Results
| Mutations: 184V, 179D, 188L, 63P Comorbidities: None Comedications: Metoprolol, Buprenorphine Treatment history: 3TC (Lamivudine/Epivir) , D4T (Stavudine/Zerit) , EFV (Efavirenz/Sustiva) , NVP (Nevirapine/Viramune) , NFV (Nelfinavir/Viracept) Current regimen: EVG/c/TAF/FTC (Genvoya) |
Adherence: Administration preference: Penalize IV/IM/SC dosing CD4: > 200 Viral load: Suppressed (<50) for more than 6 months HLA-B5701: Negative Tropism: Unknown |
View results |
to help us improve HIV-ASSIST.
HIV-ASSIST calculates a regimen's weighted score on a scale of 1 to 10, in which lower values represent preferred regimens based upon current IAS and DHHS guidelines, while factoring in treatment history, comorbidities, co-medications, and other factors entered on the input page. The weighting system utilizes standardized utility weights based on current literature evidence and expert opinion. HIV-ASSIST is an educational tool and not a substitute for clinical judgement. Click on a regimen and 'Rationale' to see all steps leading to the presented weighted score. Please note that rankings would differ if if some factors were weighed more or less than those applied within HIV-ASSIST algorithms.
The Score Code is a value from 1-5 that corresponds with the chart below.
| Score Code | HIV-ASSIST Score | Efficacy (likelihood of viral suppression) | Tolerability (side-effects and pill burden) | Notes |
|---|---|---|---|---|
| 1 | ≤ 1.5 | Strong evidence | Strong evidence | Reserved for fully- or near fully- active regimens. |
| 2 | 1.5 - 2.5 | Strong or moderate evidence | Strong or moderate evidence | Includes regimens that started at better rank but were impacted by mutations, comorbidities, and drug interactions. |
| 3 | 2.5 - 4.0 | Moderate evidence | Moderate evidence | As above. Additionally, most treatment-experienced patients will see regimens in this category. |
| 4 | 4.0 - 6.0 | Moderate to poor evidence | Moderate or poor evidence | As above. Additionally, most treatment-experienced patients will see regimens in this category. |
| 5 | ≥ 6.0 | Poor evidence | Poor evidence | As above. Additionally, these represent salvage regimens in patients with limited options. |
Signifies that there may be additional regimen warnings.
Note: We do not show regimens for which there is evidence against usage.
| Score Code | Regimen | Weighted Score | Active Drugs | Total Pills | Frequency (x/day) |
|---|---|---|---|---|---|
| 1 | BIC/TAF/FTC | 1 | 2 | 1 | 1 |
| 1 | DTG/TDF/3TC | 1 | 2 | 1 | 1 |
| 1 | DTG+TAF/FTC | 1.25 | 2 | 2 | 1 |
| 1 | DTG+TDF/FTC | 1.25 | 2 | 2 | 1 |
| 3 | DTG+DRV/c/TAF/FTC | 3 | 3 | 2 | 1 |
| 3 | DRV/c+DTG/TDF/3TC | 3.1 | 3 | 2 | 1 |
| 3 | DRV/c+BIC/TAF/FTC | 3.1 | 3 | 2 | 1 |
| 3 | DRV/c/TAF/FTC | 3.25 | 2 | 1 | 1 |
| 3 | DRV/r+BIC/TAF/FTC | 3.3 | 3 | 3 | 1 |
| 3 | DTG+DRV/c+TDF/FTC | 3.3 | 3 | 3 | 1 |
| 3 | DRV/r+DTG/TDF/3TC | 3.4 | 3 | 3 | 1 |
| 3 | DTG+DRV/r+TAF/FTC | 3.5 | 3 | 4 | 1 |
| 3 | DRV/c+TDF/FTC | 3.6 | 2 | 2 | 1 |
| 3 | DTG+DRV/r+TDF/FTC | 3.6 | 3 | 4 | 1 |
| 3 | RAL+DRV/c/TAF/FTC | 3.7 | 3 | 3 | 1 |
| 3 | DTG+DRV/c | 3.75 | 2 | 2 | 1 |
| 4 | RAL+DRV/c+TDF/FTC | 4.1 | 3 | 4 | 1 |
| 4 | RAL+DRV/r+TAF/FTC | 4.2 | 3 | 5 | 1 |
| 4 | RAL+DRV/r+TDF/FTC | 4.4 | 3 | 5 | 1 |
| 4 | DRV/r+TAF/FTC | 4.45 | 2 | 3 | 1 |
| 4 | DRV/r+TDF/FTC | 4.55 | 2 | 3 | 1 |
| 4 | DTG+DRV/r | 4.8 | 2 | 3 | 1 |
| 4 | DRV+EVG/c/TAF/FTC | 5.15 | 3 | 2 | 1 |
| 4 | DTG+LEN | 5.5 | 2 | 1 | 1 |
| 4 | DTG+3TC/AZT | 5.95 | 2 | 3 | 2 |
| 5 | EVG/c/TAF/FTC [Current regimen] | 6.05 | 2 | 1 | 1 |
| 5 | EVG/c/TDF/FTC | 6.05 | 2 | 1 | 1 |
| 5 | RAL+TAF/FTC | 6.1 | 2 | 3 | 1 |
| 5 | DTG+AZT+FTC | 6.15 | 2 | 4 | 2 |
| 5 | RAL+TDF/FTC | 6.2 | 2 | 3 | 1 |
| 5 | DTG+DRV/c+3TC/AZT | 6.4 | 3 | 4 | 2 |
| 5 | RAL+DRV/c | 6.45 | 2 | 3 | 1 |
| 5 | DTG+DRV/c+AZT+FTC | 6.6 | 3 | 5 | 2 |
| 5 | DTG+DRV/r+3TC/AZT | 6.7 | 3 | 5 | 2 |
| 5 | DTG+IBA | 6.75 | 2 | 1 | 1 |
| 5 | RAL+DRV/r | 6.75 | 2 | 4 | 1 |
| 5 | IBA+DTG/TDF/3TC | 6.75 | 3 | 1 | 1 |
| 5 | DTG+IBA+TAF/FTC | 6.75 | 3 | 2 | 1 |
| 5 | DTG+IBA+TDF/FTC | 6.75 | 3 | 2 | 1 |
| 5 | FTR+DTG/TDF/3TC | 6.75 | 3 | 3 | 2 |
| 5 | DTG+DRV/r+AZT+FTC | 6.9 | 3 | 6 | 2 |
| 5 | DTG+FTR+TAF/FTC | 6.95 | 3 | 4 | 2 |
| 5 | DTG+FTR+TDF/FTC | 6.95 | 3 | 4 | 2 |
| 5 | RAL+DRV/c+3TC/AZT | 7.1 | 3 | 5 | 2 |
| 5 | IBA+BIC/TAF/FTC | 7.25 | 3 | 1 | 1 |
| 5 | LEN+DTG/TDF/3TC | 7.25 | 3 | 1 | 1 |
| 5 | DTG+LEN+TAF/FTC | 7.25 | 3 | 2 | 1 |
| 5 | DTG+LEN+TDF/FTC | 7.25 | 3 | 2 | 1 |
| 5 | DTG+IBA+DRV/c | 7.25 | 3 | 2 | 1 |
| 5 | FTR+BIC/TAF/FTC | 7.25 | 3 | 3 | 2 |
| 5 | RAL+DRV/c+AZT+FTC | 7.3 | 3 | 6 | 2 |
| 5 | RAL+DRV/r+3TC/AZT | 7.4 | 3 | 6 | 2 |
| 5 | DTG+DRV/r+ETR | 7.45 | 2.67 | 6 | 2 |
| 5 | DTG+IBA+DRV/r | 7.55 | 3 | 3 | 1 |
| 5 | RAL+DRV/r+AZT+FTC | 7.6 | 3 | 7 | 2 |
| 5 | DTG+FTR+DRV/c | 7.65 | 3 | 4 | 2 |
| 5 | DTG+FTR | 7.7 | 2 | 3 | 2 |
| 5 | LEN+BIC/TAF/FTC | 7.75 | 3 | 1 | 1 |
| 5 | DTG+FTR+DRV/r | 7.8 | 3 | 5 | 2 |
| 5 | RAL+DRV/r+ETR | 7.95 | 2.67 | 6 | 2 |
| 5 | RAL+IBA+DRV/c | 7.95 | 3 | 3 | 1 |
| 5 | DTG+LEN+DRV/c | 8 | 3 | 2 | 1 |
| 5 | DTG+LEN+DRV/r | 8.05 | 3 | 3 | 1 |
| 5 | RAL+IBA+DRV/r | 8.25 | 3 | 4 | 1 |
| 5 | RAL+FTR+DRV/c | 8.35 | 3 | 5 | 2 |
| 5 | RAL+FTR+DRV/r | 8.5 | 3 | 6 | 2 |
| 5 | RAL+LEN+DRV/c | 8.7 | 3 | 3 | 1 |
| 5 | RAL+LEN+DRV/r | 8.75 | 3 | 4 | 1 |
| 5 | DRV/r+ETR+TAF/FTC | 8.85 | 2.67 | 5 | 2 |
| 5 | RAL+ETR+TAF/FTC | 8.85 | 2.67 | 5 | 2 |
| 5 | DRV/c+3TC/AZT | 8.95 | 2 | 3 | 2 |
| 5 | DRV/r+ETR+TDF/FTC | 8.95 | 2.67 | 5 | 2 |
| 5 | RAL+ETR+TDF/FTC | 8.95 | 2.67 | 5 | 2 |
| 5 | DRV/r+3TC/AZT | 9.15 | 2 | 4 | 2 |
| 5 | DRV/c+AZT+FTC | 9.15 | 2 | 4 | 2 |
| 5 | DRV/r+AZT+FTC | 9.35 | 2 | 5 | 2 |
| 5 | DTG+FTR+3TC/AZT | 9.6 | 3 | 5 | 2 |
| 5 | DTG+FTR+AZT+FTC | 9.8 | 3 | 6 | 2 |
| 5 | RAL+3TC/AZT | 9.9 | 2 | 4 | 2 |
| 5 | DTG+IBA+3TC/AZT | 9.95 | 3 | 3 | 2 |
| 5 | RAL+AZT+FTC | 10.1 | 2 | 5 | 2 |
| 5 | DRV/r+ETR+DTG/TDF/3TC | 10.1 | 3.67 | 6 | 2 |
| 5 | DTG+IBA+AZT+FTC | 10.15 | 3 | 4 | 2 |
| 5 | DTG+LEN+3TC/AZT | 10.2 | 3 | 3 | 2 |
| 5 | DTG+DRV/r+ETR+TAF/FTC | 10.2 | 3.67 | 7 | 2 |
| 5 | DTG+IBA+DRV/c/TAF/FTC | 10.25 | 4 | 2 | 1 |
| 5 | DTG+DRV/r+ETR+TDF/FTC | 10.3 | 3.67 | 7 | 2 |
| 5 | IBA+DRV/c+DTG/TDF/3TC | 10.35 | 4 | 2 | 1 |
| 5 | IBA+DRV/c+BIC/TAF/FTC | 10.35 | 4 | 2 | 1 |
| 5 | DTG+LEN+AZT+FTC | 10.4 | 3 | 4 | 2 |
| 5 | DTG+IBA+DRV/c+TDF/FTC | 10.55 | 4 | 3 | 1 |
| 5 | IBA+DRV/r+BIC/TAF/FTC | 10.55 | 4 | 3 | 1 |
| 5 | IBA+DRV/r+DTG/TDF/3TC | 10.65 | 4 | 3 | 1 |
| 5 | RAL+DRV/r+ETR+TAF/FTC | 10.7 | 3.67 | 7 | 2 |
| 5 | DTG+FTR+DRV/c/TAF/FTC | 10.7 | 4 | 4 | 2 |
| 5 | DTG+IBA+DRV/r+TAF/FTC | 10.75 | 4 | 4 | 1 |
| 5 | FTR+DRV/c+DTG/TDF/3TC | 10.8 | 4 | 4 | 2 |
| 5 | FTR+DRV/c+BIC/TAF/FTC | 10.8 | 4 | 4 | 2 |
| 5 | DTG+IBA+DRV/r+TDF/FTC | 10.85 | 4 | 4 | 1 |
| 5 | FTR+DRV/r+BIC/TAF/FTC | 10.85 | 4 | 5 | 2 |
| 5 | RAL+DRV/r+ETR+TDF/FTC | 10.9 | 3.67 | 7 | 2 |
| 5 | RAL+IBA+DRV/c/TAF/FTC | 10.95 | 4 | 3 | 1 |
| 5 | FTR+DRV/r+DTG/TDF/3TC | 10.95 | 4 | 5 | 2 |
| 5 | DTG+LEN+IBA+DRV/c | 11 | 4 | 2 | 1 |
| 5 | DTG+FTR+DRV/c+TDF/FTC | 11 | 4 | 5 | 2 |
| 5 | DTG+LEN+IBA+DRV/r | 11.05 | 4 | 3 | 1 |
| 5 | DTG+FTR+DRV/r+TAF/FTC | 11.05 | 4 | 6 | 2 |
| 5 | DTG+FTR+DRV/r+TDF/FTC | 11.15 | 4 | 6 | 2 |
| 5 | DTG+LEN+DRV/c/TAF/FTC | 11.25 | 4 | 2 | 1 |
| 5 | LEN+DRV/r+BIC/TAF/FTC | 11.3 | 4 | 3 | 1 |
| 5 | LEN+DRV/c+DTG/TDF/3TC | 11.35 | 4 | 2 | 1 |
| 5 | LEN+DRV/c+BIC/TAF/FTC | 11.35 | 4 | 2 | 1 |
| 5 | RAL+IBA+DRV/c+TDF/FTC | 11.35 | 4 | 4 | 1 |
| 5 | RAL+FTR+TAF/FTC | 11.4 | 3 | 5 | 2 |
| 5 | LEN+DRV/r+DTG/TDF/3TC | 11.4 | 4 | 3 | 1 |
| 5 | RAL+FTR+DRV/c/TAF/FTC | 11.4 | 4 | 5 | 2 |
| 5 | RAL+IBA+TAF/FTC | 11.45 | 3 | 3 | 1 |
| 5 | RAL+IBA+DRV/r+TAF/FTC | 11.45 | 4 | 5 | 1 |
| 5 | RAL+FTR+TDF/FTC | 11.5 | 3 | 5 | 2 |
| 5 | DTG+LEN+DRV/r+TAF/FTC | 11.5 | 4 | 4 | 1 |
| 5 | DRV/r+ETR+3TC/AZT | 11.55 | 2.67 | 6 | 2 |
| 5 | RAL+ETR+3TC/AZT | 11.55 | 2.67 | 6 | 2 |
| 5 | RAL+IBA+TDF/FTC | 11.55 | 3 | 3 | 1 |
| 5 | DTG+LEN+DRV/c+TDF/FTC | 11.55 | 4 | 3 | 1 |
| 5 | DTG+LEN+DRV/r+TDF/FTC | 11.6 | 4 | 4 | 1 |
| 5 | RAL+IBA+DRV/r+TDF/FTC | 11.65 | 4 | 5 | 1 |
| 5 | RAL+LEN+TAF/FTC | 11.7 | 3 | 3 | 1 |
| 5 | LEN+RAL+IBA+DRV/c | 11.7 | 4 | 3 | 1 |
| 5 | DRV/r+ETR+AZT+FTC | 11.75 | 2.67 | 7 | 2 |
| 5 | RAL+ETR+AZT+FTC | 11.75 | 2.67 | 7 | 2 |
| 5 | LEN+RAL+IBA+DRV/r | 11.75 | 4 | 4 | 1 |
| 5 | RAL+FTR+DRV/r+TAF/FTC | 11.75 | 4 | 7 | 2 |
| 5 | RAL+LEN+TDF/FTC | 11.8 | 3 | 3 | 1 |
| 5 | RAL+FTR+DRV/c+TDF/FTC | 11.8 | 4 | 6 | 2 |
| 5 | IBA+DRV/c | 11.9 | 2 | 1 | 1 |
| 5 | RAL+IBA | 11.9 | 2 | 2 | 1 |
| 5 | DTG+FTR+IBA+DRV/c | 11.9 | 4 | 4 | 2 |
| 5 | LEN+RAL+DRV/c/TAF/FTC | 11.95 | 4 | 3 | 1 |
| 5 | RAL+FTR+DRV/r+TDF/FTC | 11.95 | 4 | 7 | 2 |
| 5 | DTG+FTR+IBA+DRV/r | 12.05 | 4 | 5 | 2 |
| 5 | IBA+DRV/r | 12.15 | 2 | 2 | 1 |
| 5 | LEN+RAL+DRV/r+TAF/FTC | 12.2 | 4 | 5 | 1 |
| 5 | RAL+LEN | 12.24 | 2 | 2 | 1 |
| 5 | LEN+RAL+DRV/c+TDF/FTC | 12.35 | 4 | 4 | 1 |
| 5 | IBA+DRV+EVG/c/TAF/FTC | 12.4 | 4 | 2 | 1 |
| 5 | LEN+RAL+DRV/r+TDF/FTC | 12.4 | 4 | 5 | 1 |
| 5 | IBA+DRV/c/TAF/FTC | 12.5 | 3 | 1 | 1 |
| 5 | FTR+DRV/c/TAF/FTC | 12.5 | 3 | 3 | 2 |
| 5 | FTR+EVG/c/TAF/FTC | 12.55 | 3 | 3 | 2 |
| 5 | FTR+EVG/c/TDF/FTC | 12.55 | 3 | 3 | 2 |
| 5 | IBA+DRV/c+TDF/FTC | 12.6 | 3 | 2 | 1 |
| 5 | FTR+DRV+EVG/c/TAF/FTC | 12.6 | 4 | 4 | 2 |
| 5 | RAL+FTR+IBA+DRV/c | 12.6 | 4 | 5 | 2 |
| 5 | IBA+DRV/r+TAF/FTC | 12.7 | 3 | 3 | 1 |
| 5 | LEN+DRV/c | 12.74 | 2 | 1 | 1 |
| 5 | LEN+DRV/r | 12.74 | 2 | 2 | 1 |
| 5 | FTR+DRV/r+TAF/FTC | 12.75 | 3 | 5 | 2 |
| 5 | RAL+FTR+IBA+DRV/r | 12.75 | 4 | 6 | 2 |
| 5 | IBA+EVG/c/TAF/FTC | 12.8 | 3 | 1 | 1 |
| 5 | IBA+EVG/c/TDF/FTC | 12.8 | 3 | 1 | 1 |
| 5 | IBA+DRV/r+TDF/FTC | 12.8 | 3 | 3 | 1 |
| 5 | FTR+DRV/c+TDF/FTC | 12.8 | 3 | 4 | 2 |
| 5 | DTG+LEN+FTR+DRV/r | 12.8 | 4 | 5 | 2 |
| 5 | ETR+TAF/FTC | 12.85 | 1.67 | 3 | 2 |
| 5 | ETR+TDF/FTC | 12.85 | 1.67 | 3 | 2 |
| 5 | FTR+DRV/r+TDF/FTC | 12.85 | 3 | 5 | 2 |
| 5 | RAL+FTR | 12.89 | 2 | 4 | 2 |
| 5 | DTG+DRV/r+ETR+3TC/AZT | 12.9 | 3.67 | 8 | 2 |
| 5 | DTG+LEN+FTR+DRV/c | 12.9 | 4 | 4 | 2 |
| 5 | DTG+DRV/r+ETR+AZT+FTC | 13.1 | 3.67 | 9 | 2 |
| 5 | LEN+DRV+EVG/c/TAF/FTC | 13.15 | 4 | 2 | 1 |
| 5 | FTR+DRV/c | 13.19 | 2 | 3 | 2 |
| 5 | LEN+DRV/r+TAF/FTC | 13.2 | 3 | 3 | 1 |
| 5 | FTR+DRV/r | 13.24 | 2 | 4 | 2 |
| 5 | LEN+DRV/c/TAF/FTC | 13.25 | 3 | 1 | 1 |
| 5 | LEN+EVG/c/TAF/FTC | 13.3 | 3 | 1 | 1 |
| 5 | LEN+EVG/c/TDF/FTC | 13.3 | 3 | 1 | 1 |
| 5 | LEN+DRV/r+TDF/FTC | 13.3 | 3 | 3 | 1 |
| 5 | LEN+DRV/c+TDF/FTC | 13.35 | 3 | 2 | 1 |
| 5 | RAL+DRV/r+ETR+3TC/AZT | 13.4 | 3.67 | 8 | 2 |
| 5 | LEN+RAL+FTR+DRV/r | 13.5 | 4 | 6 | 2 |
| 5 | DTG+FTR+DRV/c+3TC/AZT | 13.55 | 4 | 6 | 2 |
| 5 | RAL+DRV/r+ETR+AZT+FTC | 13.6 | 3.67 | 9 | 2 |
| 5 | LEN+RAL+FTR+DRV/c | 13.6 | 4 | 5 | 2 |
| 5 | DTG+IBA+DRV/c+3TC/AZT | 13.65 | 4 | 4 | 2 |
| 5 | DTG+FTR+DRV/r+3TC/AZT | 13.7 | 4 | 7 | 2 |
| 5 | DTG+FTR+DRV/c+AZT+FTC | 13.75 | 4 | 7 | 2 |
| 5 | DRV/r+ETR | 13.85 | 1.67 | 4 | 2 |
| 5 | DTG+IBA+DRV/c+AZT+FTC | 13.85 | 4 | 5 | 2 |
| 5 | DTG+FTR+DRV/r+AZT+FTC | 13.9 | 4 | 8 | 2 |
| 5 | DTG+IBA+DRV/r+3TC/AZT | 13.95 | 4 | 5 | 2 |
| 5 | RAL+FTR+3TC/AZT | 14.05 | 3 | 6 | 2 |
| 5 | RAL+ETR | 14.1 | 1.67 | 4 | 2 |
| 5 | DTG+IBA+DRV/r+AZT+FTC | 14.15 | 4 | 6 | 2 |
| 5 | RAL+FTR+AZT+FTC | 14.25 | 3 | 7 | 2 |
| 5 | RAL+FTR+DRV/c+3TC/AZT | 14.25 | 4 | 7 | 2 |
| 5 | RAL+IBA+DRV/c+3TC/AZT | 14.35 | 4 | 5 | 2 |
| 5 | RAL+FTR+ETR | 14.4 | 2.67 | 6 | 2 |
| 5 | DTG+LEN+DRV/c+3TC/AZT | 14.4 | 4 | 4 | 2 |
| 5 | RAL+FTR+DRV/r+3TC/AZT | 14.4 | 4 | 8 | 2 |
| 5 | DTG+LEN+DRV/r+3TC/AZT | 14.45 | 4 | 5 | 2 |
| 5 | RAL+FTR+DRV/c+AZT+FTC | 14.45 | 4 | 8 | 2 |
| 5 | FTR+DRV/r+ETR | 14.5 | 2.67 | 6 | 2 |
| 5 | RAL+IBA+DRV/c+AZT+FTC | 14.55 | 4 | 6 | 2 |
| 5 | DTG+FTR+DRV/r+ETR | 14.6 | 3.67 | 8 | 2 |
| 5 | DTG+LEN+DRV/c+AZT+FTC | 14.6 | 4 | 5 | 2 |
| 5 | RAL+FTR+DRV/r+AZT+FTC | 14.6 | 4 | 9 | 2 |
| 5 | IBA+DRV/r+ETR | 14.65 | 2.67 | 4 | 2 |
| 5 | RAL+IBA+ETR | 14.65 | 2.67 | 4 | 2 |
| 5 | RAL+LEN+3TC/AZT | 14.65 | 3 | 4 | 2 |
| 5 | RAL+IBA+3TC/AZT | 14.65 | 3 | 4 | 2 |
| 5 | DTG+LEN+DRV/r+AZT+FTC | 14.65 | 4 | 6 | 2 |
| 5 | RAL+IBA+DRV/r+3TC/AZT | 14.65 | 4 | 6 | 2 |
| 5 | DTG+IBA+DRV/r+ETR | 14.75 | 3.67 | 6 | 2 |
| 5 | RAL+LEN+AZT+FTC | 14.85 | 3 | 5 | 2 |
| 5 | RAL+IBA+AZT+FTC | 14.85 | 3 | 5 | 2 |
| 5 | RAL+IBA+DRV/r+AZT+FTC | 14.85 | 4 | 7 | 2 |
| 5 | RAL+FTR+DRV/r+ETR | 15.1 | 3.67 | 8 | 2 |
| 5 | LEN+RAL+DRV/c+3TC/AZT | 15.1 | 4 | 5 | 2 |
| 5 | LEN+RAL+DRV/r+3TC/AZT | 15.15 | 4 | 6 | 2 |
| 5 | RAL+IBA+DRV/r+ETR | 15.25 | 3.67 | 6 | 2 |
| 5 | LEN+RAL+DRV/c+AZT+FTC | 15.3 | 4 | 6 | 2 |
| 5 | FTR+DRV/c+3TC/AZT | 15.35 | 3 | 5 | 2 |
| 5 | LEN+RAL+DRV/r+AZT+FTC | 15.35 | 4 | 7 | 2 |
| 5 | FTR+DRV/r+3TC/AZT | 15.4 | 3 | 6 | 2 |
| 5 | ETR+3TC/AZT | 15.55 | 1.67 | 4 | 2 |
| 5 | FTR+DRV/c+AZT+FTC | 15.55 | 3 | 6 | 2 |
| 5 | FTR+DRV/r+AZT+FTC | 15.6 | 3 | 7 | 2 |
| 5 | IBA+DRV/c+3TC/AZT | 15.7 | 3 | 3 | 2 |
| 5 | ETR+AZT+FTC | 15.75 | 1.67 | 5 | 2 |
| 5 | IBA+DRV/r+3TC/AZT | 15.9 | 3 | 4 | 2 |
| 5 | IBA+DRV/c+AZT+FTC | 15.9 | 3 | 4 | 2 |
| 5 | IBA+DRV/r+AZT+FTC | 16.1 | 3 | 5 | 2 |
| 5 | LEN+DRV/r+3TC/AZT | 16.15 | 3 | 4 | 2 |
| 5 | LEN+DRV/c+3TC/AZT | 16.2 | 3 | 3 | 2 |
| 5 | LEN+DRV/r+AZT+FTC | 16.35 | 3 | 5 | 2 |
| 5 | LEN+DRV/c+AZT+FTC | 16.4 | 3 | 4 | 2 |
| 5 | LEN+RAL+ETR | 16.8 | 2.67 | 4 | 2 |
| 5 | LEN+DRV/r+ETR | 17.05 | 2.67 | 4 | 2 |
| 5 | DTG+LEN+DRV/r+ETR | 17.15 | 3.67 | 6 | 2 |
| 5 | LEN+RAL+DRV/r+ETR | 17.65 | 3.67 | 6 | 2 |
| 5 | RAL+FTR+IBA+ETR | 19.15 | 3.67 | 6 | 2 |
| 5 | FTR+IBA+DRV/r+ETR | 19.75 | 3.67 | 6 | 2 |
| 5 | LEN+RAL+IBA+ETR | 20.3 | 3.67 | 4 | 2 |
| 5 | LEN+IBA+DRV/r+ETR | 21.05 | 3.67 | 4 | 2 |
| 5 | LEN+RAL+FTR+ETR | 21.55 | 3.67 | 6 | 2 |
| 5 | LEN+FTR+DRV/r+ETR | 22.4 | 3.67 | 6 | 2 |
Report
Preferred regimen based on the HIV-ASSIST algorithm: BIC/TAF/FTC
BIC/TAF/FTC had the lowest weighted score (1) among all regimens HIV-ASSIST evaluated. In general, lower HIV-ASSIST weighted scores are considered preferable with respect to achieving viral suppression and maximizing tolerability. Your patient may have other considerations we did not factor and this report should not be considered a guarantee of likely success with this patient. Please use clinical judgement in making final ARV selections. Other regimens you may wish to consider are listed below. A full list of ARV regimens analyzed by the HIV-ASSIST algorithm can be found by clicking the Expert Tab above.
| Score Code | Regimen | Weighted Score | Active Drugs | Total Pills | Frequency (x/day) |
|---|---|---|---|---|---|
| 1 | BIC/TAF/FTC | 1 | 2 | 1 | 1 |
The rationale behind why this regimen was chosen by our algorithm as the most appropriate is shown below:
Other highly ranked regimens
Other highly ranked regimens based on the HIV-ASSIST algorithm are shown below. For full details on these regimens, please click on the Expert Tab above.
| Score Code | Regimen | Weighted Score | Active Drugs | Total Pills | Frequency (x/day) |
|---|---|---|---|---|---|
| 1 | DTG/TDF/3TC | 1 | 2 | 1 | 1 |
| 1 | DTG+TAF/FTC | 1.25 | 2 | 2 | 1 |
| 1 | DTG+TDF/FTC | 1.25 | 2 | 2 | 1 |
| 3 | DTG+DRV/c/TAF/FTC | 3 | 3 | 2 | 1 |
Mutations
Based on the Stanford Database, we assign penalties to various regimens based on inputted (i.e., genotypic) and assumed archived mutations. We consider drugs with summed mutation scores between 10 and 29 to have low-level resistance, scores between 30 and 59 to have intermediate-level resistance, and scores above 60 to have high-level resistance.
* signifies an assumed archived mutation based on prior treatment experience.| NRTI Mutation(s) | 3TC | FTC | ABC | TAF | TDF | AZT | D4T | DDI |
|---|---|---|---|---|---|---|---|---|
| M184V | 60 | 60 | 15 | -10 | -10 | -10 | -10 | 10 |
| Total | 60 | 60 | 15 | -10 | -10 | -10 | -10 | 10 |
| NNRTI Mutation(s) | EFV | ETR | RPV | NVP | DOR |
|---|---|---|---|---|---|
| V179D | 10 | 10 | 10 | 10 | 0 |
| Y188L | 60 | 10 | 60 | 60 | 60 |
| K103N* | 60 | 0 | 0 | 60 | 0 |
| K103R + V179D | 20 | 0 | 15 | 20 | 0 |
| Total | 150 | 20 | 85 | 150 | 60 |
| PI Mutation(s) | LPVr | FPVr | TPVr | SQVr | IDVr | NFV | ATVr | ATVc | ATV | DRV | DRVr | DRVc |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Total | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| INSTI Mutation(s) | RAL | EVGc | DTG | BIC | CAB |
|---|---|---|---|---|---|
| Total | 0 | 0 | 0 | 0 | 0 |
| EI Mutation(s) | MVC | IBA | FOS |
|---|---|---|---|
| Total | 0 | 0 | 0 |
| CI Mutation(s) | LEN |
|---|---|
| Total | 0 |
Comorbidities, Side Effects, and Pregnancy Interactions
HIV-ASSIST incorporates a mathematical penalty into our algorithms for ARVs that are less preferred due to comorbidities or side-effects, based on recommendations from DHHS guidelines and HIV-ASSIST clinician and pharmacist expertise. In general, higher penalties suggest that the listed ARV is less favored in the presence of the stated comorbidity or side effect.
Co-medication Interactions
We have identified the following possible drug interactions which HIV-ASSIST factors into ARV regimen selection, based on recommendations from DHHS guidelines, University of Liverpool HIV Drug Interaction Checker, and HIV-ASSIST clinician and pharmacist expertise. Penalties less than 1.0 are typically those representing minor interactions that can be mediated by dosage adjustments, whereas a penalty of 2.0 represents medically contraindicated ARVs.
- Penalty:
- 0
- Liverpool Interaction Status:
- Green/Low: No Interaction Expected (Very Low Quality of Evidence)
- Liverpool Notes:
- Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metoprolol is mainly metabolized by CYP2D6.
- Penalty:
- 0
- Liverpool Interaction Status:
- Green/Low: No Interaction Expected (Very Low Quality of Evidence)
- Liverpool Notes:
- Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metoprolol is mainly metabolized by CYP2D6.
- Penalty:
- 0
- Liverpool Interaction Status:
- Green/Low: No Interaction Expected (Very Low Quality of Evidence)
- Liverpool Notes:
- Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metoprolol is mainly metabolized by CYP2D6.
- Penalty:
- 0
- Liverpool Interaction Status:
- Green/Low: No Interaction Expected (Very Low Quality of Evidence)
- Liverpool Notes:
- Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metoprolol is mainly metabolized by CYP2D6. Emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway. Dose Descovy according to the concomitant antiretroviral.
- Penalty:
- 0
- Liverpool Interaction Status:
- Green/Low: No Interaction Expected (Very Low Quality of Evidence)
- Liverpool Notes:
- Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metoprolol is mainly metabolized by CYP2D6.
- Penalty:
- 0
- Liverpool Interaction Status:
- Green/Low: No Interaction Expected (Very Low Quality of Evidence)
- Liverpool Notes:
- Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metoprolol is mainly metabolized by CYP2D6.
- Penalty:
- 0
- Liverpool Interaction Status:
- Green/Low: No Interaction Expected (Very Low Quality of Evidence)
- Liverpool Notes:
- Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metoprolol is mainly metabolized by CYP2D6.
- Penalty:
- 0
- Liverpool Interaction Status:
- Green/Low: No Interaction Expected (Very Low Quality of Evidence)
- Liverpool Notes:
- Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metoprolol is mainly metabolized by CYP2D6.
- Penalty:
- 0
- Liverpool Interaction Status:
- Green/Low: No Interaction Expected (Very Low Quality of Evidence)
- Liverpool Notes:
- Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metoprolol is mainly metabolized by CYP2D6.
- Penalty:
- 0
- Liverpool Interaction Status:
- Green/Low: No Interaction Expected (Very Low Quality of Evidence)
- Liverpool Notes:
- Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metoprolol is mainly metabolized by CYP2D6.
- Penalty:
- 0
- Liverpool Interaction Status:
- Green/Low: No Interaction Expected (Very Low Quality of Evidence)
- Liverpool Notes:
- Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metoprolol is mainly metabolized by CYP2D6 but rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes.
- Penalty:
- 0
- Liverpool Interaction Status:
- Green/Low: No Interaction Expected (Very Low Quality of Evidence)
- Liverpool Notes:
- Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metoprolol is mainly metabolized by CYP2D6.
- Penalty:
- 0
- Liverpool Interaction Status:
- Green/Low: No Interaction Expected (Very Low Quality of Evidence)
- Liverpool Notes:
- Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metoprolol is mainly metabolized by CYP2D6. Doravirine does not inhibit or induce CYP enzymes.
- Penalty:
- 1
- HIV-ASSIST Notes:
- Possible increase in level of beta blocker (particularly with metoprolol, timolol, carvedilol, propranolol). May need to decrease beta blocker dose. Adjust dose based on clinical response. Consider using beta blockers that are not metabolized by CYP450 enzymes (ex. Atenolol, labetalol, nadolol, sotalol). Use caution when using Sotalol as there is potential for QTc prolongation.
- Liverpool Interaction Status:
- Amber/Moderate: Interaction Expected (Very Low Quality of Evidence)
- Liverpool Notes:
- The impact on the PR interval of coadministration of Kaletra with other drugs that prolong the PR interval (including beta-adrenergic blockers) has not been evaluated. As a result, coadministration of Kaletra with these drugs should be undertaken with caution, particularly with those drugs metabolized by CYP3A. Clinical monitoring is recommended. Kaletra Prescribing Information, AbbVie Inc, October 2020. A case report describes a patient stable on lacidipine, ramipril, levothyroxine, rosuvastatin, metoprolol and acetylsalicylic acid who developed extreme bradycardia (20-25 bpm) and hypotension (50/20 mmHg) 48 hours after starting HIV post-exposure prophylaxis (tenofovir, emtricitabine, lopinavir/ritonavir). Lopinavir/ritonavir, lacidipine, ramipril and metoprolol were discontinued. Raltegravir was prescribed on day 4. Lacidipine, ramipril were re-instated on day 7 and metoprolol on day 9. Blood concentrations were analyzed approximately 12 h after the last dose of tenofovir/emtricitabine and 20 h after the last dose of lopinavir/ritonavir. Lopinavir, ritonavir, tenofovir and emtricitabine plasma concentrations were 8.40 mg/L, 0.29 mg/L, 0.059 mg/L and 0.12 mg/L, respectively. The lopinavir plasma concentration was higher than usual (3 to 7 mg/L); but the measurement was done only 3 days after treatment initiation while 2 weeks are required to see the maximal enzyme inducing effects of ritonavir. Tenofovir and emtricitabine plasma concentrations were in the normal range. Genetic analysis showed the patient to be an intermediate metaboliser for CYP2D6, a normal metaboliser for CYP3A4 and a low expressor of P-gp. The authors propose that the AV block and the hypotension were primarily associated with co-administration of the lopinavir/ritonavir combination with metoprolol and lacidipine as the patient was asymptomatic while he started antiretroviral therapy, and discontinuation of lopinavir/ritonavir, lacidipine, ramipril and metoprolol, restored normal rhythm, and further, re-introduction of lacidipine, ramipril and metoprolol without lopinavir/ritonavir induced no bradyarrythmia. Extreme bradycardia due to multiple drug-drug interactions in a patient with HIV post-exposure prophylaxis containing lopinavir-ritonavir. Puech R, Gagnieu M-C, Planus C, et al. Br J Clin Pharmacol, 2011, 71(4): 621-623., Summary:Coadministration has not been studied. Metoprolol is mainly metabolized by CYP2D6. Coadministration could potentially increase metoprolol concentrations, although to a moderate extent. Pharmacokinetic studies between lopinavir/ritonavir and drugs that prolong the PR interval including beta blockers have not been performed. An additive effect of lopinavir and these drugs cannot be excluded. A case report described a patient stable on lacidipine, ramipril, levothyroxine, rosuvastatin, metoprolol and acetylsalicylic acid who developed extreme bradycardia (20-25 bpm) and hypotension (50/20 mmHg) 48 hours after starting HIV post-exposure prophylaxis (tenofovir, emtricitabine, lopinavir/ritonavir). The authors propose that the AV block and the hypotension were primarily associated with co-administration of the lopinavir/ritonavir combination with metoprolol and lacidipine as the patient was asymptomatic while he started antiretroviral therapy. Discontinuation of lopinavir/ritonavir, lacidipine, ramipril and metoprolol, restored normal rhythm, and further, re-introduction of lacidipine, ramipril and metoprolol without lopinavir/ritonavir induced no bradyarrythmia. Note, PR interval monitoring may be warranted in patients with underlying block or those with atrioventricular nodal blocking agents.
- Penalty:
- 0.75
- HIV-ASSIST Notes:
- Possible increase in level of beta blocker (particularly with metoprolol, timolol, carvedilol, propranolol). May need to decrease beta blocker dose. Adjust dose based on clinical response. Consider using beta blockers that are not metabolized by CYP450 enzymes (ex. Atenolol, labetalol, nadolol, sotalol)
- Liverpool Interaction Status:
- Yellow/Moderate-low: Potential Weak Interaction (Very Low Quality of Evidence)
- Liverpool Notes:
- Coadministration has not been studied. Metoprolol is mainly metabolized by CYP2D6. Fosamprenavir/ritonavir could potentially increase metoprolol concentrations, although to a moderate extent. No a priori dosage adjustment is required.
- Penalty:
- 0.75
- HIV-ASSIST Notes:
- Possible increase in level of beta blocker (particularly with metoprolol, timolol, carvedilol, propranolol). May need to decrease beta blocker dose. Adjust dose based on clinical response. Consider using beta blockers that are not metabolized by CYP450 enzymes (ex. Atenolol, labetalol, nadolol, sotalol)
- Liverpool Interaction Status:
- RED/High: Do Not Coadminister (Moderate Quality of Evidence)
- Liverpool Notes:
- Co-administration of tipranavir with low dose ritonavir, with drugs that are highly dependent on CYP2D6 for clearance, such as the antiarrhythmic metoprolol (given in heart failure), is contraindicated. Based on theoretical considerations, tipranavir, co-administered with low dose ritonavir, is expected to increase metoprolol concentrations.Aptivus Summary of Product Characteristics, Boehringer Ingelheim Ltd, July 2020., Summary:Coadministration of tipranavir/ritonavir and drugs that are highly dependent on CYP2D6 for clearance, such metoprolol (given in heart failure), is contraindicated. Coadministration may increase metoprolol concentrations.
- Penalty:
- 0.75
- HIV-ASSIST Notes:
- Possible increase in level of beta blocker (particularly with metoprolol, timolol, carvedilol, propranolol). May need to decrease beta blocker dose. Adjust dose based on clinical response. Consider using beta blockers that are not metabolized by CYP450 enzymes (ex. Atenolol, labetalol, nadolol, sotalol). Use caution when using Sotalol as there is potential for QTc prolongation.
- Penalty:
- 0.75
- HIV-ASSIST Notes:
- Possible increase in level of beta blocker (particularly with metoprolol, timolol, carvedilol, propranolol). May need to decrease beta blocker dose. Adjust dose based on clinical response. Consider using beta blockers that are not metabolized by CYP450 enzymes (ex. Atenolol, labetalol, nadolol, sotalol)
- Liverpool Interaction Status:
- Yellow/Moderate-low: Potential Weak Interaction (Very Low Quality of Evidence)
- Liverpool Notes:
- Coadministration has not been studied. Metoprolol is mainly metabolized by CYP2D6. Indinavir/ritonavir could potentially increase metoprolol concentrations, although to a moderate extent. No a priori dosage adjustment is required. An interaction is unlikely with unboosted indinavir.
- Penalty:
- 0.75
- HIV-ASSIST Notes:
- Possible increase in level of beta blocker (particularly with metoprolol, timolol, carvedilol, propranolol). May need to decrease beta blocker dose. Adjust dose based on clinical response. Consider using beta blockers that are not metabolized by CYP450 enzymes (ex. Atenolol, labetalol, nadolol, sotalol)
- Penalty:
- 1
- HIV-ASSIST Notes:
- Possible increase in level of beta blocker (particularly with metoprolol, timolol, carvedilol, propranolol). May need to decrease beta blocker dose. Adjust dose based on clinical response. Consider using beta blockers that are not metabolized by CYP450 enzymes (ex. Atenolol, labetalol, nadolol, sotalol). Use caution when using Sotalol as there is potential for QTc prolongation.
- Liverpool Interaction Status:
- Amber/Moderate: Interaction Expected (Very Low Quality of Evidence)
- Liverpool Notes:
- Coadministration has not been studied. Metoprolol is mainly metabolized by CYP2D6. Atazanavir/ritonavir could potentially increase metoprolol concentrations, although to a moderate extent. Pharmacokinetic studies between atazanavir and drugs that prolong the PR interval including beta blockers (other than atenolol) have not been performed. An additive effect of atazanavir and these drugs cannot be excluded. Note, PR interval monitoring may be warranted in patients with underlying block or those with atrioventricular nodal blocking agents.
- Penalty:
- 1
- HIV-ASSIST Notes:
- Possible increase in level of beta blocker (particularly with metoprolol, timolol, carvedilol, propranolol). May need to decrease beta blocker dose. Adjust dose based on clinical response. Consider using beta blockers that are not metabolized by CYP450 enzymes (ex. Atenolol, labetalol, nadolol, sotalol). Use caution when using Sotalol as there is potential for QTc prolongation.
- Liverpool Interaction Status:
- Amber/Moderate: Interaction Expected (Very Low Quality of Evidence)
- Liverpool Notes:
- Concentrations of beta-blockers may be increased when coadministered with Evotaz. The mechanism of interaction is inhibition of CYP2D6 by cobicistat. Clinical monitoring is recommended when coadministered with Evotaz and a dose reduction of the beta-blocker may be necessary. Evotaz Summary of Product Characteristics, Bristol-Myers Squibb Pharmaceuticals Ltd, November 2018. Coadministration may increase beta-blocker concentrations but have no effect on atazanavir concentrations. Clinical monitoring is recommended when beta-blockers that are metabolized by CYP2D6 are coadministered with Evotaz. Evotaz US Prescribing Information Bristol-Myers Squibb Company, March 2018., Summary:Coadministration has not been studied. Metoprolol is mainly metabolized by CYP2D6. Atazanavir/cobicistat could potentially increase metoprolol concentrations although to a moderate extent as cobicistat is a weak inhibitor of CYP2D6. Pharmacokinetic studies between atazanavir and drugs that prolong the PR interval including beta blockers (other than atenolol) have not been performed. An additive effect of atazanavir and these drugs cannot be excluded. Note, PR interval monitoring may be warranted in patients with underlying block or those receiving known atrioventricular nodal blocking agents. The atazanavir/cobicistat SmPC recommends clinical monitoring. A dose reduction of metoprolol may be necessary.
- Penalty:
- 0.25
- HIV-ASSIST Notes:
- Possible increase in level of beta blocker (particularly with metoprolol, timolol, carvedilol, propranolol). May need to decrease beta blocker dose. Adjust dose based on clinical response. Consider using beta blockers that are not metabolized by CYP450 enzymes (ex. Atenolol, labetalol, nadolol, sotalol). Use caution when using Sotalol as there is potential for QTc prolongation.
- Liverpool Interaction Status:
- Amber/Moderate: Interaction Expected (Very Low Quality of Evidence)
- Liverpool Notes:
- Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Metoprolol is mainly metabolized by CYP2D6. Atazanavir alone does not inhibit CYP2D6. Pharmacokinetic studies between atazanavir and drugs that prolong the PR interval including beta blockers (other than atenolol) have not been performed. An additive effect of atazanavir and these drugs cannot be excluded. Note, PR interval monitoring may be warranted in patients with underlying block or those receiving known atrioventricular nodal blocking agents.
- Penalty:
- 1
- HIV-ASSIST Notes:
- Possible increase in level of beta blocker (particularly with metoprolol, timolol, carvedilol, propranolol). May need to decrease beta blocker dose. Adjust dose based on clinical response. Consider using beta blockers that are not metabolized by CYP450 enzymes (ex. Atenolol, labetalol, nadolol, sotalol)
- Liverpool Interaction Status:
- Yellow/Moderate-low: Potential Weak Interaction (Very Low Quality of Evidence)
- Liverpool Notes:
- Coadministration has not been studied. Co-administration of darunavir and ritonavir with medicinal products which are primarily metabolised by CYP2D6 (such as metoprolol) may result in increased plasma concentrations of these medicinal products, which could increase or prolong their therapeutic effect and adverse reactions. Clinical monitoring is recommended when co-administering boosted darunavir with beta-blockers. A lower dose of the beta-blocker should be considered. Prezista Summary of Product Characteristics, Janssen-Cilag Ltd, September 2022. Coadministration with darunavir/ritonavir may increase metoprolol concentrations. Clinical monitoring of patients is recommended. A dose decrease may be needed for this drug when co-administered with darunavir/ritonavir and a lower dose of the beta blocker should be considered. Prezista Prescribing Information, Janssen Pharmaceuticals Inc, March 2023., Summary:Coadministration has not been studied. Metoprolol is mainly metabolized by CYP2D6. Darunavir/ritonavir could potentially increase metoprolol concentrations, although to a limited extent. No a priori dosage adjustment is required.
- Penalty:
- 1
- HIV-ASSIST Notes:
- Possible increase in level of beta blocker (particularly with metoprolol, timolol, carvedilol, propranolol). May need to decrease beta blocker dose. Adjust dose based on clinical response. Consider using beta blockers that are not metabolized by CYP450 enzymes (ex. Atenolol, labetalol, nadolol, sotalol)
- Liverpool Interaction Status:
- Yellow/Moderate-low: Potential Weak Interaction (Very Low Quality of Evidence)
- Liverpool Notes:
- Coadministration has not been studied. Co-administration of darunavir and ritonavir with medicinal products which are primarily metabolised by CYP2D6 (such as metoprolol) may result in increased plasma concentrations of these medicinal products, which could increase or prolong their therapeutic effect and adverse reactions. Clinical monitoring is recommended when co-administering boosted darunavir with beta-blockers. A lower dose of the beta-blocker should be considered. Prezista Summary of Product Characteristics, Janssen-Cilag Ltd, September 2022. Coadministration with darunavir/ritonavir may increase metoprolol concentrations. Clinical monitoring of patients is recommended. A dose decrease may be needed for this drug when co-administered with darunavir/ritonavir and a lower dose of the beta blocker should be considered. Prezista Prescribing Information, Janssen Pharmaceuticals Inc, March 2023., Summary:Coadministration has not been studied. Metoprolol is mainly metabolized by CYP2D6. Darunavir/ritonavir could potentially increase metoprolol concentrations, although to a limited extent. No a priori dosage adjustment is required.
- Penalty:
- 1
- HIV-ASSIST Notes:
- Possible increase in level of beta blocker (particularly with metoprolol, timolol, carvedilol, propranolol). May need to decrease beta blocker dose. Adjust dose based on clinical response. Consider using beta blockers that are not metabolized by CYP450 enzymes (ex. Atenolol, labetalol, nadolol, sotalol)
- Liverpool Interaction Status:
- Yellow/Moderate-low: Potential Weak Interaction (Very Low Quality of Evidence)
- Liverpool Notes:
- Based on theoretical considerations darunavir/cobicistat is expected to increase metoprolol plasma concentrations (CYP3A inhibition). Clinical monitoring is recommended when co-administering darunavir/cobicistat with beta-blockers and a lower dose of the beta-blocker should be considered. Rezolsta Summary of Product Characteristics, Janssen-Cilag Ltd, July 2023. Coadministration is expected to increase concentrations of metoprolol. Clinical monitoring is recommended for co-administration with beta-blockers that are metabolized by CYP2D6. Prezcobix US Prescribing Information, Janssen Pharmaceuticals Inc, March 2023., Summary:Coadministration has not been studied. Metoprolol is mainly metabolized by CYP2D6. Darunavir/cobicistat could potentially increase metoprolol concentrations although to a limited extent as cobicistat is a weak inhibitor of CYP2D6. No a priori dosage adjustment is needed.
- Penalty:
- 0
- Liverpool Interaction Status:
- Green/Low: No Interaction Expected (Very Low Quality of Evidence)
- Liverpool Notes:
- Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metoprolol is mainly metabolized by CYP2D6.
- Penalty:
- 1
- HIV-ASSIST Notes:
- Possible increase in level of beta blocker (particularly with metoprolol, timolol, carvedilol, propranolol). May need to decrease beta blocker dose. Adjust dose based on clinical response. Consider using beta blockers that are not metabolized by CYP450 enzymes (ex. Atenolol, labetalol, nadolol, sotalol)
- Liverpool Interaction Status:
- Yellow/Moderate-low: Potential Weak Interaction (Very Low Quality of Evidence)
- Liverpool Notes:
- Interaction not studied with any of the components of Genvoya. Concentrations of beta-blockers may be increased when co-administered with cobicistat. Clinical monitoring is recommended and a dose decrease may be necessary when these agents are co-administered with Genvoya. Genvoya Summary of Product Characteristics, Gilead Sciences International Ltd, November 2021. Coadministration is expected to increase concentrations of beta-blockers. Clinical monitoring is recommended and a dosage decrease of the beta blocker may be necessary when these agents are coadministered with Genvoya. Genvoya Prescribing Information, Gilead Sciences Inc, September 2021., Summary:Coadministration has not been studied. Metoprolol is mainly metabolized by CYP2D6. Elvitegravir/cobicistat could potentially increase metoprolol concentrations although to a moderate extent as cobicistat is a weak inhibitor of CYP2D6. Emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway. No a priori dosage adjustment is required.
- Penalty:
- 0
- Liverpool Interaction Status:
- Green/Low: No Interaction Expected (Very Low Quality of Evidence)
- Liverpool Notes:
- Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metoprolol is mainly metabolized by CYP2D6, however, dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations.
- Penalty:
- 0
- Liverpool Interaction Status:
- Green/Low: No Interaction Expected (Very Low Quality of Evidence)
- Liverpool Notes:
- Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metoprolol is mainly metabolized by CYP2D6. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with metoprolol’s metabolic pathway.
- Penalty:
- 0
- Liverpool Interaction Status:
- Green/Low: No Interaction Expected (Very Low Quality of Evidence)
- Liverpool Notes:
- Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metoprolol is mainly metabolized by CYP2D6. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations.
- Penalty:
- 0
- Liverpool Interaction Status:
- Green/Low: No Interaction Expected (Very Low Quality of Evidence)
- Liverpool Notes:
- Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metoprolol is mainly metabolized by CYP2D6, however, maraviroc is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations.
- Penalty:
- 0
- Liverpool Interaction Status:
- Green/Low: No Interaction Expected (Very Low Quality of Evidence)
- Liverpool Notes:
- Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. No drug interaction studies have been conducted with ibalizumab: based on ibalizumab’s mechanism of action and target-mediated drug disposition, drug-drug interactions are not expected. Metoprolol undergoes hepatic metabolism whereas ibalizumab, a monoclonal antibody binding to the CD4 receptor, is likely to be eliminated via intracellular catabolism similarly to other monoclonal antibodies.
- Penalty:
- 0
- Liverpool Interaction Status:
- Green/Low: No Interaction Expected (Very Low Quality of Evidence)
- Liverpool Notes:
- Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metoprolol is mainly metabolized by CYP2D6. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. In addition, fostemsavir did not have a clinically meaningful effect on PR interval.
- Penalty:
- 0
- Liverpool Interaction Status:
- Green/Low: No Interaction Expected (Very Low Quality of Evidence)
- Liverpool Notes:
- Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metoprolol is mainly metabolized by CYP2D6. Lenacapavir is mainly cleared as unchanged drug and has no inhibitory or inducing effects on CYP2D6.
- Penalty:
- 0
- Liverpool Interaction Status:
- Green/Low: No Interaction Expected (Low Quality of Evidence)
- Liverpool Notes:
- Coadministration of buprenorphine (14-16 mg once daily, stable dose with naloxone) and lamivudine (300 mg once daily) was studied in 7 opioid-dependent patients and values compared to historical data. Coadministration had few effects on the pharmacokinetics of buprenorphine and its metabolites. Buprenorphine AUC, Cmax and Cmin increased by ~5%, ~1% and ~2%, respectively. Norbuprenorphine AUC, Cmax and Cmin increased by ~6%, ~3% and ~4%, respectively; buprenorphine-3-glucuronide AUC and Cmin increased by ~10% and ~28%, Cmax was unchanged; norbuprenorphine-3-glucuronide AUC, Cmax and Cmin increased by ~7%, ~12% and ~11%, respectively. Only the increases in norbuprenorphine-3-glucuronide AUC and Cmax were statistically significant. No subjects showed evidence of opiate withdrawal symptoms. Lamivudine concentrations during coadministration did not differ significantly from values observed in healthy, nonopioid-dependent, historical controls. The authors conclude that standard doses of lamivudine may be safely given with standard buprenorphine/naloxone treatment. Interactions between buprenorphine and antiretrovirals: nucleos(t)ide reverse transcriptase inhibitors (NRTI) didanosine, lamivudine, and tenofovir. Baker J, Rainey P, Moody D, et al. Am J Addict, 2010, 19(1): 17-29. , Summary:The interaction between buprenorphine and lamivudine was investigated in 7 HIV-negative, buprenorphine/naloxone maintained subjects. When compared to control data, no significant changes in buprenorphine pharmacokinetics were observed and buprenorphine had no statistically significant effect on NRTI concentrations.
- Penalty:
- 0
- Liverpool Interaction Status:
- Green/Low: No Interaction Expected (Very Low Quality of Evidence)
- Liverpool Notes:
- Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Buprenorphine undergoes both N-dealkylation to form norbuprenorphine (via CYP3A4) and glucuronidation (via UGT2B7 and UGT1A1). Norbuprenorphine, an active metabolite, can further undergo glucuronidation (via UGT1A3 and UGT1A1).
- Penalty:
- 0
- Liverpool Interaction Status:
- Green/Low: No Interaction Expected (Very Low Quality of Evidence)
- Liverpool Notes:
- Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Buprenorphine undergoes both N-dealkylation to form norbuprenorphine (via CYP3A4) and glucuronidation (via UGT2B7 and UGT1A1). Norbuprenorphine, an active metabolite, can further undergo glucuronidation (via UGT1A3 and UGT1A1).
- Penalty:
- 0
- Liverpool Interaction Status:
- Green/Low: No Interaction Expected (Very Low Quality of Evidence)
- Liverpool Notes:
- No clinically significant drug interactions have been either observed or are expected when Descovy is combined with buprenorphine. Descovy US Prescribing Information, Gilead Sciences Inc, January 2022., Summary:Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Buprenorphine undergoes both N-dealkylation to form norbuprenorphine (via CYP3A4) and glucuronidation (via UGT2B7 and UGT1A1). Norbuprenorphine, an active metabolite, can further undergo glucuronidation (via UGT1A3 and UGT1A1). Emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway. Dose Descovy according to the concomitant antiretroviral.
- Penalty:
- 0
- Liverpool Interaction Status:
- Green/Low: No Interaction Expected (Low Quality of Evidence)
- Liverpool Notes:
- Coadministration of buprenorphine (14-16 mg once daily, stable dose with naloxone) and tenofovir-DF (300 mg once daily) was studied in 10 opioid-dependent patients and values compared to 10 matched controls receiving tenofovir-DF alone. Coadministration had no significant effect on buprenorphine (AUC and Cmax increased by ~5% and ~9%, Cmin was unchanged) or its metabolites (norbuprenorphine AUC, Cmax and Cmin increased by ~7%, ~4% and ~1%, respectively; buprenorphine-3-glucuronide AUC and Cmin decreased by ~14% and ~9%, Cmax increased by ~9%; norbuprenorphine-3-glucuronide AUC increased by ~1%, Cmax decreased by ~3% and Cmin was unchanged). There was no effect on tenofovir disposition and concentrations of tenofovir remained in the therapeutic range during coadministration. The authors conclude that standard doses of tenofovir-DF may be safely given with standard buprenorphine/naloxone treatment. Interactions between buprenorphine and antiretrovirals: nucleos(t)ide reverse transcriptase inhibitors (NRTI) didanosine, lamivudine, and tenofovir. Baker J, Rainey P, Moody D, et al. Am J Addict, 2010, 19(1): 17-29., Summary:The interaction between buprenorphine and tenofovir-DF was investigated in 10 HIV-negative, buprenorphine/naloxone maintained subjects. When compared to values obtained from control subjects not receiving buprenorphine, no significant changes in buprenorphine pharmacokinetics were observed. When compared to controls, buprenorphine had no statistically significant effect on NRTI concentrations.
- Penalty:
- 0
- Liverpool Interaction Status:
- Green/Low: No Interaction Expected (Low Quality of Evidence)
- Liverpool Notes:
- Zidovudine pharmacokinetics were determined in opioid-dependent subjects receiving buprenorphine and zidovudine. When compared to values obtained from 17 non-opioid treated subjects, there was no significant difference in zidovudine AUC. Effect of opioid dependence pharmacotherapies on zidovudine disposition. McCance-Katz EF, et al. Am J Addict, 2001, 10: 296-307. , Summary:No significant effect of buprenorphine on zidovudine pharmacokinetics was observed in opioid-dependent subjects receiving buprenorphine and zidovudine when compared to values obtained from 17 non-opioid treated subjects.
- Penalty:
- 0
- Liverpool Interaction Status:
- Green/Low: No Interaction Expected (Very Low Quality of Evidence)
- Liverpool Notes:
- Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Buprenorphine undergoes both N-dealkylation to form norbuprenorphine (via CYP3A4) and glucuronidation (via UGT2B7 and UGT1A1). Norbuprenorphine, an active metabolite, can further undergo glucuronidation (via UGT1A3 and UGT1A1).
- Penalty:
- 0
- Liverpool Interaction Status:
- Green/Low: No Interaction Expected (Low Quality of Evidence)
- Liverpool Notes:
- Coadministration of buprenorphine (14-16 mg once daily, stable dose with naloxone) and didanosine enteric-coated formulation (400 mg once daily) was studied in 10 opioid-dependent patients and values compared to 10 matched controls receiving didanosine alone. Coadministration had no significant effect on the pharmacokinetics of buprenorphine (AUC and Cmin decreased by ~5% and ~4%, Cmax was unchanged) and its metabolites (norbuprenorphine AUC was unchanged, Cmax decreased by~5% and Cmin increased ~9%; buprenorphine-3-glucuronide AUC and Cmin decreased by ~6% and ~8%, Cmax increased ~3%; norbuprenorphine-3-glucuronide AUC was unchanged, Cmax and Cmin increased by ~8% and ~9%). No subjects showed evidence of opiate withdrawal symptoms. There was no effect on the disposition of didanosine except for a modest decrease in Cmax that was not statistically significant and concentrations of didanosine remained in the therapeutic range during coadministration. The authors conclude that standard doses of didanosine may be safely given with standard buprenorphine/naloxone treatment. Interactions between buprenorphine and antiretrovirals: nucleos(t)ide reverse transcriptase inhibitors (NRTI) didanosine, lamivudine, and tenofovir. Baker J, Rainey P, Moody D, et al. Am J Addict, 2010, 19(1): 17-29., Summary:The interaction between buprenorphine and didanosine was investigated in 10 HIV-negative, buprenorphine/naloxone maintained subjects. When compared to values obtained from control subjects not receiving buprenorphine, no significant changes in buprenorphine pharmacokinetics were observed. When compared to controls, buprenorphine had no statistically significant effect on NRTI concentrations.
- Penalty:
- 0.75
- HIV-ASSIST Notes:
- Decrease in AUC of buprenorphine by 50%. No dosage adjustments recommended. Monitor for withdrawal symptoms.
- Liverpool Interaction Status:
- Amber/Moderate: Interaction Expected (High Quality of Evidence)
- Liverpool Notes:
- Coadministration of buprenorphine/naloxone and efavirenz decreased the AUC of buprenorphine by 50% and that of norbuprenorphine by 71%. There was no clinically significant interaction for efavirenz. Despite the decrease in buprenorphine exposure, no patients exhibited withdrawal symptoms. Dose adjustment of buprenorphine or efavirenz may not be necessary when co-administered.Sustiva Summary of Product Characteristics, Bristol-Myers Squibb Pharmaceuticals Ltd, April 2015. Coadministration of efavirenz (600 mg once daily for 15 days) and buprenorphine was studied in 10 HIV-, opioid-dependent individuals who had been stable for at least 2 weeks on sublingual buprenorphine/naloxone (16/4 to 20/5 mg daily). Healthy control participants were used to determine the effect of buprenorphine on efavirenz. Efavirenz decreased the buprenorphine AUC by 50% and decreased the AUC of norbuprenorphine by 71%. Despite significant decreases in exposure to buprenorphine and norbuprenorphine, no participants showed evidence of opiate withdrawal symptoms. There was no significant effect on buprenorphine on efavirenz pharmacokinetics when compared to data from the control group. Adjustments of doses of either buprenorphine or efavirenz are not likely to be necessary when these drugs are administered for the treatment of opiate dependence and HIV disease.Interactions between buprenorphine and antiretrovirals. I. The non-nucleoside reverse-transcriptase inhibitors efavirenz and delavirdine. McCance-Katz EF, Moody DE, Morse GD, et al. Clin Infect Dis, 2006, 43 (Suppl 4): S224-234., Summary:Coadministration of efavirenz (600 mg once daily) significantly decreased buprenorphine AUC by 50% in HIV- subjects; however, no subject developed an opioid withdrawal syndrome. Efavirenz concentrations remained in the therapeutic range. Dose adjustments are unlikely to be required, but consider monitoring for withdrawal symptoms.
- Penalty:
- 0.75
- HIV-ASSIST Notes:
- Decrease in AUC of buprenorphine by 25%. No dosage adjustments recommended. Monitor for withdrawal symptoms.
- Liverpool Interaction Status:
- Yellow/Moderate-low: Potential Weak Interaction (Low Quality of Evidence)
- Liverpool Notes:
- Etravirine and buprenorphine (or buprenorphine/naloxone) can be co-administered without dose adjustments, however, clinical monitoring for withdrawal symptoms is recommended as buprenorphine (or buprenorphine/naloxone) maintenance therapy may need to be adjusted in some patients. Coadministration of etravirine and buprenorphine (individual buprenorphine/naloxone dose regimens ranging from 4/1 mg to 16/4 mg once daily) was studied in 16 subjects. Buprenorphine Cmax, AUC and Cmin decreased by 11%, 25% and 40%, respectively. Cmax of norbuprenorphine increased by 8%; AUC and Cmin decreased by 12% and 24%.Intelence US Prescribing Information, Janssen Therapeutics, July 2019., Summary:No dose adjustments required, however, clinical monitoring for withdrawal symptoms is recommended. Maintenance therapy may need to be adjusted in some patients. Coadministration decreased buprenorphine Cmax, AUC and Cmin by 11%, 25% and 40%, respectively. Cmax of norbuprenorphine increased by 8%; AUC and Cmin decreased by 12% and 24%.
- Penalty:
- 0
- Liverpool Interaction Status:
- Green/Low: No Interaction Expected (Very Low Quality of Evidence)
- Liverpool Notes:
- Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Buprenorphine undergoes both N-dealkylation to form norbuprenorphine (via CYP3A4) and glucuronidation (via UGT2B7 and UGT1A1). Norbuprenorphine, an active metabolite, can further undergo glucuronidation (via UGT1A3 and UGT1A1).
- Penalty:
- 0.1
- Liverpool Interaction Status:
- Green/Low: No Interaction Expected (Moderate Quality of Evidence)
- Liverpool Notes:
- Coadministration of nevirapine (200 mg daily for 15 days) and buprenorphine was studied in opioid-dependent, buprenorphine/naloxone-maintained, HIV-negative volunteers (n=7). Opiate withdrawal symptoms, cognitive effects, and adverse events were determined prior to and following nevirapine administration. Modest decreases were observed for AUC for buprenorphine (9%) and norbuprenorphine (14%). Clinically significant consequences of the interaction were not observed. Buprenorphine did not alter nevirapine pharmacokinetics. Dose adjustments of either buprenorphine or nevirapine are not likely to be necessary when these drugs are coadministered for the treatment of opiate dependence and HIV disease. Lack of clinically significant drug interactions between nevirapine and buprenorphine. McCance-Katz EF, Moody DE, Morse GD, et al. Am J Addict, 2010, 19(1): 30-7., Summary:Coadministration of nevirapine (200 mg daily for 15 days) to opioid-dependent, buprenorphine/naloxone-maintained, HIV-negative subjects resulted in modest decreases in AUC for buprenorphine (9%) and norbuprenorphine (14%) and had no effect on nevirapine pharmacokinetics. Clinically significant consequences of the interaction were not observed. Dose adjustments of either buprenorphine or nevirapine are unlikely to be necessary.
- Penalty:
- 0
- Liverpool Interaction Status:
- Green/Low: No Interaction Expected (Very Low Quality of Evidence)
- Liverpool Notes:
- Co-administration has not been studied but no effect on buprenorphine is expected. No dose adjustment is required. Pifeltro Summary of Product Characteristics, Merck Sharp & Dohme Ltd, November 2018., Summary:Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Buprenorphine undergoes both N-dealkylation to form norbuprenorphine (via CYP3A4) and glucuronidation (via UGT2B7 and UGT1A1). Norbuprenorphine, an active metabolite, can further undergo glucuronidation (via UGT1A3 and UGT1A1). No interaction is expected with doravirine as it does not inhibit or induce CYP450 or UGT enzymes.
- Penalty:
- 0
- Liverpool Interaction Status:
- Green/Low: No Interaction Expected (Low Quality of Evidence)
- Liverpool Notes:
- Buprenorphine (dosed at 16 mg daily) coadministered with lopinavir/ritonavir (dosed at 400/100 mg twice daily) showed no clinically significant interaction. Kaletra can be coadministered with buprenorphine with no dose adjustment. Kaletra Summary of Product Characteristics, AbbVie Ltd, January 2021. Buprenorphine and naloxone pharmacokinetics before and after 10 days of once daily lopinavir/ritonavir (800/200 mg) were determined in 12 HIV- subjects stable on buprenorphine/naloxone therapy. Lopinavir/ritonavir had no significant effect on buprenorphine AUC (46.9 vs 46.2 ng.h/ml) and Cmax (6.54 vs 5.88 ng/ml). Similarly, there was no significant effect on the AUC of norbuprenorphine (73.7 vs 52.7 ng.h/ml); however, apparent oral clearance of the metabolite significantly increased (4.87 vs 6.79 L/min; P < 0.05) and Cmax significantly decreased (5.29 vs 3.11 ng/ml; P < 0.05) in the presence of lopinavir/ritonavir. There was no effect on naloxone AUC (0.421 vs 0.374 ng.h/ml) or Cmax (0.186 vs 0.186 ng/ml). When compared to historical data, there was no effect of buprenorphine/naloxone on lopinavir AUC or Cmin. The altered norbuprenorphine clearance did not lead to objective opioid withdrawal and therefore buprenorphine/naloxone can be administered with lopinavir/ritonavir without dose modification. Pharmacokinetic interactions between buprenorphine/naloxone and once daily lopinavir/ritonavir. Bruce RD, Altice FL, Moody DE, et al. J Acquir Immune Defic Syndr, 2010, 54(5): 511-514. The effect of lopinavir (400/100 mg twice daily) on the pharmacokinetics of buprenorphine (16 mg daily in combination with naloxone) was examined in 10 HIV-subjects. There were no significant changes in buprenorphine AUC, Cmax or Cmin when given with lopinavir/ritonavir, and coadministration was not associated with opiate withdrawal symptoms. When compared with data from a control group receiving lopinavir/ritonavir alone (n=15), buprenorphine increased lopinavir AUC by ~15%, with no significant change in Cmax or Cmin. Interactions between buprenorphine and antiretrovirals. II. The protease inhibitors nelfinavir, lopinavir/ritonavir, and ritonavir. McCance-Katz EF, Moody DE, Smith PF, et al. Clin Infect Dis, 2006, 43 (Suppl 4): S235-246. , Summary:Coadministration had no significant effect on the pharmacokinetics of buprenorphine and did not result in opiate withdrawal symptoms. When compared to control data, buprenorphine increased lopinavir AUC by 15%, but had no effect on Cmax or Cmin. Lopinavir/ritonavir can be coadministered with buprenorphine with no dose adjustment.
- Penalty:
- 0.75
- HIV-ASSIST Notes:
- Decrease in AUC of norbuprenorphine when used with FPVr. No dosage adjustment necessary. Clinical monitoring recommended.
- Liverpool Interaction Status:
- Green/Low: No Interaction Expected (Moderate Quality of Evidence)
- Liverpool Notes:
- The pharmacokinetics of buprenorphine and its metabolites were detemined in opioid-dependent, buprenorphine-naloxone-maintained, HIV-negative volunteers (n=10) before and after 15 days of fosamprenavir/ritonavir (1400/200 mg once daily) administration. Amprenavir pharmacokinetics and adverse effects were compared between the buprenorphine-maintained participants and a control group of non-opioid-dependent subjects who received fosamprenavir/ritonavir (1400/200 mg once daily) alone. Fosamprenavir-ritonavir did not significantly affect the pharmacokinetics of buprenorphine or norbuprenorphine, but did significantly increase the AUC of the inactive buprenorphine-3-glucuronide. No buprenorphine related side effects or withdrawal symptoms were observed. Buprenorphine-naloxone had no significant effects on the pharmacokinetics of amprenavir with concentrations remaining within the therapeutic range during buprenorphine-naloxone treatment. Dose adjustments are not likely to be necessary when buprenorphine and fosamprenavir/ritonavir are coadministered.Interactions between buprenorphine and the protease inhibitors darunavir-ritonavir and fosamprenavir-ritonavir. Gruber VA, Rainey PM, Moody DE, et al. Clin Infect Dis, 2012, 54(3): 414-23. , Summary:Coadministration of buprenorphine and fosamprenavir/ritonavir (1400/200 mg once daily) did not result in significant pharmacokinetics changes for any of the drugs and did not produce buprenorphine related side effects or withdrawal symptoms. Coadministration with fosamprenavir/ritonavir is unlikely to require a dose adjustment for buprenorphine.
- Penalty:
- 0.75
- HIV-ASSIST Notes:
- Decrease in AUC of norbuprenorphine when used with TPVr. Consider monitoring TPV level. Clinical monitoring recommended.
- Liverpool Interaction Status:
- Amber/Moderate: Interaction Expected (Low Quality of Evidence)
- Liverpool Notes:
- Coadministration had no effect on buprenorphine pharmacokinetics, but decreased the AUC, Cmax and Cmin of norbuprenorphine by 79%, 80% and 80%. Due to reduction in the levels of the active metabolite norbuprenorphine, co-administration of tipranavir, co-administered with low dose ritonavir, and buprenorphine/naloxone may result in decreased clinical efficacy of buprenorphine. Therefore, patients should be monitored for opiate withdrawal syndrome. Aptivus Summary of Product Characteristics, Boehringer Ingelheim Ltd, July 2020. Coadministration of buprenorphine/naloxone (16/4-24/6 mg daily) and tipranavir/ritonavir (500/200 mg twice daily) was studied in 10 subjects. Buprenorphine Cmax, AUC and Cmin decreased by 14%, 1% and 6%. Tipranavir/ritonavir did not result in changes in the clinical efficacy of buprenorphine/naloxone. Compared to historical controls tipranavir Cmin was decreased approximately 40% with this combination. Dose adjustments cannot be recommended.Aptivus Prescribing Information, Boehringer Ingelheim, June 2020. The effect of tipranavir/ritonavir (500/200 mg twice daily) on the pharmacokinetics of buprenorphine and naloxone was assessed in HIV- subjects stable on buprenorphine/naloxone therapy. Coadministration had no effect (<6%) on buprenorphine AUC or Cmin, but decreased Cmax by 14%. The AUC, Cmax and Cmin of norbuprenorphine (the major metabolite) decreased by ~80%. The AUC, Cmax and Cmin of naloxone decreased by 44%, 36% and 20%, respectively. Despite these changes, there was no evidence of opioid withdrawal and no need to modify the dose of buprenorphine. When compared to historical data, there was no effect (<6%) on tipranavir Cmax, but AUC and Cmin decreased by 26% and 39%, respectively. Ritonavir Cmin was similar to historical data, but AUC decreased by 35% and Cmax decreased by 40-50%. The mechanism by which buprenorphine/naloxone affects tipranavir and ritonavir is unclear. Caution should be used if coadministered as tipranavir may be less effective due to decreased concentrations. Pharmacokinetic interactions between buprenorphine/naloxone and tipranavir/ritonavir in HIV-negative subjects chronically receiving buprenorphine/naloxone. Bruce R, Altice F, Moody D, et al. 48th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, October 2008, abstract A-967a., Summary:Coadministration of tipranavir/ritonavir (500/200 mg twice daily) and buprenorphine/naloxone had no effect (<6%) on buprenorphine AUC or Cmin, but decreased Cmax by 14%. The AUC, Cmax and Cmin of norbuprenorphine (the major metabolite) decreased by ~80%. The AUC, Cmax and Cmin of naloxone decreased by 44%, 36% and 20%, respectively. There was no evidence of opioid withdrawal and no need to modify the dose of buprenorphine. When compared to historical data, there was no effect (<6%) on tipranavir Cmax, but AUC and Cmin decreased by 26% and 39%, respectively. Ritonavir Cmin was similar to historical data, but AUC decreased by 35% and Cmax decreased by 40-50%. Caution should be used as tipranavir may be less effective due to decreased concentrations. Patients should be monitored for signs of opioid withdrawal.
- Penalty:
- 0
- Penalty:
- 0
- Liverpool Interaction Status:
- Amber/Moderate: Interaction Expected (Very Low Quality of Evidence)
- Liverpool Notes:
- Although no data from clinical trials are available (other than with ketoconazole), the use of inhibitors of CYP3A4, (e.g. ritonavir, indinavir and saquinavir) may increase exposure levels to buprenorphine and norbuprenorphine to similar degree as seen with ketoconazole and a similar dose-reduction should be considered when initiating treatment. An interaction study of buprenorphine with ketoconazole (a potent inhibitor of CYP3A4) resulted in increased Cmax and AUC of buprenorphine (approximately 70% and 50% respectively) and, to a lesser extent, of the metabolite, norbuprenorphine. Patients receiving buprenorphine should be closely monitored and the dose of buprenorphine should be halved when starting treatment with ketoconazole. Further titration of buprenorphine should be made as clinically indicated. Subutex Summary of Product Characteristics, Schering Plough Ltd, March 2008. Subjects receiving buprenorphine should be closely monitored and may require dose-reduction if inhibitors of CYP 3A4 such as HIV protease inhibitors (e.g. ritonavir, indinavir and saquinavir) are co-administered. A pharmacokinetic interaction study of ketoconazole (400 mg/day), a potent inhibitor of CYP 3A4, in 12 patients stabilized on buprenorphine (8 mg, n=1; 12 mg, n=5; 16 mg, n=6) resulted in increases in buprenorphine mean Cmax values (from 4.3 to 9.8, 6.3 to 14.4 and 9.0 to 17.1) and mean AUC values (from 30.9 to 46.9, 41.9 to 83.2 and 52.3 to 120) respectively. Subutex Prescribing Information, Reckitt Benckiser Pharmaceuticals Inc, September 2006., Summary:Coadministration may increase buprenorphine and norbuprenorphine concentrations and dose reduction may be required. Patients receiving buprenorphine should be closely monitored and the dose of buprenorphine should be halved when starting treatment; further titration of buprenorphine should be made as clinically indicated.
- Penalty:
- 0
- Penalty:
- 0.75
- HIV-ASSIST Notes:
- When used with unboosted ATV, increase in AUC of buprenorphine by 93%. AUC of norbuprenorphine increases by 76%. Possible decrease in ATV. Do not coadminister with unboosted ATV. Similar effects with ATVr. Monitor for sedation. Buprenorphine dose reduction may be necessary. Effects unknown with ATVc. Titrate buprenorphine dose using the lowest initial dose. Dose adjustment of buprenorphine may be needed. Clinical monitoring is recommended.
- Liverpool Interaction Status:
- Amber/Moderate: Interaction Expected (Low Quality of Evidence)
- Liverpool Notes:
- Coadministration of buprenorphine (stable maintenance dose, once daily) with atazanavir/ritonavir (300 mg/100 mg, once daily) was studied in healthy volunteers. Buprenorphine AUC, Cmax and Cmin increased 67%, 37% and 69%, respectively. Norbuprenorphine (active metabolite) AUC, Cmax and Cmin increased 105%, 61% and 101%, respectively. The mechanism of interaction is CYP3A4 and UGT1A1 inhibition. Concentrations of atazanavir (when given with ritonavir) were not significantly affected. Coadministration with Reyataz with ritonavir warrants clinical monitoring for sedation and cognitive effects. A dose reduction of buprenorphine may be considered. Coadministration of Reyataz without ritonavir is not recommended with buprenorphine. Reyataz Summary of Product Characteristics, Bristol-Myers Squibb Pharmaceuticals Ltd, October 2018. Coadministration of buprenorphine and Reyataz with or without ritonavir increases the plasma concentration of buprenorphine and norbuprenorphine. Coadministration of Reyataz plus ritonavir with buprenorphine warrants clinical monitoring for sedation and cognitive effects. A dose reduction of buprenorphine may be considered. Coadministration of buprenorphine and Reyataz with ritonavir is not expected to decrease atazanavir plasma concentrations. Coadministration of buprenorphine and Reyataz without ritonavir may decrease atazanavir plasma concentrations. The coadministration of Reyataz and buprenorphine without ritonavir is not recommended. Reyataz US Prescribing Information, Bristol-Myers Squibb Company, March 2018. The interaction between buprenorphine and atazanavir (400 mg once daily) or atazanavir/ritonavir (300/100 mg once daily) was investigated in opioid-dependent, buprenorphine/naloxone-maintained, HIV-negative volunteers. Pharmacokinetics of atazanavir and atazanavir/ritonavir were compared in subjects and matched, healthy controls (n=10 per group) to determine the effects of buprenorphine. When coadministered with atazanavir, buprenorphine AUC increased from 39.5 to 76.3 ng.h/ml; a similar increase was observed when coadministered with atazanavir/ritonavir (46.2 to 77.0 ng.h/ml). Concentrations of norbuprenorphine, buprenorphine glucuronide, and norbuprenorphine glucuronide also increased with both atazanavir and atazanavir/ritonavir. Buprenorphine did not significantly alter atazanavir or ritonavir concentrations. Three buprenorphine/naloxone-maintained participants reported increased sedation with atazanavir/ritonavir. A decreased buprenorphine dose may be required. Interaction between buprenorphine and atazanavir or atazanavir/ritonavir. McCance-Katz EF, Moody DE, Morse GD et al. Drug Alcohol Depend, 2007, 91(2-3): 269-278. Three case reports have recently been published on a pharmacokinetic interaction between buprenorphine and ritonavir-boosted atazanavir. The first subject had been titrated to a stable dose of buprenorphine 14 mg/day prior to the commencement of ddI (250 mg), tenofovir (300 mg) and atazanavir/ritonavir (300/100 mg), all given once daily. The next day the subject began to experience daytime somnolence and decreased mental functioning. After two weeks, during which the subject was offered additional counselling, buprenorphine was decreased to 8 mg/day and this resulted in tolerance to the sedative effects after 7 days. The subject was finally stabilised on buprenorphine 10 mg/day. The second subject was stable on once daily ddI (250 mg), tenofovir (300 mg), atazanavir/ritonavir (300/100 mg) and twice daily olanzapine (5 mg) prior to induction with buprenorphine (8 mg/day). On the second day of induction, the subject reported feeling “doped up“, and required a dose reduction of buprenorphine to 8 mg every other day to improve the feelings of opiate excess. The third subject had been receiving lamivudine (300 mg), tenofovir (300 mg) and atazanavir/ritonavir (300/100 mg) once daily prior to the initiation of buprenorphine (8 mg/day). Following the commencement of buprenorphine, the subject reported feeling dizzy, “high“ and “over-medicated“. Buprenorphine was reduced to 8 mg every other day; however, though this improved the dizziness the corresponding opiate cravings required dose modification to 8 mg daily and a further dose increase to 12 mg daily. At this dose, the subject experienced hypersomnolence but elected to remain on the higher dose as it suppressed the opiate craving. Tolerance developed over a week and the hypersomnolence gradually ceased. Phase I metabolism of buprenorphine is primarily by CYP3A4 to norbuprenorphine, with phase II metabolism being mainly through glucuronidation. The authors postulate that atazanavir and/or ritonavir inhibited CYP3A4-mediated metabolism, with atazanavir having an additional inhibitory effect on glucuronidation, resulting in increased concentrations of buprenorphine and clinical symptoms of opiate excess. They recommend caution if using buprenorphine with atazanavir or ritonavir and suggest beginning with reduced doses of buprenorphine and slower dose escalation to allow for assessment of opiate excess. Three case reports of a clinical pharmacokinetic interaction with buprenorphine and atazanavir plus ritonavir. Bruce RD, Altice FL. AIDS, 2006, 20: 783-784., Summary:Coadministration of atazanavir/ritonavir (300/100 mg once daily) and buprenorphine (stable maintenance dose, once daily) increased buprenorphine AUC, Cmax and Cmin by 67%, 37% and 69%, respectively; norbuprenorphine increased by ~2-fold. If coadministered, monitor for sedation and cognitive effects and consider a dose reduction of buprenorphine. There are three case reports of clinical symptoms of opiate excess during coadministration which required dose reduction of buprenorphine.
- Penalty:
- 0.75
- HIV-ASSIST Notes:
- When used with unboosted ATV, increase in AUC of buprenorphine by 93%. AUC of norbuprenorphine increases by 76%. Possible decrease in ATV. Do not coadminister with unboosted ATV. Similar effects with ATVr. Monitor for sedation. Buprenorphine dose reduction may be necessary. Effects unknown with ATVc. Titrate buprenorphine dose using the lowest initial dose. Dose adjustment of buprenorphine may be needed. Clinical monitoring is recommended.
- Liverpool Interaction Status:
- Amber/Moderate: Interaction Expected (Very Low Quality of Evidence)
- Liverpool Notes:
- Coadministration warrants clinical monitoring for sedation and cognitive effects. A dose reduction of buprenorphine may be considered. Coadministration of buprenorphine (stable maintenance dose, once daily) and atazanavir/ritonavir (300/100 mg once daily) increased buprenorphine AUC, Cmax and Cmin by 67%, 37% and 69%, respectively. Norbuprenorphine (active metabolite) AUC, Cmax and Cmin increased by 105%, 61% and 101%, respectively. The mechanism of interaction is CYP3A4 and UGT1A1 inhibition by atazanavir. Concentrations of atazanavir were not significantly affected. Coadministration of buprenorphine/naloxone and cobicistat increased buprenorphine AUC, Cmax and Cmin by 35%, 66% and 12%, respectively; naloxone AUC and Cmax both decreased 28%. The mechanism of interaction is CYP3A4 inhibition by cobicistat. Evotaz Summary of Product Characteristics, Bristol-Myers Squibb Pharmaceuticals Ltd, November 2018. Effects of coadministration on buprenorphine concentrations are unknown. Initiation of buprenorphine in patients taking Evotaz: carefully titrate the dose of buprenorphine to the desired effect; use the lowest feasible initial or maintenance dose. Initiation of Evotaz in patients taking buprenorphine: a dose adjustment for buprenorphine may be needed. Monitor clinical signs and symptoms. Evotaz US Prescribing Information Bristol-Myers Squibb Company, March 2018., Summary:Coadministration has not been studied. Atazanavir/ritonavir increased buprenorphine AUC by 67% and Cmin by 69%; norbuprenorphine increased by ~2-fold. Similarly, atazanavir/cobicistat is expected to increase buprenorphine concentrations. Coadministration warrants clinical monitoring for sedation and cognitive effects. A dose reduction of buprenorphine may be considered.
- Penalty:
- 0.75
- HIV-ASSIST Notes:
- When used with unboosted ATV, increase in AUC of buprenorphine by 93%. AUC of norbuprenorphine increases by 76%. Possible decrease in ATV. Do not coadminister with unboosted ATV. Similar effects with ATVr. Monitor for sedation. Buprenorphine dose reduction may be necessary. Effects unknown with ATVc. Titrate buprenorphine dose using the lowest initial dose. Dose adjustment of buprenorphine may be needed. Clinical monitoring is recommended.
- Liverpool Interaction Status:
- Amber/Moderate: Interaction Expected (Very Low Quality of Evidence)
- Liverpool Notes:
- Coadministration of buprenorphine (stable maintenance dose, once daily) with atazanavir/ritonavir (300 mg/100 mg, once daily) was studied in healthy volunteers. Buprenorphine AUC, Cmax and Cmin increased 67%, 37% and 69%, respectively. Norbuprenorphine (active metabolite) AUC, Cmax and Cmin increased 105%, 61% and 101%, respectively. The mechanism of interaction is CYP3A4 and UGT1A1 inhibition. Concentrations of atazanavir (when given with ritonavir) were not significantly affected. Coadministration with Reyataz with ritonavir warrants clinical monitoring for sedation and cognitive effects. A dose reduction of buprenorphine may be considered. Coadministration of Reyataz without ritonavir is not recommended with buprenorphine. Reyataz Summary of Product Characteristics, Bristol-Myers Squibb Pharmaceuticals Ltd, October 2018. Coadministration of buprenorphine and Reyataz with or without ritonavir increases the plasma concentration of buprenorphine and norbuprenorphine. Coadministration of Reyataz plus ritonavir with buprenorphine warrants clinical monitoring for sedation and cognitive effects. A dose reduction of buprenorphine may be considered. Coadministration of buprenorphine and Reyataz with ritonavir is not expected to decrease atazanavir plasma concentrations. Coadministration of buprenorphine and Reyataz without ritonavir may decrease atazanavir plasma concentrations. The coadministration of Reyataz and buprenorphine without ritonavir is not recommended. Reyataz US Prescribing Information, Bristol-Myers Squibb Company, March 2018., Summary:Coadministration has not been studied, but is expected to increase buprenorphine plasma concentrations. Coadministration of atazanavir/ritonavir (300/100 mg once daily) and buprenorphine (stable maintenance dose, once daily) increased buprenorphine AUC, Cmax and Cmin by 67%, 37% and 69%, respectively; norbuprenorphine increased by ~2-fold. Similarly, unboosted atazanavir is expected to increase buprenorphine exposure. Coadministration warrants clinical monitoring for sedation and cognitive effects. A dose reduction of buprenorphine may be considered.
- Penalty:
- 0.75
- HIV-ASSIST Notes:
- When used with DRVr, increase in AUC of norbuprenorphine by 46% and Cmin by 71%. No dose adjustment necessary. Clinical monitoring is recommended. Effects unknown with DRVc. Titrate buprenorphine dose using the lowest initial dose. Dose adjustment of buprenorphine may be needed. Clinical monitoring is recommended.
- Liverpool Interaction Status:
- Amber/Moderate: Interaction Expected (Moderate Quality of Evidence)
- Liverpool Notes:
- Coadministration of buprenorphine/naloxone (8/2 mg to 16/4 mg once daily) and darunavir/ritonavir decreased buprenorphine AUC and Cmax by 11% and 8%, respectively, with no change in Cmin. AUC, Cmax and Cmin of norbuprenorphine increased by 46%, 36% and 71%, respectively. There was no change in naloxone AUC or Cmax. The clinical relevance of the increase in norbuprenorphine pharmacokinetic parameters has not been established. Dose adjustment for buprenorphine may not be necessary when coadministered with boosted darunavir but a careful clinical monitoring for signs of opiate toxicity is recommended. Prezista Summary of Product Characteristics, Janssen-Cilag Ltd, September 2022. Coadministration of buprenorphine/naloxone (8/2 to 16/4 mg once daily) and darunavir/ritonavir (600/100 mg twice daily) decreased buprenorphine AUC, Cmax and Cmin by 11%, 8% and 2% respectively. AUC, Cmax and Cmin of norbuprenorphine increased by 46%, 36% and 71%, respectively. Naloxone AUC and Cmax were comparable when buprenorphine/naloxone was administered with or without darunavir/ritonavir. No dose adjustment for buprenorphine or buprenorphine/naloxone is required with concurrent administration of darunavir/ritonavir. Clinical monitoring is recommended if darunavir/ritonavir and buprenorphine or buprenorphine/naloxone are coadministered. Prezista Prescribing Information, Janssen Pharmaceuticals Inc, March 2023. The pharmacokinetics of buprenorphine and its metabolites were determined in opioid-dependent, buprenorphine-naloxone-maintained, HIV-negative volunteers (n=11) before and after 15 days of darunavir/ritonavir (800/100 mg once daily) administration. Darunavir pharmacokinetics and adverse effects were compared between the buprenorphine-maintained participants and a control group of non-opioid-dependent subjects who received darunavir/ritonavir (800/100 mg once daily) alone. Darunavir/ritonavir produced no significant changes in the pharmacokinetics of buprenorphine or norbuprenorphine. For the inactive buprenorphine-3-glucuronide, AUC and Cmax increased and CL/F decreased significantly. No buprenorphine related side effects or withdrawal symptoms were observed. Buprenorphine-naloxone had no significant effects on the pharmacokinetics of darunavir with concentrations remaining within the therapeutic range during buprenorphine-naloxone treatment. Dose adjustments are not likely to be necessary when buprenorphine and darunavir/ritonavir are coadministered. Interactions between buprenorphine and the protease inhibitors darunavir-ritonavir and fosamprenavir-ritonavir. Gruber VA, Rainey PM, Moody DE, et al. Clin Infect Dis, 2012, 54(3): 414-23. The effect of darunavir/ritonavir (600/100 mg twice daily for 7 days) on the pharmacokinetics of buprenorphine was assessed in 17 HIV- subjects stable on buprenorphine/naloxone maintenance therapy (daily doses up to 24/6 mg). There was no effect on buprenorphine AUC, Cmax or trough concentrations; however, norbuprenorphine Cmax increased by 36% and AUC increased by 46%. No subject required dose adjustment of buprenorphine/naloxone. Given the increase in norbuprenorphine concentrations, close clinical monitoring of patients is recommended. Pharmacokinetic interaction between darunavir in combination with low-dose ritonavir and buprenorphine/naloxone. Sekar VJ, Tomaka F, Meyvisch P, et al. 49th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, September 2009, abstract H-232., Summary:Coadministration of buprenorphine/naloxone and twice daily darunavir/ritonavir had no significant effect on buprenorphine or naloxone, but increased concentrations of norbuprenorphine. Coadministration with once daily darunavir/ritonavir produced no significant changes in the pharmacokinetics of buprenorphine or norbuprenorphine, but increased concentrations of the inactive buprenorphine-3-glucuronide. The clinical relevance of the increase in norbuprenorphine concentrations has not been established. Dose adjustment for buprenorphine may not be necessary but careful clinical monitoring for opiate toxicity is recommended.
- Penalty:
- 0.75
- HIV-ASSIST Notes:
- When used with DRVr, increase in AUC of norbuprenorphine by 46% and Cmin by 71%. No dose adjustment necessary. Clinical monitoring is recommended. Effects unknown with DRVc. Titrate buprenorphine dose using the lowest initial dose. Dose adjustment of buprenorphine may be needed. Clinical monitoring is recommended.
- Liverpool Interaction Status:
- Amber/Moderate: Interaction Expected (Moderate Quality of Evidence)
- Liverpool Notes:
- Coadministration of buprenorphine/naloxone (8/2 mg to 16/4 mg once daily) and darunavir/ritonavir decreased buprenorphine AUC and Cmax by 11% and 8%, respectively, with no change in Cmin. AUC, Cmax and Cmin of norbuprenorphine increased by 46%, 36% and 71%, respectively. There was no change in naloxone AUC or Cmax. The clinical relevance of the increase in norbuprenorphine pharmacokinetic parameters has not been established. Dose adjustment for buprenorphine may not be necessary when coadministered with boosted darunavir but a careful clinical monitoring for signs of opiate toxicity is recommended. Prezista Summary of Product Characteristics, Janssen-Cilag Ltd, September 2022. Coadministration of buprenorphine/naloxone (8/2 to 16/4 mg once daily) and darunavir/ritonavir (600/100 mg twice daily) decreased buprenorphine AUC, Cmax and Cmin by 11%, 8% and 2% respectively. AUC, Cmax and Cmin of norbuprenorphine increased by 46%, 36% and 71%, respectively. Naloxone AUC and Cmax were comparable when buprenorphine/naloxone was administered with or without darunavir/ritonavir. No dose adjustment for buprenorphine or buprenorphine/naloxone is required with concurrent administration of darunavir/ritonavir. Clinical monitoring is recommended if darunavir/ritonavir and buprenorphine or buprenorphine/naloxone are coadministered. Prezista Prescribing Information, Janssen Pharmaceuticals Inc, March 2023. The pharmacokinetics of buprenorphine and its metabolites were determined in opioid-dependent, buprenorphine-naloxone-maintained, HIV-negative volunteers (n=11) before and after 15 days of darunavir/ritonavir (800/100 mg once daily) administration. Darunavir pharmacokinetics and adverse effects were compared between the buprenorphine-maintained participants and a control group of non-opioid-dependent subjects who received darunavir/ritonavir (800/100 mg once daily) alone. Darunavir/ritonavir produced no significant changes in the pharmacokinetics of buprenorphine or norbuprenorphine. For the inactive buprenorphine-3-glucuronide, AUC and Cmax increased and CL/F decreased significantly. No buprenorphine related side effects or withdrawal symptoms were observed. Buprenorphine-naloxone had no significant effects on the pharmacokinetics of darunavir with concentrations remaining within the therapeutic range during buprenorphine-naloxone treatment. Dose adjustments are not likely to be necessary when buprenorphine and darunavir/ritonavir are coadministered. Interactions between buprenorphine and the protease inhibitors darunavir-ritonavir and fosamprenavir-ritonavir. Gruber VA, Rainey PM, Moody DE, et al. Clin Infect Dis, 2012, 54(3): 414-23. The effect of darunavir/ritonavir (600/100 mg twice daily for 7 days) on the pharmacokinetics of buprenorphine was assessed in 17 HIV- subjects stable on buprenorphine/naloxone maintenance therapy (daily doses up to 24/6 mg). There was no effect on buprenorphine AUC, Cmax or trough concentrations; however, norbuprenorphine Cmax increased by 36% and AUC increased by 46%. No subject required dose adjustment of buprenorphine/naloxone. Given the increase in norbuprenorphine concentrations, close clinical monitoring of patients is recommended. Pharmacokinetic interaction between darunavir in combination with low-dose ritonavir and buprenorphine/naloxone. Sekar VJ, Tomaka F, Meyvisch P, et al. 49th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, September 2009, abstract H-232., Summary:Coadministration of buprenorphine/naloxone and twice daily darunavir/ritonavir had no significant effect on buprenorphine or naloxone, but increased concentrations of norbuprenorphine. Coadministration with once daily darunavir/ritonavir produced no significant changes in the pharmacokinetics of buprenorphine or norbuprenorphine, but increased concentrations of the inactive buprenorphine-3-glucuronide. The clinical relevance of the increase in norbuprenorphine concentrations has not been established. Dose adjustment for buprenorphine may not be necessary but careful clinical monitoring for opiate toxicity is recommended.
- Penalty:
- 0.75
- HIV-ASSIST Notes:
- When used with DRVr, increase in AUC of norbuprenorphine by 46% and Cmin by 71%. No dose adjustment necessary. Clinical monitoring is recommended. Effects unknown with DRVc. Titrate buprenorphine dose using the lowest initial dose. Dose adjustment of buprenorphine may be needed. Clinical monitoring is recommended.
- Liverpool Interaction Status:
- Yellow/Moderate-low: Potential Weak Interaction (Very Low Quality of Evidence)
- Liverpool Notes:
- Based on theoretical considerations darunavir/cobicistat may increase buprenorphine and/or norbuprenorphine plasma concentrations. Dose adjustment for buprenorphine may not be necessary when co-administered with darunavir/cobicistat but a careful clinical monitoring for signs of opiate toxicity is recommended. Rezolsta Summary of Product Characteristics, Janssen-Cilag Ltd, July 2023. The effect of coadministration on concentrations of buprenorphine and naloxone is unknown. Initiation of buprenorphine or buprenorphine/naloxone in patients taking darunavir/cobicistat: carefully titrate the dose of buprenorphine or buprenorphine/naloxone to the desired effect; use the lowest feasible initial or maintenance dose. Initiation of darunavir/cobicistat in patients taking buprenorphine or buprenorphine/naloxone: a dose adjustment for buprenorphine or buprenorphine/naloxone may be needed. Monitor clinical signs and symptoms. Prezcobix US Prescribing Information, Janssen Pharmaceuticals Inc, March 2023., Summary:Coadministration has not been studied. Based on theoretical considerations, darunavir/cobicistat may increase buprenorphine and/or norbuprenorphine plasma concentrations. Dose adjustment for buprenorphine may not be necessary when coadministered with darunavir/cobicistat, but careful clinical monitoring for signs of opiate toxicity is recommended.
- Penalty:
- 0
- Liverpool Interaction Status:
- Green/Low: No Interaction Expected (Low Quality of Evidence)
- Liverpool Notes:
- Coadministration of buprenorphine/naloxone (16/4 mg, n= 9; 24/6 mg, n=2; 32/8 mg, n=1; all once daily) with raltegravir (400 mg, twice daily) was studied in HIV negative opioid-dependent patients in a cross-over trial. AUC and Cmax for buprenorphine, norbuprenorphine and naloxone were all unchanged. Raltegravir AUC and Cmax did not differ to historical controls. The authors conclude that buprenorphine/naloxone can be safely coadministered with raltegravir without dose modification. Pharmacokinetic interactions between buprenorphine/naloxone and raltegravir in subjects receiving chronic buprenorphine/naloxone treatment. Douglas B, Moody D, Chodkowski D et al. Am J Drug Alcohol Abuse, 2013, 39(2): 80-5., Summary:Coadministration of buprenorphine/naloxone and raltegravir (400 mg twice daily) had no significant effect on the AUC and Cmax of buprenorphine, norbuprenorphine and naloxone. Raltegravir AUC and Cmax did not differ to historical controls. No dose adjustment is required with buprenorphine/naloxone and raltegravir.
- Penalty:
- 0.75
- HIV-ASSIST Notes:
- Increase in AUC of buprenorphine by 35%. No dosage adjustment necessary. Clinical monitoring is recommended.
- Liverpool Interaction Status:
- Green/Low: No Interaction Expected (Very Low Quality of Evidence)
- Liverpool Notes:
- Coadministration of buprenorphine/naloxone (16/4 to 24/6 mg) and elvitegravir/cobicistat (150/150 mg once daily) increased buprenorphine AUC and Cmin by 35%, and 66%, but had no effect on Cmax. Naloxone AUC and Cmax both decreased by 28% and there was no change in the AUC, Cmin and Cmax of cobicistat and elvitegravir. No dose adjustment of buprenorphine/naloxone is required.Genvoya Summary of Product Characteristics, Gilead Sciences International Ltd, November 2021. Coadministration is expected to increase concentrations of buprenorphine and norbuprenorphine, but decrease concentrations of naloxone. No dosage adjustment of buprenorphine/naloxone is required upon coadministration with Genvoya. Patients should be closely monitored for sedation and cognitive effects. Coadministration of buprenorphine (16-24 mg once daily) and naloxone with elvitegravir/cobicistat (150/150 mg once daily) was studied in 17 subjects. Cmax, AUC and Cmin of buprenorphine increased by 12%, 35% and 66%, while those of norbuprenorphine increased by 24%, 42% and 57%, respectively. Naloxone Cmax and AUC both decreased by 28%. Genvoya US Prescribing Information, Gilead Sciences Inc, September 2021., Summary:Coadministration with Genvoya has not been studied. Coadministration of elvitegravir/cobicistat to subjects stable on buprenorphine/naloxone increased buprenorphine AUC, Cmax and Cmin by 35%, 12% and 66%, respectively. Norbuprenorphine AUC, Cmax and Cmin increased by 42%, 24% and 57%. Naloxone AUC and Cmax both decreased by 28% and there was no effect on the AUC, Cmin and Cmax of elvitegravir or cobicistat. No dose adjustment of buprenorphine/naloxone is required. Patients should be closely monitored for sedation and cognitive effects. Based on metabolism and clearance pathways, no interaction is expected between buprenorphine and emtricitabine or tenofovir alafenamide.
- Penalty:
- 0
- Liverpool Interaction Status:
- Green/Low: No Interaction Expected (Very Low Quality of Evidence)
- Liverpool Notes:
- Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Buprenorphine undergoes both N-dealkylation to form norbuprenorphine (via CYP3A4) and glucuronidation (via UGT2B7 and UGT1A1). Norbuprenorphine, an active metabolite, can further undergo glucuronidation (via UGT1A3 and UGT1A1). Dolutegravir is not expected to inhibit or induce CYP450 or UGTs enzymes at clinically relevant concentrations.
- Penalty:
- 0
- Liverpool Interaction Status:
- Green/Low: No Interaction Expected (Very Low Quality of Evidence)
- Liverpool Notes:
- Based on drug interaction studies conducted with Biktarvy or the components of Biktarvy, no clinically significant drug interactions are expected with buprenorphine. Biktarvy Summary of Product Characteristics, Gilead Sciences Ltd, June 2019., Summary:Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Buprenorphine undergoes both N-dealkylation to form norbuprenorphine (via CYP3A4) and glucuronidation (via UGT2B7 and UGT1A1). Bictegravir does not inhibit or induce CYP450 or UGTs enzymes; emtricitabine and tenofovir alafenamide do not interact with buprenorphine’s metabolic pathway.
- Penalty:
- 0
- Liverpool Interaction Status:
- Green/Low: No Interaction Expected (Very Low Quality of Evidence)
- Liverpool Notes:
- Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Buprenorphine is mainly metabolized by CYP3A4 to form the active metabolite norbuprenorphine. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects.
- Penalty:
- 0
- Liverpool Interaction Status:
- Green/Low: No Interaction Expected (Very Low Quality of Evidence)
- Liverpool Notes:
- Coadministration has not been studied, but no interaction expected. Maraviroc 300 mg twice daily and buprenorphine can be coadministered without dose adjustment. Celsentri Summary of Product Characteristics, ViiV Healthcare, September 2018., Summary:Coadministration has not been studied, but no interaction is expected.
- Penalty:
- 0
- Liverpool Interaction Status:
- Green/Low: No Interaction Expected (Very Low Quality of Evidence)
- Liverpool Notes:
- Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. No drug interaction studies have been conducted with ibalizumab: based on ibalizumab’s mechanism of action and target-mediated drug disposition, drug-drug interactions are not expected. Buprenorphine undergoes hepatic metabolism whereas ibalizumab, a monoclonal antibody binding to the CD4 receptor, is likely to be eliminated via intracellular catabolism similarly to other monoclonal antibodies.
- Penalty:
- 0.5
- HIV-ASSIST Notes:
- Buprenorphine and nor-buprenorphine AUC increased 30% and 39%, respectively. Use standard dose per manufacturer, but monitor for increased sedation.
- Liverpool Interaction Status:
- Green/Low: No Interaction Expected (Low Quality of Evidence)
- Liverpool Notes:
- Coadministration increased buprenorphine AUC and Cmax by 30% and 24%. Norbuprenorphine AUC and Cmax increased by 39% and 24%. No dose adjustment is necessary. Rukobia Summary of Product Information, ViiV Healthcare, June 2021. Based on drug interaction study results, buprenorphine/naloxone can be coadministered with fostemsavir without a dose adjustment. Coadministration of buprenorphine/naloxone (8/2 to 24/6 mg once daily) and fostemsavir (600 mg twice daily) was studied in 16 subjects. Buprenorphine Cmax, AUC and C24 increased by 24%, 30% and 39%; norbuprenorphine C24, AUC and Cmin increased by 24%, 39% and 36%. Rukobia US Prescribing Information, ViiV Healthcare, July 2020. The pharmacokinetics of buprenorphine and norbuprenorphine were determined in 16 HIV-negative subjects administered buprenorphine/naloxone alone (8/2 to 24/6 mg once daily, stable dose) or with fostemsavir (600 mg twice daily). Buprenorphine Cmax, AUC and Cmin increased by 24%, 30% and 39%; norbuprenorphine Cmax, AUC and Cmin increased by 24%, 39% and 36%. Standardized assessments of opioid pharmacodynamics were unchanged throughout administration of fostemsavir. Buprenorphine and fostemsavir can be administered without dose adjustments. Methadone and buprenorphine pharmacokinetics and pharmacodynamics when coadministered with fostemsavir to opioid-dependent, human immunodeficiency virus seronegative participants. Moore K, Magee M, Sevinsky H, et al. Br J Clin Pharmacol. 2019;85(8):1771-1780., Summary:Coadministration of fostemsavir (600 mg twice daily) in 16 individuals on stable buprenorphine/naloxone treatment (doses between 8/2 and 24/6 mg once daily) increased Cmax, AUC and C24 of buprenorphine by 24%, 30% and 39% and those of norbuprenorphine by 24%, 39% and 36%. These changes are not considered to be clinically relevant and were not associated with opioid withdrawal effects or with toxicity.
- Penalty:
- 0.25
- Liverpool Interaction Status:
- Yellow/Moderate-low: Potential Weak Interaction (Very Low Quality of Evidence)
- Liverpool Notes:
- The effects of concomitant administration on buprenorphine are unknown. Initiation of buprenorphine in patients taking lenacapavir: Carefully titrate the dose of buprenorphine to the desired effect; use the lowest feasible initial or maintenance dose. Initiation of lenacapavir in patients taking buprenorphine: A dose adjustment for buprenorphine may be needed. Monitor clinical signs and symptoms. Sunlenca Prescribing Information, Gilead Sciences Inc, December 2022., Summary:Coadministration has not been studied. Buprenorphine undergoes both N-dealkylation to form norbuprenorphine (via CYP3A4) and glucuronidation (via UGT2B7 and UGT1A1). Lenacapavir is mainly cleared as unchanged drug. Lenacapavir does not inhibit or induce UGTs in the range of clinically significant concentrations but is a moderate inhibitor of CYP3A4 and could increase buprenorphine concentrations although to a limited extent. Based on drug interaction data with the strong CYP3A4 inhibitor ritonavir, the increase in buprenorphine exposure with lenacapavir is not expected to cause significant pharmacodynamic changes in a population of opioid tolerant patients. Thus, an a priori dose adjustment of buprenorphine is not necessary, but should be guided by clinical monitoring.