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Presentor: Mabel Aloc, M.D. March 01, 2007 Ledesma Hall

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1 Presentor: Mabel Aloc, M.D. March 01, 2007 Ledesma Hall
Grand Rounds Presentor: Mabel Aloc, M.D. March 01, 2007 Ledesma Hall

2 Objectives To present a case of HIV / AIDS with multiple opportunistic infections To discuss the diagnosis and management of some of the major complications of HIV / AIDS

3 General Data R.D. 24 years old Female Married Ukrainian Lawyer

4 word-finding difficulty
Chief Complaint word-finding difficulty

5 History of Present Illness
2 weeks PTA  word-finding difficulty / headache 4 days PTA  upward rolling of eyeballs and stiffening of extremities. Consult was sought. Oxcarbazepine was prescribed. Cranial MRI was done. There was no associated fever, nausea, vomiting, dizziness.

6 Cranial MRI

7 Review of Systems + weight loss + anorexia (-) rash
(-) heat or cold intolerance (-) polyuria (-) polydipsia (-) dyspnea (-) cough (-) chest pain (-) palpitations (-) orthopnea (-) tendency to bleed or bruise easily (-) dysphagia (-) constipation (-) diarrhea (-) dysuria (-) nocturia

8 Past Medical History June 2006  admitted due to dyspnea
dx: Pneumocystis carinii pneumonia  HIV positive CD4 count 2.3% CD4/CD8 ratio 0.02 treated with TMP/SMX

9 Family History (-) Asthma (-) Diabetes Mellitus (-) Hypertension
(-) Cancer (-) HIV / AIDS

10 Personal / Social History
monogamous denies drug abuse divorced first husband due to alleged battery / physical assault ? No history of blood transfusions

11 Physical Examination General 24-year-old caucasian female, drowsy, not in cardiorespiratory distress, with difficulty in self-expression, makes eye contact BP 90/60mmHg HR 88bpm RR 18cpm T 36.9C Weight 45kg Height 5’ 7” BMI 15.5 Skin dry skin, no lesions or tenderness; nailbeds pink without clubbing; brisk capillary refill, + tattoo on lateral aspect of left ankle

12 HEENT scalp without lesions or tenderness conjunctivae pink without discharge pupils react equally to light and accommodation extraocular movements intact red reflex present discs cream colored with well-defined border bilaterally A-V ratio 2:3 cornea, lens, and vitreous clear retina pink, no hemorrhages or exudates macula yellow visual acuity 20/25 no ear / nose discharge buccal mucosa pink and moist

13 Neck trachea midline, freely movable, thyroid not palpable; lymph nodes nonpalpable
Chest and Lungs symmetric chest expansion, tactile fremitus symmetric, resonant percussion throughout, no crackles, no wheezes

14 Heart Apex beat and PMI at 5th intercostal space, LMCL; S1 heard best at apex, S2 heard best at base, no murmurs; regular rhythm Blood Vessels no neck vein engorgement; no bruits Abdomen full, soft, nontender; liver, spleen, and kidney not palpable

15 Lymphatic no palpable lymph nodes in neck, supraclavicular, axillary, epitrochlear, or inguinal areas Musculoskeletal muscles appear symmetric with appropriate and equal strength bilaterally, full range of active and passive motion

16 Neurologic Exam Mental Status Exam conscious, coherent, good attention
impaired verbal fluency Intact word comprehension impaired repetition Impaired naming Impaired reading comprehension Impaired writing

17 Cranial Nerve Examination
I - intact sense of smell; II - no visual field cuts, no papilledema II, III - pupils isocoric at 3mm EBRTL III, IV, VI - full EOM V - intact facial sensation, strong muscles of mastication VII - Right central facial palsy VIII - Weber’s test is midline, Rinne’s test – AC > BC, AU IX, X - + gag reflex, uvula at midline XI - able to shrug shoulders and turn head against resistance XII - tongue at midline, no atrophy noted

18 Motor Examination individual muscle groups are graded 5/5 on all extremities
Sensory Examination intact to pain, temperature, light touch, vibration and position sense, (-) Romberg’s test Deep Tendon Reflex +2 on all extremities

19 Cerebellar Tests able to do finger to nose test, able to do rapid alternating pronation / supination of the hands, no nystagmus Meningeal Tests supple neck, (-) Kernig’s sign, (-) Brudzinski sign Pathologic Reflexes (-) Babinski sign, (-) Grasp reflex Gait Exam able to walk on heels, toes, and tandem walk well

20 Salient Features 24y/o female causasian Expressive aphasia, headache
MRI: T/C cerebral infection Hx: Pneumocystis carinii pneumonia, HIV positive BMI 15.5 Impaired verbal fluency, repetition, naming, reading comprehension, and writing Right central facial palsy

21 Initial Impression Acquired Immune Deficiency Syndrome
CNS Infection, r/o Parasitic Disease with Abscess Formation

22 Course in the Wards On admission  mannitol, citicholine, oxcarbazepine started  Infectious Disease referral: started Pyrimethamine Sulfadoxine (Fansidar) and Clindamycin, and Folinic acid

23 2nd H.D.  Referral to Gastroenterology service due to elevated liver transaminases
 Fansidar and Clindamycin shifted to Trimethoprim/Sulfamethoxazole  UTZ: no hepatobiliary abnormalities  Anti HCV reactive  HCV RNA > 850,000 iu/mm  started nutritional and liver support

24 7th H. D. . Referral to Ophthalmology. service due to blurring of
7th H.D.  Referral to Ophthalmology service due to blurring of vision. Fluorescein angiography was done and CMV retinitis was diagnosed. CMV antigenemia wbc/smear  Valganciclovir started

25 Fluorescein Angiography

26 Fluorescein Angiography


28 8th H.D.  increasing aphasia
 TMP/SMX shifted to Fansidar and Azithromycin  Toxoplasma IgG: negative

29 Stereotactic Brain Biopsy

30 Final Histopathologic Report:
Inflammatory process with necrosis. No definite Toxoplasma cyst identified. No malignant cells.

31 Acid fast, silver, and PAS stains were negative.
Aerobic culture of brain tissue was negative and mycobacterial culture remained negative by the first week of incubation. Repeat Toxoplasma IgG was negative.

32 9th H.D.  developed oral thrush
 Nystatin started Antiretroviral therapy and tests for CD4 count and HIV viral load were deferred until the acute opportunistic infections stabilized. The patient was discharged on the 14th H.D. alert, headache-free, without seizure recurrence but with persistent expressive aphasia.

33 1/22 1/23 1/27 1/29 1/31 2/1 WBC 2.3x109/L 2.8x109/L 2.4x109/L 3.41x109/L Segmenters 36% 55% 72% 75% Lymphocytes 49% 30% 22% 13% Monocytes 14% 12% 4% 7% Hb / Hct 13.2/ 41.2 12.8/ 40.7 11.4 / 36 11.8 / 35.8 Platelet count 138,000 141,000 105,000 123,000 SGPT (IU/L) 124 139 117 SGOT(IU/L) 214 268 199 GGTP(IU/L) 835 Ammonia 170UG/DL

34 Final Diagnosis Acquired Immune Deficiency Syndrome
CNS lesion, probable Toxoplasma Encephalitis CMV Retinitis Hepatitis C Oral Candidiasis Pneumocystis carinii Pneumonia, Resolved

35 Acquired Immune Deficiency Syndrome

36 History First recognized in mid-1981  clusters of Pneumocystis carinii pneumonia and Kaposi’s sarcoma reported in young, previously healthy homosexual men in New York City, Los Angeles, and San Francisco Subsequent documentation of cases among persons with hemophilia, blood transfusion recipients, and heterosexual injecting drug users and their sex partners

37 1983  cytopathic retrovirus isolated
1985  serologic tests to detect evidence of infection with HIV had been developed and licensed






43 Natural History of HIV Infection


45 Antiretroviral Therapy

46 Indications for Initiating ART for Chronic HIV Patients

47 Testing for Plasma HIV RNA Levels and CD4+ T Cell Count to Guide Decisions Regarding Therapy
ART-naïve On ART HIV RNA At the time of diagnosis and every 3-4months thereafter Immediately before and at 2-8weeks after initiation of tx, then every 3-4months CD4+ T Cell At the time of diagnosis and every 3-6months thereafter





52 Recommended Anti Retroviral Agents for Initial Treatment of Established HIV

53 ART for Patients with Acute Opportunistic Infection
The potential benefit of ART must be weighed against other factors: 1. For ART-naïve patients, the initiation of ART may produce an enhanced inflammatory response that could be detrimental in the short term. 2. Poor adherence or less than optimal absorption may diminish effectiveness of ART and enhance the likelihood of emergence of drug-resistant HIV-strains

54 3. Changing drug regimens could alter pharmacokinetics and result in suboptimal or, alternatively, toxic serum drug concentrations, which could enhance the likelihood of development of HIV resistance to antiretroviral agents


56 at the beginning of the AIDS epidemic, Toxoplasma encephalitis was the most common cerebral mass lesion in patients with AIDS caused by a reactivation of latent infection by Toxoplasma gondii as a result of progressive loss of cellular immunity

57 Life Cycle of Toxoplasma gondii

58 Clinical Presentation
90% - CD4+ T-lymphocyte counts <200/uL 75% - CD4+ T-lymphocyte counts <100/uL Headache, confusion, fever, lethargy, seizures, focal signs (hemiparesis, cranial nerve palsies, ataxia, sensory deficits) Subacute, ranging from a few days to a month

59 Laboratory Investigations
serum anti-Toxoplasma IgG antibodies can be detected, whereas IgM antibodies are rarely found CSF – mild elevation of protein, moderate mononucleated pleocytosis (<60 cells/mm3), slight decrease in glucose CSF analysis more useful to rule out other infectious process than to confirm the diagnosis of TE

60 Imaging Studies multiple lesions in 2/3 of cases, and 90% of them display ring enhancement after administration of contrast material MRI more sensitive than CT to detect multiple lesions Localized at the corticomedullary junction in the white matter, or the basal ganglia; and are surrounded by edema; and induce mass effect on surrounding structures

61 Brain Biopsy necrotic abscesses with blood vessel with blood vessel thrombosis and necrosis cysts containing bradyzoites, the dormant form of T. gondii, coexist with numerous active tachyzoites

62 Management of HIV-infected Patient with CNS Lesion

63 Treatment pyrimethamine+sulfadiazine (Fansidar) – synergistic and sequential block on folic acid metabolism Pyrimethamine 200mg D1, then 75mg OD sulfadiazine 6g/day in 6 divided doses Folinic acid 10-50mg/day

64 Alternative to (+) sulfonamide allergy:
1. clindamycin 600mg IV or 450mg, 2. Azithromycin 1200 to 1500mg p.o. OD, 3. Atovaquone 750mg p.o. QID side effects: cytopenia, rashes, diarrhea, elevated liver enzymes


66 Corticosteroids in TE to diminish cerebral edema
has not been shown to be either beneficial or harmful in TE because high doses of steroids reduce the size of CNS lymphoma lesions, they should be administered only in cases with impending cerebral herniation during the initial medical treatment of presumed TE

67 Neurologic improvement clinically apparent in >50% by D3 of therapy and in most cases by D7
failure to improve or worsening of symptoms should prompt repeat imaging studies by D10 to 14

68 Secondary Prophylaxis
maintenance therapy to prevent relapse which is likely to occur after a delay of 6-8 weeks of interruption of treatment pyrimethamine 25-75mg/day + folinic acid 10mg OD + sulfadiazine 2-4g/day in 4 divided doses OR clindamycin 300mg QID or 450mg TID CD4+ T-cell counts above 200/uL for more than 3 months – discontinue prophylaxis

69 CMV Retinitis

70 CMV Retinitis risk determined by CD4+ cell count and CMV DNA level in the peripheral blood CD4+ cell counts <200/mm3 – annual risk 4-12% Aviremic patients <1% risk per year even at low CD4+ cell counts

71 CMV Retinitis: Symptoms
painless, progressive visual loss, blurring, and “floaters” usually unilateral, but may progress to the contralateral retina retinal detachments (sudden loss of vision, “like a curtain falling”) – erosion of retinal border at the site of a necrotic lesion allows the retina to be lifted off underlying tissues

72 CMV Retinitis: Fundoscopy
Fundoscopy: coalescing white exudates in a vascular pattern with surrounding hemorrhage and edema lesions are peripheral initially, involve the fovea later, and result in visual loss Retinal detachment as a late complication

73 CMV Retinitis: Treatment
For immediate sight-threatening lesions: Ganciclovir (GCV) intraocular implant + valganciclovir 900mg PO qd For peripheral lesions: Valganciclovir 900mg PO bid x days, then 900mg PO qd

74 CMV Retinitis: Chronic Maintenance Therapy
Ganciclovir 5-6mg/kg BW/day IV 5-7 days weekly or 1000mg PO tid; or Foscarnet mg/kg BW IV qd; or For retinitis, ganciclovir sustained-release implant every 6-9 months plus ganciclovir g PO tid

75 CMV Retinitis: Duration of Chronic Maintenance Therapy
Implant - replace every 6-8 months until immune recovery on ART Systemic therapy – continue for life or until immune recovery on ART

76 Hepatitis C

77 HCV / HIV Co-infection increased rate of progression to cirrhosis (three-fold higher) especially in older people, and those with lower CD4+ T lymphocyte count and with history of alcoholism HCV infection might accelerate progression of HIV increased frequency of antiretroviral-associated hepatotoxicity

78 HCV: Diagnosis Initial testing for detection of antibody to HCV  test for HCV RNA with a qualitative assay with a lower limit of detection of ≤ 50 iu/ml  more sensitive anti HCV testing with RIBA if negative HCV RNA Screen for HCC using AFP and hepatic UTZ ALT levels to assess activity of liver disease

79 Liver biopsy is recommended for all HIV-1 infected persons with chronic HCV co-infection who are candidates for antiviral therapy

80 HCV Treatment

81 Treatment of HCV / HIV Co-infection
Ribavirin should not be given with didanosine because of the potential of drug-drug interactions leading to pancreatitis and lactic acidosis Some NRTIs and all NNRTIs and PIs are potentially hepatotoxic Zidovudine combined with ribavirin is associated with higher rates of anemia

82 Growth factors to manage interferon-associated neutropenia and ribavirin-associated anemia may be required


84 Thank You


86 CN VII Central Lesion Peripheral Lesion


88 Standard Indications for HCV Therapy
detectable plasma HCV RNA liver biopsy showing bridging or portal fibrosis

89 HCV: Clinical Manifestations
low grade fever mild RUQ pain Nausea Vomiting anorexia Dark urine Jaundice Fatigue Spider angiomata Splenomegaly Caput medusa Ascites Jaundice Pruritus Encephalopathy


91 CD4 lymphocyte count and plasma viral load – best prognostic markers for subsequent disease course in an HIV-infected individual CD4+ lymphocyte count – sensitive predictor of the development of symptomatic HIV infection and AIDS in the near term

92 HIV-1 RNA – predictor of disease course over a more extended period of time and is strongly associated with the rate of subsequent CD4+ cell count decline higher baseline viral load – more rapid decline in CD4+ count, faster clinical progression, and decreased survival

93 viral load measures replicative rate of infection and its destructive potential for the cellular immune system CD4+ count gauges the extent of immune compromise and the present risk of opportunistic disease

94 AIDS develops in <5% of HIV-infected adults within 2 years of infection
without therapy, AIDS develops in 20-25% within 6 years of infection, and in 50% within 10 years long-term nonprogressors – 5-8% of HIV-infected individuals remain clinically asymptomatic with normal CD4 T lymphocyte count for >8 years after infection


96 T1-Weighted Image after Gadolinium Injection

97 T2-Weighted Image



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