Comparative effectiveness of bictegravir versus dolutegravir, raltegravir, and efavirenz-based antiretroviral therapy among treatment-naïve individuals with HIV. Bictegravir or dolutegravir based antiretroviral therapy are first-line HIV treatments. However, no trial has recruited enough participants to estimate the most effective treatment, and there is little evidence on the comparative effectiveness of bictegravir and other available antiretrovirals, like efavirenz and raltegravir. We emulated a four-arm target trial using country-wide data from Mexico. The eligibility criteria of the target trial were people with HIV, treatment naïve with viral load >500 copies/mL, without tuberculosis, not pregnant, and started either bictegravir, dolutegravir, efavirenz or raltegravir-based treatment
Adipose tissue transcriptome in patients switching efavirenz or a protease inhibitor to raltegravir compared to people without HIV. To study the subcutaneous adipose tissue (SAT) transcriptome in people with HIV (PWH) switching efavirenz (EFV) or a protease inhibitor (PI) to raltegravir and to compare the transcriptome of PWH to those of people without HIV (PWoH). PWH (n = 36) on EFV (n = 22
Implementation and Uptake of Raltegravir Granules in Newborns Diagnosed With HIV Through Birth Testing in Maternity Settings in Zimbabwe During the COVID-19 Pandemic. Zimbabwe introduced raltegravir (RAL) granules at 14 facilities providing point-of-care HIV birth testing, aiming to initiate all newborns with HIV on a RAL-based regimen. From June 2020 to July 2021, we tested 3172 of the 6989 (45
Switch to a raltegravir-based antiretroviral regimen in people with HIV and non-alcoholic fatty liver disease: A randomized controlled trial. The effect of antiretroviral therapy (ART), particularly integrase strand transfer inhibitors (INSTIs), on non-alcoholic fatty liver disease (NAFLD) in people with HIV remains unclear. We evaluated the effect of switching non-INSTI backbone antiretroviral medications to raltegravir on NAFLD and metabolic parameters. This was a single-centre, phase IV, open-label, randomized controlled clinical trial. People living with HIV with NAFLD and undetectable viral load while receiving a non-INSTI were randomized 1:1 to the switch arm (raltegravir 400 mg twice daily) or the control arm (continuing ART regimens not containing INSTI). NAFLD was defined as hepatic
Efficacy and safety of raltegravir plus lamivudine maintenance therapy. Decreasing medication burden with raltegravir plus lamivudine in virologically suppressed persons with HIV (PWH) maintained efficacy and was well tolerated at 24 weeks, but more comprehensive data over longer follow-up are required. Prospective 48 week extension phase of the raltegravir plus lamivudine arm from a previous 24 week pilot randomized clinical trial in which virologically suppressed PWH were randomized 2:1 to switch to fixed-dose combination 150 mg lamivudine/300 mg raltegravir twice daily or to continue therapy. In this 48 week extension phase, raltegravir was dosed at 1200 mg/day and lamivudine 300 mg/day. Primary outcome was the proportion of PWH with treatment failure at Week 48. Secondary outcomes were
Long-term follow-up of HIV-1 multi-drug-resistant treatment-experienced participants treated with etravirine, raltegravir and boosted darunavir: towards drug-reduced regimen? ANRS CO3 Aquitaine Cohort 2007-2018. To assess the efficacy of raltegravir, etravirine and darunavir/ritonavir (TRIO regimen) in treatment-experienced patients with human immunodeficiency virus-1 (HIV-1) infection
Gut microbiota alterations after switching from a protease inhibitor or efavirenz to raltegravir in a randomized, controlled study. To study gut microbiota before and 24 weeks after a single antiretroviral agent switch. HIV-positive patients with efavirenz (EFV) or a protease inhibitor (PI)-based antiretroviral therapy (ART) were randomized to switch EFV or PI to raltegravir (RAL group, n = 19
Raltegravir (Isentress) - human immunodeficiency virus in neonates Published 9 July 2018 Statement of Advice: raltegravir 100mg granules for oral suspension (Isentress®) SMC2101 Merck Sharp & Dohme Limited 8 June 2018 ADVICE: in the absence of a submission from the holder of the marketing authorisation raltegravir (Isentress®) is not recommended for use within NHSScotland. Indication
Immunologic Change over 72 Weeks Following Raltegravir- Versus Efavirenz-Based Therapy in HIV/HCV-Coinfected Individuals in Vietnam. The impact of HIV antiretroviral therapy (ART) on immune dysregulation associated with hepatitis C virus (HCV)/HIV coinfection is incompletely understood. We serially assessed monocyte activation (neopterin, sCD14, and sCD163) and T cell activation (HLA-DR, CD38 ) and immune exhaustion [program cell death protein 1 (PD1), TIGIT] in HIV/HCV-coinfected individuals who participated in a randomized trial performed in Vietnam designed to assess the hepatotoxicity of raltegravir (RAL)- versus efavirenz (EFV)-based therapy when used as first-time ART in combination with tenofovir disoproxil fumarate and emtricitabine. Baseline pre-ART values were compared with those from
Effects of Initiating Raltegravir-Based Versus Efavirenz-Based Antiretroviral Regimens During Pregnancy on Weight Changes and Perinatal Outcomes: NICHD P1081. Integrase inhibitors have been associated with excess gestational weight gain that may lead to adverse pregnancy outcomes (APOs). This post hoc analysis of NICHD P1081 compared antepartum changes in weight and body mass index (BMI ) in pregnant women initiating raltegravir- or efavirenz-based combined antiretroviral therapy (cART) and examined associations between rates of weight gain and APOs. NICHD P1081 enrolled antiretroviral-naive pregnant women living with HIV in the second and third trimester in Brazil, Tanzania, South Africa, Thailand, Argentina, and the United States. Two hundred eighty-one women enrolled between 20 and 31
Raltegravir 1200 mg once daily as maintenance therapy in virologically suppressed HIV-1 infected adults: QDISS open-label trial. Raltegravir (RAL) has favorable tolerability and safety profile, with few and manageable drug interactions. The use of RAL 1200 mg once daily (qd) for first-line therapy is well established. We assessed efficacy and safety of RAL 1200 mg qd, as part of triple combined
Raltegravir-based Postnatal HIV Prophylaxis Therapy in a Neonate After in Utero Dolutegravir Exposure. We present a case report of a neonate receiving raltegravir-based postnatal HIV prophylaxis after in utero dolutegravir exposure. High levels of raltegravir and dolutegravir can potentially cause bilirubin toxicity as they compete for albumin binding and follow the same metabolic pathway through UGT1A1. This case suggests delaying initiation of raltegravir-based postnatal prophylaxis by 24-48 hours after in utero dolutegravir exposure.
A Health Literate Patient-focused Approach to the Redesign of the Raltegravir (ISENTRESS) Pediatric Kit and Instructions for Use. Limited data exist regarding how medications for pediatric use can be developed to minimize medication errors. The integrase inhibitor raltegravir was developed for use in neonates (≥2 kg). Anticipating that neonatal administration would be performed primarily by mothers with varying degrees of health literacy, a health literate, patient-focused, iterative process was conducted to update/redesign the raltegravir granules for oral suspension pediatric kit and instructions for use (IFU) for neonatal use to be ready for regulatory submission. Prototypes of an updated/redesigned raltegravir IFU were systematically assessed through multi-stage, iterative testing
Spectrum of Activity of Raltegravir and Dolutegravir Against Novel Treatment-Associated Mutations in HIV-2 Integrase: A Phenotypic Analysis Using an Expanded Panel of Site-Directed Mutants. Integrase inhibitors (INIs) are a key component of antiretroviral therapy for human immunodeficiency virus-1 (HIV-1) and HIV-2 infection. Although INI resistance pathways are well-defined for HIV-1, mutations to raltegravir and dolutegravir using a single-cycle indicator cell assay. We observed extensive cross-resistance between raltegravir and dolutegravir in HIV-2ROD9. HIV-2-specific integrase mutations Q91R, E92A, A153G, and H157Q/S, which have not been previously characterized, significantly increased the half maximum effective concentration (EC50) for raltegravir when introduced into 1 or more mutational
Pharmacokinetic interaction between raltegravir and rifampicin in an infant with HIV exposed to active TB: a case report. We report a case of an infant with HIV receiving raltegravir granules for oral suspension and rifampicin-based TB prophylaxis. Raltegravir trough levels remained subtherapeutic and viral load increased during concurrent rifampicin therapy despite using double-dosed raltegravir . Even after rifampicin therapy, a higher dose was needed. This highlights the importance of therapeutic drug monitoring and dose adjustments of raltegravir in infants with rifampicin as comedication.
Pharmacokinetic/pharmacodynamic investigation of raltegravir with or without lamivudine in the context of HIV-1 pre-exposure prophylaxis (PrEP). To characterize their potential use in pre-exposure prophylaxis (PrEP) we compared the pharmacokinetics of raltegravir and lamivudine in genital tissue against ex vivo tissue infection with HIV-1. Open-label trial of 36 HIV-negative females and males randomized to 7 days raltegravir 400 mg twice daily and 7 days raltegravir 400 mg+lamivudine 150 mg twice daily (after washout), or vice versa. Blood, saliva, rectal fluid, rectal tissue, vaginal fluid and vaginal tissue were sampled at baseline and on and off PrEP during a total of 12 days, for pharmacokinetics and antiviral activity via ex vivo HIV-1BaL challenge. Ex vivo infectivity was compared
Liver Fat, Adipose Tissue, and Body Composition Changes After Switching from a Protease Inhibitor or Efavirenz to Raltegravir. Integrase inhibitors appear to increase body weight, but paradoxically some data indicate that raltegravir (RAL) may decrease liver fat. Our objective was to study the effects of switching from a protease inhibitor (PI) or efavirenz (EFV) to RAL on liver fat, body
A phase IV, open-label three-arm study investigating the impact of a combination of tenofovir disoproxil fumarate/emtricitabine with raltegravir or dolutegravir or elvitegravir/cobicistat on renal function in HIV-1 antiretroviral naïve patients. Tenofovir DF (TDF) remains one of the preferred backbone agents for naïve HIV patients starting antiretroviral treatment (ART). The impact of TDF on renal function and metabolic parameters may vary by anchor agent. We investigated the impact of TDF in combination with 3 different integrase inhibitors on tubular and glomerular function, and metabolic parameters in ART-naïve patients. Sixty patients with normal renal function were randomised (20 per arm) to TDF/emtricitabine (FTC) plus either raltegravir (RAL) (400 mg b.d.), dolutegravir (DTG