- |||||||||| [VIRTUAL] CABOTEGRAVIR AND RILPIVIRINE PK FOLLOWING LONG-ACTING HIV TREATMENT DISCONTINUATION ([VIRTUAL]) - Mar 2, 2020 - Abstract #CROI2020CROI_366;
Both CAB and RPV have a low drug interaction potential as perpetrators. Alternative ART selection after discontinuing CAB LA + RPV LA may include CYP3A and/or UGT1A1 inducers or inhibitors, without efficacy or safety concerns despite potential for transient increases in CAB and RPV concentrations by inhibitors.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
[VIRTUAL] SAFETY AND EFFICACY OF DTG VS EFV AND TDF VS TAF IN PREGNANCY: IMPAACT 2010 TRIAL ([VIRTUAL]) - Mar 2, 2020 - Abstract #CROI2020CROI_323;
Pregnant women with HIV-1 in 9 countries were randomized 1:1:1 to start open-label DTG+FTC/TAF, DTG+FTC/TDF, or EFV/FTC/TDF at 14-28 weeks gestational age (GA)...DTG+FTC/TAF had the lowest composite frequency of adverse pregnancy outcomes. Maternal and infant AE outcomes were similar by arm.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
[VIRTUAL] DOLUTEGRAVIR-CONTAINING ART DOES NOT REDUCE ETONOGESTREL IMPLANT CONCENTRATIONS ([VIRTUAL]) - Mar 2, 2020 - Abstract #CROI2020CROI_322;
Our findings suggest that no detrimental drug-drug interactions exist with concomitant use of ENG implants and DTG. DTG-containing ART represents a preferable alternative to efavirenz-containing ART for women already using or desiring an ENG implant.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
[VIRTUAL] PD-1 BLOCKADE AT TIME OF ART WITHDRAWAL FACILITATES EARLY POST-PEAK VIRAL CONTROL ([VIRTUAL]) - Mar 2, 2020 - Abstract #CROI2020CROI_310;
30 RM were IV inoculated with 200 ffu of SIVmac239 and after 12 days began receiving ART (tenofovir/emtricitabine/dolutegravir)...RM are continuing to be followed to determine long-term pvl set points. PD-1 blockade had no effect on reactivation and early spread of virus following ART release, but maintaining PD-1 blockade following ART release appears to facilitate early control of virus replication, likely by enhancing the functional activity of SIV-specific T cells expanding in response to SIV replication.
- |||||||||| rifampicin / Generic mfg., Tivicay (dolutegravir) / ViiV Healthcare
[VIRTUAL] ADEQUATE DOLUTEGRAVIR EXPOSURE DOSED BID WITH RIFAMPICIN IN CHILDREN 6 TO ([VIRTUAL]) - Mar 2, 2020 - Abstract #CROI2020CROI_290;
P2/3
AUC0-24h GMRs in children 20kg receiving WHO 2019-recommended DTG 50mg dose was 1.00 (0.61-1.62) and 1.47 (0.99-2.19) for children on 25mg dose. One child on DTG 25mg QD without RIF had Ctrough Twice daily dolutegravir dosing was safe and sufficient to overcome rifampicin enzyme-inducing effect in HIV/TB co-infected children aged 6-<18 years, including in children 20kg receiving new WHO doses (DTG 50mg).
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare, Vemlidy (tenofovir alafenamide) / Gilead, Vitekta (elvitegravir) / Japan Tobacco, Gilead
[VIRTUAL] GREATER WEIGHT GAIN AFTER SWITCH TO InSTI-BASED REGIMEN FROM NNRTI VS PI REGIMENS ([VIRTUAL]) - Mar 2, 2020 - Abstract #CROI2020CROI_277;
Women, non-whites and older PWH with viral suppression had greater annualized weight gain after switch from NNRTI- to INSTI-based ART, which was greatest for dolutegravir, whereas those switched from a PI had slowing of weight gain. These findings may reflect a heterogenous effect of ART class and agent on body weight regulation.
- |||||||||| efavirenz / Merck (MSD), Generic mfg., Tivicay (dolutegravir) / ViiV Healthcare
[VIRTUAL] CYP2B6 GENOTYPE AND WEIGHT-GAIN DIFFERENCES BETWEEN DOLUTEGRAVIR AND EFAVIRENZ ([VIRTUAL]) - Mar 2, 2020 - Abstract #CROI2020CROI_238;
In Africans starting EFV-based ART CYP2B6 metaboliser genotype was associated with weight gain and, in women, with changes in limb fat. The similar weight gain observed between CYP2B6 extensive metabolisers in the EFV/TDF/FTC arm and the DTG/TDF/FTC arm suggests off-target effects (e.g. mitochondrial toxicity) impairing weight gain in EFV slow/intermediate metabolisers could explain the greater weight gain observed with DTG in African trials.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
[VIRTUAL] POSTPARTUM WEIGHT CHANGES IN WOMEN INITIATING DTG VS EFV IN PREGNANCY: DOLPHIN-2 ([VIRTUAL]) - Mar 2, 2020 - Abstract #CROI2020CROI_193;
P3
There are growing concerns about weight gain with dolutegravir (DTG) use, with some suggestion of heterogeneity of effects across populations especially among women...DolPHIN-2 (NCT03249181) is an open label trial randomising (1:1) pregnant women from Uganda and South Africa (SA) initiating ART from 28w gestation to DTG vs efavirenz (EFV) plus 2 NRTIs...These randomised data show no differences in PP weight changes between DTG and EFV in women initiating ART late in pregnancy. Substantial PP weight gain among SA women points to potential heterogeneity across populations that requires further investigation.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
[VIRTUAL] POSTPARTUM WEIGHT CHANGES IN WOMEN INITIATING DTG VS EFV IN PREGNANCY: DOLPHIN-2 ([VIRTUAL]) - Mar 2, 2020 - Abstract #CROI2020CROI_192;
P3
There are growing concerns about weight gain with dolutegravir (DTG) use, with some suggestion of heterogeneity of effects across populations especially among women...DolPHIN-2 (NCT03249181) is an open label trial randomising (1:1) pregnant women from Uganda and South Africa (SA) initiating ART from 28w gestation to DTG vs efavirenz (EFV) plus 2 NRTIs...These randomised data show no differences in PP weight changes between DTG and EFV in women initiating ART late in pregnancy. Substantial PP weight gain among SA women points to potential heterogeneity across populations that requires further investigation.
- |||||||||| lamivudine / Generic mfg., Tivicay (dolutegravir) / ViiV Healthcare
[VIRTUAL] PROSPECTIVE ENHANCED MONITORING OF DOLUTEGRAVIR-BASED FIRST LINE IN MALAWI ([VIRTUAL]) - Mar 2, 2020 - Abstract #CROI2020CROI_157;
Among TLD-initiators, 54% had a CD4 count In a cohort highly suppressed on NNRTI-first-line ART, VL-suppression was well maintained at 6 months post-transitioning to TLD, and VL-suppression was high among the few ART-initiators. Of concern are 2 cases of DTG resistance detected after 6 months on TLD, emphasizing the importance of further monitoring and resistance surveillance
- |||||||||| bictegravir (GS-9883) / Gilead, Tivicay (dolutegravir) / ViiV Healthcare
[VIRTUAL] STRUCTURAL BASIS OF SECOND-GENERATION HIV INTEGRASE INHIBITOR ACTION AND VIRUS ESCAPE ([VIRTUAL]) - Mar 2, 2020 - Abstract #CROI2020CROI_147;
The expanded chemical scaffolds of the second-generation drugs mediate novel interactions with the protein backbone, which are critical for antagonising Q148H/G140S mutant virus. Our results reveal that binding to magnesium ions underpins a fundamental weakness of the INSTI pharmacophore that is exploited by the virus and provide structural framework for the development of this important class of anti-HIV/AIDS therapeutics.
- |||||||||| bictegravir (GS-9883) / Gilead, Tivicay (dolutegravir) / ViiV Healthcare
Enrollment change, Trial completion date, Trial withdrawal, Trial primary completion date, Adverse events: NEPALE: Evaluation of the Neurological and Psychiatric Adverse Events of Dolutegravir and Bictegravir in Real Life (clinicaltrials.gov) - Feb 27, 2020
P=N/A, N=0, Withdrawn,
N=400 --> 1 | Suspended --> Terminated; Unfavourable opinion of ethical comittee for Amendment Nr 3 N=360 --> 0 | Trial completion date: Aug 2021 --> Sep 2019 | Not yet recruiting --> Withdrawn | Trial primary completion date: Aug 2021 --> Sep 2019
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
Journal: Pregnancy and Neonatal Outcomes Following Prenatal Exposure to Dolutegravir. (Pubmed Central) - Feb 25, 2020
N=360 --> 0 | Trial completion date: Aug 2021 --> Sep 2019 | Not yet recruiting --> Withdrawn | Trial primary completion date: Aug 2021 --> Sep 2019 Our findings are reassuring regarding dolutegravir treatment of HIV infection during pregnancy but remain inconclusive due to small sample sizes.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare, abacavir/lamivudine / Generic mfg., Vemlidy (tenofovir alafenamide) / Gilead
Journal: HIV 101: fundamentals of antiretroviral therapy. (Pubmed Central) - Feb 25, 2020
Patients with continuously undetectable viral load on ART pose virtually no risk of transmitting infection through sexual contact. This article is based on a case-based presentation by Michael S. Saag, MD, at the 2018 Clinical Conference at the National Ryan White Conference on HIV Care & Treatment in December 2018 and intended for clinicians who are new to HIV disease management.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
Journal: Barrier to resistance of dolutegravir in two-drug combinations. (Pubmed Central) - Feb 22, 2020
We evaluated the emergence of drug-resistant mutants in a passage study with constant concentrations of two drugs simultaneously. The barrier to resistance of dolutegravir-containing two-drug combinations was higher than the other combinations evaluated in this study.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare, Vitekta (elvitegravir) / Japan Tobacco, Gilead
Clinical, Journal: Is there a safety signal for dolutegravir and integrase inhibitors during pregnancy? (Pubmed Central) - Feb 22, 2020
Nevertheless, our data do not support a pharmacovigilance signal on neural tube defects in women exposed to dolutegravir during pregnancy, as well as for raltegravir or elvitegravir. Due to a small number of pregnancy outcomes, these results need to be confirmed with further studies.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
Journal: HIV-1 integrase tetramers are the antiviral target of pyridine-based allosteric integrase inhibitors. (Pubmed Central) - Feb 22, 2020
Live cell imaging of single viral particles revealed that KF116 treatment during virion production compromises the tight association of IN with capsid cores during subsequent infection of target cells. We have synthesized the highly active (-)-KF116 enantiomer, which displayed EC of ~7 nM against wild type HIV-1 and ~10-fold higher, sub-nM activity against a clinically relevant dolutegravir resistant mutant virus suggesting potential clinical benefits for complementing dolutegravir therapy with pyridine-based ALLINIs.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
Review, Journal: Antiretroviral agents in pre-exposure prophylaxis: emerging and advanced trends in HIV prevention. (Pubmed Central) - Feb 22, 2020
Some of the most common pre-exposure prophylactic strategies employed currently are the use of inhibitors, namely entry inhibitors, non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, integrase and protease inhibitors. In addition, we have also discussed on the adverse effects caused by ART in PrEP, pharmacoeconomics factors and the use of antiretroviral prophylaxis in serodiscordant couples.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
Enrollment open: DO-REAL: Dolutegravir in Real Life in Lesotho (clinicaltrials.gov) - Feb 13, 2020
P=N/A, N=3000, Recruiting,
The low risk of treatment-limiting toxicities in ART-naïve as well as in treated individuals reassures on the use of DTG in everyday clinical practice. Not yet recruiting --> Recruiting
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
Trial completion, Trial completion date, Trial primary completion date: PRJ2203: Dolutegravir Post Authorization Safety Study (PASS) (clinicaltrials.gov) - Feb 6, 2020
P=N/A, N=1, Completed,
No abstract available Active, not recruiting --> Completed | Trial completion date: Jun 2019 --> Dec 2019 | Trial primary completion date: Jun 2019 --> Dec 2019
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
Enrollment closed, Trial completion date, Trial primary completion date: Clinical Trial to Evaluate the Efficacy, Pharmacokinetics (PK) Interactions and Safety of Dolutegravir Plus 2 Nucleoside Reverse Transcriptase Inhibitors (NRTIs) in HIV-1-Infected Solid Organ Transplant Patients (clinicaltrials.gov) - Feb 5, 2020
P4, N=20, Active, not recruiting,
Active, not recruiting --> Completed | Trial completion date: Jun 2019 --> Dec 2019 | Trial primary completion date: Jun 2019 --> Dec 2019 Recruiting --> Active, not recruiting | Trial completion date: Jan 2020 --> Jan 2021 | Trial primary completion date: Jan 2020 --> Jul 2020
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
Trial completion, Enrollment change: Effect of Dolutegravir on Etonogestrel Levels in HIV-infected Women in Botswana (clinicaltrials.gov) - Feb 5, 2020
P=N/A, N=148, Completed,
Recruiting --> Active, not recruiting | Trial completion date: Jan 2020 --> Jan 2021 | Trial primary completion date: Jan 2020 --> Jul 2020 Recruiting --> Completed | N=270 --> 148
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