- |||||||||| Triumeq (dolutegravir/abacavir/lamivudine) / ViiV Healthcare, bictegravir (GS-9883) / Gilead, Tivicay (dolutegravir) / ViiV Healthcare
Journal: An up-to-date evaluation of dolutegravir/abacavir/lamivudine for the treatment of HIV. (Pubmed Central) - Feb 26, 2022
Bictegravir with tenofovir alafenamide and emtricitabine offers the benefit of same day initiation and efficacy in hepatitis B co-infection, while new two-drug regimens enhance the simplicity of HIV treatment. Continued study is required into the mechanisms and optimal management strategies for weight gain for many regimens, including DTG/ABC/3TC.
- |||||||||| irinotecan / Generic mfg.
Clinical, Journal: UGT1A1 regulatory variant with potential effect on efficacy of HIV and cancer drugs commonly prescribed in South Africa. (Pubmed Central) - Feb 22, 2022
A novel cis-eQTL, rs28967009, was identified for UGT1A1, which is predicted to upregulate UGT1A1 expression thereby potentially affecting the metabolism of dolutegravir and irinotecan, which are extensively prescribed in SA for HIV and colorectal cancer treatment, respectively. As increased UGT1A1 expression could affect the clinical outcome of dolutegravir and irinotecan treatment by increasing drug clearance, patients with the rs28967009A variant may require increased drug doses to reach therapeutic levels or should be prescribed alternative drugs.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare, Isentress (raltegravir) / Merck (MSD), Vitekta (elvitegravir) / Japan Tobacco, Gilead
Journal: Integrase Inhibitors are Associated with Neuropsychiatric Symptoms in Women with HIV. (Pubmed Central) - Feb 19, 2022
Raltegravir was associated with less hyperarousal, but only among women aged ≤ 45 years(P = 0.001). The adverse neuropsychiatric effects of INSTIs do not appear to be consistent across all WWH. Key characteristics (e.g., age, hepatitis positivity) may need consideration to fully weight the risk-benefit ratio of dolutegravir and elvitegravir in WWH.
- |||||||||| trimethoprim/sulfamethoxazole / Generic mfg.
Crystalline Nephropathy Due to Trimethoprim-Sulfamethoxazole in the Setting of HIV-1 and Pneumocystis Pneumonia (Area K, Hall F (North Building, Exhibition Level), Moscone Center) - Feb 19, 2022 - Abstract #ATS2022ATS_1214;
Antiretroviral therapy with dolutegravir and emtricitabine-tenofovir were initiated...TMP-SMX and emtricitabine-tenofovir were discontinued while atovaquone, dapsone, and abacavir/lamivudine were initiated...RRT may be required for azotemia and correction of electrolytes. TMP-SMX induced crystalline nephropathy is an uncommon event that should be taken into consideration when selecting an agent for treatment of PJP in patients with HIV.
- |||||||||| Journal: Advanced HIV Infection in Treatment-Naïve Individuals: Effectiveness and Persistence of Recommended 3-Drug Regimens. (Pubmed Central) - Feb 17, 2022
Compared with B/F/TAF, bDRV initiators were statistically less likely to suppress to <50 copies/mL (aHR, 0.72; 95% CI, 0.52-0.99) and <200 copies/mL (aHR, 0.55; 95% CI, 0.43-0.70); no statistically significant difference was detected with DTG or EVG/c. Among people with advanced HIV infection, those initiating B/F/TAF were less likely to discontinue/modify their regimen than those on any other regimen, and more likely to achieve viral suppression compared with those on bDRV but not compared with those on other integrase inhibitors.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
Trial completion date, Trial primary completion date: DISCO: Population Effectiveness of Dolutegravir Implementation in Sub-Saharan Africa (clinicaltrials.gov) - Feb 16, 2022
P=N/A, N=1000, Recruiting,
Among people with advanced HIV infection, those initiating B/F/TAF were less likely to discontinue/modify their regimen than those on any other regimen, and more likely to achieve viral suppression compared with those on bDRV but not compared with those on other integrase inhibitors. Trial completion date: Oct 2021 --> Jun 2023 | Trial primary completion date: Oct 2021 --> Jun 2023
- |||||||||| Roctavian (valoctocogene roxaparvovec) / BioMarin
Valoctocogene roxaparvovec gene transfer in participants with HIV (hall 1; hall 2; hall 3; hall 4; hall 5) - Feb 16, 2022 - Abstract #GTH2022GTH_302;
P3
P2 received darunavir, dolutegravir, and ritonavir...Prednisone 60 mg/d was initiated on d109; AEs resolved...Following discussion between P3, a hepatologist, and the investigator on d65, his HIV treatment was replaced with raltegravir and emtricitabine/tenofovir alafenamide... Of 3 HIV+ participants, 2 had reduced bleeding and no or G1 LFT AEs; 1 had hepatic enzyme elevation unresponsive to corticosteroids, likely due to an interaction between gene therapy and efavirenz, a known hepatotoxic agent.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
Journal: INSTIs and NNRTIs Potently Inhibit HIV-1 Polypurine Tract Mutants in a Single Round Infection Assay. (Pubmed Central) - Feb 15, 2022
Dolutegravir (DTG) is a leading INSTI that is given, usually in combination with nucleoside reverse transcriptase inhibitors (NRTIs), to treat HIV-1 infections...No measurable loss in potency was observed for either INSTIs or NNRTIs against the HIV-1 PPT mutants. This suggests that HIV-1 PPT mutants are not able, by themselves, to confer resistance to INSTIs or NNRTIs.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare, Isentress (raltegravir) / Merck (MSD)
Journal: Raltegravir-based Postnatal HIV Prophylaxis Therapy in a Neonate After in Utero Dolutegravir Exposure. (Pubmed Central) - Feb 15, 2022
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.
- |||||||||| ritonavir / Generic mfg.
Review, Journal: Covid-19 and Artificial Intelligence: Genome sequencing, drug development and vaccine discovery. (Pubmed Central) - Feb 9, 2022
The growth of AI techniques in health care opened a broad gate for discovering the genomic sequences of the COVID-19 virus and the VOC. AI helps also in the development of vaccines and drugs (including drug repurposing) to obtain potential preventive and therapeutic agents for controlling the COVID-19 pandemic.
- |||||||||| bictegravir (GS-9883) / Gilead
SOME InSTIs INDUCE TOXICITY AND DIFFERENTIATION IN HUMAN EMBRYONIC STEM CELLS ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_1193;
Our objective was to characterize the effects of four InSTIs in two human embryonic stem cell (hESC) lines, with respect to markers of pluripotency, early differentiation, and cellular healt H9 and CA1S hESCs (n=6 and n=3 independent experiments, respectively) were exposed to DTG, cabotegravir (CAB), bictegravir (BIC), or raltegravir (RAL) at doses ranging from 0.01X to 1X peak plasma drug concentrations (Cmax) or DMSO diluent control...Given their use in first-line ARV regimens, including by women of reproductive age or pregnant, it is imperative to elucidate their long-term safety in the context of pregnancy and embryonic development. These data also indicate that RAL appears to show a safe profile, a reassuring finding that warrants further investigation.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
BIRTH OUTCOMES FOLLOWING PRENATAL EXPOSURE TO DOLUTEGRAVIR: THE DOLOMITE-EPPICC STUDY ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_1190;
The prevalence rate for overall birth defects here is the same as recently reported from the Antiretroviral Pregnancy Registry for periconception exposure to DTG. Dolomite-EPPICC will continue to monitor use and safety of DTG-based regimens in pregnancy, noting that our sample size of periconception exposures is currently too small to exclude potential associations with rare birth defects like NTDs.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
NEURAL TUBE DEFECTS AND PRENATAL EXPOSURE TO DOLUTEGRAVIR: UNITED STATES, 2008-2019 ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_1189;
The results are reassuring, as they do not demonstrate an increased risk of NTD in the U.S., and support the current U.S. federal perinatal guidelines. In the absence of nationwide surveillance, the pregnancy algorithm we developed can be used with administrative databases to study correlates of rare outcomes such as NTD and to monitor adverse pregnancy outcomes of ARV use in U.S. women.
- |||||||||| bictegravir (GS-9883) / Gilead
TRANSMITTED DRUG RESISTANCE TO INTEGRASE-BASED FIRST-LINE TREATMENT IN EUROPE ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_1123;
Here we describe the most recent data on transmitted drug resistance to integrase based first line regimens in Mediterranean Europe. Given the low prevalence of clinically relevant resistance to second generation integrase inhibitors and to first line NRTIs, in the years 2018-2021 it is very unlikely that a newly diagnosed patient in MeditRes countries would present with baseline resistance to a first line regimen based on second generation integrase inhibitors.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
WEIGHT GAIN AMONG ADOLESCENTS ON DOLUTEGRAVIR: A REAL CONCERN? ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_957;
In this cohort study including children and adolescents, no association between exposure to dolutegravir and weight gain was found. Although these data are reassuring, larger studies and longer follow-up are needed in order to address the long-term effects of dolutegravir on weight during the unique period of adolescence.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
MENTAL HEALTH AND TREATMENT OUTCOMES IN ADOLESCENTS LIVING WITH HIV IN WEST AFRICA ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_954;
From February to October 2021, 317 ALHIV were enrolled at a median age of 14 years (interquartile range: 12–16), 85% were >12 years, 52% were female, 30% at WHO clinical stage 3/4; 74% were treated with a Dolutegravir (DTG) based regimen...In these West-African ALHIV cohorts, ALHIV were mainly switched on DTG regimen, but VS remains suboptimal and worsened by mental health conditions. Tailored interventions are urgently needed to address both depression or anxiety and ART treatment adherence among West African ALHIV.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
RECTAL TISSUE HIV RNA IS ASSOCIATED WITH SYSTEMIC INFLAMMATION IN PERSONS WITH HIV ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_820;
Treatment-naïve PWH initiating dolutegravir-based antiretroviral therapy (ART) underwent blood and RT sampling pre-ART (wk 0) and post-ART (wk 2, 6, 12) between 2/2015 and 9/2019 (NCT 02924389)...Early tissue HIV RNA viral dynamics may predict patterns of systemic inflammation and hypercoagulation even during rapid plasma virologic suppression. Larger studies of virally-suppressed patients on long-term ART are needed to confirm findings and assess additional endpoints of subclinical/clinical end-organ disease.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
VIRAL LOAD BEFORE SWITCHING TO DOLUTEGRAVIR & ASSOCIATION WITH HIV TREATMENT OUTCOMES ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_795;
Patients who switched to DTG with a VL ?1000 copies/mL or without a recent VL test had worse HIV treatment outcomes than those who switched with a VL known to be suppressed. These patients should receive additional monitoring and possibly adherence support during and after the programmatic transition to DTG to prevent differentially adverse outcomes.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare, Isentress (raltegravir) / Merck (MSD)
IMPACT OF BRAZILIAN HEALTH POLICIES ON GENDER/AGE GAPS IN HIV TREATMENT INDICATORS ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_791;
However, remaining gaps are still evident, with lower proportions of older patients receiving timely ART, and lower proportions of children and women achieving VLS. Additional policies, including the implementation of new treatment options in the pediatric regimens, dolutegravir for pregnant women and women planning to conceive, and the promotion of HIV screening and early ART initiation for older adults, could further reduce HIV treatment gaps in Brazil.
- |||||||||| Prezista (darunavir) / J&J, Tivicay (dolutegravir) / ViiV Healthcare
GENERIC DARUNAVIR AND DOLUTEGRAVIR ARE COST-EFFECTIVE IN SECOND-LINE ART ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_778;
In most settings It is highly cost-effective to replace LPV/r and ATV/r with DRV/r with a less than 1x GDP threshold. The most optimal strategy is to maximize use of DTG in 2L, which was the most effective and cheapest scenario across all comparisons.
- |||||||||| abacavir/lamivudine / Generic mfg.
PHARMACOKINETICS/SAFETY OF DTG, ABC/3TC DISPERSIBLE TABLETS IN THAI CHILDREN ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_706;
DTG 20 mg in the lowest weight band produced higher drug exposure and C24. These initial data suggested that a DTG and ABC/3TC regimen with a slightly modified WHO weight band doses will be efficacious and safe for Thai children weighing <20 kg.
- |||||||||| zidovudine / Generic mfg.
TAF/TFV PHARMACOKINETICS WHEN GIVEN WITH PI/InSTI ART IN THE CHAPAS-4 PEDIATRIC TRIAL ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_704;
Pharmacokinetic (PK) data on the use of TAF with boosted protease inhibitors (PIs) and dolutegravir (DTG) in children is currently lacking...919 African children aged 3-15 years failing first-line ART were randomised to TAF versus standard of care (SOC: abacavir or zidovudine) and to DTG, atazanavir/r (ATV/r), darunavir/r (DRV/r) or lopinavir/r (LPV/r) in a factorial design and are being followed for 96 weeks...Further PK data collection is ongoing including measurement of intracellular TFV levels in dried blood spots and population pharmacokinetic modelling. Safety is being monitored in all children.
- |||||||||| rifampicin / Generic mfg.
SUBOPTIMAL LOPINAVIR EXPOSURE ON 8-HOURLY LPV/r 4:1 IN HIV/TB-COINFECTED CHILDREN ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_703;
LPV/r oral solution given in increased doses 8-hourly alongside rifampicin did not reach adequate LPV concentrations, and therefore unsuitable for HIV/TB co-infected children. The subtherapeutic exposures observed after TB treatment raise questions about the bioavailability of LPV/r oral solution in this population and supports the rapid transition to dolutegravir-based ART.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
HIGH DRUG RESISTANCE AND NEED FOR ART CHANGE IN CHILDREN WITH VIRAL FAILURE IN KENYA ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_698;
Another 12 (14%) CHIV underwent ART regimen change per facility staff as part of the national programmatic transition to dolutegravir (DTG).The CMC did not recommend an ART regimen change for the remaining 34 CHIV, the majority of whom (29; 85%) were on protease inhibitor (PI)-based ART without any major PI DR...Over 80% of CLHIV undergoing targeted DRT had major drug mutations detected and more than half required ART regimen change to address drug resistance and/or to optimize the regimen. Targeted use of DRT in CLHIV with VF may improve viral suppression, retention, and clinical outcomes.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
DOLUTEGRAVIR REVERSIBLY INDUCES MITOCHONDRIAL FRAGMENTATION AND TOXICITY IN VITRO ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_668;
Taken together, our findings suggest that DTG-containing regimens induce mitochondrial toxicity and fragmentation of mitochondrial networks, something not seen with RAL. Given that HIV treatment is life-long and the global use of DTG, further investigations are warranted to understand the mechanisms and long-term effects of these toxicities.
- |||||||||| Prezista (darunavir) / J&J, Tivicay (dolutegravir) / ViiV Healthcare
METABOLIC PERTURBATIONS BY INTEGRASE INHIBITORS IN DIFFERENTIATED HUMAN ADIPOCYTES ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_667;
The observed increases in lactate production and decreased oxygen consumption in preadipocytes and adipocytes treated with DTG indicate impairments in mitochondrial function. These alterations in metabolism combined with suppression of key regulatory adipokines may help explain the increased weight gain observed in individuals taking INSTIs.
- |||||||||| bictegravir (GS-9883) / Gilead
ADIPOCYTE DIFFERENTIATION AND ANTIRETROVIRAL DRUGS: AN IN VITRO MODEL ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_666;
Our results confirm that INSTIs could increase adipogenesis, while, on the other hand, in our 3T3L1 cells in vitro model of adipogenesis, TAF shows an inhibitory effect, being able to effectively contrast the increased adipogenesis caused by other INSTIs, in particular DTG and BIC. Taken together, these evidences are suggestive for an antagonistic effect on adipocyte differentiation by different antiretroviral drugs routinely used in therapeutic association.
|
