What is the treatment for Human Immunodeficiency Virus (HIV)?

HIV Treatment: Combination Antiretroviral Therapy

The standard treatment for HIV infection is combination antiretroviral therapy (ART) consisting of three drugs from at least two different drug classes, typically two nucleoside reverse transcriptase inhibitors (NRTIs) plus either an integrase strand transfer inhibitor (InSTI), a non-nucleoside reverse transcriptase inhibitor (NNRTI), or a boosted protease inhibitor (PI). 1

First-Line Treatment Regimens

Preferred Regimens

Current guidelines strongly recommend InSTI-based regimens as first-line therapy for treatment-naïve patients:

• Bictegravir + tenofovir + emtricitabine (or lamivudine)
• Dolutegravir + tenofovir + emtricitabine (or lamivudine)
• Dolutegravir + lamivudine (two-drug regimen for selected patients)

These regimens are preferred due to their high efficacy, high barrier to resistance, favorable side effect profiles, and once-daily dosing. 1

Alternative Regimens

• NNRTI-based: Efavirenz + 2 NRTIs 2
• PI-based: Boosted darunavir + 2 NRTIs
• Other InSTI-based: Raltegravir + 2 NRTIs 3

Treatment Goals

1. Virologic suppression: Achieve and maintain undetectable HIV RNA (<50 copies/mL)
2. Immunologic restoration: Increase CD4+ T cell count
3. Reduced morbidity and mortality: Delay progression to AIDS and death
4. Prevention of HIV transmission: Undetectable viral load prevents sexual transmission

When to Start Treatment

ART is now recommended for all HIV-infected individuals regardless of CD4+ count or clinical status 4. Early initiation of ART is associated with:

• Reduced risk of disease progression
• Prevention of irreversible immune damage
• Decreased risk of HIV transmission
• Improved clinical outcomes

Monitoring Treatment Response

• Viral load: Primary marker of treatment efficacy
  • Check 2-4 weeks after starting therapy, then every 4-8 weeks until suppressed
  • Once suppressed, monitor every 3-6 months
• CD4+ count: Measure of immune recovery
  • Monitor every 3-6 months initially, then annually once stable
• Drug resistance testing: Perform before starting therapy and when virologic failure occurs
• Medication adherence: Critical for treatment success

Managing Treatment Challenges

Virologic Failure

Defined as HIV RNA >200 copies/mL after initial suppression 1:

1. Assess adherence and potential drug interactions
2. Perform resistance testing while patient is on failing regimen
3. Switch to a new regimen with at least 2-3 fully active drugs

Blips and Low-Level Viremia

• Blips (transient HIV RNA 20-200 copies/mL) do not require treatment change 1
• Persistent low-level viremia (HIV RNA 50-200 copies/mL) may indicate emerging resistance

Treatment Switches in Virologically Suppressed Patients

Reasons to switch therapy despite viral suppression:

• Adverse effects or toxicity
• Drug-drug interactions
• Simplification (reduced pill burden)
• Pregnancy
• Comorbidities requiring regimen modification

Special Considerations

Drug Resistance

• Resistance testing is crucial before starting ART and when changing regimens due to failure
• The presence of drug-resistant HIV strongly predicts virologic failure and disease progression 1

Adherence Support

• Critical for treatment success
• Strategies include:
  • Once-daily regimens
  • Fixed-dose combinations (single tablets)
  • Medication reminders
  • Addressing barriers (side effects, mental health, substance use)

Advanced HIV Disease

For patients with extensive multiclass resistance:

• Novel mechanism agents like ibalizumab, fostemsavir, or lenacapavir may be necessary 1
• Long-acting injectable formulations may be considered in specific circumstances

Future Directions

While current ART is highly effective, it is not curative and requires lifelong adherence. Research continues on:

• Long-acting formulations (monthly or biannual dosing)
• Two-drug regimens to reduce toxicity while maintaining efficacy 5
• Functional cure strategies and eradication approaches 6

Common Pitfalls to Avoid

• Initiating therapy without baseline resistance testing: May lead to treatment failure
• Underestimating adherence challenges: Address barriers proactively
• Ignoring drug interactions: Review all medications, including over-the-counter drugs
• Delayed recognition of treatment failure: Regular viral load monitoring is essential
• Inappropriate two-drug regimens: Not all two-drug combinations are equally effective
• Discontinuing tenofovir in patients with hepatitis B: Can cause severe hepatitis flares

Remember that successful HIV treatment requires a long-term commitment to therapy, regular monitoring, and ongoing adherence support to achieve optimal outcomes in terms of morbidity, mortality, and quality of life.