HIV Basics: Clinical Tests and Guidelines ACTHIV 2010 Zelalem Temesgen MD Mayo Clinic
Topics Baseline laboratory evaluation Laboratory monitoring through the continuum of care Patients not on antiretroviral therapy Patients on antiretroviral therapy This presentation will not discuss any non-fda-approved or investigational uses of any products/devices.
Sources Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents December 1, 2009 http://aidsinfo.nih.gov/contentfiles/adultandadolescentgl.pdf Primary Care Guidelines for the Management of Persons Infected with Human Immunodeficiency Virus: 2009 Update by the HIV Medicine Association of the Infectious Diseases Society of America Clinical Infectious Diseases 2009; 49:651 81
Learning Objectives At the conclusion of this presentation, participants should be able to: Apply recommended best practices for baseline laboratory evaluation of the HIV-infected patient in your practice Apply recommended best practices for routine laboratory monitoring of the HIV-infected patient in your practice
Baseline Evaluation Classifying disease status Baseline safety laboratory tests Screening for comorbidities Screening for drug-resistance mutations
Classifying Disease Status Level of HIV viremia HIV-1 RNA (viral load) Immune function CD4 cell count and percentage
HIV-1 RNA Several FDA-approved assays Varying lower (48 400) and upper (100,000 10 million) limits of quantification Variable accuracy in the detection of non B HIV-1 subtypes Use the same assay in an individual patient over time
HIV-1 RNA (Viral Load) Measure HIV-1 RNA in plasma copies/ml Log 10 changes (power of 10) 0.5 log = 3-fold 1 log = 10-fold 3 log = 1000-fold Biologic variability about 0.3 log10 Meaningful changes need to be at least 0.5 log in magnitude
What affects Viral Load? Intercurrent illness Vaccination Increases could be significant Return to baseline in 4 weeks Do not check viral load within 4 weeks of above events
CD4 Count T lymphocytes CD4 provide help to other immune cells CD8 mediate cytotoxicity CD4 measurement Total WBC Percent lymphocytes Percent CD4
What Affects CD4 Cell Counts? Intra subject variability approx. 25% Diurnal 12:30 low; 20:30 peak Intercurrent illnesses Surgery Corticosteroids Interferon HTLV-I, splenectomy - increase
CD4 Percentage Less variable Meaningful changes > 3% 500/mm 3 29% 200/mm 3 14%
Baseline Safety Laboratory Tests CBC with differential Chemistry panel Liver function Creatinine Fasting glucose Fasting lipid profile Urinalysis Calculated creatinine clearance
Screening for Comorbidity and Coinfection Tuberculosis Viral hepatitis Sexually transmitted infections Toxoplasmosis If negative Avoid primary exposure Recheck when CD4 < 100 for prophylaxis
Screening for Tuberculosis Tuberculin skin test Induration >5mm is positive Interferon γ release assay More consistent, less subjective Higher specificity (92-97%) Less cross reactivity with BCG and other mycobacteria
Screening for Hepatitis B Hepatitis B screen HBsAg HBsAb HBcAb If negative HBsAg and HBsAb but positive HBcAb, check HBV DNA If negative screen 3-dose HBV vaccine series 1-2 months post vaccine, HBsAb titer should be > 10 IU/mL Revaccinate with a 3-dose series Higher dose?, wait for higher CD4 count? CDC IDSA NIH HIVMA Guidelines 2009
Screening For Hepatitic C Anti-HCV antibody HCV RNA Confirmation of + anti-hcv If CD4 < 200 Recent exposure to HCV Abnormal LFT Active IVDU
Screening for Hepatitis A Total anti-hav If negative - vaccinate
Screening for Hepatitis A: Rationale Immunization recommended Those with increased risk of acquiring hepatitis A IVDU MSM Hemophiliacs Those with increased risk of decompensation if HAV acquired Chronic hepatitis B and hepatitis C
Sexually Transmitted Infections Syphilis VDRL RPR Antibody test Chlamydia Urine nucleic acid amplification test Gonorrhea Urine NAAT Trichomonas
Cervical Cancer Screening Cervical Pap smear at baseline and at 6 months Annually thereafter if negative If abnormal Colposcopy and biopsy
Baseline Drug-Resistance Testing Why? 6-16% risk that transmitted virus will be resistant to at least one antiretroviral drug 3-5% risk of resistance to more than one class Transmission of drug-resistant HIV strains leads to suboptimal virologic response
Baseline Drug-Resistance Testing Genotypic HIV drug resistance testing is recommended for persons with HIV infection when they enter into care regardless of whether therapy will be initiated immediately or deferred If therapy is deferred, consider repeat testing at the time of antiretroviral therapy initiation
Laboratory Monitoring of Established Patients Patients not on antiretroviral therapy Viral load q 3-4 months CD4 cell count q 3-4 months Fasting glucose q 6-12 months Fasting lipid profile q 6-12 months TB screening periodically, based on risk and symptoms STI screening periodically, based on risk and symptoms
Laboratory Monitoring of Established Patients on Antiretroviral Therapy Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents December 1, 2009
Test Entry into care Prior to Starting ART or Switch 2-8 Weeks Post New ART or Switch Every 3-6 Months Every 6 Months Every 12 Months HIV 1 RNA X X X X CD4 cell count X X X Resistance testing X X X CBC X X X (ZDV) Chemistry panel (ALT, AST, electrolytes, total and direct bilirubin, Cr) X X X Fasting glucose X X X (if abnormal) X X (if normal) Fasting lipid profile X X X X Urinalysis X X X (HIVAN) X (TDF)
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