- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
WEIGHT CHANGE FOLLOWING SWITCH TO DOLUTEGRAVIR IN RURAL KENYA ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_663;
In contrast to reports of weight gain following switch to DTG in high-income settings, we observed slightly less weight increase than predicted based on pre-switch trajectory among ART-experienced adults in rural Kenya. When restricting to those on TDF pre and post-switch, switch from NNRTI to DTG was not associated with weight gain except in those underweight at switch.
- |||||||||| bictegravir (GS-9883) / Gilead
PHARMACOGENETICS OF WEIGHT GAIN AFTER SWITCH TO INTEGRASE INHIBITOR-BASED REGIMENS ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_662;
In a prior study of 101 PWH who switched from efavirenz (EFV)- to INSTI-based ART, CYP2B6 genotypes (which predict higher plasma EFV levels) were associated with greater post-switch weight gain...174 eligible participants switched ART from 2007 to 2019, with 80 normal, 75 intermediate, and 19 poor CYP2B6 metabolizers; 147 males and 27 females; 93 White, 51 Black, and 27 Hispanic participants; 70 switched to dolutegravir (DTG), 55 to raltegravir (RAL), 41 to elvitegravir (EVG), and 8 to bictegravir...CYP2B6 poor metabolizer genotype was associated with greater weight gain after switch from EFV- to INSTI-based ART, but results were inconsistent. Weight gain in this setting is likely complex and multifactorial.
- |||||||||| Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide) / Gilead
HIV-1 RNA DECAY IN SEMEN AND RECTUM WITH DTG PLUS 3TC VERSUS BIC/FTC/TAF ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_643;
HIV decay in semen and rectum have not yet been described for the dual combination dolutegravir (DTG) plus lamivudine (3TC)...At week 12 and week 24 most subjects had HIV-1 RNA <20 copies per mL (or swab) in BP, SP and RF (Table 1). Both DTG+3TC and BIC/F/TAF achieved rapid HIV-1 RNA suppression in SP and RF and no significant differences were observed between treatment groups in all study timepoints from BL through week 24.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
LONG-TERM OUTCOMES OF DOLUTEGRAVIR AND EFAVIRENZ-400 AS FIRST-LINE ART IN CAMEROON ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_641;
Fourth-year of follow-up of HIV-1 infected ARV-naive adults in LMIC, who started on DTG-based and low-dose EFV-based regimen, suggested superiority of DTG based regimen; low EFV-related and no DTG-related resistance mutations rates were observed. However, weight gain tendency is important among women on DTG, a close cardiovascular and metabolic monitoring should be recommended to take into account risks related to weight-gain.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
48-WEEK OUTCOMES AFTER PROGRAMMATIC TRANSITION TO DOLUTEGRAVIR IN UGANDA ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_635;
Nonetheless, an 8% failure rate in HIV-endemic countries corresponds to a large population of individuals. Long-term surveillance of this population, strategies to combat imperfect adherence, and continued attention to treatment options after failure on TLD may be needed.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
RESUPPRESSION AFTER VIROLOGICAL FAILURE IN DOLUTEGRAVIR AND EFAVIRENZ-BASED REGIMENS ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_634;
In ADVANCE and NAMSAL, participants taking DTG regimens with HIV RNA >1,000 copies/mL after being suppressed were more likely to resuppress without a change in treatment with low rates of resistance. EFV based regimens were more likely to show sustained viremia and higher resistance compared to DTG based regimens.
- |||||||||| bictegravir (GS-9883) / Gilead
2DR VS 3DR INTEGRASE INHIBITOR-BASED REGIMENS INITIATION AND CD4+/CD8+ RATIO RECOVERY ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_630;
This study provides new evidence that CD4/CD8 ratio recovery rates are similar during the first 48 weeks after ART initiation with 2DR or 3DR INSTI-based therapies. Next studies should address the potential long-term differences between these strategies.
- |||||||||| Prezista (darunavir) / J&J, Tivicay (dolutegravir) / ViiV Healthcare
SWITCHING TO A NRTI-FREE 2 DRUG REGIMEN (2DR) – A SUB-ANALYSIS OF THE DUALIS STUDY ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_628;
Switching from a three-drug regimen (3DR: boosted darunavir [bDRV] and two nucleoside reverse transcriptase inhibitors [NRTIs]) to a two-drug regimen (2DR: bDRV and dolutegravir) demonstrated non-inferiority with regard to viral suppression in people living with HIV (PLWH) in the DUALIS study...In the 3DR arm, a switch to the tenofovir alafenamid-backbone during the study period resulted in an increase in body weight by +0.5 (-0.8 to +4.0) kg and in BMI by +0.2 (-0.3 to +1.2) kg/m2...The LDL-fraction changed by + 8.0 (-3.0 to +27.0) mg/dL on TAF versus -1.0 (-14.0 to +16.0) mg/dL on TDF (p=0.1043). While being non-inferior in terms of viral suppression, sparing the NRTI backbone showed no advantages in metabolic or renal parameters over 48 weeks.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
TENOFOVIR URINE POINT-OF-CARE TEST PREDICTS VIREMIA AND DRUG RESISTANCE DURING ART ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_625;
P3
Recommended first-line ART in low- and middle-income countries (LMIC) is dolutegravir (DTG), tenofovir disoproxil fumarate (TDF), and lamivudine (3TC) or emtricitabine (FTC) accompanied by annual HIV viral load (VL) testing for treatment monitoring...We performed a nested case-control study within the ADVANCE RCT (NCT03122262) in which HIV-infected adults newly initiating ART were randomized to receive either DTG/TAF/FTC, DTG/TDF/FTC or EFV/TDF/FTC...In participants with viremia, a positive urine TFV test indicated a higher risk of resistance to the NRTI backbone, which may confer an increased risk of selection of integrase resistance. These results support clinical implementation of POC TFV urine detection to rapidly provide insight into adherence, suppression, and drug resistance during ART in LMIC.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
TRANSFORMATION OF DOLUTEGRAVIR INTO A YEAR-LONG PARENTERAL PRODRUG FORMULATION ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_622;
The extended NM2DTG PK profile paralleled nanocrystal dissolution and pH-dependent prodrug activation. NM2DTG produced plasma DTG levels at or above the PA-IC90 for one year following a single intramuscular injection in rodents.
- |||||||||| bictegravir (GS-9883) / Gilead
REVERSIBILITY OF CENTRAL NERVOUS SYSTEM ADVERSE EVENTS IN COURSE OF ART ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_613;
Central nervous system (CNS) adverse events (AE) can occur during various antiretroviral therapies (ART), as well as being a major cause of treatment discontinuation during dolutegravir-containing ART (DTG)...Sixty SNC-AE leading to ART discontinuation were reported, 26/3613 (0.7%) in non DTG-cohorts (2/731 lopinavir, 1/616 atazanavir, 2/721 darunavir, 8/421 rilpivirine, 5/514 raltegravir, 3/339 elvitegravir and 5/211 bictegravir), and 34/1138 (3.1%) in DTG-cohort...AE leading to ART discontinuation were more frequent in DTG than non-DTG treated PLWH. However, most AE resolved after ART switch, with similar frequency in DTG and non-DTG cohorts.
- |||||||||| Vemlidy (tenofovir alafenamide) / Gilead
TENOFOVIR ALAFENAMIDE IS ASSOCIATED WITH SHORTER TELOMERE LENGTH IN PEOPLE WITH HIV ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_599;
The inconsistent findings between TAF and TDF may be because intracellular TFV concentrations are higher with TAF than with TDF. A limitation is that TAF was not used at the first visit since it was not yet approved for clinical use so the findings should be confirmed in controlled trials.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
CHANGES IN THE HIV-1 3′-PPT IN PATIENTS FAILING DOLUTEGRAVIR IN BRAZIL ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_560;
In the remaining 3 patients, mutations were detected at the 8th or 9th position of the 3′-PPT (borderline significant due to low numbers), which are relatively conserved suggesting selection of these mutations by selective pressure of DTG. The phenotypic effect of the 3′-PPT mutations detected here on INSTI susceptibility and HIV-1 replication capacity are still unknown and will be investigated further.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare, Vemlidy (tenofovir alafenamide) / Gilead
HIV DRUG RESISTANCE IN WOMEN RANDOMIZED TO DTG VS EFV OR TDF VS TAF IN PREGNANCY ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_557;
We compared VF and HIVDR by study arm in IMPAACT 2010, a randomized trial of 3 ART regimens started in pregnancy (DTG+emtricitabine (FTC)/tenofovir alafenamide (TAF); DTG+FTC/tenofovir disoproxil fumarate (TDF); or efavirenz (EFV)/FTC/TDF...Women in the EFV arm were more likely to experience VF and to select new HIVDR mutations at VF compared to the DTG arms. While VF was uncommon with DTG, it is notable that mutations to DTG were seen in one woman during a relatively short treatment period.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
HOW MUTATIONS IN THE HIV-1 3’-POLYPURINE TRACT CONFER DOLUTEGRAVIR RESISTANCE ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_555;
The mutations stimulate production of a non-integrating (episomal) DNA intermediate, which may allow a low level of integration-independent HIV replication. Further analysis of the mechanism of PPT-mediated DTG-resistance and the impact on viral fitness is important for a complete understanding of this potent and very popular drug class.
- |||||||||| bictegravir (GS-9883) / Gilead, Tivicay (dolutegravir) / ViiV Healthcare
PHARMACOKINETICS OF DOLUTEGRAVIR AND BICTEGRAVIR IN OBESE PEOPLE LIVING WITH HIV ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_542;
PBPK modelling is a useful tool to overcome limited clinical data. Our predictions verified with clinical data indicate that obesity has a modest effect on the pharmacokinetics of dolutegravir and bictegravir which does not warrant a dosage adjustment in this special population.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
PREDICTORS OF NEURODEVELOPMENT IN HIV-EXPOSED–UNINFECTED INFANTS ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_449;
Among HEU infants, 50% received AZT+NVP regimens and 63% were exposed to maternal dolutegravir (DTG)...The mechanism underlying higher neurodevelopment scores with maternal ART duration and infant combination ART is unclear and could reflect undetected differences in infant exposure to maternal virus or other factors. Longitudinal evaluation will be useful to discern biologic and sociocultural determinants of neurodevelopment among HEU infants.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
SIMILAR EARLY GROWTH IN HEU AND HUU INFANTS WITH MATERNAL ART OPTIMIZATION ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_448;
While early growth differences between HIV exposed uninfected (HEU) and HIV unexposed uninfected infants (HUU) have been demonstrated, it is not known if these persist in the era of optimized maternal antiretroviral therapy (ART), including dolutegravir (DTG)...All WLHIV were on ART in pregnancy with 62% on DTG-based and 29% on Efavirenz-based regimens...HEU infants had similar growth in early infancy compared to HUU peers. Optimized maternal ART regimens and early ART initiation may result in similar early growth among HEU infants.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
ACCUMULATION OF HIV-1 Env MUTATIONS LEADS TO HIGH-LEVEL RESISTANCE TO DOLUTEGRAVIR ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_437;
High-level DTG resistance in culture can arise via the accumulation of multiple Env mutations. These findings advance the understanding of how HIV-1 can evolve resistance antiretrovirals including the potent INSTI DTG in the absence of mutations in genes targeted by the drug.
- |||||||||| Prezista (darunavir) / J&J, Tivicay (dolutegravir) / ViiV Healthcare
NUCLEOSIDES AND DARUNAVIR/DOLUTEGRAVIR IN AFRICA (NADIA) TRIAL: OUTCOMES AT 96 WEEKS ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_392;
Tenofovir is superior to zidovudine and may protect against dolutegravir resistance. Guidelines that recommend switch from tenofovir to zidovudine for second-line therapy in the public health approach should be reconsidered.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
A RANDOMIZED TRIAL OF SWITCHING TREATMENT-EXPERIENCED ADULTS FROM PI/r TO DTG ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_391;
Dolutegravir (DTG) has shown good efficacy and tolerability among treatment-experienced adults with HIV...Participants discontinuing study drug due to any AE was 1 (0.3%) on DTG and 3 (0.8%) on PI/r. Switching from PI/r to DTG may be an effective and safe strategy for treatment-experienced virally suppressed adults with no prior INSTI-exposure, even without knowledge of prior resistance.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
DOLUTEGRAVIR WITH RECYCLED nRTIs IS NONINFERIOR TO PI-BASED ART: VISEND TRIAL ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_390;
We conducted a 144 week, randomized, open-label, phase 3 noninferiority trial in Zambia where we randomized adults on tenofovir disoproxil fumarate (TDF), lamivudine (3TC) plus efavirenz (EFV) or nevirapine (NVP)...In Arm B, those with VL ?1000 copies/mL were randomized to TLD, TAFED, or the standard-of-care (SOC) second line protease inhibitor (PI/r)-based regimen lopinavir/ritonavir (LPV/r) or atazanavir/r (ATV/r), zidovudine (ZDV), 3TC...In the VISEND trial, HIV-positive adults with virologic failure to TDF/3TC/NNRTI, had favorable outcomes when switched to DTG with either TAF/FTC or TDF/3TC compared to those switched to SOC boosted-PI ART. Women receiving DTG, however, due to significant weight gain, may be at heightened risk for non-communicable diseases and/or metabolic complications hence longer-term follow up is needed.
- |||||||||| Selzentry (maraviroc) / ViiV Healthcare, Tivicay (dolutegravir) / ViiV Healthcare
ACTG A5324: A RANDOMIZED TRIAL OF ART INTENSIFICATION FOR COGNITIVE IMPAIRMENT IN PWH ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_384;
Participants were randomized to add dolutegravir (DTG)+ MVC, DTG+ placebo, or dual placebo, then repeated NP testing at weeks 24, 48, 72, and 96...Participants who received DTG+MVC had greater increases in CD4+ and CD8+T-cells than those in the other arms. The trial result does not support empiric ART intensification as a treatment for cognitive impairment in PWH on suppressive ART.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
IS THERE A ROLE OF NOVEL ART REGIMENS IN THE DECLINING PREVALENCE OF HAND? ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_383;
Main characteristics at NPA were: male 82%, MSM 45%, HCVAb+ 22%, median (IQR) of 10 (4-20) years of infection and 13 (8-14) of education; HIV-RNA <40 cp/mL in 85%, median CD4+of 600 (419-790) cell/mm3, nadir CD4+<200 cell/mm3 in 35%; 42% of pts were receiving NRTI+NNRTI, 19% NRTI+bPI, 18% NRTI+INSTI, 8% a dual regimen (4% INSTI-based); 8% of pts received dolutegravir...In this large cohort of ART-treated PLWH, mostly virologically suppressed, we observed a clear decrease in HAND prevalence over the last decade. Besides HIV-related factors and patient characteristics, the reduced risk of HAND observed with dual and INSTI-based regimens along with a more recent initiation of ART, could suggest a potential role of new treatment strategies in this decline, due to their greater virological efficacy and better tolerability.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
THE IMPACT OF FREE ANTIRETROVIRAL THERAPY FOR NONCITIZEN PREGNANT WOMEN IN BOTSWANA ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_341;
Use of dolutegravir (DTG)-based ART increased post-expansion in non-citizens (42.7% vs. 6.7%, p<0.0001), as in citizens (44.6% vs 21.5%, p<0.0001)...Following the expansion of free ART to non-citizens in Botswana, gaps narrowed in antenatal care and ART use in pregnancy between citizens and non-citizens living with HIV. Prior disparities in adverse birth outcomes were no longer observed following the expansion of free DTG-based ART to non-citizens.
- |||||||||| Vocabria (cabotegravir oral) / ViiV Healthcare, Tivicay (dolutegravir) / ViiV Healthcare
LONG-ACTING INJECTABLE FOR PREVENTION OF HIV AND UNPLANNED PREGNANCY ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_325;
ISFIs were loaded with one of two ARVs, dolutegravir (DTG) or cabotegravir (CAB), and one of two contraceptives, etonogestrel (ENG) or medroxyprogesterone acetate (MPA)...Furthermore, plasma concentrations of ENG and MPA were at, or above target levels based on their marketed products (Nexplanon® and Depo-Provera®) for 90 days and MPA demonstrated zero-order release kinetics...Our results demonstrated (1) the ability to co-formulate an ARV (DTG or CAB) and contraceptive (ENG or MPA) in a single ISFI, (2) sustained and target drug release kinetics in vivo for 90 days and (3) all formulations were safe and well-tolerated. Future studies include assessing PK and efficacy in non-human primates.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
DTG PK IN PEOPLE WITH HIV RECEIVING DAILY 1HP FOR LATENT TB TREATMENT (ACTG A5372) ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_319;
RPT is a known inducer of drug metabolizing enzymes and may decrease dolutegravir (DTG) concentrations and increase the risk of virologic failure...A decrease in trough concentrations from day 3 to 28 is suggestive of a time dependent induction of DTG metabolism by RPT/INH. These interim PK, virologic suppression, and safety data provide evidence for twice daily DTG in combination with the 1HP regimen.
- |||||||||| Roctavian (valoctocogene roxaparvovec) / BioMarin
VALOCTOCOGENE ROXAPARVOVEC GENE TRANSFER IN PARTICIPANTS WITH HIV ([VIRTUAL]) - Jan 28, 2022 - Abstract #EAHAD2022EAHAD_332;
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.
- |||||||||| Trial completion, Trial completion date, Trial primary completion date, Combination therapy: Bictegravir/Emtricitabine/Tenofovir Alafenide Plus Doravirine (clinicaltrials.gov) - Jan 28, 2022
P4, N=20, Completed,
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. Active, not recruiting --> Completed | Trial completion date: Apr 2021 --> Nov 2021 | Trial primary completion date: Apr 2021 --> Nov 2021
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
Review, Journal: CNS Considerations in ART Simplification Strategies. (Pubmed Central) - Jan 27, 2022
In cases of related neurotoxicity, switching from either efavirenz (EFV) or DTG to another equally effective drug with better CNS tolerability usually leads to complete resolution of CNS symptoms. However, improvement may be incomplete when factors other than ART that cannot be easily modified are involved.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
Trial completion: Second-line Switch to Dolutegravir Study (clinicaltrials.gov) - Jan 27, 2022
P4, N=795, Completed,
This performance underscores its usefulness in monitoring integrase-resistance mutations and supporting the scale-up of dolutegravir-based regimens in LMICs. Active, not recruiting --> Completed
- |||||||||| Prezista (darunavir) / J&J
ACUTE KIDNEY INJURY DUE TO CRYSTAL NEPHROPATHY SECONDARY TO DARUNAVIR (Poster Area (Virtual)) - Jan 21, 2022 - Abstract #ISNWCN2022ISN_WCN_562;
Protease inhibitors cause kidney damage, which can manifest as crystalluria, leukocyturia, nephritis, nephrolithiasis, nephropathy and urolithiasis, secondary to the fact that they are poorly soluble in urine and tend to precipitate in the urine at physiological pH. In our case, the patient presented a significant improvement in renal function after withdrawal of Darunavir and initiation of prednisone.
- |||||||||| zidovudine / Generic mfg.
PK/PD data, Review, Journal: A Review on Pharmacokinetics properties of antiretroviral drugs to treat HIV-1 infections. (Pubmed Central) - Jan 18, 2022
These drugs are Fuzeon, Selzentry, Complera, Epivir, Retrovir, Emtriva, Ziagen, Edurant, Intelence, Pifeltro, Sustiva, Viramune, Isentress, Genvoya, Tivicay, Reyataz, Prezista, Lexiva, Invirase, Aptivus etc. classified into five major classes: fusion inhibitors, Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs), Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs), Integrase Strand transfer inhibitors (INSTIs) and Protease inhibitors (PIs). This review may be helpful for the future development of potent antiretroviral drugs with improved pharmacokinetic properties.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
Clinical, Journal: Dolutegravir as First- or Second-Line Treatment for HIV-1 Infection in Children. (Pubmed Central) - Jan 13, 2022
P2/3
In this trial involving children and adolescents with HIV-1 infection who were starting first- or second-line treatment, dolutegravir-based ART was superior to standard care. (Funded by ViiV Healthcare; ODYSSEY ClinicalTrials.gov number, NCT02259127; EUDRACT number, 2014-002632-14; and ISRCTN number, ISRCTN91737921.).
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