- |||||||||| Difficult-to-Treat HIV in Sweden: Describing the Current Landscape (Poster hall) - Mar 16, 2024 - Abstract #CROI2024CROI_694;
Although 9% of the HIV cohort in Sweden in 2023 were classified as having difficult-to-treat HIV, a large proportion of these were virally suppressed. Challenges such as advanced resistance and need for salvage therapy are rare in the current Swedish cohort.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
Safety and Pharmacokinetics of Ultra-Long-Acting Dolutegravir In-Situ Forming Implant (Poster hall) - Mar 16, 2024 - Abstract #CROI2024CROI_608;
We demonstrated the first ULA injectable of DTG for HIV PrEP that can be removed if needed. This comprehensive study further characterized the PK tail via a full biodistribution, and future directions include safety, PK and efficacy studies in non-human primates.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
Cost-Effectiveness of a Urine Tenofovir Point-of-Care Assay for ART Adherence Feedback in Namibia (Poster hall) - Mar 16, 2024 - Abstract #CROI2024CROI_547;
Background: Virologic failure (VF) in patients on TLD often results from non-adherence given dolutegravir's high resistance barrier...The study evaluates the cost and cost-effectiveness of incorporating a POC urine TFV test into counseling for ongoing viremia on TLD; the intervention was less expensive and improved health compared to SoC. An upcoming clinical trial will compare SoC EAC to urine assay counseling in a large sample with further CE analysis with hopes of eventual wide implementation of the urine assay worldwide to reduce VF, viral resistance, and transmission.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
Retrospective data, Review, Adverse events: Comparative risk of adverse perinatal outcomes associated with classes of antiretroviral therapy in pregnant women living with HIV: systematic review and meta-analysis. (Pubmed Central) - Mar 13, 2024
Integrase strand transfer inhibitor (INSTI) dolutegravir (DTG)-based antiretroviral therapy (ART) is recommended by World Health Organisation as preferred first-line regimen in pregnant women living with human immunodeficiency virus (HIV) (WLHIV)...Specifically, lopinavir/ritonavir (LPV/r) was associated with an increased risk of SGA (RR 1.40, 95% CI [1.18, 1.65], p?=?0.003) and VSGA (RR 1.84, 95% CI [1.37, 2.45], p?=?0.002), compared to efavirenz, but not compared to nevirapine...Our findings support the recommendation of INSTI-ART as first-line ART regimen for use in pregnant WLHIV. However, the increased risks of SGA and VGSA associated with PI-ART, compared to NNRTI-ART, may impact choice of second- and third-line ART regimens in pregnancy.Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021248987.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
Journal: Epistatic pathways can drive HIV-1 escape from integrase strand transfer inhibitors. (Pubmed Central) - Mar 5, 2024
To elucidate INSTI resistance mechanisms, we propagated HIV-1 in the presence of escalating concentrations of the INSTI dolutegravir...We demonstrate that INSTIs are more readily overwhelmed by high MOI than other classes of antiretrovirals. Our findings advance the understanding of how HIV-1 can evolve resistance to antiretrovirals, including the potent INSTIs, in the absence of drug-target gene mutations.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
Long-Acting Dolutegravir Formulation Reduces Fetal Drug Exposure (Poster hall) - Mar 5, 2024 - Abstract #CROI2024CROI_511;
Our findings advance the understanding of how HIV-1 can evolve resistance to antiretrovirals, including the potent INSTIs, in the absence of drug-target gene mutations. This work suggests that long-acting drug delivery can prevent DTG-linked neurodevelopmental deficits by limiting drug exposure to the embryo brain.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
Pharmacogenetics of Dolutegravir During Rifapentine/Isoniazid Treatment of Latent TB in ACTG A5372 (Poster hall) - Mar 5, 2024 - Abstract #CROI2024CROI_501;
In PWH receiving DTG 50 mg twice daily with 1HP, AADAC rs1803155 was associated with lower day-28 DTG trough (still >324 ng/mL, the DTG EC90 for wild-type HIV-1), likely due to higher RPT concentrations causing greater hepatic enzyme induction. Individuals with concomitant AADAC slow metabolizer + UGT1A1 normal metabolizer genotypes (17% of Africans, 15-30% of people worldwide) may be at risk for low DTG trough concentrations with once daily DTG and RPT.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
48-Week Outcomes After Programmatic Transition to Dolutegravir in South Africa (Poster hall) - Mar 5, 2024 - Abstract #CROI2024CROI_484;
However, using an observational cohort approach with intensive outcome monitoring, only 81% of participants were virally suppressed and in care at 48 weeks. Over half of those who did not achieve the primary endpoint were lost from care or deceased.
- |||||||||| bictegravir (GS-9883) / Gilead
Bictegravir as Universal Initial Antiretroviral Therapy: A National Target Trial Emulation Study (Poster hall) - Mar 5, 2024 - Abstract #CROI2024CROI_482;
Over half of those who did not achieve the primary endpoint were lost from care or deceased. Background: Bictegravir (BIC) has been shown to be non-inferior to dolutegravir (DTG) as initial antiretroviral therapy (ART) in non-inferiority randomized controlled trials (RCTs)...However, BIC has not been compared to efavirenz (EFV) or raltegravir (RAL) (commonly prescribed in Mexico) and no superiority trials have been performed.We used data from the national antiretroviral surveillance system in Mexico to perform three target trial (TT) emulations for initial ART among PWH starting ART from 2019 onwards: BIC vs DTG, BIC vs EFV, and BIC vs RAL...People with missing viral load (VL), VL <500 copies/mm3, and/or missing CD4 count within the last year before ART start, those started on double-dose DTG and/or reduced-dose emtricitabine, lamivudine or tenofovir disoproxil fumarate were excluded...BIC is superior to RAL and EFV, but not DTG, as initial ART in treatment na
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
HIV Detectable Low-Level Viremia Suggests a Revised Threshold for Viral Suppression in Cameroon (Poster hall) - Mar 5, 2024 - Abstract #CROI2024CROI_480;
Background: Transitioning to dolutegravir-based therapy in Cameroon has improved viral suppression (VS) rates, known as low-level viremia (LLV) <1000copies/ml...Even though VS rate appears encouraging, there is a significant increasing proportion of patients with detectable LLV in this DTG-era. Of note, LLV with 50-200 copies appears highly predominant, suggesting a revision of threshold for VS at a maximum of 200 copies/ml in resource-limited settings like Cameroon.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
Role of Dolutegravir in the Emergence of the S147G Integrase Resistance Mutation (Poster hall) - Mar 5, 2024 - Abstract #CROI2024CROI_475;
In such a context it can be associated with up to 6 other INSTI-RM, including T97A and/or N155H in the majority of cases. Thus the S147G mutation needs to be added to the DTG resistance profile in the ANRS algorithm.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
High-Level Resistance to Integrase Inhibitors Conferred by Mutations Outside Integrase (Poster hall) - Mar 5, 2024 - Abstract #CROI2024CROI_473;
Thus the S147G mutation needs to be added to the DTG resistance profile in the ANRS algorithm. The aim of the study is to elucidate INSTI resistance mechanisms and pathways.One-year passaging of HIV-1 was conducted using the SupT1 T-cell line and primary PBMCs with an escalating concentration of the INSTI dolutegravir (DTG)...These findings demonstrate that multiple regions in the HIV-1 genome
- |||||||||| bictegravir (GS-9883) / Gilead, Tivicay (dolutegravir) / ViiV Healthcare, Vitekta (elvitegravir) / Japan Tobacco, Gilead
Weight Gain After Initiating ART Close to HIV Seroconversion: Is There a Return to Health Effect? (Poster hall) - Mar 5, 2024 - Abstract #CROI2024CROI_413;
As reported in seroprevalent cohorts, Bictegravir and Elvitegravir combined with TAF were associated with the fastest increases in weight. Given that ART was initiated soon after SC, it is unlikely that this is a return to health phenomenon, although the effect of unmeasured confounders can't be disregarded.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
Dolutegravir Targets the Hypothalamus to Suppress Energy Expenditure via Estrogen Receptor (Poster hall) - Mar 5, 2024 - Abstract #CROI2024CROI_412;
Tissue analyses revealed that DTG activates the hypothalamic AMPK pathway, which suppresses thermogenesis. In vitro study using murine primary hypothalamic neurons and human hypothalamic organoids showed that DTG inhibits estrogen-mediated hypothalamic regulation of thermogenesis.
- |||||||||| Switching to Integrase Strand Transfer Inhibitors and the Risk of Diabetes in Persons With HIV (Poster hall) - Mar 5, 2024 - Abstract #CROI2024CROI_410;
PWH who switched to bictegravir, dolutegravir, elvitegravir, or raltegravir were assigned to the INSTI group and PWH who were continued on an NNRTI or PI were assigned to the non-INSTI group...We adjusted for age, sex, race, year of cohort entry, body mass index, coronary artery disease, chronic kidney and liver diseases, cerebrovascular disease, dyslipidemia, heart failure, hypertension, and co-prescription of anticoagulants, antidepressants, antihypertensives, antiplatelets, antipsychotics, antilipemics, tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide fumarate (TAF).Our sample included 2,354 PWH, of whom 891 PWH switched to an INSTI and contributed an encounter to the INSTI group...Switching from an NNRTI or PI to INSTI-based ART did not appreciably increase the risk of incident diabetes. These findings can inform antiretroviral prescribing in the common clinical scenarios, where switching to INSTI-based therapy is considered in the care of PWH.
- |||||||||| efavirenz / Generic mfg.
TDF and Efavirenz but Not InSTI or TAF Use Are Associated With Weight Gain During cART (Poster hall) - Mar 5, 2024 - Abstract #CROI2024CROI_404;
Background: Combination antiretroviral therapy (cART) containing integrase strand transfer inhibitors (INSTIs) and/or tenofovir alafenamide (TAF) has been associated with greater weight gain (WG) than cART without these drugs...From 2008-2022 we studied all patients who initiated cART with either dolutegravir (DTG), bictegravir, elvitegravir, raltegravir, atazanavir, darunavir (DRV), rilpivirine (RIL), or efavirenz (EFV) as exclusive anchor drug if used in combination with either TAF, tenofovir disoproxil fumarate (TDF), or abacavir (ABC) as backbone...Over a 15-year period, our demographically diverse patient population experienced substantial WG in the first 3 years after cART initiation. Among 11 examined ARVs, only EFV and TDF were independently associated with (decreased) WG.
- |||||||||| Pharmacogenetic Associations With HIV-1 Virologic Suppression Among Patients with TB/HIV in Brazil (Poster hall) - Mar 5, 2024 - Abstract #CROI2024CROI_379;
Among 11 examined ARVs, only EFV and TDF were independently associated with (decreased) WG. Here we evaluated associations between pre-specified genetic variants and HIV virologic suppression (VS) among patients treated for TB and HIV.We included TB/HIV RePORT-Brazil participants who initiated standard TB treatment [2 months of isoniazid/rifampicin (or rifabutin)/pyrazinamide/ethambutol, then 4 months or more of isoniazid/rifampicin (or rifabutin)], and who also received antiretroviral therapy (ART) during this period...We genotyped [i]UGT1A1[/i] rs887829 that affects dolutegravir (DTG) and raltegravir (RAL) PK, and [i]CYP2B6[/i] rs3745274, rs28399499, rs4803419 that affect efavirenz (EFV) PK; all have defined normal, intermediate, and poor metabolizer groups...RAL was the most frequent INSTI (n=88, 88%), and EFV the most frequent NNRTI (n=76, 99%; and one participant used etravirine)...In this cohort of patients treated for TB/HIV, genetic variants that affect ART PK were not significantly associated with likelihood of VS.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
High Prevalence of Depression and Anxiety in Women Without HIV and Women With HIV on DTG-ART (Poster hall) - Mar 5, 2024 - Abstract #CROI2024CROI_360;
Compared to women without HIV, women living with HIV on DTG-based ART had numerically higher prevalence of depression, anxiety, and suicide ideation, but differences were not statistically significant We referred more than 20% of women for mental health services. Additional mental health services are urgently needed to meet the high demand.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
Dolutegravir Versus Efavirenz: Depression, Anxiety, and Sleep Disorders in Pregnancy and Postpartum (Poster hall) - Mar 5, 2024 - Abstract #CROI2024CROI_359;
No statistically significant differences were observed across these measures between pregnant and post-partum women treated with efavirenz- or dolutegravir containing regimens. Rates of depression on the EPDS were high, but decreased over the course of time and confirm the need for psychological support after initial HIV diagnosis in pregnancy.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare, Vemlidy (tenofovir alafenamide) / Gilead
Breast Milk Transfer and Infant Exposures to DTG, TAF, and TFV: Results From IMPAACT 2010/VESTED (Poster hall) - Mar 5, 2024 - Abstract #CROI2024CROI_354;
We evaluated concentrations of these antiretroviral (ARV) drugs in time-matched samples (maternal plasma, breast milk, and infant plasma) in a post hoc analysis of IMPAACT 2010, a randomized trial that evaluated three ARV treatment regimens in pregnancy.Pregnant women with HIV in 9 countries were randomized 1:1:1 to start open-label ART with DTG+emtricitabine (FTC)/TAF, DTG+FTC/tenofovir disoproxil fumarate (TDF), or efavirenz (EFV)/FTC/TDF at 14-28 weeks of gestation...Breast milk transfer of DTG, TAF, and TFV is low and results in minimal systemic exposure in predominantly breastfed infants. The clinical relevance of subtherapeutic concentrations of these ARVs in breast milk is unknown but should be considered in the context of risk of drug resistance in infants who acquire HIV.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
Strategic Advice and Expert Procurement Accelerates the Optimization to DTG in the Americas (Poster hall) - Mar 5, 2024 - Abstract #CROI2024CROI_283;
Background: The WHO guidelines recommend dolutegravir (DTG) as the preferred anchor drug for first-line ART, as for second-line ART after a NNRTI failure...SF and PAHO technical cooperation increased the access to generic DTG-based ART for adults and children in Latin America and the Caribbean. The transition to DTG represented significant savings due to the lower price of DTG compared to non-DTG regimens, in particular for children, which was a strong incentive for transitioning to more effective and safer treatments in the Region.
- |||||||||| dolutegravir/emtricitabine/tenofovir alafenamide (DTG/FTC/TAF) / Viatris, Tivicay (dolutegravir) / ViiV Healthcare
Elevated Plasma IL-10 and Type I Interferon Predict Faster HIV Reservoir Decay in Acute Treated HIV (Poster hall) - Mar 5, 2024 - Abstract #CROI2024CROI_260;
These cytokines are well known to exert variable effects on the host immune response depending on stage of disease (e.g., favorable during acute but detrimental during chronic infection). Our findings add insight into the complexity of these pleiotropic cytokines and highlight the need for potential stage-specific targeting of these cytokines in future HIV cure strategies.
- |||||||||| Observational data, Journal: Virologic outcomes on dolutegravir-, atazanavir-, or efavirenz-based ART in urban Zimbabwe: A longitudinal study. (Pubmed Central) - Feb 27, 2024
Notably, from week 48 onward, VL suppression seemed to stabilize across all regimen groups, with an estimated 89.1% (95% CrI 86.9-90.9%) VL suppression in EFV, 74.5% (95%-CrI 68.0-80.7%) in DTG, and 72.9% (95%-CrI 69.5-76.1%) in ATV/r at week 48, showing little change for longer follow-up times. Virologic monitoring and adherence support remain essential even in the DTG era to prevent second-line treatment failure in settings with limited treatment options.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
Journal: Comprehensive Analysis of HIV-1 Integrase Resistance-Related Mutations in African Countries. (Pubmed Central) - Feb 23, 2024
The growing emergence of non-nucleoside reverse transcriptase inhibitor (NNRTI) HIV drug resistance in sub-Saharan Africa (SSA) led to the World Health Organization (WHO) recommending, in 2018, a transition to dolutegravir (DTG) as a first-line antiretroviral therapy (ART) in SSA...The variability of accessory INSTI-DRMs depended on the HIV subtypes, with implications for susceptibility to DTG. Our findings provide new perspectives on the molecular epidemiology and drug resistance profiles of INSTIs in SSA, emphasizing the need for ongoing surveillance and customized treatment approaches to address the continent's varied HIV subtypes and changing resistance patterns.
- |||||||||| rifampicin / Generic mfg.
Trial completion date, Trial primary completion date: ORCHID: Pharmacokinetics of Twice or Once Daily DTG (50mg) in Children With HIV and TB (clinicaltrials.gov) - Feb 15, 2024
P4, N=20, Recruiting,
Therefore, baseline blood glucose, lipid profiles, and high-sensitivity C-reactive protein levels should be routinely measured in patients on these regimens. Trial completion date: Feb 2023 --> Jul 2025 | Trial primary completion date: Aug 2022 --> Jul 2025
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