What are the steps for diagnosing HIV and the first-line treatment regimen for a patient suspected of having HIV?

HIV Diagnosis and First-Line Treatment

Diagnostic Algorithm

All persons aged 15-65 years should undergo routine opt-out HIV screening at least once in their lifetime using a fourth-generation HIV antigen/antibody combination assay, which detects both HIV antibodies and p24 antigen, allowing detection of acute infection approximately 2 weeks earlier than antibody-only tests 1, 2, 3.

Initial Screening Test

• Perform a fourth-generation HIV antigen/antibody combination assay as the initial screening test 1, 2, 3
• If fourth-generation testing is unavailable, use a rapid HIV test or conventional ELISA, though these are less sensitive for acute infection 4
• Rapid tests can be performed on whole blood (fingerstick or venipuncture), plasma, serum, or oral fluid specimens, though oral fluid tests have higher false-positive rates 4

Confirmatory Testing

• All reactive screening tests must be confirmed with HIV-1/HIV-2 antibody differentiation immunoassay to confirm infection and differentiate between HIV-1 and HIV-2 1, 2, 3
• If the differentiation assay is negative or indeterminate, perform HIV RNA testing (nucleic acid amplification test) 1, 2, 3
• If confirmatory testing is negative or indeterminate, repeat testing on a blood specimen collected 4 weeks after the initial reactive result 4

Acute HIV Infection

• If clinical suspicion exists for acute HIV infection (recent high-risk exposure with symptoms such as fever, lymphadenopathy, rash), perform HIV RNA testing immediately even if antibody tests are negative 4
• Do not disclose a positive HIV diagnosis based on screening test alone without confirmatory testing, as false positives can have devastating consequences 3

Post-Diagnosis Baseline Evaluation

Before initiating antiretroviral therapy, obtain comprehensive baseline testing including: 1, 2, 3

• HIV RNA viral load level (quantitative)
• CD4 cell count with percentage
• Genotypic resistance testing (HIV genotype)
• HLA-B*5701 testing (to avoid abacavir hypersensitivity)
• CCR5 tropism testing if considering maraviroc
• Hepatitis B and C screening
• Tuberculosis screening
• Sexually transmitted infection screening (gonorrhea, chlamydia, syphilis)
• Baseline renal function (creatinine clearance)
• Baseline liver function tests

First-Line Antiretroviral Therapy

All persons diagnosed with HIV should be offered antiretroviral therapy immediately upon diagnosis, regardless of CD4 count or viral load 1, 2, 3.

Preferred Initial Regimen

The preferred first-line regimen consists of an integrase strand transfer inhibitor (INSTI) plus two nucleoside reverse transcriptase inhibitors (NRTIs) 1, 2, 4.

Specific Recommended Regimens:

• Dolutegravir 50 mg once daily plus tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF) plus emtricitabine or lamivudine 4, 1, 5, 6
• Alternative INSTIs include bictegravir or raltegravir if dolutegravir is contraindicated 4
• Dolutegravir demonstrated superior efficacy with 88% of treatment-naïve subjects achieving HIV-1 RNA <50 copies/mL at 48 weeks 5

Dosing Considerations:

• Dolutegravir: 50 mg once daily (increase to 50 mg twice daily if using with certain medications that reduce dolutegravir levels) 5
• Lamivudine: 300 mg once daily or 150 mg twice daily 6
• Tenofovir/emtricitabine: Available as fixed-dose combination, dosed once daily 4

Treatment Initiation Timing:

• Same-day ART initiation is reasonable if HIV is confirmed by rapid assay and baseline labs can be drawn, without waiting for all results 4, 1
• For acute HIV infection, initiate fully suppressive ART immediately to suppress initial viral burst and potentially alter disease progression 4

Monitoring During Treatment

Initial Monitoring:

• Measure HIV RNA viral load 4-6 weeks after starting ART to assess initial response 1, 2
• Continue viral load monitoring every 3 months until HIV RNA <50 copies/mL for at least 1 year 1
• Measure CD4 counts every 6 months until counts are >250/μL for at least 1 year with concomitant viral suppression 1, 2

Long-Term Monitoring:

• Once virologically suppressed and stable, viral load monitoring can occur every 6 months 1
• Monitor renal function (creatinine clearance) annually, or every 3-6 months in patients at increased risk (age >50 years, baseline creatinine clearance <90 mL/min, diabetes, hypertension) 4
• Screen for sexually transmitted infections quarterly at contact sites (urine, throat, anal, vaginal) and blood syphilis testing 4
• Test for hepatitis C antibody annually, more frequently (every 3-6 months) in people who inject drugs or men who have sex with men who engage in sex while using drugs 4

Treatment Failure Management:

• If adherence appears sufficient but viral suppression is not achieved, perform genotypic resistance testing 2
• Switch to a fully suppressive regimen based on resistance testing results 2
• Ensure systematic monitoring of ART adherence using self-reported adherence and pharmacy refill data 2

Special Populations:

Pregnant Women:

• All pregnant persons must be screened for HIV, including those who present in labor with unknown HIV status 2
• Pregnant women with preliminary positive HIV test results should receive antiretroviral prophylaxis immediately while awaiting confirmatory testing 4

Pediatric Patients:

• Infants <15-18 months born to HIV-positive mothers require two positive HIV RNA PCR or viral culture tests on separate specimens for definitive diagnosis, as maternal antibodies make standard antibody tests unreliable 3
• Weight-based dosing of dolutegravir and lamivudine is available for pediatric patients 5, 6

Common Pitfalls to Avoid:

• Never diagnose HIV based on screening test alone—always confirm with differentiation assay and/or HIV RNA testing 3
• Do not use oral fluid-based rapid tests in post-exposure prophylaxis contexts, as they are less sensitive for acute infection than blood-based tests 3
• Do not withhold treatment while awaiting resistance testing results—initiate a recommended regimen immediately and adjust if needed 4, 1
• Avoid prescribing PrEP without excluding HIV infection first, as partial treatment can lead to resistance 4
• Do not prescribe more than 90 days of PrEP without interval HIV testing 4