File 7 of 8 from HHS Adult ART Guidelines: Initial Therapy

Laboratory Testing and Monitoring in People with HIV


Laboratory Testing and Monitoring in People with HIV
Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents

January 2020

About This Presentation
These slides were developed using the Guidelines updated in December 2019.
The intended audience is clinicians involved in the care of patients with HIV.
Because the field of HIV care is rapidly changing, users are cautioned that the information in this presentation may become out of date quickly.
It is intended that these slides be used as prepared, without changes in either content or attribution. Users are asked to honor this intent.
March 2020

Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents
Developed by the Department of Health and Human Services (DHHS) Panel on Antiretroviral Guidelines for Adults and Adolescents – A Working Group of the Office of AIDS Research Advisory Council (OARAC)
March 2020

Laboratory Testing: Outline
HIV RNA monitoring
CD4 count monitoring
Testing for drug resistance
HLA-B*5701 test
Coreceptor tropism test
Other laboratory testing

March 2020

HIV RNA Monitoring (viral load, VL) (1)
HIV RNA used to determine response to ART
Goal of antiretroviral therapy (ART): HIV RNA below limit of detection (i.e., <20-75 copies/mL, depending on assay)
Pretreatment VL factors into selection of initial ART – some regimens less effective if VL is high
Commercially available assays do not detect HIV-2
VL monitoring
At entry to care
At treatment initiation
Monitoring in those not on ART ̶ optional

March 2020

HIV RNA Monitoring (2)
2-4 weeks (not more than 8 weeks) after start or change of ART, then every 4-8 weeks until suppressed
Every 3-4 months for stable, suppressed patients. May consider every 6 months for stable, adherent patients with VL suppression >2 years.
Isolated “blips” may occur (transient low-level RNA, typically <400 copies/mL), are not thought to predict virologic failure
Virologic failure: confirmed HIV RNA >200 copies/mL
March 2020

CD4 Count Monitoring (1)
The major indicator of immune function
Best predictor of risk for disease progression, survival
Key factor in determining need for OI prophylaxis, urgency of ART initiation
Important in determining immunologic response to ART
Adequate response: CD4 increase 50-150 cells/µL per year
March 2020

CD4 Count Monitoring (2)
At entry to care
At treatment initiation
For those not on ART*, every 3-6 months

*ART is recommended at all CD4 counts
3 months after ART start
During first 2 years of ART, or if CD4 <300 cells/µL: every 3-6 months
After 2 years on ART with HIV RNA consistently suppressed
CD4 300-500 cells/µL: every 12 months
CD4 >500 cells/µL: optional
More frequent testing if on medications that may lower CD4 count, or if clinical decline

March 2020

Testing for Drug Resistance (1)
Before initiation of ART:
Transmitted resistance in 10-17% of persons with HIV (PWH)
In absence of ART, resistance mutations may decline over time and become undetectable by current assays, but may persist and cause treatment failure when ART is started
Identification of resistance mutations may optimize treatment outcomes
Resistance testing (genotype) recommended for all at entry to care; include INSTI resistance testing if INSTI resistance is suspected
Recommended for all pregnant persons 

March 2020

Testing for Drug Resistance (2)
Patients with virologic failure:
Perform while person is taking ART, or ≤4 weeks after discontinuing ART
Resistance mutations may decay with time off ART and may not be detected
Interpret in combination with history of ARV exposure and ARV adherence 
March 2020

Testing for Drug Resistance: Limitations
Insensitive to minor viral species
May not detect resistant viruses that comprise <10-20% of circulating virus population (eg, in absence of selective drug pressure)
May not be successful if VL is <500-1,000 copies/mL
March 2020

Drug Resistance Testing: Recommendations (1)
Recommended in both acute/recent HIV infection and chronic HIV infection where patient is ART-naïve
To determine if resistant virus was transmitted; guide ART decisions
Recommended at entry to care
Transmitted resistance mutations are more likely to be detected earlier in the course of HIV infection, but may be detectable later
ART should not be delayed while resistance test results are pending (ART can be changed, if indicated by test result)
If ART is deferred, consider repeat testing at time of ART initiation
Genotype preferred
Consider integrase genotypic resistance assay if transmitted integrase inhibitor resistance is a concern and/or if treatment with integrase inhibitor is considered

March 2020

Drug Resistance Testing: Recommendations (2)
Virologic failure during ART
To assist in selecting active ARVs for a new regimen
Genotype preferred if patient is on 1st or 2nd regimen; add phenotype if known or suspected complex resistance pattern
If virologic failure on integrase inhibitor (INSTI), do specific INSTI genotype resistance test
Do coreceptor tropism test if considering use of CCR5 antagonist; consider if virologic failure on CCR5 antagonist
Suboptimal VL suppression after starting ART
To assist in selecting active ARVs for a new regimen

March 2020

Drug Resistance Testing: Recommendations (3)
Recommended before initiation of ART
Recommended for all on ART with detectable HIV RNA levels
ART should not be delayed while resistance test results are pending; ARV regimen can be modified if needed
Genotype usually preferred; add phenotype if complex drug-resistance mutation pattern

March 2020

Drug Resistance Testing: Recommendations (4)
Undetectable VL or low-level viremia on ART
Proviral DNA resistance tests:
Can consider if history of multiple virologic failures and unknown previous genotype results
Interpret with caution - may successfully identify resistance mutations, but also may miss some or all existing resistance mutations
Clinical utility not yet known

March 2020

Other Tests to Guide ART Selection: HLA-B*5701
Recommended before starting abacavir (ABC), to reduce risk of hypersensitivity reaction (HSR)
HLA-B*5701-positive patients should not receive ABC
Positive status should be recorded as an ABC allergy
(If HLA-B*5701 testing is not available, ABC may be started after counseling and with appropriate monitoring for HSR)
March 2020

Other Tests to Guide ART Selection: Coreceptor tropism assay
Obtain: if a CCR5 antagonist is being considered, or if virologic failure on a CCR5 antagonist (though does not rule out resistance to CCR5 antagonist)
Phenotypic assay preferred; genotypic test is alternative
Proviral DNA tropism test can be used if HIV VL is undetectable
If CXCR4-tropic (or dual/mixed-tropic) virus is detected, do not use CCR5 antagonist 
March 2020

Other Assessment and Monitoring Studies
See Guidelines for recommendations on other laboratory tests, including CBC; hepatitis A, B, and C serologies; renal and liver tests; glucose; lipids; STIs; pregnancy test

March 2020

Websites to Access the Guidelines
AETC National Coordinating Resource Center
March 2020

About This Slide Set
This presentation was prepared by Susa Coffey, MD, for the AETC National Resource Center in March 2020.
See the AETC NCRC website for the most current version of this presentation: