Navin presentation for hiv disease


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HIV disease and its cardiovascular manifestations:-diagnosis

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Navin presentation for hiv disease

  2. 2. AIDS (Acquired Immunodeficiency Syndrome) was 1st described in 1981 It is a chronic infection caused by HIV 1 & 2 It continuously replicates leading to progressive dysfunction and gradual depletion of CD4 + lymphocytes. ( can also infect macrophages and B lymphocytes) The total no infected HIV/ AIDS globally as of Dec 2000, 58 million, of whom 21.8 million died since beginning of the epidemic.
  3. 3. Acquired Immunodeficiency Syndrome (AIDS) History  1950s: Blood samples from Africa have HIV       antibodies. 1976: First known AIDS patient died. 1980: First human retrovirus isolated (HTLV-1). 1981: First reports of “Acquired Immuno-deficiency Syndrome” in Los Angeles. 1983: Virus first isolated in France (LAV). 1984: Virus isolated in the U.S. (called HTLV-III and AIDS-Related Virus, ARV). 1985: Development and implementation of antibody test to screen blood donors.
  4. 4. Acquired Immunodeficiency Syndrome (AIDS) History (Continued)  1986: Consensus name Human Immunodeficiency Virus (HIV-1). Related virus (HIV-2) identified.  1992: AIDS becomes the leading cause of death among adults ages 25-44 in the U.S.  1997: Mortality rates of AIDS starts to decline due to the introduction of new drug cocktails.  2001: World Health Organization predicts up to 40 million infected individuals. More than 22 million have already died.
  5. 5. Asymptomatic infection (CDC Category A)  Viral replication takes place in lymphoid tissue.  Sustained viremia with steady decline in CD4 count (50-150 cells/year).  Persistent generalized lymphadenopathy, but the patient remains well.
  6. 6. Mildly symptomatic Disease (CDC category B)  Median interval from infection to development of symptoms is 10 years HIV infection and one of the following:  Bacillary angiomatosis  Candidiasis, oropharyngeal, vulvovaginal; persistent or poorly responsive to therapy  Cervical dysplasia/CIN  Fever>38.5 C, diarrhoea > 1m  Oral hairy leukoplakia  Herpes zoster involving more than one dermatome or 2 distinct episodes  ITP  Listeriosis  PID, particularly if complicated by tuboovarian abscess  Peripheral neuropathy
  7. 7. AIDS (CDC category C) (CD4 < 200/cmm or one of the  Esophageal or tracheobronchial candidiasis following)  CMV retinitis  CMV disease (other than liver, spleen or lymph nodes)  Pulmonary or extrapulmonary TB, recurrent pneumonia  Mycobacterium avium complex, M. kansasii, other        species, disseminated or extrapulmonary Cryptococcosis, extrapulmonary Cryptosporidiosis, intestinal (>1m duration) Toxoplasmosis of brain Kaposi’s sarcoma Burkitt’s lymphoma Primary CNS lymphoma, HIV-associated encephalopathy Wasting syndrome
  8. 8.  At the end of 2002, the Joint United Nations Programme on       HIV/AIDS estimated that worldwide, more than 40 million adults and children were living with HIV/AIDS. In India, 2.4 million adults live with the virus. Overall prevalence – 0.3%. Before the advent of antiretroviral therapy (ART), clinically significant cardiac disease was unusual in the HIV-infected population and was detected in most cases only at autopsy(40%) In the late 1980s, cardiac abnormalities were detected more often on ECHO (25%) than would be expected from clinical symptoms and physical examination (<10%). Prevalence of cardiac manifestations: 28-73%. Death due to HIV related cardiac disease <2%. In HIV – infected children <10 y of age, 25% die with chronic cardiac disease and 28% experience serious cardiac events after an AIDS– defining illness.
  9. 9. Potential mechanisms of cardiac complications in AIDS Mechanism Effect Direct infection of cardiac myocytes Cardiomyopathy/myocarditis Toxicity of HIV components Impaired myocardial contractility Immune processes involving MHC I, anti-αmyosin Ab, cytokines Cardiomyopathy and endothelial dysfunction Nutritional deficiencies (carnitine, Se, thiamine) Cardiomyopathy Drug toxicity (HAART, antifungals, antivirals) Cardiomyopathy, conduction disorders, glucose intolerance, CAD, CVA
  10. 10. Laboratory findings in HIV ELISA – screening test, sensitivity >99.9% Western blot – confirmatory test (P24 ++ gp120/160 or gp41 +gp120/160) to avoid false positives, all repeatedly +ve EIA results must be confirmed with WB Specificity when combined with ELISA >99.99% Indeterminate result – early HIV inf, HIV- 2, auto immune disease, pregnancy, recent TT administration False +ve tests – 0.0004 – 0.0007% due to technical errors, HIV vaccines (Arch Intern Med 2003, 163, 1857) False –ve tests – high prevalence population (seroprevalence>30%)- 0.3% (JID 1993, 168; 327) low prevalence populatiion 0.001% (NEJM;1991; 325;1;593) during time between transmission and seroconversion, agammaglobulinemia, antigenically distinct strain infection (Subtype O / N HIV- I)
  11. 11. CBP: anemia, neutropenia, thrombocytopenia Absolute CD4 count: CD4 lymphocyte %: more reliable than counts HIV viral loads: Best test available for diagnosis of acute HIV inf, progression and response to ART. <500c/ml false +ve
  12. 12. PCR test: Qualitative plasma HIV DNA PCR used when non antibody dependent test is necessory. Sensitivity 9798 %, specificity 98% Not useful for screening, 2-9% of false positives (viral loads <10000c/ml) Rapid tests OraQuick Rapid HIV I test Reveal rapid Antibody test UniGold Recombigen HIV test results available in 20- 30 mins sensitivity and specificity >99% Negative result considered definitive –ve unless tested in window period +ve results should be confirmed with WB or IFA
  13. 13. Guidelines for monitoring cardiac dysfunction in patients with HIV  Asymptomatic or symptomatic cardiovascular disease     with normal initial ECHO – repeat ECHO every 1-2 years if asymptomatic. Initial ECHO is abnormal – Rx of CCF if systolic dysfunction, investigate and manage pericardial effusion, consider HAART, specific management for mass or vegetation. LV systolic dysfunction in clinically stable patients – repeat ECHO after 2 weeks. If repeat ECHO at 2 weeks shows improvement and patient continues to improve clinically – yearly ECHO. Persistent or worsened systolic function – consider endomyocardial biopsy, CAG, immunomodulatory therapy.
  14. 14. ENDOCARDITIS  Prevalence of 6.4% – 34%, independent of HAART regimen.  Overall incidence of IE is same as in HIV negative patients with increased risk in IV drug abusers.  May be less likely to sustain valvular damage due to impaired immune response.  S. aureus (>75%), Salmonella spp., Str. pneumoniae, Hemophilus influenzae, Candida albicans, Aspergillus fumigatus and Cryptococcus may be responsible.
  15. 15.  Mobile mass, variable size localised on the auricular surface of the auriculo-ventricular valves or ventricular surfaces of semilunar valves. Valve abscess and rupture are common.  Clinical features and management are as in HIV negative patients.
  16. 16.  Potent antiretroviral therapy (ART) dramatically improves morbidity & mortality from HIV infection  ART may increase cardiovascular disease (CVD) risk Friis-Moller N et al. NEJM 2003; 349: 1993-2003 DAD Study Group. NEJM 2007; 356: 1723-35  Traditional Framingham prediction may underestimate CVD risk in HIV infected patients on ART Law MG et al. HIV Med 2006; 7: 218-30 De Socio GV et al. J Infect 2008; 57: 33-40
  17. 17.  Inflammation, oxidant stress, & endothelial dysfunction are central to the pathogenesis of atherosclerosis/CVD 1390-5 Deakin S et al. Atheroscler Thromb Vasc Biol 2007; 27:  HIV-infection &/or ART may influence these factors  hsCRP correlates with CVD outcomes in the general population; limited data in HIV infection Pearson TA et al. Circulation 2003; 107: 499-511  A urinary marker (isoprostane) of oxidant stress correlated with traditional CVD risk factors Wang B et al. Atherosclerosis 2006; 184: 425-30 Basarici I et al. Coron Artery Dis 2007; 18: 615-20  Vascular reactivity appears impaired in HIV infection Torriani F et al. 4th IAS Conference 2007. Abstr WEAB302 Solages A et al. Clin Infect Dis 2006; 42: 1325-32
  18. 18. SMART El-Sadr NEJM 2006 HIV-infected patients with CD4+ cell count > 350 cells/mm3 (N = 5472) Deferred Arm Intermittent ART (n = 2720; 228 not receiving ART at trial start) Immediate Arm Continuous ART (n = 2752; 249 not receiving ART at trial start) Study halted prematurely; mean follow-up: 18 mos In short term ARV prevents artherosclerosis Emery S, et al. J Infect Dis. 2008;197:1133-1144.
  19. 19. Carotid IMT in HIV infected and uninfected individuals (Hsue AIDS 2009)
  20. 20. Plasma LPS in HIV Infected Patients (Hunt 2008)
  21. 21. The Gut and Inflammation  ART fails to completely restore normal health in HIV infected patients  Persistent immune activation may drive CVD risk  Microbial translocation and Th17 depletion causing persistent immune activation  Role of Th17 and Treg imbalance in pathogenesis of arthrosclerosis (Siliciano 2007,Cheng Clin Imm 2009,Xie Cytokine 2010)
  22. 22. Carotid IMT is Increased in HIV Elite Controllers ( Hsue AIDS 2009)
  23. 23. Role of CRP and CVD Risk in HIV (Hasson NEJM 2005)  hsCRP elevated in HIV and associated  Mortality  RR of MI  Elevated D-Dimer, not CRP is associated with CV events in HIV patients  Fibrinogen is independent predictor of mortality in HIV infected individuals  hsCRP,IL-6,D-Dimer and cystatin C are elevated even after ART (Neuhaus JID 2010)
  24. 24. Effects of Individual ART on Lipids (Hills HIV Clin Trials 2009)
  25. 25. Treatment of Hyperlipidemia in HIV Infected Patients (Ho Circulation 2009)
  26. 26. Prevalence of Congenital Cardiovascular Malformations in Children of Human Immunodeficiency Virus-Infected Women  There was no statistically significant difference in congenital cardiovascular alformation prevalence in HIV infected versus HIV-uninfected children born to HIV-infected women.  With the use of early screening echocardiography, rates of congenital cardiovascular malformations in both the HIV-infected (8.9%) and HIV-uninfected children (5.6%) were five- to ten-fold higher than rates reported in population-based epidemiologic studies but not higher than in normal populations similarly screened.  Potentially important subclinical congenital cardiovascular malformations were detected. (J Am Coll Cardiol 1998;32:1749 –55)
  27. 27. DRUGS  NRTIs – Zidovudine has been associated with mitochondrial        abnormalities and can lead to myocarditis, skeletal muscle myopathy, lactic acidosis, hypotension. NNRTIs – altered mitochondrial DNA replication. Delavirdine increases toxicity of antiarrhythmics and CCBs. Protease inhibitors – implicated in premature CAD, dyslipidemia, insulin resistance, fat redistribution. Ritonavir – most potent CYP3A activator and P-glycoprotein inhibitor; most likely to interact. Indinavir, amprenavir, nelfinavir – intermediate probability Saquinavir – lowest probability to interact Cautious use with other drugs metabolized through this pathway – simvastatin, cisapride, antihistamines, sildenafil, antiarrhythmics like amiodarone, lidocaine, quinidine. Ritonavir and nelfinavir induce glucuronidation – lessen efficacy of fibrates.
  28. 28. DRUGS  Rifampin – reduces therapeutic effect of digoxin by inducing intestinal P-glycoprotein, reduces protease inhibitor concentration and effect.  Erythromycin – torsades, orthostatic hypotension, VT  Trimethoprim-sulfamethoxazole – increases warfarin effects, QT prolongation, hypokalemia, torsades
  29. 29. DRUGS  Ganciclovir – VT, hypotension  Foscarnet – reversible cardiac failure  Pentamidine – QT prolongation, torsades, hyperglycemia     and hypoglycemia, hypomagnesemia and SCD. Vincristine and doxorubicin – can decrease Digoxin levels, associated with MI, autonomic neuropathy Human IFN-α ACS, hypotension, hypertension, DCM, arrhythmias, AV block IL-2 – capillary leak, hypotension, arrhythmias, MI, SCD, thyroid alterations Corticosteroids – hyperglycemia, HTN, cardiomyopathy, increase gastric ulceration in combination with salicylates.
  30. 30. HIV treatment  Antiretroviral treatment is recommended for all patients with symptomatic HIV disease and for asymptomatic patients with <250 CD4 cells/µL, acute HIV syndrome and with >50,000 copies/ml of HIV RNA.  HAART consists of 4 broad classes, nucleoside inhibitors (NRTI), non-nucleoside inhibitors (NNRTI), protease inhibitors (PI) and fusion inhibitors.  NRTIs – Ziduvudine, Lamivudine, Stavudine, DDI, DDC, Abacavir, Emtricitabine  NNRTIs – Nevirapine, Delavirdine, Efavirenz  PIs – Saquinavir, Ritonavir, Indinavir, Nelfinavir, Amprenavir, Lopinavir, Ataza navir  Fusion inhibitor - Enfuviritide
  31. 31. Postexposure prophylaxis  Risk of HIV infection following percutaneous exposure to HIV contaminated blood is 0.3%, and after a mucous membrane exposure, 0.09%.  Following universal precautions.  Cleansing of wound and application of antiseptic immediately.  2 NRTIs for 4 weeks or 2 NRTIs plus a third drug for 4 weeks are usually used.