HIV pre-exposure prophylaxis (PrEP) is the use of antiretroviral medicines to prevent acquiring HIV from sex or injection drug use. The US Food and Drug Administration (FDA) has approved 3 medications for use as HIV PrEP, including 2 daily oral forms (emtricitabine with tenofovir alafenamide [F/TAF] and emtricitabine with tenofovir disoproxil fumarate [F/TDF]) and 1 long-acting injectable form (cabotegravir). Laboratory testing is an important component of PrEP use. The Centers for Disease Control and Prevention (CDC) recommends laboratory testing before starting PrEP (baseline) and at regular intervals during PrEP use (follow-up).1

This Test Guide provides an overview of laboratory testing recommended by the CDC for HIV PrEP but is not an exhaustive presentation of laboratory-associated recommendations. For more information, refer to "Preexposure Prophylaxis for the Prevention of HIV Infection in the United States—2021 Update: A Clinical Practice Guideline."1 For PrEP prescribing information, warnings, and side effects, refer to the manufacturer’s approved labeling. The information in this Test Guide is provided for educational purposes only and is not intended as medical advice. Test selection and interpretation, diagnosis, and patient management decisions should be based on the physician’s education, clinical expertise, and assessment of the patient.

PrEP is indicated for people at high risk of acquiring HIV, including1

• Sexually active adults and adolescents (weighing ≥77 lb) who have had anal or vaginal sex in the past 6 months and any of the following:
• An HIV-positive sexual partner
• A bacterial sexually transmitted infection (STI) in the past 6 months
• A history of inconsistent or no condom use with sexual partner(s)
• People who inject drugs (PWID) and have any of the following:
• An HIV-positive injecting partner
• A history of sharing injection equipment

Quest Diagnostics offers 10 tests for patients who are taking or considering taking PrEP for HIV (Table 1).

Table 1. Available Tests for HIV PrEP

Recommended testing protocols differ based on patient characteristics and whether the PrEP regimen is oral (Table 2) or injectable (Table 3). Specific recommendations and rationale for each test are discussed below.

Table 2. Recommended Schedule of Laboratory Tests For Oral PrEPa

Table 3. Recommended Schedule of Laboratory Tests For Injectable PrEPa

HIV: Patients are required to be tested for HIV-1/HIV-2 before and during PrEP.1 Because PrEP can cause drug-resistant infection in people with HIV, a person must be negative for HIV to receive PrEP.1,3 However, because PrEP medications can affect the performance of certain HIV tests, different testing approaches are recommended at baseline and follow-up visits (ie, for patients who have vs have not used PrEP recently), as described below.

Baseline testing: Based on recommendations from the CDC, the testing approach offered by Quest to assess HIV status and PrEP eligibility at baseline (Figure 1) is intended for patients who have not taken oral PrEP or post-exposure prophylaxis (PEP) in the past 3 months nor received injectable PrEP in the past 12 months.1

Figure 1: Laboratory Testing to Assess HIV Status for PrEP Provision at Baseline (Patients Without Recent PrEP Use)
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Patients should first be assessed for signs and symptoms of acute HIV (ie, fever, fatigue, myalgia, skin rash, headache, pharyngitis, cervical adenopathy, arthralgia, night sweats, and diarrhea).1 Patients should only proceed with HIV testing if they do not currently have signs or symptoms of acute HIV; if they do have signs or symptoms, the CDC recommends that HIV testing be delayed 2 to 4 weeks.1

Baseline testing begins by testing for HIV-1/2 antigens and antibodies (test code 13595). A reactive (positive) result indicates that the patient is HIV-positive and thus ineligible for PrEP.

Nonreactive (negative) or indeterminate results are interpreted differently depending on whether the patient has had both (1) an HIV exposure-prone event (eg, condomless sex with an HIV-infected partner, injection drug use with shared injection equipment) in the past 4 weeks and (2) signs and symptoms of acute HIV in the past 4 weeks. If a patient has not had both an exposure-prone event and acute HIV symptoms, then nonreactive or indeterminate results indicate that the patient is HIV-negative and thus eligible for PrEP. If a patient has had both an exposure-prone event and acute HIV symptoms, then nonreactive or indeterminate results should be followed by an HIV-1 RNA test (test code 13600). RNA results below the level of detection indicate that the patient is HIV-negative (eligible for PrEP), RNA results ≥200 copies/mL indicate that the patient is HIV-positive (ineligible for PrEP), and RNA results that are detectable but <200 copies/mL should be followed by a retest.

Follow-Up testing: Based on recommendations from the CDC, the testing approach offered by Quest to assess HIV status during follow-up (Figure 2) is intended for patients who have taken oral PrEP or PEP in the past 3 months or received injectable PrEP in the past 12 months.1 Patients should be tested for HIV every 2-3 months during PrEP to establish that they are still HIV-negative.1 Follow-up testing begins with combined HIV-1/2 antigen and antibody and HIV-1 RNA testing (test code 13590).

Figure 2: Laboratory Testing to Assess HIV Status for PrEP Provision at Follow-Up (Patients With Recent PrEP Use)
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Positive results to both the antigen/antibody test and the RNA test indicate that the patient is HIV-positive, and negative results to both tests indicate that the patient is HIV-negative. Discordant (1 positive and 1 negative) results should be followed by another HIV-1 RNA test with a new specimen. Detectable RNA results indicate that the patient is HIV-positive, and undetectable results indicate that the patient is HIV-negative.

Sexually transmitted infections: Because STIs are common in individuals at high risk for HIV, STI testing is recommended for all sexually active patients at baseline and during follow-up.1,4 At baseline, all sexually active patients should be tested for syphilis, gonorrhea, and chlamydia.1 At follow-up visits,

• Gay, bisexual, and other men who have sex with men (MSM) and transgender women who have sex with men (TGW) should be tested for syphilis, gonorrhea, and chlamydia every 3-4 months.1,2
• Other sexually active patients should be tested for syphilis and gonorrhea every 6 months.1,2
• Other heterosexually active patients should be tested for chlamydia every 12 months.1,2

Specimens for STI testing should be taken from anatomic sites of likely exposure.4 The HIV PrEP tests for chlamydia and gonorrhea listed above are for urogenital specimens, but tests are also available for rectal (test code 16506) and pharyngeal (test code 70051) specimens.

Pregnancy: A US Department of Health and Human Services panel recommends that patients who can become pregnant be tested for pregnancy (test code 13696) at baseline and as indicated during follow-up.5 F/TDF is currently the only FDA-approved PrEP regimen known to be safe and effective during pregnancy.5 The decision to test for pregnancy may therefore depend on the PrEP regimen, potential fetal risk, and patient preference.

Hepatitis B and C viruses (oral PrEP only): Before starting oral PrEP, all patients should be tested for hepatitis B virus (HBV, test code 13660) to identify those with HBV and those who should be vaccinated.1 Patients with HBV can safely use oral PrEP but may be at risk of hepatitis flares when stopping PrEP. The CDC therefore recommends that providers consult an HBV treatment expert when prescribing PrEP to patients with HBV.1 Testing for hepatitis C virus (HCV, 13667) is only recommended for MSM, TGW, and PWID patients because HCV is more common in these groups than the general population. For these patients, HCV testing is recommended at baseline and every 12 months.1

Creatinine (oral PrEP only): Because F/TDF and F/TAF can mildly decrease kidney function, creatinine clearance (CrCl) should be screened in all patients before starting these medications.1,3 Estimated CrCl (eCrCl) can be derived from serum creatinine (Cr, test code 13697) using the Cockcroft-Gault formula, which can be done with an online calculator (eg, https://www.kidney.org/professionals/kdoqi/gfr_calculatorcoc) or the following formula1,2:

eCrCl, mL/min = (140−age) × weight, kg / (72 × Cr, mg/dL) × 0.85 for female patients

Patients with eCrCl ≥60 mL/min can safely use either F/TDF or F/TAF, while patients with eCrCl between 30 and 60 mL/min can safely use F/TAF only.1 Follow-up testing is recommended every 6 months for patients age ≥50 or with a baseline eCrCl <90 mL/min and every 12 months for other patients.1

Lipid profile (F/TAF only): For F/TAF only, the CDC recommends lipid (triglyceride and cholesterol level, test code 7600) testing at baseline and every 12 months.1 This testing is recommended because results of a clinical trial indicated that F/TAF may increase triglyceride levels, which could pose a long-term risk for patients with pre-existing cardiovascular risk factors.1