Tolerability of bictegravir/tenofovir alafenamide/emtricitabine versus dolutegravir/lamivudine as maintenance therapy in a real-life setting.

While both the burden of therapy and the individual drugs in bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) and dolutegravir/lamivudine differ, it is unclear whether their real-life tolerability may be also different. Single-centre, clinical cohort analysis of all virologically suppressed persons with HIV (PWH) who were first prescribed bictegravir as BIC/TAF/FTC or dolutegravir as dolutegravir/lamivudine and had taken ≥1 dose of study medication. Major outcomes were discontinuations either for any reason or due to toxicity. Incidence was calculated as number of episodes per 100 person-years adjusted through propensity score analysis. Relative to persons treated with BIC/TAF/FTC (n = 1231), persons treated with dolutegravir/lamivudine (n = 821) were older and had more AIDS-defining conditions although better HIV control. After a median follow-up of 52 weeks, adjusted incidence rates for discontinuation were 6.68 (95% CI 5.18-8.19) and 8.44 (95% CI 6.29-10.60) episodes per 100 person-years for BIC/TAF/FTC and dolutegravir/lamivudine, respectively; adjusted incidence rate ratio for dolutegravir/lamivudine was 1.26 (95% CI 0.89-1.78) relative to BIC/TAF/FTC (P = 0.1847). Adjusted incidence rates for discontinuation due to toxicity were 3.88 (95% CI 2.70-5.06) and 4.62 (95% CI 3.05-6.19) episodes per 100 person-years for BIC/TAF/FTC and dolutegravir/lamivudine, respectively; adjusted incidence rate ratio for dolutegravir/lamivudine was 1.19 (95% CI 0.75-1.90) relative to BIC/TAF/FTC (P = 0. 4620). Adverse events leading to discontinuation were neuropsychiatric (n = 42; 2%), followed by gastrointestinal (n = 23; 1%), dermatological (n = 15; 1%) and weight increase (n = 15; 1%), without differences between regimens. Switching to BIC/TAF/FTC or dolutegravir/lamivudine showed no difference in the risks of overall or toxicity-related discontinuations or in the profile of adverse events leading to discontinuation.

Rocabert A ，Borjabad B ，Berrocal L ，Blanch J ，Inciarte A ，Chivite I ，Gonzalez-Cordon A ，Torres B ，Ambrosioni J ，Martinez-Rebollar M ，Laguno M ，De La Mora L ，Foncillas A ，Sempere A ，Rodriguez A ，Solbes E ，Llobet R ，Miro JM ，Mallolas J ，Blanco JL ，De Lazzari E ，Martinez E ... -  《-》

[Translated article] Real-world persistence with dolutegravir/lamivudine versus bictegravir/emtricitabine/tenofovir-alafenamide among persons with HIV.

The main objective was to compare the persistence between dolutegravir/lamivudine (DTG/3TC) and bictegravir/emtricitabine/tenofovir-alafenamide (BIC/FTC/TAF) and to analyze reasons for discontinuation. We conducted a retrospective, non-interventional, descriptive, and longitudinal study. All human immunodeficiency virus (HIV) patients over 18 years treated with DTG/3TC or BIC/FTC/TAF in our center were included. Persistence after first year was compared using the χ2 test. Kaplan-Meier survival analysis was performed. Three hundred fifty-eight patients were included. 99.5% versus 90.99% of patients were persistent after the first year for DTG/3TC and BIC/FTC/TAF respectively (p=.001). Persistence with DGT/3TC was 1237 days (IC95% 1216-1258) and persistence with BIC/FTC/TAF was 986 days [(IC95% 950-1021); p<.001]. The difference was remained after adjusting for covariates with the cox regression model [HR=8.2 (IC95% 1.03-64.9), p=.047]. The main reasons for discontinuation for BIC/FTC/TAF were toxicity/tolerability. In our study, patients have a high persistence. Patients on DTG/3TC treatment are more persistent compared to BIC/FTC/TAF, although BIC/FTC/TAF have worse baseline characteristics. The main reason for discontinuation of BIC/FTC/TAF is tolerability/toxicity.

Martín-Zaragoza L ，Sánchez-Rubio-Ferrández J ，Onteniente-González A ，Gómez-Bermejo M ，Rodríguez-Álvarez SJ ，Monereo-Alonso A ，Molina-García T ... -  《-》

Switching to fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide from dolutegravir plus abacavir and lamivudine in virologically suppressed adults with HIV-1: 48 week results of a randomised, double-blind, multicentre, active-controlled, phas

Bictegravir, co-formulated with emtricitabine and tenofovir alafenamide, has shown good efficacy and tolerability, and similar bone, renal, and lipid profiles to dolutegravir, abacavir, and lamivudine, in treatment-naive adults with HIV-1 infection, without development of treatment-emergent resistance. Here, we report 48-week results of a phase 3 study investigating switching to bictegravir, emtricitabine, and tenofovir alafenamide from dolutegravir, abacavir, and lamivudine in virologically suppressed adults with HIV-1 infection. In this multicentre, randomised, double-blind, active-controlled, non-inferiority, phase 3 trial, HIV-1-infected adults were enrolled at 96 outpatient centres in nine countries. Eligible participants were aged 18 years or older and on a regimen of 50 mg dolutegravir, 600 mg abacavir, and 300 mg lamivudine (fixed-dose combination or multi-tablet regimen); had an estimated glomerular filtration rate of 50 mL/min or higher; and had been virologically suppressed (plasma HIV-1 RNA <50 copies per mL) for 3 months or more before screening. We randomly assigned participants (1:1), using a computer-generated randomisation sequence, to switch to co-formulated bictegravir (50 mg), emtricitabine (200 mg), and tenofovir alafenamide (25 mg; herein known as the bictegravir group), or to remain on dolutegravir, abacavir, and lamivudine (herein known as the dolutegravir group), once daily for 48 weeks. The investigators, participants, study staff, and individuals assessing outcomes were masked to treatment assignment. The primary endpoint was the proportion of participants with plasma HIV-1 RNA of 50 copies per mL or higher at week 48 (according to the US Food and Drug Administration snapshot algorithm); the prespecified non-inferiority margin was 4%. The primary efficacy and safety analyses included all participants who received at least one dose of study drug. This study is ongoing but not actively recruiting participants and is in the open-label extension phase, wherein participants are given the option to receive bictegravir, emtricitabine, and tenofovir alafenamide for an additional 96 weeks. This trial is registered with ClinicalTrials.gov, number NCT02603120. Between Nov 11, 2015, and July 6, 2016, 567 participants were randomly assigned and 563 were treated (282 received bictegravir, emtricitabine, and tenofovir alafenamide, and 281 received dolutegravir, abacavir, and lamivudine). Switching to the bictegravir regimen was non-inferior to remaining on dolutegravir, abacavir, and lamivudine for the primary outcome: three (1%) of 282 in the bictegravir group had HIV-1 RNA of 50 copies per mL or higher at week 48 versus one (<1%) of 281 participants in the dolutegravir group (difference 0·7%, 95·002% CI -1·0 to 2·8; p=0·62). Treatment-related adverse events were recorded in 23 (8%) participants in the bictegravir group and 44 (16%) in the dolutegravir group. Treatment was discontinued because of adverse events in six (2%) participants in the bictegravir group and in two (1%) participants in the dolutegravir group. The fixed-dose combination of bictegravir, emtricitabine, and tenofovir alafenamide might provide a safe and efficacious option for ongoing treatment of HIV-1 infection. Gilead Sciences.

Molina JM ，Ward D ，Brar I ，Mills A ，Stellbrink HJ ，López-Cortés L ，Ruane P ，Podzamczer D ，Brinson C ，Custodio J ，Liu H ，Andreatta K ，Martin H ，Cheng A ，Quirk E ... -  《Lancet HIV》

Real-world persistence with dolutegravir/lamivudine versus bictegravir/emtricitabina/tenofovir-alafenamide among people with HIV.

The main objective was to compare the persistence between dolutegravir/lamivudine (DTG/3TC) and bictegravir/emtricitabine/tenofovir-alafenamide (BIC/FTC/TAF) and to analyze reasons for discontinuation. We conducted a retrospective, non-interventional, descriptive and longitudinal study. All human immunodeficiency virus (HIV) patients over 18 years treated with DTG/3TC or BIC/FTC/TAF in our center were included. Persistence after first year was compared using the χ2 test. Kaplan-Meier survival analysis was performed. Three hundred fifty-eight patients were included. 99.5% versus 90.99% of patients were persistent after the first year for DTG/3TC and BIC/FTC/TAF respectively (p = 0.001). Persistence with DGT/3TC was 1,237 days (IC95% 1,216-1,258) and persistence with BIC/FTC/TAF was 986 days ([IC95% 950-1,021]; p < 0.001). The difference was remained after adjusting for covariates with the cox regression model (HR= 8.2 [IC95% 1.03-64.9], p = 0.047). The main reasons for discontinuation for BIC/FTC/TAF were toxicity/tolerability. In our study patients had a high persistence. Patients on DTG/3TC treatment were more persistent compared to BIC/FTC/TAF, although BIC/FTC/TAF have worse baseline characteristics. The main reason for discontinuation of BIC/FTC/TAF was tolerability/toxicity.

Martín-Zaragoza L ，Sánchez-Rubio-Ferrández J ，Onteniente-González A ，Gómez-Bermejo M ，Rodríguez-Álvarez SJ ，Monereo-Alonso A ，Molina-García T ... -  《-》

Fixed-dose combination bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir-containing regimens for initial treatment of HIV-1 infection: week 144 results from two randomised, double-blind, multicentre, phase 3, non-inferiority trials

In the primary week-48 analyses of two phase 3 studies, coformulated bictegravir, emtricitabine, and tenofovir alafenamide was non-inferior to a dolutegravir-containing regimen in treatment-naive people with HIV. We report week-144 efficacy and safety results from these studies. We did two double-blind, active-controlled studies (now in open-label extension phase). Study 1 randomly assigned (1:1) HLA-B*5701-negative adults without hepatitis B virus co-infection to receive coformulated bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg, or coformulated dolutegravir 50 mg, abacavir 600 mg, and lamivudine 300 mg once daily. Study 2 randomly assigned (1:1) adults to bictegravir, emtricitabine, and tenofovir alafenamide, or dolutegravir 50 mg given with coformulated emtricitabine 200 mg and tenofovir alafenamide 25 mg. We previously reported non-inferiority at the primary endpoint. Here, we report the week-144 secondary outcome of proportion of participants with plasma HIV-1 RNA less than 50 copies per mL at week 144, by US Food and Drug Administration Snapshot algorithm, analysed in the same manner. These studies were registered with ClinicalTrials.gov, NCT02607930 and NCT02607956. 629 participants were randomly assigned and treated in study 1 (314 to bictegravir, emtricitabine, and tenofovir alafenamide, and 315 to dolutegravir, abacavir, and lamivudine) and 645 in study 2 (327 to bictegravir, emtricitabine, and tenofovir alafenamide, 325 to dolutegravir, emtricitabine, tenofovir alafenamide). At week 144, bictegravir, emtricitabine, and tenofovir alafenamide was non-inferior to both dolutegravir-containing regimens for efficacy. In study 1, 256 (82%) of 314 participants had plasma HIV-1 RNA less than 50 copies per mL in the bictegravir, emtricitabine, and tenofovir alafenamide group and 265 (84%) of 315 in the dolutegravir, abacavir, and lamivudine group (difference -2·6%, 95% CI -8·5 to 3·4). In study 2, 262 (82%) of 320 participants had plasma HIV-1 RNA less than 50 copies per mL in the bictegravir, emtricitabine, and tenofovir alafenamide group and 273 (84%) of 325 in the dolutegravir, emtricitabine, and tenofovir alafenamide group (difference -1·9%, -7·8 to 3·9). In both studies, no participant had treatment-emergent resistance to study drugs up to week 144. All treatment regimens were well tolerated with additional exposure. Adverse events that led to study drug discontinuation were reported for no participants in the bictegravir, emtricitabine, and tenofovir alafenamide group versus five (2%) of 315 in the dolutegravir, abacavir, and lamivudine group (study 1), and six (2%) of 320 in the bictegravir, emtricitabine, and tenofovir alafenamide versus six (2%) of 325 in the dolutegravir, emtricitabine, and tenofovir alafenamide group (study 2). In study 1, statistically significant differences were observed in median changes from baseline in fasting total cholesterol (14 mg/dL vs 10 mg/dL; p=0·034), direct LDL (21 mg/dL vs 14 mg/dL; p=0·004), and total cholesterol to HDL ratio (-0·1 vs -0·3; p=0·007) at week 144; no differences were observed between groups in study 2. Weight gain was seen across all treatment groups in both studies, with no differences in median changes from baseline in weight at week 144 for either study. These long-term data support the use of bictegravir, emtricitabine, and tenofovir alafenamide as a safe, well tolerated, and durable treatment for people with HIV, with no emergent resistance. Gilead Sciences.

Orkin C ，DeJesus E ，Sax PE ，Arribas JR ，Gupta SK ，Martorell C ，Stephens JL ，Stellbrink HJ ，Wohl D ，Maggiolo F ，Thompson MA ，Podzamczer D ，Hagins D ，Flamm JA ，Brinson C ，Clarke A ，Huang H ，Acosta R ，Brainard DM ，Collins SE ，Martin H ，GS-US-380-1489 ，GS-US-380-1490 study investigators ... -  《Lancet HIV》