What baseline laboratory tests and screenings are recommended before initiating dolutegravir (DTG) combined with tenofovir (TDF) therapy?

Baseline Laboratory Tests Before Initiating Dolutegravir Plus Tenofovir Therapy

Before starting dolutegravir (DTG) combined with tenofovir disoproxil fumarate (TDF), you must obtain: HIV-1 RNA level, HIV genotype for resistance testing, hepatitis B serology (HBsAg), estimated creatinine clearance, serum phosphorus, urine glucose, and urine protein. 1, 2

Essential Pre-Treatment Testing

HIV-Specific Tests

• HIV-1 RNA (viral load): Required to determine eligibility for certain regimens. DTG/3TC cannot be used if HIV RNA ≥500,000 copies/mL, but DTG plus TDF/FTC has no viral load restrictions 1

• HIV genotype (resistance testing): Must be drawn before initiating therapy, especially if:

  • Patient acquired HIV while on PrEP (TAF/FTC or TDF/FTC) 1
  • Patient was exposed to cabotegravir for PrEP (requires InSTI genotyping) 1
  • Lamivudine resistance testing is needed if considering DTG/3TC 1

• CD4+ T-cell count: While not strictly required for starting therapy, it helps guide clinical decisions. DTG/3TC has limited data in patients with CD4 <200 cells/μL 1

Hepatitis B Screening

• Hepatitis B surface antigen (HBsAg): Mandatory before starting any tenofovir-containing regimen 1, 2
  • If HBV co-infection is present, DTG/3TC cannot be used (requires 3-drug regimen with tenofovir) 1
  • All HIV patients should be tested for HBV before initiating TDF 2

Renal Function Assessment

Critical for tenofovir safety - TDF is nephrotoxic and requires comprehensive renal monitoring 2:

• Estimated creatinine clearance (eCrCl): Required in all patients before starting TDF 2

  • If eCrCl <50 mL/min: dose adjustment needed
  • If eCrCl <30 mL/min: contraindication for DTG/3TC regimen 1

• Serum phosphorus: Must be checked at baseline, especially in patients at risk for renal dysfunction 2

• Urine glucose: Screen for proximal renal tubulopathy (Fanconi syndrome risk) 2

• Urine protein: Baseline assessment required 2

Additional Considerations

When Rapid ART Initiation Is Planned

The 2025 IAS-USA guidelines explicitly state that DTG/3TC should NOT be used for rapid ART initiation when genotype, HIV RNA, and HBV serology results are not yet available 1. In rapid-start scenarios:

• Use DTG plus TDF/FTC (or TAF/FTC) as a 3-drug regimen
• Draw blood for genotype and HBV testing before starting
• Modify regimen once results return if needed

Pregnancy Testing

• Pregnancy test in persons of childbearing potential
• DTG plus TDF/FTC is recommended during pregnancy 1
• DTG/3TC is NOT recommended to initiate during pregnancy due to inadequate data 1

Monitoring During Therapy

Once therapy is initiated with TDF, the FDA label mandates 2:

• Periodic monitoring of eCrCl, serum phosphorus, urine glucose, and urine protein
• More frequent monitoring in patients at risk for renal dysfunction
• Avoid concurrent nephrotoxic agents (NSAIDs, aminoglycosides)

Common Pitfalls to Avoid

1. Do not start DTG/3TC without knowing: HIV RNA level, lamivudine resistance status, and HBV status 1

2. Do not skip renal function tests: TDF can cause acute renal failure and Fanconi syndrome; baseline assessment is mandatory 2

3. Do not forget HBV screening: Missing HBV co-infection could lead to hepatitis flare if using DTG/3TC (which lacks HBV activity) 1, 2

4. Do not use DTG/3TC for test-and-treat: When immediate ART is needed before lab results return, use a 3-drug regimen 1