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

• Log10 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/mm3 — 29%

• 200/mm3 — 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

ARTor

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)

X

Chemistry panel (ALT, AST, electrolytes, total and direct bilirubin, Cr)

X X X

Fasting glucose X X X (if abnormal)

X (if normal)

Fasting lipid profile X X X X

Urinalysis X X X (HIVAN)

X(TDF)

Thank You