Evaluating the Patient w Newly Diagnosed HIV Infection. Steven C. Zell MD / AAHIVMS
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1 Evaluating the Patient w Newly Diagnosed HIV Infection Interpreting tests, clinical findings and symptomatic complaints Steven C. Zell MD / AAHIVMS Professor of Medicine University of Nevada School of Medicine Co-director Nevada AETC
2 Client Intake to Establish Care Purpose: 3 key functions prioritize immune status / overall health screen for public health purposes communicable dz treat STDs / administer vaccines Goals: two-fold advanced disease need be seen more quickly protocols to offer CD4 guided OI prophylaxis PCP / toxo / MAC / Herpes / Thrush screen for the company kept w HIV STDs: syphilis / GC / Chlamydia / HSV Hepatitis B and C Personnel: nurse / medical assistant
3 Requisite Evaluation-Initial Intake The Newly diagnosed HIV CD4 lymph count HIV-1 RNA by PCR quant STD screen: Syphilis RPR or VDRL titer and confirm w TPPA GC / Chlamydia: NAA 1 st void urine or APTIMA Unisex Swab CxR: TST (PPD) or QuantiFERON-TB Gold test? Only in most advanced cases CBC / chem panel / fasting lipids / urinalysis Hepatitis panel for A / B / C Total antibody for Hep A / anti-hcv HBsAg / anti-hbs HBV DNA if surface antigen positive
4 Initial clinician medical evaluation Purpose: key issues to address Screening and Tx for OIs Response to screening serology for Hepatitis / STDs Screening for significant co-morbid conditions Type 2 DM / DLD / CKD Goals: multi- fold Reduce short-term illness from OIs Respond to screening tests to treat underlying STDs Vaccinate as dictated by intake serology Personnel: MD / PA / NP Antiretroviral therapy is never an emergency as long as appropriate prophylaxis against 0I is provided
5 Diagnostic Tests-Initial Clinical Exam CD4 ct and VL done to establish immune pattern HIV-1 genotype for naïve patients or 1 st line failure Phenosense- GT for class-experienced failures Specific labs to guide ARV Testing-drawn if considering abacavir or entry Inhbitior HLA-B5701 to assess Abacavir HSR (Epzicom) Co-receptor tropism assay for use of Selzentry Trofile or Trofile DNA (if VL< limits) Specific labs to guide OI screening G6PD screen for Septra DS allergic Toxoplasma IgG?
6 Eosinophilic folliculitis
7 Subtle Laboratory Findings Seen in Chronic HIV Hematologic parameters of note: Leukopenia / thrombocytopenia Chemistries fasting triglycerides high: abnormal albumin to globulin ratio (decreased) polyclonal increase a result of frequent infections? high LDH level-surrogate for NHL / PCP / MAC? The company HIV keeps Hepatitis C / Hepatitis B / RPR positivity
8 Physical exam in HIV infection Eyes CMV retinitis / HIV retinopathy Mouth thrush / KS /apthous ulcers / OHL / angular chelitis Skin infectious bacterial: syphillis / BA / folliculitis infectious viral: HZV / HSV / molluscum / KS miscellaneous: exaggerated response in HIV psoriasis / eczema / seborrhea / xerosis / eosinophilic folliculitis
9 Oral thrush
10 Oral Kaposi s
11 Apthous ulcers
12 Angular chelitis
13 Necrotizing gingivitis
14 HIV Retinopathy
15 CMV Retinitis
16 Primary syphillis
17 Bacterial folliculitis
18 HSV infection Type 2
19 HSV infection advanced disease
20 Herpes Simplex type 1
21 Herpes Zoster
22 Molluscum Contagiosum
23 Seborrheic dermatitis
24 Eczema
25 Initial Clinical Exam (continued) Tests to better define co-morbidity Metabolic syndrome: fat / htn / FBS / lipids Insulin Resistance: 75 gm 2 hr OGTT >140 mg c/w impaired glucose +1 proteinuria or > excretion Urine P/C spot ratio or 24 hr collection >150 mg is worrisome Tests in response to specific serology Anti-HCV + = HCV RNA quant by PCR If detectable-hcv genotyping HBsAg + = HBV DNA quant by PCR
26 Genotypic Testing: Attributes Looks at gene sequence for replication / assembly of HIV virus: RT (reverse transcriptase) Replicates HIV RNA to DNA Pr (protease enzyme) Cleaves transcribed HIV RNA into assemnly Indirect measure of resistance Not to be confused w culture and sensitivity! Requires interpretation utilizing expert algorithm Derived from clinical trials Must be updated as knowledge advances
27
28 Phenotypic Testing: PhenoSense Measures the sensitivity of a patient s HIV to medications isolated virus vs. varying levels of ARV drug in test tube IC 50 level determined for patient isolate Compared to lab standard (Wild type) Fold change in susceptibility reported Quantitative measure of resistance Fold changes in susceptibility relate to clinical trial data Used to make final assessment Exception: biologic or assay cut-offs
29 Phenotypic Testing Advantages: Direct measure of resistance Can be used with new drugs Quantitative (more than a yes or no answer) Report form: easy to read; easier to interpret Limitations: Can be less sensitive to mixtures Can t test for synergy of drug combinations
30 PhenoSense HIV Test Report
31
32 The HIV Life Cycle Provides Many Targets for Therapeutic Intervention Adapted from Janeway C, et al. Immunobiology. 5 ed. New York,NY:Garland Publishing;2001:
33 Co-Receptor Binding Is an Essential Step for Viral Entry Attachment Co-Receptor Binding Fusion Viral gp120 protein binds to CD4 on host cell gp120-cd4 complex binds to CCR5 or CXCR4 on host cell Adapted from Moore J, et al. Proc Nat Acad Sci U S A. 2003;100: Virus fuses with host cell membrane, facilitating viral entry
34 Why is Trofile DNA Needed? Trofile is the original assay and gold standard for determining tropism viral loads greater than or equal to 1,000 copies/ml The ability to determine tropism has been precluded by the viral load requirement Inability to switch out to R5 antagonist Drug intolerance to other agents in a suppressed regimen Trofile DNA will enable tropism determination in those patients whose virus is undetectable
35 Trofile DNA Tropism Determination Via Cell-Associated DNA Cell-associated viral DNA may be from two sources: Integrated DNA Cytoplasmic DNA HIV Virus RNA
36 Comparison of Trofile and Trofile DNA Trofile HIV RNA is isolated from plasma (front end of assay) gp 160 envelope sequences are amplified from the extracted RNA and incorporated into the test vector. Remaining steps are identical. Trofile DNA Cell-associated HIV DNA is isolated from whole blood (front end of assay) gp 160 envelope sequences are amplified from the extracted DNA and incorporated into the test vector. Remaining steps are identical. Requires > 1,000 copies/ml of virus Consider when viral load is below the limit of detection The RNA viral load level in the plasma does not match the DNA viral load level
37 Trofile DNA - Report
38 Expected Abnormal Lab results: CBC Leukopenia: WBC < 4,000 / ul Prevalence up to 45% : frequent in advanced disease / AZT Neutropenia: PMNs < 1500 /ml and <1200 /ml (blacks) Degrees of neutropenia Mild Moderate Severe <500 Bacteremia in patients with advanced disease is rare Absolute CD4 count, not ANC = the predictor of morbidity Most OIs a function of poor cell mediated immunity USPHS/IDSA guidelines for OI prophylaxis do not recommend routine use of G-CSF in neutropenic HIV-infected pts Theoretical (in vitro) risk of activating latent CD4s?
39 Expected Abnormal Lab results: CBC Thrombocytopenia: platelet ct < 100,000/mm 3 Spontaneous bleeding rare till <10,000 / mm 3 Consider treatment 30-50,000 /mm 3 Mechanism of action: Almost always immune mediated / reduced survival Complex, not well understood Platelet - Ab, Ag-Ab complexes, Ab-anti-HIV? Normal or increased megakaryocytes in BM Platelet Assoc Ab (IgG): false positives high Rare: decreased production / infiltrative disease BM aspirate if Platelet IgG negative?
40 Expected Abnormal Lab results: CBC Anemia: hemoglobin < gm / dl Common in HIV / less since AZT decreased 30% prevalence w CD4 counts< 50 Macrocytosis is almost expected w HAART Therapy MCV in ranges Standard w/u: Ferritin plus Fe / TIBC % saturation Caution to Ferritin levels Often very high: HIV / chronic liver dz Special concerns: Pure red cell aplasia: consider parvovirus B19 infection parvovirus B19-DNA detection by PCR Anemia w reticulocytosis: peripheral destruction Coombs test / haptoglobin / LDH / indirect bilirubin (<4)
41 Expected Laboratory Abnormalities-CMP Albumin / globulin ratio: often deceased polyclonal increase a result of frequent infections? Abnormal LFTs: in absence of Hep B or C / HAART Tx Fatty infiltration of liver (NAFL)? May not always see evidence on ultrasound TNF-α has a role in regulating in vivo insulin sensitivity. Induction of free fatty acids via stimulation of lipolysis Classic workup : non-infectious increase in LFTs ANA / smooth muscle Ab / mitochondrial Ab / Ferritin Caution: ferritin often in HIV» Fe/TIBC %Sat > 60 specific for Hemochromatosis
42 Expected lab Abnormalities-Proteinuria Proteinuria: 30% incidence at baseline evaluation Usually w preserved renal function Trace proteinuria: less < 1+ dipstick Benign causes include: fever, intense activity or exercise, dehydration Repeated positive: requires urine microabl / cr ratio Elevated ratio may warrant more close f/u CKD / CAD / HIV progression? Significant Proteinuria: +1 or greater Quantification: 24 hr or Urine P / C ratio (spot) >150 mg = abnormal Nephro Consult: Target groups: black race / CD4<200 / Hep C
43 Expected lab Abnormalities-Hyperglycemia Impaired fasting glucose: 99 < blood sugar <126 Common: baseline HIV pts incidence HAART worsens metabolic syndrome Insulin resistance (IR) antedates Type 2 DM Metformin of value in HIV pts (pre-diabetic)» AUC for insulin less post-tx / less VAT GlycoHbg insensitive indicator for early IR 1 st effect: inability to dispose of a high glycemic meal Better physiologic test: 75 gm 2 hr OGTT Normal: < 140 mg% Impaired: mg% Diabetic: >200 mg%
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