dolutegravir/emtricitabine/tenofovir alafenamide (DTG/FTC/TAF) / Viatris - LARVOL DELTA

Opti-DOR: A Randomised, Phase 3 Non-inferiority Study of DOR/3TC/TDF Compared to DTG/TAF/FTC in Participants Infected With HIV-1 Starting First-line Antiretroviral Therapy (clinicaltrials.gov) - P3 | N=600 | Active, not recruiting | Sponsor: Professor Francois Venter | Recruiting ➔ Active, not recruiting

Enrollment closed • Human Immunodeficiency Virus • Infectious Disease

Tenofovir alafenamide promotes weight gain and impairs fatty acid metabolism-related signaling pathways in visceral fat tissue compared to tenofovir disoproxil fumarate. (PubMed, Antiviral Res) - "We utilized a humanized mouse model of HIV-infection and administered two clinically relevant ART combinations TAF/dolutegravir (DTG)/emtricitabine (FTC) and TDF/DTG/FTC. Specifically, KEGG pathway analysis indicated that TAF/DTG/FTC treated mice showed suppression of multiple fatty acid metabolism related pathways, while TDF/DTG/FTC treated mice showed evidence for increased thermogenesis. The results suggest that weight gain associated with TAF-based ART may be due to impaired adipocyte mediated lipid handling, while suppressed weight gain with TDF-based ART may be secondary to increased browning of visceral adipocytes, although independent validation is necessary."

Journal • Human Immunodeficiency Virus • Infectious Disease • LEP

Bone mineral content, growth, and renal health of infants with perinatal exposure to maternal dolutegravir vs efavirenz and tenofovir disoproxil fumarate vs tenofovir alafenamide: the randomized IMPAACT 2010 (VESTED) trial. (PubMed, J Acquir Immune Defic Syndr) - "It is reassuring that maternal DTG-based ART during pregnancy and breastfeeding was associated with higher infant spine bone mineral content, better growth, and less stunting than EFV/FTC/TDF."

Journal • Genetic Disorders • Human Immunodeficiency Virus • Infectious Disease • Obesity

UNIVERSAL1: UNIVERSAL 1: Pharmacokinetic Study of a Novel DTG/FTC/TAF Dose Ratio for Children (clinicaltrials.gov) - P2 | N=50 | Recruiting | Sponsor: PENTA Foundation | Not yet recruiting ➔ Recruiting

Enrollment open • Human Immunodeficiency Virus • Infectious Disease

UNIVERSAL1: UNIVERSAL 1: Pharmacokinetic Study of a Novel DTG/FTC/TAF Dose Ratio for Children (clinicaltrials.gov) - P2 | N=50 | Not yet recruiting | Sponsor: PENTA Foundation | Trial completion date: Dec 2025 ➔ Aug 2025

Trial completion date • Human Immunodeficiency Virus • Infectious Disease

Outcomes following prenatal exposure to DTG‐containing antiretroviral therapy regimens: data from the DOLOMITE‐EPPICC study (HIV-Glasgow 2024) - "Our analysis focussed on five DTG-containing regimens: DTG+lamivudine (3TC) +abacavir (ABC), DTG+tenofovir disoproxil fumarate (TDF) +emtricitabine (FTC), DTG+tenofovir alafenamide (TAF) +FTC, DTG+3TC and DTG+rilpivirine (RPV)...The earliest DTG-containing regimen was DTG+3TC+ABC in 468 (56.2%), DTG+TDF+FTC in 132 (15.9%), DTG+TAF+FTC in 23 (2.8%), DTG+3TC/RPV in seven (0.8%) pregnancies. Of the remaining 203 (24.4%) pregnancies with other first DTG-containing regimens, most (78.8% [160/203]) were on regimens containing a drug from an additional anchor class (e.g. darunavir/ritonavir+TDF+FTC+DTG, atazanavir/ritonavir+TDF+FTC+DTG)...aDTG+3TC (n = 3) or DTG+RPV (n = 4)... The birth defect prevalence reported here is consistent with rates reported for DTG-exposed pregnancies in the Antiretroviral Pregnancy Registry (3.96%). Monitoring of use and safety of DTG-containing regimens in pregnancy is ongoing in EPPICC, as sample size for some groups is too small to exclude..."

Human Immunodeficiency Virus • Infectious Disease • Small for Gestational Age

Effectiveness of a dual therapy based on DTG/3TC on reduction of the viral reservoir, immune recovery and immune activation compared with a triple antiretroviral therapy based on DTG/TAF/FTC in patients with HIV infection without prior treatment (HIV-Glasgow 2024) - P4 | "After this comprehensive assessment, we did not find differences between 2DR and 3DR in viral reservoir dynamics, CD4+ and CD8+ phenotypic changes, inflammatory profile and immune recovery. Abbreviations: 2DR, two-drug regimen; 3DR, three-drug regimen; HLA-DR, human leukocyte antigen-DR; hsCRP, high sensitivity C reactive protein; IFN-γ, interferon-γ; IL-1β, interleukin-1β; IL-6, interleukin-6; IL-8, interleukin-8; IP-10, interferon gamma-induced protein 10; IPDA, intact provirus DNA assay; IVRA, intact viral RNA assay; LAG-3, lymphocyte-activation gene 3; PD-1, programmed death-1; sCD14, soluble cluster of differentiation 14; sCD16, soluble cluster of differentiation 16; TIGIT, T-cell immunoreceptor with Ig and ITIM domains; TIM-3, T-cell immunoglobulin and mucin containing protein-3; TNF-α, tumour necrosis factor-α."

Clinical • IO biomarker • Human Immunodeficiency Virus • Infectious Disease • Oncology • ANXA5 • B2M • B3GAT1 • CD14 • CD38 • CD8 • CRP • CXCL8 • HAVCR2 • IL1B • IL6 • LAG3 • PD-1 • TIGIT • TNFA

Economic Evaluation of the Co-Formulated Antiretroviral Efavirenz 400mg/Lamivudine/Tenofovir Disoproxil Fumarate for the Treatment of HIV-1 Infection in Adult Patients From the Perspective of the Mexican Public Health System (ISPOR-EU 2024) - "The comparators included bictegravir+emtricitabine(FTC)+tenofovir alafenamide (TAF), dolutegravir(DTG)+abacavir+3TC, DTG+FTC+TAF, DTG+((FTC+TAF) or (FTC or 3TC [XTC]+tenofovir disoproxil [TDx]])), DTG+3TC, doravirine+TDx+3TC, efavirenz(EFV)+TDx, darunavir+cobicistat+ ((TAF+FTC) or (TDx+FTC or 3TC)), doravirine+((TAF+FTC) or (TDx+FTC or 3TC)), EFV+((TAF+FTC) or (TDx+XTC)), raltegravir+((TAF+FTC) o (TDx+FTC or 3TC)), darunavir+cobicistat+ 3TC. EFV400/3TC/TDF shows no statistically significant differences in viral suppression and safety. It is a cost-saving option with savings of up to 75.1% compared to some of its competitors, making it a valuable option for the National Health System in Mexico for treating HIV-1 infection in adult patients."

Clinical • HEOR • Human Immunodeficiency Virus • Infectious Disease

Impact of Dolutegravir plus Lamivudine as First-Line Antiretroviral Treatment on HIV-1 Reservoir and Inflammatory Markers in Peripheral Blood. (PubMed, J Infect Dis) - "First-line ART with DTG+3TC resulted in a similar reduction of HIV-1 persistence parameters in peripheral blood, and comparable changes in immune-associated soluble and T-cell markers compared with DTG+FTC/TAF. These findings support recommendation of DTG/3TC among preferred options for first-line ART in PWH."

Journal • Human Immunodeficiency Virus • Infectious Disease • CD8 • IL6

Effects of switching to Dolutegravir/Lamivudine from Tenofovir Alafenamide Fumarate/Emtricitabine/Dolutegravir or Abacavir/Lamivudine/Dolutegravir on body weight and lipid profile in Japanese people living with HIV. (PubMed, J Infect Chemother) - "Switching from ABC/3TC/DTG to DTG/3TC lowered lipids significantly, but not with TAF/FTC/DTG. Neither switch affected body weight or other markers."

Journal • Fibrosis • Human Immunodeficiency Virus • Immunology • Infectious Disease • CD4 • CD8

Efficacy, Safety, and Tolerability of Switching From Bictegravir/Emtricitabine/Tenofovir Alafenamide to Dolutegravir/Lamivudine Among Adults With Virologically Suppressed HIV: The DYAD Study. (PubMed, Open Forum Infect Dis) - "Switching to DTG/3TC was noninferior to continuing B/F/TAF among adults with virologic suppression at week 48. Drug-related AEs and withdrawals were higher in the DTG/3TC arm, which is likely consistent with the open-label nature of this switch study."

Clinical • Journal • Human Immunodeficiency Virus • Infectious Disease

Lipid and glucose profiles in pregnant women with HIV on tenofovir-based antiretroviral therapy. (PubMed, Clin Infect Dis) - "Pregnant women randomized to start TAF/FTC+DTG had higher lipids than those randomized to TDF/FTC+DTG within eight weeks of ART initiation. However, lipid levels were within normal reference ranges."

Journal • Dyslipidemia • Human Immunodeficiency Virus • Infectious Disease

Characterizing HIV drug resistance in cases of vertical transmission in the VESTED randomized antiretroviral treatment trial. (PubMed, J Acquir Immune Defic Syndr) - P3 | "VESTED (NCT03048422) compared the safety and efficacy of three antiretroviral treatment (ART) regimens in pregnant and postpartum women: dolutegravir+emtricitabine/tenofovir alafenamide fumarate; dolutegravir+emtricitabine/tenofovir disoproxil fumarate (TDF); efavirenz/emtricitabine/TDF...Their infants received postnatal nevirapine+/-zidovudine prophylaxis and were breastfed...VT was rare. New-onset NNRTI HIVDR in Case mothers was likely from efavirenz-ART prescribed prior to study dolutegravir-ART, and in one case appeared transmitted to the infant despite nevirapine prophylaxis."

Clinical • Journal • Human Immunodeficiency Virus • Infectious Disease • Small for Gestational Age

Health care resource utilization and costs for treatment-experienced people with HIV switching or restarting antiretroviral regimens since 2018. (PubMed, J Manag Care Spec Pharm) - "We examined all-cause HCRU and costs and HIV-related HCRU and combined costs to the health plan and direct patient costs by site of service and compared between INSTI-based regimens: bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (single tablet) vs dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) (single tablet), dolutegravir + emtricitabine/tenofovir alafenamide (DTG+FTC/TAF) (multitablet), and dolutegravir + emtricitabine/tenofovir disoproxil fumarate (DTG+FTC/TDF) (multitablet). HIV-related medical costs during the LOT were lowest for PWH treated with INSTI-based single-tablet regimens. Simplifying treatment regimens may help PWH maintain lower health care costs."

HEOR • Journal • Retrospective data • Human Immunodeficiency Virus • Infectious Disease

Prenatal dolutegravir-based regimen use, and pregnancy and birth outcomes: data from the Antiretroviral Pregnancy Registry (AIDS 2024) - "BACKGROUND: The objective of this analysis is to assess pregnancy and neonatal outcomes among pregnancies with pre-natal exposure to specific dolutegravir-based regimens (DBRs) using data from the APR through 31July2023. The APR is a prospective exposure-registration cohort study, monitoring for early warning signals of major teratogenic effects of antiretrovirals used during pregnancy. APR data do not demonstrate an increased risk of overall birth defects with use of DTG+3TC+ABC, DTG+TDF+FTC or DTG+TAF+FTC above the population expected rate of defects (2.72-4.17 per 100 live births from Metropolitan Atlanta Congenital Defects Program and Texas Birth Defects Registry respectively). While no definitive conclusions can be drawn on DTG+3TC use in pregnancy due to limited number of pregnancies on the regimen, the APR data on individual drugs demonstrate no increase in risk for defects."

Impact of different INSTIs on BMI among HIV treatment-naive patients in Shenzhen, China: a real-world data analysis (AIDS 2024) - "Compared to people who used TDF+3TC/DTG?TAF/FTC/EVG/c and TAF/FTC/BIC, people who used 3TC/DTG gained more BMI per year after ART initiation (Figure1). Compared with NNRTIs, INSTIs can lead to an increase in BMI. Particularly, the increase in BMI caused by DTG is prominent. TDF may be associated with weight loss."

Clinical • Real-world • Real-world evidence • Human Immunodeficiency Virus • Infectious Disease

Dolutegravir with recycled nucleoside reverse transcriptase inhibitors maintains better viral suppression than protease inhibitor based antiretroviral therapy over 144 weeks: VISEND Trial (AIDS 2024) - "We randomized adults with viral load (VL) < 1000 copies/mL on tenofovir disoproxil fumarate (TDF), lamivudine (3TC) plus efavirenz (EFV) or nevirapine (NVP) to TDF,3TC,DTG (TLD) or tenofovir alafenamide fumarate (TAF), emtricitabine (FTC), DTG (TAFED) [Arm A]. Participants with VL < 1000 copies/mL were randomized to TLD or TAFED or standard-of-care (SOC) second line comprising Lopinavir/ritonavir (LPV/r) or atazanavir/r (ATV/r), zidovudine (ZDV), 3TC [Arm B]...In those randomised to TDF/3TC/DTG and TAF/FTC/DTG, 61% and 52% had no predicted tenofovir activity respectively; whereas 75% had no predicted lamivudine or emtricitabine activity in both groups... In the VISEND trial, HIV-positive adults with virologic failure to TDF/3TC/NNRTI, had favourable outcomes when switched to DTG with recycled NRTIs compared to those switched to SOC boosted-PI despite high baseline resistance to NRTIs. No emergent INSTI mutations were reported at week 144. We recommend recycling of..."

Late-breaking abstract • Human Immunodeficiency Virus • Infectious Disease

Blood pressure increases are associated with weight gain and not antiretroviral regimen or kidney function: a secondary analysis from the ADVANCE trial in South Africa. (PubMed, J Int AIDS Soc) - P3 | "In the ADVANCE cohort, weight gain and age accounted for increases in BP and risk of treatment-emergent hypertension. HIV treatment programmes may need to integrate the management of obesity and hypertension into routine care."

Clinical • Journal • Cardiovascular • Genetic Disorders • Human Immunodeficiency Virus • Hypertension • Infectious Disease • Obesity

Dolutegravir- Versus Efavirenz-Based Treatment in Pregnancy: Impact on Red Blood Cell Folate Concentrations in Pregnant Women and Their Infants. (PubMed, J Infect Dis) - "In IMPAACT 2010/VESTED, pregnant women were randomized to initiate dolutegravir (DTG)+emtricitabine (FTC)/tenofovir alafenamide (TAF), DTG+FTC/tenofovir disoproxil fumarate (TDF), or efavirenz (EFV)/FTC/TDF. The DTG+FTC/TAF arm had an 8% lower infant-maternal folate ratio (0.92, 95%CI 0.78, 1.09) versus EFV/FTC/TDF. Results are consistent with no clinically meaningful differences between arms for all RBC-folate outcomes and they suggest that cellular uptake of folate and folate transport to the infant do not differ in pregnant women starting DTG- vs. EFV-based ART."

Journal • Human Immunodeficiency Virus • Infectious Disease • CD4

Prophylaxis and treatment of HIV infection in pregnancy, Swedish guidelines 2024. (PubMed, Infect Dis (Lond)) - "In May 2024, the Swedish Reference Group on Antiviral Therapy updated the guidelines on management of HIV infection in pregnancy. The most important recommendations and revisions were: (i) ART during pregnancy should be started as early as possible and continue after delivery; (ii) Suppressive ART should normally not be modified; (iii) The treatment target of HIV RNA <20 copies/ml remains; (iv) Dolutegravir/emtricitabine/tenofovir DF is the first-line drug combination also in pregnant women and women planning pregnancy; (v) There is no evidence of an increased risk of neural tube defects associated with dolutegravir; (vi) Mode of delivery for women with effective ART and HIV RNA <200 copies/ml should follow standard obstetric procedures; (vii) Caesarean section is recommended if HIV RNA ≥200 copies/ml; (viii) Scalp electrode, foetal blood sampling and/or vacuum delivery should be used on strict indications, but does not necessitate intensified infant prophylaxis;..."

Journal • Human Immunodeficiency Virus • Infectious Disease • Obstetrics

Tenofovir, emtricitabine, lamivudine and dolutegravir concentrations in plasma and urine following drug intake cessation in a randomized controlled directly observed pharmacokinetic trial to aid point-of-care testing. (PubMed, J Antimicrob Chemother) - "These data support use of a urinary tenofovir threshold of <1500 ng/mL (tenofovir disoproxil fumarate-based regimens) as a marker of three or more missed doses for a POCT platform. However, due to low dolutegravir concentrations in urine, POCT would be limited to a readout of recent dolutegravir intake (one missed dose)."

Journal • PK/PD data

Treatment Persistence Among Treatment-Experienced People With HIV (PWH) Switching To Integrase Strand Transfer Inhibitor (INSTI)-Based HIV Antiretroviral Regimens (ISPOR 2024) - "Individuals in the dataset between 01 January 2018 to 31 July 2023 were included if they had HIV-1, were ≥ 18 years old with known sex, had ≥ 1 pharmacy claim for an ARV with a newer INSTI-based regimen (CAB+RPV, DTG/ABC/3TC, BIC/FTC/TAF, DTG/3TC, DTG+FTC/TDF, DTG+FTC/TAF) from 01 January 2020 to 31 December 2022 (index date), and were continuously treated with a complete ARV regimen for at least 6 months before initiating an INSTI-based therapy. Nearly one in 10 treatment-experienced PWH experienced a secondary switch in therapy. PWH initiating BIC/FTC/TAF were significantly less likely than those starting other INSTI-based regimens to subsequently switch."

Human Immunodeficiency Virus • Infectious Disease

Higher Risks of Hypertension With Use of DTG Versus PI/r in the VISEND Trial (CROI 2024) - "Use of tenofovir alafenamide (TAF) and dolutegravir (DTG) have been associated with higher risks of hypertension in some randomized trials and cohort studies, but other studies have not shown these associations. In VISEND, risks of Grade 1 HTN and changes in systolic BP were higher for TAF/3TC/DTG and TDF/FTC/DTG versus ZDV/3TC/ATV/r or ZDV/3TC/LPV/r. Results were not consistent when comparing TAF/3TC/DTG and TDF/FTC/DTG, where there were no significant differences for change in systolic BP, but there were differences when comparing the risk of Grade 1 HTN."

Cardiovascular • Human Immunodeficiency Virus • Hypertension • Infectious Disease

Impact of DTG+3TC as First-Line ART on HIV-1 Reservoir and Inflammatory Markers in Peripheral Blood (CROI 2024) - "First-line dual ART with DTG+3TC resulted in a similar decay in parameters of HIV-1 persistence in periphery as well as in immune-associated markers compared to 3DR with DTG+FTC/TAF. Our results further support recommendation of DTG/3TC as one preferred option for first-line ART in PWH."

Clinical • IO biomarker • Human Immunodeficiency Virus • Infectious Disease • CD38 • CD8 • IL6 • PD-1 • TIGIT

Antiretroviral Concentrations in Post-Mortem Tissues: Preliminary Results From the Last Gift Program (CROI 2024) - "The results were normalized by weight and the mean values were reported as results.21 tissue biopsies per participant were isolated from different anatomical sites in 6 volunteers on different ART regimens: 3 on tenofovir alafenamide/emtricitabine (TAF/FTC) and dolutegravir (DTG), 1 on TAF/FTC+DTG plus rilpivirine (RPV), 1 on DTG and darunavir/cobicistat (DRV/c) and 1 on abacavir/lamivudine (ABC/3TC)/DTG. Scarce data on human intra-tissue ARV penetration are reported in literature. This is the first study to report different ARV concentrations in different anatomical sites in humans. Previous studies on non-human primates showed similar results about the poor, but rather uniform, concentrations of DTG in all the districts of the CNS, and higher concentrations in kidney and intestine."

Human Immunodeficiency Virus • Infectious Disease