Laboratory Testing

Laboratory Testing for Initial Assessment and Monitoring of Patients with HIV Receiving Antiretroviral Therapy

Several laboratory tests are important for initial evaluation of people with HIV upon entry into care, and some tests should be performed before and after initiation or modification of antiretroviral therapy (ART) to assess the virologic and immunologic efficacy of ART and to monitor for laboratory abnormalities that may be associated with antiretroviral (ARV) drugs. Table 3 outlines recommendations on the frequency of testing from the Panel on Antiretroviral Guidelines for Adults and Adolescents. As noted in the table, some tests may be repeated more frequently if clinically indicated.

Two surrogate markers are used to monitor people with HIV: plasma HIV RNA (viral load) to assess level of HIV viremia and CD4 T lymphocyte cell count to assess immune function. Standard (reverse transcriptase and protease) genotypic resistance testing should be used to guide selection of an ARV regimen; if transmitted integrase strand transfer inhibitor resistance is a concern, testing should also include the integrase gene (see Drug-Resistance Testing). For guidance on ART regimens to use when resistance testing results are unavailable, clinicians should consult What to Start. A viral tropism assay should be performed before initiation of a CCR5 antagonist or at the time of virologic failure that occurs while a patient is receiving a CCR5 antagonist. HLA-B*5701 testing should be performed before initiation of abacavir (ABC). Patients should be screened for hepatitis B and hepatitis C virus infection before initiating ART and, if indicated, periodically after ART initiation, as treatment of these coinfections may affect the choice of ART and likelihood of drug-induced hepatotoxicity. The rationale for and utility of some of these laboratory tests are discussed in the corresponding sections of the guidelines.

Table 3. Laboratory Testing Schedule for Monitoring People with HIV Before and After Initiation of Antiretroviral Therapya
Laboratory Test Timepoint or Frequency of Testing
Entry Into Care ART Initiationb or Modification 2 to 8 Weeks After ART Initiation or Modification Every 3 to 6 Months Every 6 Months Every 12 Months Treatment Failure Clinically Indicated If ART Initiation is Delayedc
HIV Serology

If HIV diagnosis has not been confirmed

               
CD4 Cell Count  

During first 2 years of ART, or if viremia develops while patient is on ART, or if CD4 count is <300 cells/mm3

 

After 2 Years on ART with Consistently Suppressed Viral Load
CD4 Count 300–500 cells/mm3:

  • Every 12 months
CD4 Count >500 cells/mm3:
  • CD4 monitoring is optional.

Every 3–6 months

HIV Viral Load d e e   Repeat testing is optional.
Resistance Testing f f         f f f
HLA-B*5701 Testing  

If considering ABC

             
Tropism Testing  

If considering a CCR5 antagonist

       

If considering a CCR5 antagonist, or for patients experiencing virologic failure on a CCR5 antagonist-based regimen

 
Hepatitis B Serology

(HBsAb, HBsAg, HBcAb total) g,h,i

May repeat if patient is nonimmune and does not have chronic HBV infectionh

     

May repeat if patient is nonimmune and does not have chronic HBV infectionh

 

Including prior to starting HCV DAA (see HCV/HIV Coinfection)

 
Hepatitis C Screening

(HCV antibody or, if indicated, HCV RNA)j
       

Repeat HCV screening for at-risk patientsk

   
Basic Chemistryl,m      

Every 6–12 months

ALT, AST, Total Bilirubin      

Every 6–12 months

CBC with Differentialn

 

When monitoring CD4 cell count; perform CBC cell count and CD4 concurrently

 

When no longer monitoring CD4 cell count

 

Every 3–6 months

Random or Fasting Lipid Profileo    

 

 

 

If normal at baseline, annually

Random or Fasting Glucosep  

 

 

 

If normal at baseline, annually

Urinalysism,q    

If on TDFl

   
Pregnancy Testr            
a This table pertains to laboratory tests done to select an ARV regimen and monitor for treatment responses or ART toxicities. Please refer to the HIV Primary Care Guidelines for guidance on other laboratory tests generally recommended for primary health care maintenance of HIV patients.1

b If ART is initiated soon after HIV diagnosis and entry into care, repeat baseline laboratory testing is not necessary.

c ART is indicated for all individuals with HIV and should be started as soon as possible. However, if ART initiation is delayed, patients should be retained in care, with periodic monitoring as noted above.

d If HIV RNA is detectable at 2–8 weeks, repeat testing every 4–8 weeks until viral load is suppressed to <200 copies/mL. Thereafter, repeat testing every 3–6 months.

e In patients on ART, viral load typically is measured every 3–4 months. More frequent monitoring may be considered in individuals who are having difficulties with ART adherence. However, for adherent patients with consistently suppressed viral load and stable immunologic status for more than 2 years, monitoring can be extended to 6-month intervals.

f Based on current rates of transmitted drug resistance to different ARV medications, standard genotypic drug-resistance testing in ARV-naive persons should focus on testing for mutations in the reverse transcriptase and protease genes. If transmitted INSTI resistance is a concern or if a person presents with viremia while on an INSTI, providers should also test for resistance mutations to this class of drugs. In ART-naive patients who do not immediately begin ART, repeat testing before initiation of ART is optional if resistance testing was performed at entry into care. In patients with virologic suppression who are switching therapy because of toxicity or for convenience, viral amplification will not be possible; see the section on Drug Resistance Testing for discussion of the potential limitations and benefits of proviral DNA assays in this situation. Results from prior resistance testing can be helpful in constructing a new regimen.

g If patient has HBV infection (as determined by a positive HBsAg or HBV DNA test result), TDF or TAF plus either FTC or 3TC should be used as part of the ARV regimen to treat both HBV and HIV infections (HBV/HIV).

h If HBsAg, HBsAb, and HBcAb test results are negative, hepatitis B vaccine series should be administered. Refer to the HIV Primary Care Guidelines and the Adult and Adolescent Opportunistic Infection Guidelines for detailed recommendations.1,2

i Most patients with isolated HBcAb have resolved HBV infection with loss of HBsAb. Consider performing an HBV viral load test for confirmation. If the HBV viral load test is positive, the patient may be acutely infected (and will usually display other signs of acute hepatitis) or chronically infected. If the test is negative, the patient should be vaccinated. Refer to the HIV Primary Care Guidelines and the Adult and Adolescent Opportunistic Infection Guidelines for more detailed recommendations.1,2

j The HCV antibody test may not be adequate for screening in the setting of recent HCV infection (defined as acquisition within the past 6 months), or advanced immunodeficiency (CD4 count <100 cells/mm3). HCV RNA screening is indicated in persons who have been successfully treated for HCV or who spontaneously cleared prior infection. HCV antibody-negative patients with elevated ALT may need HCV RNA testing.

k Injection drug users, persons with a history of incarceration, men with HIV who have unprotected sex with men, and persons with percutaneous/parenteral exposure to blood in unregulated settings are at risk of HCV infection.

l Serum Na, K, HCO3, Cl, BUN, creatinine, glucose, and creatinine-based estimated glomerular filtration rate. Serum phosphorus should be monitored in patients with chronic kidney disease who are on TDF-containing regimens.3

m Consult the Guidelines for the Management of Chronic Kidney Disease in HIV-Infected Patients: Recommendations of the HIV Medicine Association of the Infectious Diseases Society of America for recommendations on managing patients with renal disease.3 More frequent monitoring may be indicated for patients with evidence of kidney disease (e.g., proteinuria, decreased glomerular dysfunction) or increased risk of renal insufficiency (e.g., patients with diabetes, hypertension).

n CBC with differential should be done when a CD4 count is performed. When CD4 count is no longer being monitored, the recommended frequency of CBC with differential is once a year. More frequent monitoring may be indicated for persons who are receiving medications that potentially cause cytopenia (e.g., ZDV, TMP-SMX).

o If random lipids are abnormal, fasting lipids should be obtained. Consult the 2018 Guideline on the Management of Blood Cholesterol for diagnosis and management of patients with dyslipidemia.4

p If random glucose is abnormal, fasting glucose should be obtained. HbA1C is no longer recommended for diagnosis of diabetes in persons with HIV on ART (see the ADA Guidelines).5

q Urine glucose and protein should be assessed before initiating TAF- or TDF-containing regimens and monitored during treatment with these regimens.

r For people of childbearing potential.

Key: 3TC = lamivudine; ABC = abacavir; ALT = alanine aminotransferase; ART = antiretroviral therapy; ARV = antiretroviral; AST = aspartate aminotransferase; BUN = blood urea nitrogen; CBC = complete blood count; CD4 = CD4 T lymphocyte; Cl = chloride; DAA = direct-acting antiviral; FTC = emtricitabine; HbA1C = hemoglobin A1c; HBcAb = hepatitis B core antibody; HBsAb = hepatitis B surface antibody; HBsAg = hepatitis B surface antigen; HBV = hepatitis B virus; HCO3 = bicarbonate; HCV = hepatitis C virus; INSTI = integrase strand transfer inhibitor; K = potassium; Na = sodium; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate; TMP-SMX = trimethoprim-sulfamethoxazole; ZDV = zidovudine

References

  1. Aberg JA, Gallant JE, Ghanem KG, Emmanuel P, Zingman BS, Horberg MA. Primary care guidelines for the management of persons infected with HIV: 2013 update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2014;58(1):e1-34. Available at: http://www.ncbi.nlm.nih.gov/pubmed/24235263.
  2. Panel on Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. 2019. Available at: adult_oi.pdf.
  3. Lucas GM, Ross MJ, Stock PG, et al. Clinical practice guideline for the management of chronic kidney disease in patients infected with HIV: 2014 update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2014;59(9):e96-138. Available at: http://www.ncbi.nlm.nih.gov/pubmed/25234519.
  4. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. Circulation. 2019;139(25):e1082-e1143. Available at: https://www.ncbi.nlm.nih.gov/pubmed/30586774.
  5. American Diabetes Association. Classification and diagnosis of diabetes: standards of medical care in diabetes-2019. Diabetes Care. 2019;42(Suppl 1):S13-S28. Available at: https://www.ncbi.nlm.nih.gov/pubmed/30559228.
 

Laboratory Testing

Laboratory Testing for Initial Assessment and Monitoring of Patients with HIV Receiving Antiretroviral Therapy

Table 3. Laboratory Testing Schedule for Monitoring People with HIV Before and After Initiation of Antiretroviral Therapya
Laboratory Test Timepoint or Frequency of Testing
Entry Into Care ART Initiationb or Modification 2 to 8 Weeks After ART Initiation or Modification Every 3 to 6 Months Every 6 Months Every 12 Months Treatment Failure Clinically Indicated If ART Initiation is Delayedc
HIV Serology

If HIV diagnosis has not been confirmed

               
CD4 Cell Count  

During first 2 years of ART, or if viremia develops while patient is on ART, or if CD4 count is <300 cells/mm3

 

After 2 Years on ART with Consistently Suppressed Viral Load
CD4 Count 300–500 cells/mm3:

  • Every 12 months
CD4 Count >500 cells/mm3:
  • CD4 monitoring is optional.

Every 3–6 months

HIV Viral Load d e e   Repeat testing is optional.
Resistance Testing f f         f f f
HLA-B*5701 Testing  

If considering ABC

             
Tropism Testing  

If considering a CCR5 antagonist

       

If considering a CCR5 antagonist, or for patients experiencing virologic failure on a CCR5 antagonist-based regimen

 
Hepatitis B Serology

(HBsAb, HBsAg, HBcAb total) g,h,i

May repeat if patient is nonimmune and does not have chronic HBV infectionh

     

May repeat if patient is nonimmune and does not have chronic HBV infectionh

 

Including prior to starting HCV DAA (see HCV/HIV Coinfection)

 
Hepatitis C Screening

(HCV antibody or, if indicated, HCV RNA)j
       

Repeat HCV screening for at-risk patientsk

   
Basic Chemistryl,m      

Every 6–12 months

ALT, AST, Total Bilirubin      

Every 6–12 months

CBC with Differentialn

 

When monitoring CD4 cell count; perform CBC cell count and CD4 concurrently

 

When no longer monitoring CD4 cell count

 

Every 3–6 months

Random or Fasting Lipid Profileo    

 

 

 

If normal at baseline, annually

Random or Fasting Glucosep  

 

 

 

If normal at baseline, annually

Urinalysism,q    

If on TDFl

   
Pregnancy Testr            
a This table pertains to laboratory tests done to select an ARV regimen and monitor for treatment responses or ART toxicities. Please refer to the HIV Primary Care Guidelines for guidance on other laboratory tests generally recommended for primary health care maintenance of HIV patients.1

b If ART is initiated soon after HIV diagnosis and entry into care, repeat baseline laboratory testing is not necessary.

c ART is indicated for all individuals with HIV and should be started as soon as possible. However, if ART initiation is delayed, patients should be retained in care, with periodic monitoring as noted above.

d If HIV RNA is detectable at 2–8 weeks, repeat testing every 4–8 weeks until viral load is suppressed to <200 copies/mL. Thereafter, repeat testing every 3–6 months.

e In patients on ART, viral load typically is measured every 3–4 months. More frequent monitoring may be considered in individuals who are having difficulties with ART adherence. However, for adherent patients with consistently suppressed viral load and stable immunologic status for more than 2 years, monitoring can be extended to 6-month intervals.

f Based on current rates of transmitted drug resistance to different ARV medications, standard genotypic drug-resistance testing in ARV-naive persons should focus on testing for mutations in the reverse transcriptase and protease genes. If transmitted INSTI resistance is a concern or if a person presents with viremia while on an INSTI, providers should also test for resistance mutations to this class of drugs. In ART-naive patients who do not immediately begin ART, repeat testing before initiation of ART is optional if resistance testing was performed at entry into care. In patients with virologic suppression who are switching therapy because of toxicity or for convenience, viral amplification will not be possible; see the section on Drug Resistance Testing for discussion of the potential limitations and benefits of proviral DNA assays in this situation. Results from prior resistance testing can be helpful in constructing a new regimen.

g If patient has HBV infection (as determined by a positive HBsAg or HBV DNA test result), TDF or TAF plus either FTC or 3TC should be used as part of the ARV regimen to treat both HBV and HIV infections (HBV/HIV).

h If HBsAg, HBsAb, and HBcAb test results are negative, hepatitis B vaccine series should be administered. Refer to the HIV Primary Care Guidelines and the Adult and Adolescent Opportunistic Infection Guidelines for detailed recommendations.1,2

i Most patients with isolated HBcAb have resolved HBV infection with loss of HBsAb. Consider performing an HBV viral load test for confirmation. If the HBV viral load test is positive, the patient may be acutely infected (and will usually display other signs of acute hepatitis) or chronically infected. If the test is negative, the patient should be vaccinated. Refer to the HIV Primary Care Guidelines and the Adult and Adolescent Opportunistic Infection Guidelines for more detailed recommendations.1,2

j The HCV antibody test may not be adequate for screening in the setting of recent HCV infection (defined as acquisition within the past 6 months), or advanced immunodeficiency (CD4 count <100 cells/mm3). HCV RNA screening is indicated in persons who have been successfully treated for HCV or who spontaneously cleared prior infection. HCV antibody-negative patients with elevated ALT may need HCV RNA testing.

k Injection drug users, persons with a history of incarceration, men with HIV who have unprotected sex with men, and persons with percutaneous/parenteral exposure to blood in unregulated settings are at risk of HCV infection.

l Serum Na, K, HCO3, Cl, BUN, creatinine, glucose, and creatinine-based estimated glomerular filtration rate. Serum phosphorus should be monitored in patients with chronic kidney disease who are on TDF-containing regimens.3

m Consult the Guidelines for the Management of Chronic Kidney Disease in HIV-Infected Patients: Recommendations of the HIV Medicine Association of the Infectious Diseases Society of America for recommendations on managing patients with renal disease.3 More frequent monitoring may be indicated for patients with evidence of kidney disease (e.g., proteinuria, decreased glomerular dysfunction) or increased risk of renal insufficiency (e.g., patients with diabetes, hypertension).

n CBC with differential should be done when a CD4 count is performed. When CD4 count is no longer being monitored, the recommended frequency of CBC with differential is once a year. More frequent monitoring may be indicated for persons who are receiving medications that potentially cause cytopenia (e.g., ZDV, TMP-SMX).

o If random lipids are abnormal, fasting lipids should be obtained. Consult the 2018 Guideline on the Management of Blood Cholesterol for diagnosis and management of patients with dyslipidemia.4

p If random glucose is abnormal, fasting glucose should be obtained. HbA1C is no longer recommended for diagnosis of diabetes in persons with HIV on ART (see the ADA Guidelines).5

q Urine glucose and protein should be assessed before initiating TAF- or TDF-containing regimens and monitored during treatment with these regimens.

r For people of childbearing potential.

Key: 3TC = lamivudine; ABC = abacavir; ALT = alanine aminotransferase; ART = antiretroviral therapy; ARV = antiretroviral; AST = aspartate aminotransferase; BUN = blood urea nitrogen; CBC = complete blood count; CD4 = CD4 T lymphocyte; Cl = chloride; DAA = direct-acting antiviral; FTC = emtricitabine; HbA1C = hemoglobin A1c; HBcAb = hepatitis B core antibody; HBsAb = hepatitis B surface antibody; HBsAg = hepatitis B surface antigen; HBV = hepatitis B virus; HCO3 = bicarbonate; HCV = hepatitis C virus; INSTI = integrase strand transfer inhibitor; K = potassium; Na = sodium; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate; TMP-SMX = trimethoprim-sulfamethoxazole; ZDV = zidovudine

Updated
Reviewed
Dec. 18, 2019

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