What is the best practice for treating Human Immunodeficiency Virus 1 (HIV-1)?

Best Practice for Treating HIV-1

All individuals with HIV-1 infection should start antiretroviral therapy (ART) immediately upon diagnosis, regardless of CD4 count, using an integrase strand transfer inhibitor (InSTI)-based regimen combined with two nucleoside reverse transcriptase inhibitors (NRTIs). 1

When to Initiate ART

• Start ART as soon as possible after HIV diagnosis, including same-day initiation if the patient is ready to commit to therapy 1, 2, 3
• Remove structural barriers (staffing, services availability, insurance issues) that delay ART receipt to enable treatment at the first clinic visit 1
• Same-day ART initiation significantly reduces time to viral suppression (median 1.8 months vs 4.3 months with delayed start) and improves retention in care 4, 5
• For acute HIV infection, immediate ART is critical due to extremely high viral loads and transmission risk during this period 1, 3
• Each day of delay in starting ART after diagnosis reduces the likelihood of optimal immune recovery (CD4 >900 cells/μL and CD4/CD8 ratio >1.0) 6

Recommended Initial Regimens (Listed Alphabetically)

Generally Recommended First-Line Options:

• Bictegravir/tenofovir alafenamide (TAF)/emtricitabine 1, 2, 3
• Dolutegravir/abacavir/lamivudine (requires negative HLA-B*5701 test first) 1, 2
• Dolutegravir plus TAF/emtricitabine 1, 2
• Dolutegravir/lamivudine (only if baseline HIV RNA <500,000 copies/mL, no HBV co-infection, and no resistance mutations) 3

Alternative Regimens When First-Line Options Unavailable:

• Darunavir/cobicistat plus TAF or TDF/emtricitabine 1
• Raltegravir plus TAF/emtricitabine 1
• Elvitegravir/cobicistat/TAF/emtricitabine 1

Critical Pre-Treatment Testing

Before starting ART, draw blood for the following tests, but do NOT delay treatment while waiting for results 1:

• HIV-1 RNA viral load 1, 7
• CD4 cell count and percentage 1, 7
• HIV genotype resistance testing for NRTI, NNRTI, and protease inhibitor mutations 1, 7
• HLA-B*5701 allele testing if considering abacavir (must have result before giving abacavir due to potentially life-threatening hypersensitivity reaction) 1, 2
• Hepatitis B and C serology 1, 7
• Basic chemistry panel and liver function tests 3, 7

Regimens to AVOID for Rapid ART Start

• Do not use NNRTIs (efavirenz, rilpivirine) for same-day or rapid ART initiation due to higher resistance risk and need for baseline viral load thresholds 1
• Do not use abacavir for same-day start until HLA-B*5701 results are available 1

Monitoring Treatment Response

• Measure HIV RNA 4-6 weeks after starting ART to assess initial virologic response 2, 3, 7
• Continue viral load monitoring every 3 months until suppression (<200 copies/mL) is maintained for at least 1 year 2, 7
• After 1 year of sustained suppression with good adherence, reduce monitoring to every 6 months 2, 7
• Monitor CD4 count every 6 months until >250 cells/μL for at least 1 year with viral suppression, then can discontinue routine CD4 monitoring 2, 7

Special Situations: Opportunistic Infections

Tuberculosis Co-infection:

• If CD4 <50 cells/μL: Start ART within 2 weeks of beginning TB treatment 1, 3
• If CD4 ≥50 cells/μL: Start ART within 2-8 weeks of beginning TB treatment 1, 3

Cryptococcal Meningitis:

• Delay ART for 2-4 weeks after starting antifungal therapy in high-resource settings with optimal antifungal treatment and aggressive intracranial pressure management 1, 3
• Monitor closely for immune reconstitution inflammatory syndrome 1

Other Opportunistic Infections:

• Start ART within 2 weeks of diagnosis for most other OIs (Pneumocystis pneumonia, toxoplasmosis, etc.) 1

Malignancy:

• Initiate ART immediately upon cancer diagnosis, with careful attention to drug-drug interactions with chemotherapy 1, 3

Prophylaxis Recommendations

• Primary Pneumocystis pneumonia prophylaxis: Start if CD4 <200 cells/μL 1
• Mycobacterium avium complex (MAC) prophylaxis: No longer recommended if effective ART is initiated promptly 1
• Cryptococcal prophylaxis: Not recommended in high-resource settings with low disease prevalence 1

Adherence Support Strategies

• Systematic adherence monitoring is essential for treatment success 2, 7
• Use once-daily, fixed-dose combination regimens whenever possible to reduce pill burden 1, 7
• Implement brief psychosocial counseling, motivational interviewing, and cognitive behavioral therapy 1
• For persons who inject drugs, integrate directly observed ART with methadone maintenance programs 1, 2
• Utilize pharmacy refill data and self-reported adherence assessments routinely 7
• Personal telephone calls and interactive text message reminders improve adherence 7

Managing Treatment Failure

• If viral load has not declined after starting ART, first assess adherence and medication tolerability 2, 7
• If adherence appears adequate but viral suppression not achieved, perform genotypic resistance testing 2, 7
• For persistent low-level viremia (50-200 copies/mL), reassess for causes of failure and monitor closely 7

Common Pitfalls to Avoid

• Do not delay ART while waiting for laboratory results (except HLA-B*5701 if using abacavir) 1, 3
• Do not use efavirenz for rapid start due to neuropsychiatric side effects and need for baseline assessment 1, 8
• Do not use tenofovir disoproxil fumarate (TDF) in patients with kidney disease or osteoporosis; use TAF instead 1
• Do not assume "elite controllers" (undetectable viral load without treatment) don't need ART; they still have increased immune activation and cardiovascular risk 1
• Dosing at bedtime improves tolerability of central nervous system side effects if they occur 1, 8

HIV Prevention for At-Risk Individuals

• Pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate/emtricitabine is recommended for individuals at high risk (annual HIV incidence ≥2%) 1, 2, 7
• Long-acting injectable cabotegravir every 8 weeks is an alternative PrEP option where available 1
• Condoms remain essential for prevention of non-HIV sexually transmitted infections 2

Expected Outcomes

• With current InSTI-based regimens and good adherence, survival rates among HIV-infected adults retained in care approach those of uninfected adults 1, 2
• Patients with sustained viral suppression on ART pose virtually no risk of sexual HIV transmission (U=U: Undetectable = Untransmittable) 9
• Rapid ART initiation achieves viral suppression faster, reducing both individual morbidity and community transmission 4, 5, 10