What is the recommended treatment for a patient with a recent high-risk exposure to HIV, presenting with acute retroviral syndrome characterized by prolonged fever, subsequent headache, and rash?

Acute Retroviral Syndrome: Immediate Diagnostic and Treatment Approach

Immediate Diagnostic Action

This clinical presentation—fever for 2 weeks followed by headache and then rash—is highly suspicious for acute retroviral syndrome (ARS), and you must immediately order HIV RNA testing (nucleic acid test/NAT) even if antibody testing is negative or indeterminate. 1

Critical Diagnostic Steps

• Order HIV RNA (PCR or bDNA assay) immediately as the definitive diagnostic test, since antibody tests will be negative or indeterminate during acute infection 1
• Diagnostic NAT can detect HIV approximately 10-14 days after exposure, while fourth-generation antigen/antibody tests require 18-24 days 2
• If HIV RNA testing is unavailable, p24 antigen testing may be useful, but a negative result does NOT rule out acute infection 1
• Perform a fourth-generation HIV antigen/antibody combination test simultaneously, but do not wait for results to proceed with RNA testing 2

Common pitfall: Acute HIV infection is frequently missed in primary care because symptoms mimic influenza or mononucleosis 1. The sequential timing of fever → headache → rash over 3 weeks strongly suggests ARS rather than a self-limited viral illness.

Treatment Recommendation

If HIV RNA is detectable (confirming acute HIV infection), initiate antiretroviral therapy immediately with a three-drug regimen consisting of two nucleoside reverse transcriptase inhibitors (NRTIs) plus one integrase strand transfer inhibitor (INSTI), specifically bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as a single-tablet regimen. 3

Preferred Treatment Regimen

• First-line: Bictegravir 50mg/emtricitabine 200mg/tenofovir alafenamide 25mg once daily 3
• Alternative: Dolutegravir 50mg once daily PLUS emtricitabine/tenofovir alafenamide 200mg/25mg once daily 3
• Older guidelines from 1998 recommended two NRTIs plus a protease inhibitor 1, but current evidence supports INSTI-based regimens for superior tolerability and adherence 3

Treatment Duration and Goals

• Continue therapy for a minimum of 28 days, though most experts recommend indefinite treatment once initiated 3
• The goal is to suppress plasma HIV RNA to undetectable levels 1
• Start all drugs simultaneously at full dose (except nevirapine and ritonavir, which require dose escalation, but these are not preferred agents) 1

Rationale for Immediate Treatment

The theoretical and clinical rationale for treating acute HIV infection includes:

• Suppressing initial viral replication burst and decreasing virus dissemination throughout the body 1
• Decreasing severity of acute symptoms (your patient's fever, headache, and rash) 1
• Altering the viral "set-point" which affects long-term disease progression 1
• Preserving immune function before irreversible CD4+ T-cell depletion occurs 1
• Reducing viral mutation rates through suppression of replication 1

While older guidelines (1998) noted that treatment was based on "theoretical considerations" with limited clinical trial data 1, more recent evidence demonstrates superior viral suppression and improved outcomes with early treatment 4, 5.

Confirming the Diagnosis Before Treatment

Do not treat for HIV infection until it is documented by HIV RNA testing, except in the post-exposure prophylaxis setting. 1

• If HIV RNA is positive with negative/indeterminate antibody test, this confirms acute infection 1, 2
• Obtain confirmatory testing with both ELISA and Western Blot once antibodies develop 1
• Resistance testing should be performed at baseline before or immediately after starting treatment 1

Follow-Up Testing Schedule

After initiating treatment for confirmed acute HIV infection:

• Within 72 hours: Clinical evaluation and assessment for drug toxicity 3
• At 4-6 weeks: HIV antigen/antibody test PLUS HIV RNA to assess viral suppression 3, 2
• At 12 weeks: Laboratory-based HIV antigen/antibody combination immunoassay AND HIV RNA 3, 2
• Every 3 months thereafter: Ongoing viral load monitoring and toxicity assessment 1

Counseling and Prevention

• Counsel the patient about preventing secondary transmission during the acute phase when viral loads are extremely high 3
• Instruct the patient to seek immediate evaluation for worsening symptoms, as acute infection can cause multi-system dysfunction 6
• Discuss the need for partner notification and testing 1
• Provide behavioral and psychosocial support, as patients are often distressed by new HIV diagnosis 1

Critical caveat: The risks of treatment include drug toxicities, adherence challenges with lifelong therapy, and potential development of resistance if viral suppression is incomplete 1. However, the benefits of early treatment—particularly preventing irreversible immune damage and reducing transmission risk—outweigh these concerns in acute infection 1, 4.