Aids approach patients


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    Hello dear friend and thank you for joining our group 'CHILDREN OF THE WORLD' of the Community Slideshare ! Very Good day. See you again soon !... Bernard

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  • Several antiretroviral drugs are both CYP 450 & P-gp substrates, it is therefore not uncommon to encounter interactions among them or with agents used to treat other conditions. NRTIs: are eliminated renally and are not substrates for the CYP 450 enzymes or drug transport proteins and thus not prone to the most common pharmacokinetic drug interactions. Integrase inhibitors are also not metabolised via CYP450, raltegravir undergoes glucoronidation and is less susceptible to drug interactions. Most of the drug interactions known to affect UGT, non are known to affect raltegravir’s efficacy and no dosage adjustments have been recommended.The NNRTIs, PIs, and CCR5 inhibitors are all substrates of CYP450 and most available drugs are substrates of CYP4503A making them prone to a number of drug interactions.
  • Aids approach patients

    1. 1. STAND<br />UNDER<br />ACQUIRED<br />DEFICIENCY<br />IMMUNO<br />SYNDROME<br />
    2. 2.
    3. 3. WE NEED TO KILL THEM<br />
    4. 4. BEFORE THEY KILL US?<br />
    5. 5. SO<br />WE<br />MUST<br />KEEP TRYING<br />
    6. 6. …AND KEEP TRYING<br />
    7. 7. UNTIL<br />THE END<br />
    8. 8. "You Cannot Teach Old Dogs New Tricks" <br />Prof Adeeba<br />
    9. 9. Normal <br />Immune <br />System<br />…will protects the body<br />
    10. 10. It consists of<br />LYMPHOID<br />organs and<br />tissues<br />..which kills<br />bad organism<br />
    11. 11. HIV will attack<br />THE SYSTEM<br />AIDS<br />and it becomes<br />
    12. 12. AIDS<br />COMES FROM<br />
    13. 13.
    14. 14. also from…<br />
    15. 15. blood transfusion<br />
    16. 16. to<br />Mother<br />baby<br />
    17. 17. IF U<br />HAVE THESE<br />
    18. 18. ORAL CANDIDIASIS<br />
    19. 19. Oral Hairy <br />Leukoplakia<br />
    20. 20. …or these…<br />
    21. 21.
    22. 22. Acquired Immunodeficiency Syndrome (AIDS) <br />Acquired Immunodeficiency Syndrome (AIDS) is caused by a retrovirus known as the Human immunodeficiency Virus (HIV). <br />
    23. 23. Acquired Immunodeficiency Syndrome (AIDS) - definition<br />Is a conglomerate of signs and symptoms arising from the development of opportunistic infections and unusual tumours which arise as a result of a failing immune system.<br />Clinical definition of AIDS consist:<br />
    24. 24. AIDS defining diagnosis<br />
    25. 25. Immunology and Natural History of HIV/AIDS<br />
    26. 26. The Normal lmmune System<br />
    27. 27. Human Immunodeficiency Virus<br />HIV is a retrovirus. (RNA)<br />Uses host’s DNA (lymphocytes) to make viral DNA and to replicate itself. <br />Host lymphocytes infected with HIV have a very short lifespan.<br />HIV continuously uses new lymphocyte to replicate itself.<br />Up to 10 million individual viruses are produced daily.<br /><ul><li>Causing severe damage to and eventually destroys the immune system.</li></li></ul><li>
    28. 28.
    29. 29. HIV Co-receptors<br />
    30. 30. Viral variation in HIV infection<br />
    31. 31. The effect of HIV on the immune system is monitored by measuring the CD4 lymphocyte count in the blood. <br /> A normal CD4 count 600 and 1,200 cells/µ.<br />CD4 counts <350 cells/µL indicate that some impairment of immune function.<br /> CD4 counts <200 cells/µL - risk of serious opportunistic infections <br />
    32. 32. HIV: Two Types Recognized<br />
    33. 33. Epidemiology<br />
    34. 34. AIDS - Classification<br />
    35. 35. Modes of Transmission<br />
    37. 37.
    38. 38. Incubation<br />2 - 4 weeks after exposure but may be as long as 6 weeks. <br />Symptoms tend to develop abruptly and last for 1.5 - 2 weeks. <br />
    39. 39.
    40. 40. Acute Sero-conversion Phase or Primary HIV-1 infection<br />60-90%<br />difficult to identify (not remember the flu-like illness, common cold). <br />This glandular fever  2 to 6 weeks after exposure. <br />However this mononucleosis-like illness  prolonged and may last 2-4 weeks. <br />acute encephalitis-like illness with reversible encephalopathy<br />disorientation, <br />impairment of consciousness <br />cognitive functions<br />Recovery is complete and the patient will feel well. <br />Occasionally the acute seroconversionillness may be completely asymptomatic.<br />
    41. 41. Asymptomatic HIV infection<br />early stages<br />progressive fall of CD4+ T-lymphoeyte<br />symptoms and signs will become apparent. <br />2 to 7 years before the appearance of constitutional symptoms which may herald the onset of AIDS.<br />
    42. 42. Persistent Generalised Lymphadenopathy (PGL) - Symptoms<br />CD4+ T-lymphocytes progressively decline<br />The commonest not specific symptoms and signs encountered in the early stages are:<br />· Malaise<br />· Lethargy<br />· Loss of appetite<br />· Loss of weight<br />· Diarrhoea<br />· Intermittent fever<br />
    43. 43. Persistent Generalised Lymphadenopathy (PGL) - Signs<br />weight loss of more the 10% the ideal body weight, <br />prolonged fevers of more than 3 months, <br />Persistent generalised Iymphadenopathy of more than two groups of Iymph nodes. <br />multi-dermatomalherpes zoster, <br />oral candidiasis <br />oral hairy leukoplakia<br />
    44. 44. Herpes Zoster<br />Herpetic lesions in HIV-infected patients are caused by reactivation of the latent virus. Although mucocutaneous lesions may appear in any region of the body, the most common sites are the genital, perianal area.<br />
    45. 45. Oral Candidiasis<br />Oral candidiasis "thrush" is an infection of yeast fungi of the genus Candida on the mucous membranes of the mouth. It is frequently caused by Candida albicans, or less commonly by Candida glabrata or Candida tropicalis.<br />Oral Hairy Leukoplakia<br />Hairy leukoplakia is seen in severe defects of immunity, particularly in HIV infection. The cause of this condition is an opportunistic infection by the Epstein-Barr virus (EBV). After the primary EBV infection has been overcome, the virus stays latent in the B cells and also causes lytic infection in the oropharynx, controlled by the immune system. Uncontrolled lytic infection in the oropharynx is manifested as oral hairy leukoplakia in immunosuppressed hosts. Oral hairy leukoplakia is not associated with any malignant potential.<br />
    46. 46. Persistent Generalised Lymphadenopathy (PGL) - Labs<br />Lymphopenia<br />Leukopenia<br />Thrombocytopenia<br />Anaemia<br />Reduced CD4+ T-lymphocyte count<br />Decrease ratio of CD4+/CD8+<br />Raised gamma-globulins<br />Cutaneous Anergy<br />
    47. 47. Persistent Generalised Lymphadenopathy (PGL) - Markers<br />Absolute platelet counts<br />Total Lymphocyte count<br />CD4+ T-lymphocyte count (cells/uL)<br />CD4+/CD8+ Ratio<br />p24 antigen<br />beta 2-microglobulins<br />Serum Neopterin<br />PCR-RNA-HIV<br />
    48. 48. AIDS<br />10% of patients develop an AIDS-defining illness with a CD4 count above 200 cells/mm3. <br />The median time to development of an AIDS defining illness is 12 – 18 months (if not on opportunistic infection prophylaxis or antiretroviral therapy). <br />Median CD4 count at the time of developing an AIDS-defining illness is 67 cells/mm3.<br />Median survival after CD4 count falls below 200 cells/mm3 is 38 – 40 months.<br />
    49. 49. AIDS<br />Consist of<br />Pulmonary TB, Recurrent pneumonia, Invasive Cervical Cancer<br />CD4+ T-lymphocyte counts<br />declining immunity<br />opportunistic infections <br />atypical tumours.<br />
    50. 50. Advance AIDS (CD4 < 50)<br />Median survival is 12 – 18 months (if not on opportunistic infection prophylaxis or antiretroviral therapy).<br />Cytomegalovirus disease and disseminated Mycobacterium avium complex tend to occur at this stage.<br />
    51. 51. Factors affecting rate of progression<br />Acute HIV syndrome: <br />Prolonged presence of symptoms correlates with a more rapid progression of disease. <br />Strong HIV-specific CD8 cytotoxic T cell and CD4 T cell responses correlate with a slower progression of CD4 cell decline.<br />Co-infections<br />Hepatitis <br />Cytomegalovirus<br />Mode of transmission<br />Blood transfusion recipients progress more rapidly than patients who acquire it sexually or by injection drug use.<br />
    52. 52. Factors affecting rate of progression<br />Age.<br />Older patients progress faster than younger patients.  <br />Viral load.<br />Patients with higher viral loads will progress more rapidly.<br />Genetic modifiers.<br />Strain variations.<br />
    53. 53. Factors affecting rate of progression<br />Effect of prophylaxis of opportunistic infections on the course of HIV disease<br />PCP<br />Disseminated MAC<br />Experience of the medical provider<br />
    54. 54. Factors affecting rate of progression<br />Effect of antiretroviral therapy on the course of HIV disease. <br />3-drug therapy (HAART) >> 2-drug therapy > Monotherapy<br />When therapy is started in the early asymptomatic infection period the estimated mean time to development of AIDS is 8 months for patients treated with monotherapy, 9.8 years with double therapy and 20 years with HAART<br />
    55. 55. Kaposi’s Sarcoma<br />tumour of the blood vessel. <br />Classical:<br />elderly males of Mediterranean descent.<br />confined to the lower limbs.<br /> previously healthy young males will suggest the presence of concomitant HIV<br />numerous and fairly extensive. <br />confined to the skin, lungs with hemorrhagicpleural effusion.<br />
    56. 56. Kaposi Sarcoma<br />With the rise of the AIDS epidemic, KS, as initially one of the most common AIDS symptoms, was researched more intensively in hopes that it might reveal the cause of AIDS. The disease was erroneously referred to as the "AIDS rash".<br />
    57. 57. Natural History: <br />
    58. 58. Clinical Features<br />
    59. 59. Acute Retroviral Rash<br />5-10 mm macular or papular erythematous lesions usually on face and trunk but may involve extremities. <br />Rash usually starts 48-72 hours after the fever starts and may last for 5 – 8 days. <br />It may be slightly pruritic but usually is not.<br />Oral, esophageal, anal or genital ulcerations are painful, shallow and well demarcated.<br />
    60. 60.
    61. 61. Opportunistic Infection<br />
    62. 62. CD4 count and OIs<br />TB<br />PCP, thrush<br />Toxo, Esoph thrush<br />Below 200<br />PML<br />
    63. 63. HIV-Related Complications<br />
    64. 64. Pneumocystis Carinii (PCP)<br />Pneumonia with hypoxemia<br />Insidious<br />CXR with bilateral disease but can vary<br />High morbidity and mortality<br />CD4 generally below 200 or < 14%<br />Significant alveolar disease (elevated LDH)<br />Silver stain of sputum or BAL for diagnosis<br />
    65. 65. PCP - Interstitial Infiltrates<br />
    66. 66. Treatment of PCP<br />Determine level of hypoxemia and need for hospitalization<br />TMP-SMX is the most efficacious treatment<br />Alternatives exist in those allergic to sulfa<br />Steroids indicated if pO2 < 70<br />May get worse before improvement seen <br />Usually need to R/O other pathogens<br />
    67. 67. Prevention of PCP<br />Oral TMP-SMX is prophylaxis of choice<br />Alternatives exist (dapsone, pentamidine, etc)<br />10 prophylaxis: CD4 < 200<br />20 prophylaxis with history of prior PCP<br />Still being determined is whether prophylaxis can be withdrawn after beneficial effects of HAART<br />
    68. 68. CNS Toxo vs CNS Lymphoma<br />
    69. 69. Toxoplasmosis<br />
    70. 70. Treatment / Prevention of Toxo<br />Rx: Sulfadiazine + Pyrimeth. + Folinic Acid<br />Sulfa allergic: Clinda + Pyrimeth. + Folinic A.<br />Repeat MRI to make sure lesions smaller<br />Maintenance therapy after induction<br />Consider steroids and anticonvulsants<br />TMP-SMX is adequate 10 prophylaxis<br />dapsone and pentamidine is not protective<br />should protect when CD4 < 100 if IgG +<br />
    71. 71. Cryptococcal Meningitis<br />Very subtle presentation at times<br />HA, fever, lethargy, nausea<br />Imaging studies usually normal<br />CSF generally with high opening pressure, mild lymphocytic pleocytosis<br />CSF with + India Ink, crypto Ag, yeast<br />Serum crypto Ag can screen HIV cohorts<br />
    72. 72. Cryptococcus - India Ink Stain<br />
    73. 73. Treatment of Crypto Meningitis<br />Most induce with ampho B +/- 5FC<br />Can also use high dose fluconazole if unable to tolerate Ampho B<br />Will need chronic maintenance to control infection as cannot be generally cured<br />High risk for recurrent elevated ICP which can result in hydrocephalous<br />May require periodic removal of CSF<br />
    74. 74. CMV Retinitis<br />Results in floaters and decreased vision<br />Seen in those with CD4 < 50-100<br />Diagnosis by ophthalmologic exam<br />It is a disseminating infection<br />Difficult systemic treatment with an induction and maintenance treatment<br />gancyclovir, foscarnet, cidofovir<br />
    75. 75. Mycobacterium Avium Complex<br />Not uncommon when CD4 < 75<br />Chronic constitutional symptoms such as fever, sweats, and weight loss<br />Labs may reveal anemia, leukopenia,and elevated alk phos<br />CT of abdomen may see periaortic or retroperitoneal adenopathy and HSM with a relative paucity of peripheral adenopathy <br />
    76. 76. MAC Diagnosis and Treatment<br />AFB BC has high yield but takes weeks<br />Bone marrow staining and culture<br />Treatment requires a minimum of 2 meds chronically as it is quite resistant<br />macrolide, ethambutol (amikacin, rifabutin, cipro)<br />10 Prophylaxis with macrolide in those with CD4 <75<br />
    77. 77. Oropharyngeal Infections<br />Candidiasis<br />Oral Hairy Leukoplakia (OHL)<br />Ulcer Disease<br />Periodontal Disease<br />Kaposi’s Sarcoma<br />
    78. 78. Oral Candidiasis<br />>60% of patients with CD4 <100 cells/mm3<br />Often Asymptomatic or altered taste, burning, odynophagia<br />Four Forms<br />Pseudomembranous<br />Erythematous<br />Angular Cheilitis<br />Hyperkeratotic<br />
    79. 79. Pseudomembranous Oral Candidiasis<br />White patches that can be scraped off leaving erythematous base<br />
    80. 80. Erythematous Oral Candidiasis<br />Smooth red patches, found on tongue and cheeks<br />
    81. 81. Angular Cheilitis<br />Cracking and fissures at corner of mouth<br />
    82. 82. Hyperkeratotic Oral Candidiasis<br />Thickened white patches, do not scrape off<br />
    83. 83. Oral Candidiasis: Diagnosis<br />Diagnosis is often clinical, based on typical appearance<br />KOH preparation of scraping for hyphae, pseudohyphae, and budding yeast<br />Helpful especially for erythematous and hyperkeratotic disease<br />
    84. 84. Oral Candidiasis: Treatment<br />Initial topical therapy<br />Clotrimazole troches 10mg 5x/day<br />Nystatin swish & swallow 500,000 units QID<br />Refractory to topical treatment<br />Fluconazole 100 mg QD<br />Itraconazole 100 mg BID<br />
    85. 85. Oral Candidiasis: Treatment<br />Fluconazole Refractory Disease<br />Higher dose fluconazole (200-800 mg/d)<br />Itraconazole 200 mg BID<br />Amphotericin B 0.3-0.5 mg/kg/day<br />Capsofungin 50mg IV QD<br />Duration of Therapy<br />7-14 days or until disease resolution<br />
    86. 86. Oral Candidiasis: Treatment<br />Relapsing Disease<br />Intermittent therapy vs. chronic suppressive treatment <br />Decreased azole resistance with chronic suppression vs. intermittent therapy if recurrences are very frequent.<br />Avoid maintenance therapy unless relapses are frequent – increased azole resistance<br />
    87. 87. Oral Hairy Leukoplakia<br />Caused by Epstein-Barr Virus infection<br />Does not scrape off with tongue blade<br />NOT a premalignant condition<br />Targeted therapy not recommended<br />Responds to HAART<br />
    88. 88. Oral Hairy Leukoplakia<br />Linear white patches at edge of tongue. Do not scrape off.<br />
    89. 89. Oral Ulcer Diseases<br />Several Etiologies<br />Most Important Differential Diagnoses:<br />Herpes Simplex Virus<br />Cytomegalovirus<br />Aphthous Ulcers<br />
    90. 90. Herpes Simplex Virus<br />Multiple vesicular lesions of lips, buccal mucosa, soft palate<br />Diagnosis often clinical, also may diagnose by Tzanck smear, viral culture, immunofluorescence assay<br />Treatment recommended in patients with HIV<br />
    91. 91. Herpes Simplex Virus<br />Multiple ulcers with some confluence of buccal mucosa<br />
    92. 92. Herpes Simplex Virus<br />Tzanck smear with multinucleated giant cells<br />
    93. 93. Herpes Simplex Virus:Treatment<br />Oral Therapy:<br />Acyclovir 400 mg 5x/day 14-21d<br />Famciclovir 500 mg BID x 7d<br />Valacyclovir 1g PO BID x 7d<br />Parenteral Therapy (severe disease)<br />Acyclovir 5mg/kg q 8 hours<br />Foscarnet or Cidofovir <br />for acyclovir resistant disease<br />
    94. 94. Cytomegalovirus (CMV)<br />Visually indistinguishable from HSV oral ulcer disease<br />Often associated with other systemic manifestations of CMV (esophagitis, colitis, retinitis)<br />Usually diagnosed in “HSV” refractory to therapy<br />Viral Culture/ cytology, IFA, CMV serum antigen testing, CMV PCR<br />
    95. 95. CMV Oral Ulcers<br />Viral swab demonstrated typical “owl’s eye” intracytoplasmic inclusions. CMV PCR (+)<br />
    96. 96. CMV - Treatment<br />Limited oral ulcer disease management unclear, but likely a precursor to manifestation at other site (esophagitis, colitis, retinitis)<br />Induction Therapy<br />Ganciclovir 5mg/kg IV Q 12 hours<br />Valganciclovir 900 mg BID<br />Foscarnet 90 mg IV Q 12 hours<br />Cidofovir 5 mg/kg IV q week PLUS<br />Probenecid (to decrease renal toxicity)<br />Each then followed by suppressive treatment<br />
    97. 97. Aphthous Ulcers<br />Present as crops of ulcers from 1-2 mm to 2-3 cm<br />Painful lesions lead to odynophagia, dysphagia, secondary weight loss<br />Can involve esophagus, other parts of GI tract<br />Visually similar to HSV and CMV<br />
    98. 98. Aphthous Ulcers<br />1.5 cm ulcer of buccal mucosa<br />
    99. 99. Aphthous Ulcers<br />Diagnosis: <br />viral studies for HSV, CMV (-)<br />Biopsy: nonspecific inflammatory changes<br />Treatment<br />Anesthetic mouth washes<br />Topical fluocinonide 0.05%<br />SEVERE DISEASE<br />Prednisone 40 mg/day 4-6 weeks<br />Thalidomide 200 mg po QD<br />
    100. 100. Kaposi’s Sarcoma<br />Can involve any portion of the GI tract.<br />Usually symptomatic if oral lesions or intestinal obstruction<br />Associated with HHV-8 infection<br />
    101. 101. Oral Kaposi’s Sarcoma<br />
    102. 102. Kaposi’s Sarcoma<br />Presentation:<br />Usually in patients with CD4 <200 cells/mm3<br />Skin most common site of involvement, but GI tract involved in 40% of visceral cases<br />Diagnosis<br />Usually based on pathologic specimen<br />Must be distinguished from Bacillary Angiomatosis (Bartonella Henselae)<br />
    103. 103. Kaposi’s Sarcoma: Treatment<br />Often improves with HAART<br />Localized Disease<br />HAART<br />Sclerotherapy<br />Intralesional Chemotherapy<br />Cryotherapy<br />Radiation therapy<br />Widespread<br />Systemic Chemotherapy<br />interferon-alfa ,etoposide, vincristine, vinblastine and bleomycin <br />
    104. 104. AIDS Cholangiopathy<br />Late manifestation of HIV<br />CD4 < 100 cells/mm3<br />May be present with or without papillary stenosis<br />Clinical Presentation <br />Fever, RUQ pain, nausea, vomiting. Weight loss<br />Markedly Elevated Alkaline Phosphatase<br />Causes Include:<br />Cryptosporidium, CMV, microsporidia<br />40% of cases – no clear etiology<br />
    105. 105. AIDS Cholangiopathy<br />Diagnosis<br />Ultrasound: may be normal or show intra- and extra-hepatic ductal dilatation<br />ERCP: allows imaging of biliary ductal system, sampling of fluid for culture and cytology<br />Treatment<br />Sphincterotomy for papillary stenosis, biliary stents, targeted therapy at causative agent (if identified)<br />
    106. 106. Diarrhea in HIV/AIDS<br />Occurs in 50-60% of AIDS patients<br />Evaluation should include travel history, pets, medications, foods<br />Stool studies<br />Stool culture for Shigella, Salmonella, E. Coli, campylobacter<br />Stool O&P, acid fast staining<br />C. Difficile Toxin Assay<br />If Fever: Blood Culture, AFB blood Culture, CMV Antigenemia/ PP65<br />
    107. 107. Salmonella<br />Commonly S. typhimurium, S. enteritidis <br />20-100 greater incidence in AIDS<br />Bacteremia common<br />Recurrent bacteremia – AIDS defining<br />Diagnosis: stool and/or blood cultures<br />Treatment: ciprofloxacin, ceftriaxone, amoxicillin, TMP/SMX<br />Suppressive Therapy: consider for recurrent disease<br />
    108. 108. Shigella<br />S. flexneri, S. dysenteriae<br />Presentation: bloody diarrhea, fever, abdominal pain<br />Complications: megacolon, perforation, bacteremia (50%)<br />Treatment: Same as salmonella <br />ciprofloxacin, ceftriaxone, amoxicillin, TMP/SMX<br />
    109. 109. Clostridium Difficile<br />Approximately 8% of AIDS diarrhea<br />Diagnosis: <br />Detection of toxin in stool<br />Thickened bowel wall on CT<br />Pseudomembrane on colonoscopy<br />Treatment<br />Metronidazole 250 mg po QID x 10-14 days<br />Vancomycin 125 mg po QID x 10-14 days (if failure of metronidazole)<br />
    110. 110. Mycobacterium Avium Complex<br />Usually seen with CD4 <100 cells/mm3<br />Presentation: fever, abdominal pain, diarrhea, weight loss<br />Diagnosis<br />Culture: stool, tissue, blood<br />CT scan: hepatosplenomegally, abdominal lymphadenopathy<br />Treatment<br />Clarithromycin 500 mg BID OR azithromycin 500 mg po QD<br />PLUS ethambutol 15-20 mg/kg/day<br />
    111. 111. Cryptosporidium<br />Found in stool of 10-20% of AIDS patients with diarrhea<br />Acquired via contaminated water or fecal-oral route<br />May also cause biliary tract disease<br />Diagnosed by acid fast stain of stool, immunofluorescence<br />
    112. 112. Cryptosporidium<br />Acid-fast stain of stool demonstrating oocysts<br />
    113. 113. Cryptosporidium: Treatment<br />Mainstay is restoration of immunity with HAART<br />Specific Therapy (disappointing efficacy)<br />Paromomycin 1500-2000 mg/d x 14-28 days then 500 mg BID<br />Paromomycin 1 g BID PLUS Azithromycin 600 mg QD x 28 days THEN Paromomycin alone<br />Octreotide 50-500 units SQ TID<br />Reduces stool volume<br />Nitazoxanide 500 mg BID<br />Currently under clinical trial<br />
    114. 114. Isospora Belli<br />Acid Fast protozoan<br />Symptoms: watery diarrhea, weight loss, cramps<br />AFB of stool; larger than cryptosporidium; typical elliptical shape<br />Treatment: TMP/SMX DS po QID x 10 days<br />Pyrimethamine (for sulfa allergy)<br />
    115. 115. Isospora Belli<br />Oocyte on modified acid-fast stain of stool<br />
    116. 116. Microsporidia<br />2 species implicated in most diarrheal disease in AIDS<br />Enterocytozoon bieneusi<br />Encephalitazoon intestinalis<br />Found in 5-50% of AIDS patients with unexplained diarrhea<br />Clinical: chronic non-bloody diarrhea, malabsorption, cholangitis, cholecystitis<br />
    117. 117. Microsporidia<br />Diagnosis <br />stool modified trichrome or chemofluorescent staining<br />Small bowel biopsy<br />Treatment:<br />Albendazole 400-800 mg PO >21 days [for E. septata]<br />E. bieneusi – limited efficacy<br />Metronidazole, atovaquone<br />
    118. 118. AIDS Wasting Syndrome<br />Unintentional Loss of 10% of body weight<br />AIDS defining illness in 15-20% of cases<br />Contributing factors:<br />Medication related anorexia, depression, oral/esophageal disease, malabsorption<br />
    119. 119. AIDS Wasting Syndrome<br />Treatment<br />Nutritional Supplements<br />Oral supplements usually adequate<br />TPN for excessive diarrhea from cryptosporidiosis<br />Appetite Stimulants<br />Megestrol, Dronabinol – weight gain mostly fat<br />Resistance Exercise<br />
    120. 120. AIDS Wasting Syndrome<br />Anabolic Steroids<br />Most weight gain is lean body mass (anabolic>androgenic effect)<br />Nandrolone <br />Oxandrolone<br />Oxymetholone<br />Testosterone<br />Indicated for hypogonadism with or without wasting<br />Improved quality of life, libido, energy, lean body mass<br />
    121. 121. Non TB Mycobacteria<br />MAC rarely cause pulmonary disease<br />M.kansasii most common<br />CD4< 50<br />Interstitial / lobar pneumonia<br />Nodules, cavities, adenopathy<br />Diagnosis: Cx from respiratory specimen<br />Treatment: RIF/ETB/INH 15-18 mo<br />
    122. 122.
    123. 123. CMV Pneumonias<br />Most important AIDS associated viral pulmonary pathogen<br />Late <br />B/L interstitial/alveolar infiltrates<br />Diagnosis:<br />CMV culture( not specific)<br />CMV inclusions<br />
    124. 124. CMV: Treatment<br />GCV 2.5 mg/kg Q 8h x 20 d or Valgancyclovir 900 mg BID<br /> + IVIG 500mg/kg QOD x 10 days<br /> then GCV 5 mg/kg/d x3-5/wk + IVIG 500mg/kg 2x/wk x8 doses<br />Foscarnet 90 mg/kg IV Q 12h x 14-21 days<br /> then 90 mg/kg QD maintenance<br />Cidofovir 5 mg/kg IV Q wk w/ probenecid<br />
    125. 125.
    126. 126.
    127. 127.
    128. 128. Pulmonary Cryptococcosis<br />Inhaled pathogen<br /><15% develop pneumonia<br />UL lesions, lobar, B/L, miliary pneumonia<br />Pleural effusion, cryptococcoma<br />Cavity: rare<br /> meningitis primary presentation in HIV<br />
    129. 129. Pulmonary Cryptococcosis<br />Treatment<br />Ampho B 0.7-1 mg/kg/d + 5-FC 25 mg/kg q 6h x 2 wks<br />Then Fluconazole 400 mg/d x 10wks<br />Suppression 200 mg/d until CD4 > 100<br />Surgery for cryptococcoma<br />
    130. 130.
    131. 131.
    132. 132. Pulmonary Penicillosis<br />Endemic: SE Asia, China, Manipur State of India<br />Thermally dimorphic fungus<br />Infiltrates, nodules, cavities, abscess, adenopathy<br />Disseminated diseases<br />Diagnosis: Fungal Culture<br />Treatment: Ampho B Itra, 50% relapse<br />
    133. 133.
    134. 134. Rhodococcus equi<br />GP coccobacilli<br />Synergistic hemolysis<br />Antagonism : IMP, β-lactam<br />
    135. 135. Rhodococcus equi<br />TB like syndrome with negative smear<br />cavitary/nodular pneumonia<br /> bacteremia<br />½ extrapulmonary<br />2/3 mortality<br />Tx: 2-3 drugs<br />Vanc, IMP,AMG, cipro, Rifampim, E-mycin<br />
    136. 136.
    137. 137.
    138. 138.
    139. 139. Non Infectious Pulmonary Diseases<br />KS<br />Lymphoma<br />Nonspecific interstitial pneumonitis<br />Lymphocytic interstitial pneumonitis<br />BOOP<br />PE<br />
    140. 140. TB: Early Clinical Picture<br />General complaints:<br />non-specific <br />excessive fatigue <br />weight loss<br />anorexia <br />irritability<br />Symptoms of chronic infection:<br />low-grade fever <br />night sweats <br />vague digestive disturbances <br />recurrent headaches <br />
    141. 141. TB: Early Clinical Picture<br />SPUTUM:<br /> at first dry, and later productive<br /> purulent sputum <br /> hemoptysis<br />Pleuritic pain from TB pleurisy with effusion, may be a presenting symptom in early stages <br /> Cough rarely associated with pulmonary TB in children.<br />
    142. 142. Severe Pulmonary TB<br /> Most INFECTIOUS CASES <br />Extensive cavities<br />Positive smear<br />High bacilli output <br /> > 10 /HPField or >500,000/ml<br />High mortality <br />without treatment (75%)<br />Very infectious<br /> 50% of close contacts infected<br />RAPID evolution<br />
    143. 143. Chest Xrays in TB Control<br />DIAGNOSTIC EXAMINATION of a suspected case<br />EVALUATION OF A CASE during treatment <br />BUT not a substitute to SPUTUM EXAM <br />only sputum monitors response of MTB to drugs<br />only sputum provides early warning about resistance<br />BASELINE XRAY at the end of treatment<br />Evaluation of a CONTACT or an INFECTED <br />
    144. 144. Tuberculin Test<br />
    145. 145. Tuberculosis Screening – Skin Tests<br />15mm<br />Person from LOW prevalence area<br />NO medical risk factors<br />NO known exposure to TB<br />10mm<br />Person from HIGH prevalence area:<br />Asia, Africa, Latin America ³1%<br />MEDICAL RISK factors<br />5mm<br />CLOSE CONTACTS to infectious TB<br />OLD TB LESIONS<br />HIV INFECTION<br />
    146. 146. TB Treatment <br />Start with 4 drugs in all patients<br />INH, RIF, PZA and EMB or SM until sensitivities return<br />If pan sensitive, D/C EMB or SM<br />After 2 months of therapy, D/C PZA<br />Continue INH & RIF for 4 more months for total of 6 months<br />Must have culture conversion by 2 months<br />6 month regimen good for HIV(-) and (+)<br />Can use BIW regimen / TIW for HIV (+)<br />Monitor adherence and toxicity<br />DOT, combination pills for self administered (exceptions)<br />
    147. 147. Resistance<br />Primary resistance to any of the 4 major drugs (INH, Rif, Emb, Sm) was estimated at 12% in the USA in 1995. It ranged in 1994-97 from a low of 2.0 in the Czech Republic to a high of 41% in the Dominican Republic (Global surveillance for anti-tb drug resistance. NEJM 1998, 338,23).<br />Median prevalences were:<br />INH 7.3%<br />Streptomycin 6.5%<br />Rifampin 1.8%<br />Ethambutol 1%<br />All 4 0.2%<br />
    148. 148. Clinical Significance of Resistance<br />If pan sensitive>95% chance of cure<br />If resistant to INH>90% chance of cure<br />If resistant to rifampin>70% chance of cure<br />If resistant to INH and RIF~50% chance of cure<br />Before chemotherapy~50% chance of cure<br />
    149. 149. Causes of Resistance<br />Irregular Self Administration with Failure to closely supervise<br />Care of patients by non specialists<br />Increased immigration<br />
    150. 150. Epidemiology of TB and HIV<br />Both have afflicted similar populations<br />Both are socially stigmatizing<br />Globally, TB is the 2nd leading cause of death from an infectious disease (behind HIV)<br />TB is the leading cause of death in HIV globally<br />Active TB may accelerate HIV replication<br />
    151. 151. TB/HIV: Epidemiology<br />Thirty-six million HIV infected individuals worldwide<br />One-third of them co-infected with MTB<br />68%- Sub Saharan Africa, 22%- SEA<br />Leading cause of death amongst HIV infected individuals worldwide<br />Prevalence of HIV in TB patients (India) 20%<br />
    152. 152. TB/HIV: Pathogenesis<br />Immunity to MTB partly under control of MHC Class II restricted CD4 cells<br />Loss of CD4 cells increases risk of<br />Reactivation of latent infection<br />Primary infection<br />Active TB up-regulates HIV replication, leading to accelerated progression of HIV<br />
    153. 153. TB/HIV: Pathogenesis<br />Life time risk in HIV negative persons: 10%<br />5% within first two years<br />5% remainder of their lives<br />HIV positive persons have 8% risk per year<br />HIV+ incidence: 5-16/100 person-years<br />Two mechanism<br />Reactivation<br />Re-infection<br />Immune reconstitution TB on HAART<br />
    154. 154. HIV/TB: Treatment<br />Do you need to add higher number of drugs?<br />Do you need to prolong duration of therapy?<br />Can ARV be used concomitantly with ATT (anti-Tuberculosis Therapy)?<br />Is there increased incidence of AE’s?<br />Is there increased incidence of MDR-TB?<br />Should latent tuberculosis be treated? (international)<br />
    155. 155. Laboratory Testing<br />
    156. 156. Serologic Tests<br />
    157. 157. Baseline Laboratory Tests<br />CD4 count and viral load to establish the stage of the disease <br />Exposed other infectious diseases<br />Other recommended baseline tests include: <br /><ul><li>CBC
    158. 158. Serum Chemistry Panel
    159. 159. Syphilis serology
    160. 160. Chest X-ray
    161. 161. Mantoux
    162. 162. PAP smears</li></ul>Hep B and C<br />
    163. 163. Laboratory features<br />Leukopenia and lymphopenia initially, then lymphocytosis.<br />Elevated CD8 cells, decreased CD4 cells.<br />
    164. 164. Diagnosis of Acute HIV<br />Seroconversion usually occurs within 4 –10 weeks (median 63 days).<br />Plasma viral load peaks in three weeks post-exposure (100,000 – 1,000,000 copies RNA/mm3) and then declines to nadir at ~120 days. <br />p24 antigen levels may be as high as 100 pg/ml. <br />
    165. 165. Management of HIV infection<br />MOHD HANAFI RAMLEE<br />
    166. 166. Medical and Nursing Care<br />
    167. 167. Clinical Care <br />(medical & nursing)<br />VCT , PMTCT<br />preventive therapy (OIs, TB) <br />management of STIs and OIs<br />palliative care, nutritional support <br />antiretroviral therapy <br />Socioeconomic Support<br />Psychosocial Support<br />counseling <br />material support<br />orphan care<br />economic security <br />n<br />community support services<br />food security <br />p<br />spiritual support <br />o<br />Human Rights & Legal Support<br />r<br />stigma & discrimination reduction<br />e<br />i<br />succession planning <br />PLHA participation<br />v<br />e<br />n<br />Adults and Children <br />Affected by <br />HIV/AIDS <br />t<br />
    168. 168. Stage of Management<br />
    169. 169. Mx 1 – Risk Assessment<br />full history + detailed sexual + drug history<br />physical examination  stage <br />Initial laboratory tests will include:<br />a. A Full Blood Count with differential count, particular attention to be given to platelet and Iymphocyte counts<br />b. A Mantoux Test with 1 Tuberculin unit intradermally<br />c. A Chest Radiograph<br />
    170. 170. Mx 2 – Establish Diagnosis<br />HIV antibody Testing:<br />ELISA and or Particle agglutination tests<br />Confirmed by supplementary test<br />a. voluntary basis<br />b. anonymously or<br />c. confidential basis<br />
    171. 171. Mx 3 – Ascertain Stage<br />to assess progression of the disease is by measuring the CD4+ Tlymphocyte count and percentage. <br />recommended  all HIV infected individuals should have a baseline CD4+ <br />Infants born  ELISApositive. <br />If the infant is not HIV infected  ELISA fall within 18 months after birth.<br />Therefore, a better indicator of HIV infection in an infant younger then 18 months will be the measurement of p24 antigen, by doing a polymerase chain reaction (PCR) test, or detection of the virus itself<br />
    172. 172. SPECTRUM OF HIV<br />MohdHanafiRamlee<br />
    173. 173. Group 1 HIV disease (acute seroconversion illness)<br />Acute neurological disease <br />meningitis<br />encephalitis<br />olyneuritis<br />myelopathy<br />brachial neuritis<br />GuillianBarre syndrome<br />2-4 weeks after the initial HIV<br />The symptoms include:<br />Flu-like illness<br />fever<br />arthralgia<br />malaise<br />myalgia<br />headache<br />photophobia<br />maculopapularrash<br />GI disturbances and<br />neurological manifestations<br />lasts 2-4 weeks  low platelet and Iymphocyte counts, and a low CD4+ T-lymphocyte counts, with a reversed CD4+/CD8+ ratio. <br />In the asymptomatic phase the CD4+ Tlymphocyte counts will rise to almost normal levels (600-1200/uL).<br />
    174. 174.
    175. 175. Group 2 Asymptomatic Phase disease<br />3-7 years from the initial HIV infection.<br />feels and looks well<br />CD4+ T-cell counts can be normal. <br />counselled<br />towards change of behaviour, <br />maintain good health and practise behaviour<br />prevent further transmission of HIV.<br />assessment for antiretroviral therapy <br />6-monthly CD4+ T cell count.<br />
    176. 176. Symptomatic Phase (Group 3 and 4) disease<br />Viral markers <br />p24 antigen<br />polymerase chain reaction (PCR) <br />p24 antibody (babies, health care workers)<br />clinical predictors <br />herpes zoster (multi-dermatornal)<br />oral candidiasis<br />oral hairy leukoplakia<br />Prolonged fever, might sweets<br />Progressive weight loss<br />Laboratory predictors of progression to AIDS:<br />thrombocytopenia<br />falling CD4+ T. cell counts<br />high p24 antigen<br />Preliminary investigations <br />Chest X-ray<br />Full blood count and differential count, ESR<br />Stool examination for cryptosporidia/ isospora (when diarrhoea is present)<br />Blood cultures for MAI/Mtb, Cryptococcus, Salmonella sp.<br />Toxoplasma, Cytomegalovirus, Herpes Antibody titres.<br />Sputum for PCP<br />Immunological markers <br />CD4+ T-cell counts<br />CD4+/CD8+ ratio <br />CD4+ percentage <br />
    177. 177. Perinatal HIV Transmission<br />Can occur:<br />during pregnancy (intrauterine), 25%--40% <br />during labor and delivery (intrapartum), 60%--75% <br />after delivery through breast-feeding (postpartum). <br />In a randomized trial of formula feeding versus breast-feeding, approximately 44% of HIV infection was attributed to breast-feeding <br />Risk factors are associated with perinatal HIV transmission <br />immunologically or clinically advanced HIV disease in the mother <br />high plasma viral load <br />maternal injection-drug use during pregnancy <br />preterm delivery <br />breast-feeding <br />No antiretroviral therapy<br />HIV subtype<br />Obstetric factors : Delivery >4 hours after the rupture of the fetal membranes; maternal infection with another sexually transmitted disease or coinfection with HSV-2 increased risk of HIV transmission; chorioamnionitis <br />
    178. 178. Diagnosis of HIV Infection in Newborns<br />Nearly all infants born to HIV-infected mothers passively acquire maternal antibody and, antibody will remain positive until age 18 months regardless of whetherthey are infected.<br /> Definitive diagnosis of HIV infection in early infancy requires: <br /> nucleic acid amplification (e.g., polymerase chain reaction [PCR]) or viral culture. <br /> HIV infection is diagnosed by two positive assays (PCR or viral culture) on twoseparate specimens.<br />Infant HIV testing should be done as soon after birth as possible so appropriate treatment interventions can be implemented quickly.<br />UMMC: PCR quantitative assay<br />
    179. 179. HIV: Reproductive and Women’s Health Issues<br />Differences in HIV disease between men and women <br />Levels of HIV RNA may be lower in women at seroconversion. <br />Mean VL becomes similar within 5-6 yrs. <br />CD4 may be higher in women. <br />Rates of disease progression do not differ <br />No changes in treatment guidelines <br />Abnormal Pap Smears<br />30%-60% Pap smears have cytologic abnormality <br />Cervical cancer presents with high grade pathologic features <br />- Uniform relapse after therapy (prior to HAART) <br />- Short survival <br />HAART has been independently associated with regression of cervical disease. <br />
    180. 180. NRTI / NNRTI<br />Protease inhibitor<br />Entry inhibitor<br />Receptor inhibitors<br />CCR5 or CXCR4<br />Integrase inhibitors<br />
    181. 181. Immune Reconstitution Syndrome<br />Immune Reconstitution Syndrome<br />The use antiretroviral therapy resulted dramatic improvement in outcomes typically associated with an increase in CD4+ lymphocytes, reduced HIV viral loads and partial recovery of T-cell–specific immune responses. <br />Recovery of immune function correlates with the number of circulating CD4+ cells. It is safe to discontinue prophylaxis (primary or secondary) for a variety of pathogens including Pneumocystis jiroveci, Mycobacterium avium complex (MAC), and Toxoplasma gondii.<br />Some patients experience a clinical deterioration following the introduction of potent antiretroviral therapy believed to be related to the restored ability to mount an inflammatory response. <br />The incidence of IRS to be 10% to 25%. In patients undergoing simultaneous treatment of HIV infection and tuberculosis, the incidence of IRS has been reported to be 11% to 45%. <br />
    182. 182. Diagnosis of IRS<br />
    184. 184. Antiretroviral Agent: Zidovudine<br />Zidovudine (ZDV)<br />a nucleoside analogue, when it is phosphorylated inside HIV -infected cell, inhibits reverse transcriptase. <br />Usage<br />improved survival<br />decreases frequency of opportunistic infections<br />Improve quality of life<br />cuts down length of hospital stay. <br />effective against replicating virus<br />can inhibit replication of sensitive strains.<br />gold standard in HIV management.<br />
    185. 185. Zidovudine: When to Start?<br />assessment first<br />weight <br />opportunistic infections <br />immunological status <br />if the CD4+ counts are below 200/uL, <br />Give zidovudine at 500-600mg per day in 2 or 3 divided doses (250mg b.i.d. or 200mg t.i.d).<br />If the CD4+ counts are 200 or less, <br />chemoprophylaxis against Pneumocystis carinii pneumonia (PCP)<br />Close monitoring & Follow up: 1x/2w  1x/3m 1x/36ml<br />
    186. 186. Zidovudine: Site effects<br />
    187. 187. Commencing Antiretroviral Therapy <br />WHEN ?<br />
    188. 188. General Goals of Antiretroviral Therapy<br />to prolong survival <br />decrease morbidity in those infected <br />to improve the patient’s quality of life and reduce the burden on his family and the community. <br />To promote prevention of transmission<br />
    189. 189. Specific Goals of Antiretroviral Therapy<br />to suppress HIV replication <br />to reduce plasma viral load to below undetectable levels for a maximum duration <br />to improve, maintain and prevent the ongoing decline of CD4 cells. <br />
    190. 190. Recommendation on when to commence HAART [MSIDC]<br />
    191. 191. Selection of Antiretroviral Agents<br />
    192. 192. Successful Antiretroviral Therapy: Critical Factors<br />Efficacy<br />Tolerability<br />Convenience<br />-<br />-<br />Adherence<br />Successful Therapy<br />Durable viral load <br />Suppression<br />
    193. 193. Antiretroviral Agents in Malaysia<br />
    194. 194. Commencing Antiretroviral Therapy<br />WHAT ?<br />
    195. 195. HAART<br /> H = Highly<br /> A = Active SLOWS DOWN<br /> A = Anti- VIRAL<br /> R = Retroviral REPLICATION!<br /> T = Therapy <br /> 3 or more ARVs. Only recommended ARV treatment – for long term effect.<br />
    196. 196. What makes ARVs work?<br />Function of ARVs  suppress viral replication<br />Virus suppressed  immune system recovers<br />Immune system recovery means  CD4 count goes up <br />CD4 count up no more opportunistic infections<br />
    197. 197. Protease Inhibitor<br />Integrase Inhibitor<br />NNRTI<br />NRTI<br />Mechanism of Action of ARVs<br />Fusion <br />Inhibitor &<br />Chemokine<br />Receptor <br />Antagonist<br />Illustration by David Klemm<br />
    198. 198. <ul><li> Entering </li></ul> CD4 cell<br />The virus <br /> NNRTI <br />NVP, Stocrin<br /> NRTI (nukes) & nucleotide <br /> 3TC, d4T<br /> The ‘factory’<br /><ul><li> New virus</li></ul> ‘budding’<br />
    199. 199. 3. Integration into <br />host cell’s nucleus<br />4. Reproduction of viral components<br />Assembly and release of new viruses<br />2. The virus changes <br />from RNA to DNA<br />How do PIs work?<br />1. Attachment to host cell<br />
    200. 200. Pharmacokinetics<br />Absorption, Distribution, Metabolism, Elimination<br />Renal Elimination<br />Liver/GI Metabolism<br />Phase I: Oxidation (ie, CYP 450 enzymes)<br />Phase II: Conjugation (ie, glucuronidation)<br />Antiretrovirals<br />Many ARVs (and other medications) undergo Phase I metabolism<br />Many ARVs increase or decrease activity of CYP450 (Phase I) enzymes<br />
    201. 201. CYP 450 Inhibition<br />Leads to blocking of the specific CYP 450 enzyme<br />If a drug is metabolized by the CYP 450 enzyme that is blocked<br /> drug concentration<br />Example: Ritonavir<br />
    202. 202. CYP 450 Induction<br />Leads to production of more CYP 450 enzyme<br />If a drug is metabolized by the CYP 450 enzyme that is now in high amounts<br /> drug concentration<br />Example: Efavirenz<br />
    203. 203. Drug Interaction Potential<br />
    204. 204. NRTIs (Nucleoside Reverse Transcriptase Inhibitors)<br />Cytidine<br />Tymidine<br />Adenosine<br />Guanosine<br />Zidovudine (AZT)<br />
    205. 205. NRTIs (Nucleoside Reverse Transcriptase Inhibitors)<br /><ul><li>Note: Lactic acidosis can occur with any NRTIs</li></ul>*dose reduce for renal dysfunction<br />
    206. 206. NRTIs<br />*dose reduce for renal dysfunction<br />
    207. 207. NNRTIs (Non-nucleoside reverse transcriptase inhibitors)<br />
    208. 208. NNRTIs<br />*Pregnancy Class D<br />
    209. 209. Protease Inhibitors (PIs):<br />Protease enzyme cleaves HIV precursor proteins (gag/pol polyproteins) into active proteins that are needed to assemble a new, mature HIV virus. <br />PIs bind to protease preventing the cleavage and inhibiting the assembly of new HIV viruses<br />
    210. 210. Protease Inhibitors<br />X<br />
    211. 211. Ritonavir as a PI Booster<br />Ritonavir used only to ‘boost’ concentrations of other protease inhibitors<br />Dosed 100-200mg QD-BID<br />Available as 100mg capsules and tablets<br />Side effects: GI upset; hyperlipidemia*; insulin resistance*<br />* All PIs except atazanavir alone<br />
    212. 212. Lipodystrophy Illustrations<br />“Buffalo hump”<br />“Central obesity”<br />“Facial and peripheral wasting”<br />
    213. 213. Protease Inhibitors<br />(1) Take with Food (2) Must be refrigerated<br />** All PIs except atazanavir can increase lipids and cause insulin resistance<br />
    214. 214. Protease Inhibitors<br />(1) Take with Food (2) Must be refrigerated<br />** All PIs except atazanavir can increase lipids and cause insulin resistance<br />
    215. 215. Entry Inhibitors:Fuzeon : Enfuvirtide (T-20)<br />FDA-approved fusion inhibitor; 36 AA peptide<br />Requires 106 steps to manufacture<br />Dose: 90 mg sq bid<br />side effects: <br />injection site rxn, hypersensitivity (rare)<br />resistance: changes in gp41 (cell surface protein) <br />
    216. 216. Chemokine Receptor Antagonists<br />Maraviroc (Selzentry®)<br />CCR5 or CXCR4 receptors on cell surface <br />Virus will bind to one of the 2 receptors <br />Some patients’ virus will bind to either receptor<br />Maraviroc blocks viral entry at CCR5<br />Dosed 300mg BID<br />150mg BID with P450 <br /> inhibitors<br />600mg BID with P450 <br /> inducers<br />Tropism<br />
    217. 217. Integrase Inhibitors<br />Raltegravir (Isentress™)<br />Dosed 400mg BID (1 tab BID)<br />No induction or inhibition on CYP450 enzymes or Pgp<br />Metabolized by UGT1A1 (glucuronidation)<br />Only affected by drugs <br />that inhibit or induce UGTs <br />(ie, rifampin)<br />
    218. 218. Integrase Inhibitor<br />
    219. 219. Metabolic Dysfunction in HIV-Infected <br />Patients on HAART<br />HIV INFECTION<br />InsulinResistance<br />Dyslipidemia<br />Body Fat Redistribution<br />HAART<br />215<br />
    220. 220. Toxicities in Summary<br />NRTIs: Lactic acidosis<br />Zidovudine: Anemia<br />Stavudine and Didanosine: Pancreatitis and Peripheral Neuropathy<br />Abacavir: Hypersensitivity (can lead to death); ? CVD<br />Tenofovir: renal toxicity<br />NNRTIs:<br />Efavirenz: nervous system side effects; rash<br />Nevirapine: rash, liver toxicity<br />Etravirine: rash<br />PIs: GI effects, increased lipids, increased BG<br />Atazanavir: increased bilirubin, PR prolongation<br />Indinavir: kidney stones (LOTS of water)<br />Fosamprenavir: rash<br />Tipranavir: liver toxicity; bleeding<br />
    221. 221. How Do We Treat HIV?<br />
    222. 222. Antiretroviral Therapy<br />DHHS Guidelines<br />Last updated December 1, 2009<br /><br />International AIDS Society- 2008<br />Hammer, et al. JAMA Aug 6, 2008<br />IDSA Primary Care HIV Guidelines-2009<br />Aberg, et al CID Sept 1, 2009<br />
    223. 223. Factors to Consider for Initial Regimen Selection<br />Potential drug interactions<br />Pre-treatment CD4+ T cell count<br />Gender<br />Pregnancy potential<br />Patient lifestyle/ social situation<br />Co-morbidities<br />Adherence potential<br />Dosing convenience (pill burden, dosing frequency, food, fluid restriction)<br />Potential adverse effects<br />HIV Resistance Testing<br />DHHS 4/7/2005,<br />
    224. 224. Initiating Therapy in Treatment Naïve Patients<br />If AIDS-defining illness or CD4 < 350<br />Regardless of CD4 count in: <br />Pregnancy<br />HIV-associated nephropathy <br />HBV co-infection<br />Recommended if CD4 count between 350 – 500<br />Panel split on initiating in CD4 > 500<br />Make a lifelong commitment and understand adherence importance<br />DHHS 2009 Guidelines<br />
    225. 225. Preferred Regimens for Naïve Patients<br /><ul><li>NNRTI-based regimen </li></ul>Efavirenz+ tenofovir+ emtricitabine<br /><ul><li>PI-based regimen </li></ul>Atazanavir/r + tenofovir+ emtricitabine<br />Darunavir/r QD + tenofovir + emtricitabine<br /><ul><li>INSTI-based regimen</li></ul>Raltegravir + tenofovir+ emtricitabine<br />DHHS 2009 Guidelines<br />
    226. 226. HIV Resistance Testing<br />Genotypes<br />Sequences patient’s virus by blood sample<br />Mutations reported as compared to wild type<br />Phenotypes<br />Similar to antimicrobial susceptibility testing<br />Reports IC50 for patient’s virus <br />Compares to wild type virus<br />Virtual Phenotypes<br />Often reported along with genotypes<br />Information obtained from a database of genotypes and matching phenotypes<br />An estimate of patient’s phenotype<br />
    227. 227. Summary<br />HIV infection rates are not declining<br />Combination Therapy is CRITICAL<br />100% Adherence is ABSOLUTELY NECESSARY<br />Drug Interactions are ANTICIPATED<br />Adverse Effects occur often <br />Some can be managed<br />Some are dangerous<br />If any doubt, call the physician or ME!<br />
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