Isentress (Raltegravir) for HIV-1 Treatment
Raltegravir is administered as 400 mg orally twice daily in adults when combined with other antiretroviral agents, and is positioned as an alternative initial regimen or for use in specific clinical scenarios including high risk of drug interactions, pregnancy, and treatment-experienced patients. 1
Dosing Regimens
Adults
- Standard dose: 400 mg film-coated tablet twice daily with or without food 1
- Once-daily formulation: 1200 mg (two 600 mg tablets) once daily is available as an alternative for improved convenience 2
- With rifampin co-administration: 800 mg twice daily (applies only to adults; no pediatric data available) 1
Pediatric Patients
- ≥25 kg and able to swallow tablets: 400 mg twice daily (same as adult dose) 1
- ≥25 kg unable to swallow: Weight-based chewable tablets
- 25 to <28 kg: 150 mg (1.5 × 100 mg chewable) twice daily
- 28 to <40 kg: 200 mg (2 × 100 mg chewable) twice daily
- ≥40 kg: 300 mg (3 × 100 mg chewable) twice daily 1
- 4 weeks to <25 kg: Oral suspension or chewable tablets at approximately 6 mg/kg/dose twice daily based on weight bands 1, 3
Critical caveat: The formulations are NOT bioequivalent—never substitute chewable tablets or oral suspension for the 400 mg film-coated tablet. 1
Clinical Positioning in Treatment Guidelines
Initial Therapy
Raltegravir is listed as an "other recommended" initial regimen, not a preferred first-line option. 4 The International Antiviral Society-USA Panel (2020) recommends raltegravir-based regimens in specific situations:
- Patients at high risk of drug-drug interactions (raltegravir has minimal drug interactions) 4
- Patients intolerant to other integrase inhibitors (dolutegravir or bictegravir) 4
- Patients with childbearing potential trying to conceive (due to early concerns about dolutegravir and neural tube defects, though this has evolved) 4
- Pregnant patients: Raltegravir is the recommended integrase inhibitor during pregnancy 4, 5
The preferred initial regimens prioritize newer integrase inhibitors (bictegravir, dolutegravir) over raltegravir due to superior convenience and higher genetic barrier to resistance. 6
Treatment-Experienced Patients
Raltegravir demonstrates excellent efficacy in treatment-experienced patients with multidrug resistance, as it represents a different mechanism of action (integrase inhibition) compared to older drug classes. 7 In clinical trials, raltegravir plus optimized background therapy significantly improved virological and immunological responses compared to placebo plus optimized background therapy at 16 and 48 weeks. 7
Virological Failure Management
When switching regimens due to virological failure, avoid raltegravir if the patient has nucleoside reverse transcriptase inhibitor (NRTI) resistance mutations and is switching from a boosted protease inhibitor, as raltegravir has a low genetic barrier to resistance. 4
If raltegravir or elvitegravir resistance develops, switch to dolutegravir (dosed twice daily) plus at least one fully active agent. 4 This recommendation reflects that dolutegravir maintains activity against some raltegravir-resistant strains when dosed twice daily. 4
Special Populations
Pregnancy
- Raltegravir is the preferred integrase inhibitor during pregnancy due to established safety data 4, 5
- Combine with tenofovir disoproxil fumarate (TDF) plus emtricitabine or lamivudine 4
- Do not use elvitegravir/cobicistat during pregnancy due to pharmacokinetic concerns 4
- Dolutegravir is now also considered safe during pregnancy based on updated data 5
Tuberculosis Co-infection
- For TB co-infection requiring rifampin, use dolutegravir 50 mg twice daily rather than raltegravir, as this is better studied 5
- If raltegravir must be used with rifampin in adults, increase dose to 800 mg twice daily 1
Pediatric Use
Long-term safety and efficacy data support raltegravir use in children as young as 4 weeks, with virological success rates of 44-87% at 240 weeks depending on formulation and prior treatment history. 8 However, use caution in older children with extensive prior antiretroviral therapy, as resistance development is more common in this population. 8
Key Clinical Considerations
Resistance Profile
Raltegravir has a lower genetic barrier to resistance compared to dolutegravir, which is why it is not a preferred first-line agent. 4 Among patients with virological failure, raltegravir resistance was documented in 38% of those with virological rebound after initial suppression. 8
Tolerability
Raltegravir is generally well tolerated with minimal drug interactions, making it valuable for patients on complex medication regimens. 4, 7 The once-daily formulation (1200 mg) shows similar tolerability to the twice-daily 400 mg regimen. 2
Monitoring
- Obtain resistance testing before initiating therapy to guide regimen selection 6
- Monitor HIV RNA within 6 weeks of starting treatment 5
- If virological failure occurs (HIV RNA >200 copies/mL), perform resistance testing while the patient is still taking the failing regimen (or within 4 weeks of stopping) 4
Common Pitfalls to Avoid
- Do not use raltegravir monotherapy—it must always be combined with other active antiretroviral agents 4, 1
- Do not substitute formulations—the film-coated tablets, chewable tablets, and oral suspension are not bioequivalent 1
- Do not add a single active agent to a failing raltegravir regimen—switch to a fully suppressive new regimen based on resistance testing 4
- Do not overlook the need for dose adjustment with rifampin in adults (increase to 800 mg twice daily) 1