dolutegravir and rilpivirine
Regulatory sources consulted
Approved indications
- Replacement of the current regimen in adults with HIV-1 suppressed for at least 6 months, without prior failure or resistance to its components.
Contraindications
Absolute
- Concomitant fampridine, proton-pump inhibitors, strong CYP3A inducers, repeated systemic dexamethasone, or St John’s wort.
- Hypersensitivity to dolutegravir, rilpivirine, or excipients.
Clinical warnings
- It may cause hypersensitivity, hepatotoxicity, depressive disorders, and severe skin reactions. — CIMA/AEMPS, ficha técnica 1181282001
- Major warning · Rilpivirine may prolong QT at high exposures. — CIMA/AEMPS, ficha técnica 1181282001
Drug interactions
- HighAntacids and H2 antagonists
Mechanism: Cations affect dolutegravir and higher pH reduces rilpivirine.
Recommendation: Give antacids and cation supplements 6 hours before or 4 hours after; calcium or iron may be taken together with a meal. Give H2 antagonists 12 hours before or 4 hours after. PPIs are contraindicated.
CIMA/AEMPS, ficha técnica 1181282001
- ModerateOther antiretrovirals and metformin
Mechanism: Juluca is a complete regimen; dolutegravir increases metformin exposure through OCT2/MATE.
Recommendation: Do not add other antiretrovirals. With metformin, monitor glucose and renal function and adjust as needed.
CIMA/AEMPS, ficha técnica 1181282001
Adverse events
Common (≥1%)
Headache and diarrhea
Rare but serious
Hypersensitivity, hepatotoxicity, DRESS, and suicidal behavior
Pregnancy and lactation
It is preferable to avoid during pregnancy; if continued, monitor viral load closely. Do not breastfeed during HIV treatment.
Recent literature (PubMed)
Switching to the 2-drug regimen dolutegravir + rilpivirine demonstrated noninferiority vs continuing a 3-drug or 4-drug current antiretroviral regimen (CAR) at week 48 and maintained high levels of virologic suppression to week 148 in the SWORD studies. We report inflammation and atherogenesis biomarkers postswitch to dolutegravir + rilpivirine. SWORD-1: 65 centers, 13 countries; SWORD-2: 60 centers, 11 countries. Virologically suppressed adults were randomized to switch to dolutegravir + rilpivirine (early-switch group; n = 513) or continue CAR (n = 511). Participants continuing CAR switched to dolutegravir + rilpivirine at week 52 (late-switch group; n = 477). Biomarkers were evaluated from Baseline to week 48 for dolutegravir + rilpivirine and CAR and noncomparatively for dolutegravir + rilpivirine postswitch through 148 weeks (early-switch) and 96 weeks (late-switch). Through week 48, changes in biomarkers did not significantly differ between dolutegravir + rilpivirine and CAR groups, except for increases in soluble CD14 and decreases in fatty acid-binding protein-2, which favored dolutegravir + rilpivirine. For inflammation biomarkers through week 148, there was no marked change in C-reactive protein, inconsistent changes in soluble CD14 and interleukin-6, and increases in soluble CD163. For atherogenesis biomarkers through week 148, fatty acid-binding protein-2 and soluble vascular cell adhesion molecule-1 showed sustained reductions; D-dimer showed inconsistent increases between early-switch vs late-switch groups. No consistent pattern of change in biomarkers postswitch to dolutegravir + rilpivirine was observed through weeks 48 and 148 in SWORD-1/SWORD-2, suggesting no association of increased inflammation or atherogenesis with the 2-drug regimen while maintaining virologic suppression.