑΙ HIV ΛΟΙΜΩΞΗ Η HIV λοίμωξη συνδυάζεται με δυσλειτουργία/ανεπάρκεια ανεπάρκεια της Τ- κυτταρικής ανοσίας ενώ το βρογχικό άσθμα με υπέρμετρη δραστηριότητα των Τ-λεμφοκυττάρων Αυξημένη επίπτωση bronchial hyperresponsiveness σε καπνιστές με HIV λοίμωξη. Οι μισοί ασθενείς είχαν τουλάχιστον 1 επεισόδιο βρογχόσπασμου τους τελευταίους 12 μήνες (Poirier et al, Am J Resp Crit Care Med 2001) Σε παιδιά με HIV λοίμωξη, η ανοσολογική ανασύσταση συνδυάζεται με αυξημένη επίπτωση άσθματος (Foster SB, J Allergy Clin Immunol 2008) Η συχνότητα του άσθματος μπορεί να υποεκτιμάται στους PLWHA

77 ΑΣΘΜΑ ΚΑΙ ΝΟΣΟΣ HIV

78 SMOKING AND NON-AIDS DEFINING CANCERS IN PLWHA

79 Engels et al J Clin Oncol 2006 ELEVATED PREVALENCE OF LUNG CANCER IN PLWHA IN COMPARISON TO THE GENERAL POPULATION

80 LUNG CANCER IN HIV HIV Infection Is Associated with an Increased Risk for Lung Cancer, Independent of Smoking. Kirk et al, Clin Infect Dis 2007 (additional reasoning for smoking cessation in PLWHA)

81 SMOKING AND LUNG CANCER IN PLWHA Lavole et al, Lung Cancer 2006

82

83 ΛΕΜΦΟΚΥΤΤΑΡΙΚΗ ΔΙΑΜΕΣΗ ΠΝΕΥΜΟΝΙΑ Χρόνια ή υποξεία πορεία Ακτινολογική εικόνα παρόμοια με PJP CD4>200 κύτταρα/μl Φυσιολογική LDH Εικόνα λεμφοκυτταρικής κυψελιδίτιδας (κυρίως CD8) χωρίς μικροοργανισμούς Όχι σπάνια χρειάζεται ανοικτή βιοψία για τη διάγνωση Θεραπεία : κορτικοειδή?σύνδρομο ανοσολογικής ανασύστασης

84 ΣΑΣ ΕΥΧΑΡΙΣΤΩ ΓΙΑ ΤΗΝ ΠΡΟΣΟΧΗ ΣΑΣ!!