emtricitabine and tenofovir alafenamide
Sources réglementaires consultées
Indications approuvées
- Traitement combiné du VIH-1 chez l’adulte et l’adolescent d’au moins 12 ans et 35 kg, avec cette teneur et le troisième agent approprié.
Contre-indications
Absolues
- Hypersensibilité à l’emtricitabine ou au ténofovir alafénamide.
Mises en garde cliniques
- L’arrêt en cas de coinfection VHB peut provoquer une exacerbation sévère ; surveiller la fonction hépatique. — CIMA/AEMPS, ficha técnica 1161099001
- Atteinte rénale, tubulopathie proximale et syndrome de Fanconi ont été rapportés. — CIMA/AEMPS, ficha técnica 1161099001
Interactions médicamenteuses
- SévèreInducteurs P-gp tels que rifampicine, carbamazépine ou millepertuis
Mécanisme: Ils réduisent le ténofovir alafénamide et peuvent entraîner une perte d’efficacité.
Recommandation: L’association n’est pas recommandée.
CIMA/AEMPS, ficha técnica 1161099001
- SévèreProduits contenant emtricitabine, lamivudine, TAF, TDF ou adéfovir
Mécanisme: Ils dupliquent les analogues et peuvent augmenter la toxicité ou compromettre le schéma.
Recommandation: Ne pas les coadministrer ; surveiller la fonction rénale pendant le traitement.
CIMA/AEMPS, ficha técnica 1161099001
Effets indésirables
Communs (≥1%)
Nausées
Rares mais graves
Exacerbation du VHB, insuffisance rénale et syndrome de Fanconi
Grossesse et allaitement
N’utiliser pendant la grossesse que si le bénéfice justifie le risque potentiel. Ne pas allaiter pendant le traitement.
Bibliographie récente (PubMed)
Although single-tablet, oral bictegravir, emtricitabine, and tenofovir alafenamide or dolutegravir and lamivudine are preferred regimens in several major guidelines and are widely used in many countries, they have not been compared in a fully powered trial. This study aimed to prospectively compare the 48-week results of dolutegravir and lamivudine versus bictegravir, emtricitabine, and tenofovir alafenamide as maintenance therapies for people with HIV. PASO-DOBLE is a randomised, multicentre, open-label, non-inferiority trial done over 48 weeks at 30 sites in Spain. Adults (aged ≥18 years) with HIV-1, without previous viral failure, who had reached virological suppression on oral regimens containing at least one pill a day, cobicistat, efavirenz, or tenofovir disoproxil fumarate and no previous use of dolutegravir or bictegravir, and plasma HIV-1 RNA <50 copies per mL for at least 24 weeks were eligible. Participants were randomly assigned (1:1) to switch regimens to dolutegravir 50 mg and lamivudine 300 mg or bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg once daily, using random block permutation, stratified by tenofovir alafenamide presence at baseline and sex assigned at birth. The primary endpoint was the proportion of participants with HIV RNA ≥50 copies per mL at week 48 in the intention-to-treat exposed population (ie, all participants who received at least one dose of study medication). The primary and safety analysis was done in the intention-to-treat exposed population. The non-inferiority margin was 4%. This trial is registered with ClinicalTrials.govNCT04884139 and is incomplete. Between July 14, 2021, and March 24, 2023, 553 participants initiated dolutegravir and lamivudine (n=277) or bictegravir, emtricitabine, and tenofovir alafenamide (n=276). The difference in the proportion of participants with HIV RNA ≥50 copies per mL between the dolutegravir and lamivudine group (six [2%] of 277) and bictegravir, emtricitabine, and t
Cabotegravir plus rilpivirine is the only approved complete long-acting regimen for the maintenance of HIV-1 virological suppression dosed every 2 months. The SOLAR study aimed to compare long-acting cabotegravir plus rilpivirine every 2 months with continued once-daily bictegravir, emtricitabine, and tenofovir alafenamide for the maintenance of HIV-1 virological suppression in adults living with HIV. SOLAR is a randomised, open-label, multicentre, phase 3b, non-inferiority study. The study was done in 118 centres across 14 countries. Participants with HIV-1 RNA less than 50 copies per mL were randomly assigned (2:1), stratified by sex at birth and BMI, to either long-acting cabotegravir (600 mg) plus rilpivirine (900 mg) dosed intramuscularly every 2 months or to continue daily oral bictegravir (50 mg), emtricitabine (200 mg), and tenofovir alafenamide (25 mg). Participants randomly assigned to long-acting therapy had a choice to receive cabotegravir (30 mg) plus rilpivirine (25 mg) once daily as an optional oral lead-in for approximately 1 month. The primary efficacy endpoint was the proportion of participants with virological non-response (HIV-1 RNA ≥50 copies per mL; the US Food and Drug Administration snapshot algorithm, 4% non-inferiority margin; modified intention-to-treat exposed population) at month 11 (long-acting start with injections group) and month 12 (long-acting with oral lead-in group and bictegravir, emtricitabine, and tenofovir alafenamide group). The study is registered with ClinicalTrials.gov, NCT04542070, and is ongoing. 837 participants were screened between Nov 9, 2020, and May 31, 2021, and 687 were randomly assigned to switch treatment or continue existing treatment. Of 670 participants (modified intention-to-treat exposed population), 447 (67%) switched to long-acting therapy (274 [61%] of 447 start with injections; 173 [39%] of 447 with oral lead-in) and 223 (33%) continued bictegravir, emtricitabine, and tenofovir alafenamide. Baseline c
Once-weekly oral islatravir plus lenacapavir (ISL+LEN) has the potential to address adherence challenges with daily HIV-1 treatment. To evaluate efficacy and safety of once-weekly ISL+LEN. Phase 2, randomized, open-label, active-controlled study. (ClinialTrials.gov: NCT05052996). 44 U.S. sites. Adults with HIV-1 RNA viral load of less than 50 copies/mL receiving daily bictegravir, emtricitabine, and tenofovir alafenamide combination (B/F/TAF) for 24 weeks or more. Once-weekly oral ISL, 2 mg, plus LEN, 300 mg, or daily oral B/F/TAF. Proportion with HIV-1 RNA viral load of 50 copies/mL or more at week 24 (primary end point; U.S. Food and Drug Administration Snapshot Algorithm). Secondary end points: proportion of participants with HIV-1 RNA viral load of 50 copies/mL or more (weeks 12 and 48) and HIV-1 RNA viral load of less than 50 copies/mL (weeks 12, 24. and 48), safety, and CD4+ T-cell and lymphocyte count changes (weeks 12, 24, and 48). A total of 104 participants were randomly assigned and treated (n = 52 per group). At week 24, one ISL+LEN participant and no B/F/TAF participants had HIV-1 RNA viral load of 50 copies/mL or more (difference, 1.9% [95% CI, -5.2% to 10.5%]); 94.2% of participants in both groups had HIV-1 RNA viral load of less than 50 copies/mL (difference, 0% [CI, -10.9% to 10.9%]). At week 48, 94.2% and 92.3% of ISL+LEN and B/F/TAF participants, respectively, had HIV-1 RNA viral load of less than 50 copies/mL (difference, 1.9% [CI, -9.3% to 13.6%]); no participant had HIV-1 RNA viral load of 50 copies/mL or more. Two ISL+LEN participants discontinued treatment (before week 24) due to adverse events (AEs) unrelated to the study drug. No AEs that were grade 3 or greater or serious were related to treatment in either group. Changes in CD4+ T-cell and lymphocyte counts from baseline to week 48 were similar between groups, with no discontinuations of study drug treatment due to decreased CD4+ T cells or lymphocytes. Open-label, modest sample size, and
For most adults with HIV-1 and hepatitis B virus (HBV) coinfection, initial recommended treatment is a tenofovir-containing antiretroviral regimen, but no randomised studies have compared tenofovir disoproxil fumarate with tenofovir alafenamide. We aimed to investigate whether bictegravir, emtricitabine, and tenofovir alafenamide is non-inferior to dolutegravir, emtricitabine, and tenofovir disoproxil fumarate for viral suppression in individuals with HIV-1 and HBV coinfection at 48 and 96 weeks. We did this randomised, double-blind, active-controlled, phase 3, non-inferiority trial at 46 outpatient centres in China, Dominican Republic, Hong Kong, Japan, Malaysia, South Korea, Spain, Taiwan, Thailand, Turkey, and the USA. Eligible participants were treatment-naive adults (aged ≥18 years) with plasma HIV-1 RNA of at least 500 copies per mL and plasma HBV DNA of at least 2000 IU/mL. Participants were randomly assigned (1:1) to receive daily oral bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg, or dolutegravir 50 mg, emtricitabine 200 mg, and tenofovir disoproxil fumarate 300 mg, each with corresponding matching placebo. Randomisation was stratified by hepatitis B e antigen (HBeAg) status (positive vs negative), HBV DNA (<8 vs ≥8 log10 IU/mL), and CD4 count (<50 vs ≥50 cells per μL) at screening. All investigators, participants, and staff providing treatment, assessing outcomes, and collecting data were masked to study treatment for 96 weeks. Coprimary endpoints were the proportion of participants with plasma HIV-1 RNA less than 50 copies per mL (defined by the US Food and Drug Administration snapshot algorithm) and plasma HBV DNA less than 29 IU/mL (using the missing-equals-failure approach) at week 48, with a prespecified non-inferiority margin of -12%. Coprimary endpoints were assessed in the full analysis set, which included all randomly assigned participants who received at least one dose of study drug and had at least one post-baseline HI
Crushing or dissolving bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) tablets is not recommended because there are no data supporting this practice. A crossover, randomized trial in healthy adults (NCT04244448) investigated the bioavailability of two off-label uses of BIC/TAF/FTC (50/200/25 mg), dissolved in water or crushed in apple compote, compared with the solid tablet. Pharmacokinetic (PK) parameters were estimated from sequential intensive plasma antiretroviral concentrations over a 72 h period post dose. Bioequivalence was met if the 90% CIs of the geometric least-squares means ratios comparing BIC/TAF/FTC exposures (AUC and Cmax) from the experimental phases were within 80%-125% of the reference. Eighteen subjects participated in each of the three phases. Dissolved tablet Cmax geometric mean ratio (90% CI) for BIC/TAF/FTC was 105% (93-119)/97% (87-108)/96% (74-124), respectively. Dissolved tablet AUC geometric mean ratio (90% CI) for BIC/TAF/FTC was 111% (100-122)/100% (94 to 105)/99% (81 to 120), respectively. Crushed tablet Cmax geometric mean ratio (90%) CI for BIC/TAF/FTC was 110% (97 to 124)/70% (63-78)/66% (51-85), respectively. Crushed tablet AUC geometric mean ratio (90%) CI for BIC/TAF/FTC was 107% (96-118)/86% (82-91)/84% (69-103), respectively. Crushing BIC/TAF/FTC tablets may lead to suboptimal emtricitabine and tenofovir alafenamide drug exposures. Dissolving BIC/TAF/FTC in water may be acceptable if the tablet cannot be swallowed whole.