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Kenneth H. Mayer and H.F. Pizer, editors Elsevier Academic Press, Amsterdam, the Netherlands, and Boston, Massachusetts, 2005 ISBN: 0-12-465271-9 Pages: 537; Price: US $84.95 As we enter the third decade [...]

Background: Bictegravir, coformulated with emtricitabine/tenofovir alafenamide as a fixed-dose combination (B/F/TAF), is recommended for treatment of HIV-1-infection. Multiple studies of B/F/TAF in treatment-naive and virologically suppressed cohorts have shown high efficacy and tolerability with no treatment-emergent resistance through 48 weeks. Participants in these studies have been predominantly men. We report 48-week results from a phase 3 study evaluating switching to B/F/TAF, specifically in a globally distributed trial population of women., Methods: In this multicenter, randomized, open-label, active-controlled, noninferiority trial (ClinicalTrials.gov NCT02652624), women living with HIV who were virologically suppressed (HIV-1 RNA levels <50 copies/mL) on a regimen containing either TAF or tenofovir disoproxil fumarate were randomly assigned (1:1) to switch to B/F/TAF (50/200/25 mg) or stay on baseline regimen (SBR) once daily for 48 weeks. Primary endpoint was proportion of participants with plasma HIV-1 RNA ≥50 copies/mL at week 48 (U.S. Food and Drug Administration snapshot algorithm); prespecified noninferiority margin was 4%., Findings: We randomized 472 participants and treated 470 (234 B/F/TAF, 236 SBR). Switching to B/F/TAF was noninferior to SBR for the primary outcome, as 1.7% (4/234) vs 1.7% (4/236) had HIV-1 RNA ≥50 copies/mL at week 48 (difference 0.0%, 95.001% confidence interval: -2.9% to 2.9%). No individual receiving B/F/TAF developed treatment-emergent resistance. Both treatments were well-tolerated; no participant discontinued treatment because of an adverse event., Interpretation: Fixed-dose combination B/F/TAF provides a safe and efficacious option for ongoing treatment of HIV in women. This study contributes important data on safety, tolerability, and outcomes of antiretroviral therapy among women living with HIV.

Background: Current treatment for HIV-infected individuals with renal failure on haemodialysis frequently requires complex regimens with multiple pills. A daily single-tablet regimen of coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide is approved in Europe, the USA, and in other regions for use in HIV-1-infected individuals with mild-to-moderate chronic kidney disease (creatinine clearance 30-69 mL/min). We aimed to assess the safety, efficacy, and pharmacokinetics of this regimen in HIV-infected adults with end-stage renal disease on chronic haemodialysis., Methods: We did an open-label, single-arm, multicentre, phase 3b trial at 26 outpatient clinics in Austria, France, Germany, and the USA. Participants were HIV-1-infected adults with end-stage renal disease (creatinine clearance <15 mL/min), on chronic haemodialysis for at least 6 months before screening. Virological suppression (ie, plasma HIV-1 RNA <50 copies per mL) on a stable antiretroviral regimen was required for at least 6 months before screening with a CD4 count of at least 200 cells per μL. We switched all participants to coformulated elvitegravir 150 mg, cobicistat 150 mg, emtricitabine 200 mg, and tenofovir alafenamide 10 mg once daily, taken after haemodialysis for up to 96 weeks. We did assessments at study visits at weeks 2, 4, 8, 12, 24, 36, and 48, and every 12 weeks thereafter up to 96 weeks. The primary endpoint was the incidence of treatment-emergent adverse events of grade 3 or higher up to week 48. All participants who received at least one dose of study drug were included in the primary analysis. This study is registered with ClinicalTrials.gov (NCT02600819) and is closed to new participants., Findings: Between Feb 1, and Nov 3, 2016, 55 participants were enrolled and received at least one dose of study drug. Through week 48, 18 of 55 participants (33%, 95% CI 20-45) had an adverse event of grade 3 or higher on study treatment. Treatment-emergent grade 3 or higher adverse events that occurred in more than one participant included anaemia, osteomyelitis, prolonged electrocardiogram QT, fluid overload, hyperkalaemia, hypertension, and hypotension (all n=2). No adverse event of grade 3 or higher was considered by the site investigators to be treatment related. Three participants (5%, 95% CI 0-11) discontinued treatment because of adverse events; one of these (grade 1 allergic pruritus) was considered treatment related. Treatment-related adverse events were reported for six individuals (11%, 95% CI 3-19), the most common of which was nausea (in four individuals [7%]); all treatment-related adverse events were grade 1 or 2 in severity., Interpretation: At 48 weeks, switching to the single-tablet regimen of elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide was well tolerated. This regimen might provide a tolerable and convenient option for ongoing treatment of HIV-1 infection in adults with end-stage renal disease on chronic haemodialysis., Funding: Gilead Sciences., (Copyright © 2018 Elsevier Ltd. All rights reserved.)