- |||||||||| bictegravir (GS-9883) / Gilead, Tivicay (dolutegravir) / ViiV Healthcare, Vitekta (elvitegravir) / Japan Tobacco, Gilead
Retrospective data, Review, Journal: Meta-analysis and systematic review of the efficacy and resistance for human immunodeficiency virus type 1 integrase strand transfer inhibitors. (Pubmed Central) - Mar 5, 2020
Pooled analysis of resistance data indicated that development of resistance to DTG and bictegravir (BIC) was rare, while EVG and RAL had low genetic barriers to resistance and that the intensive cross-resistance between them limits INSTI efficiency. Efficient means of monitoring emergence of resistance to INSTIs and development of drugs with high genetic barriers are clear paths for future research.
- |||||||||| bictegravir (GS-9883) / Gilead, Tivicay (dolutegravir) / ViiV Healthcare, Vitekta (elvitegravir) / Japan Tobacco, Gilead
[VIRTUAL] RESISTANCE TO INTEGRASE STRAND TRANSFER INHIBITORS AMONG MSM IN THE US: HPTN 078 ([VIRTUAL]) - Mar 2, 2020 - Abstract #CROI2020CROI_1239;
Two cases of potential transmitted INSTI resistance mutations were identified. These findings highlight the need for improved HIV care in this high-risk population, and the importance of including baseline integrase resistance testing when selecting ART regimens for MSM in the US.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
[VIRTUAL] MUTATIONS IN THE HIV-1 ENVELOPE GLYCOPROTEIN CONFER BROAD DRUG RESISTANCE ([VIRTUAL]) - Mar 2, 2020 - Abstract #CROI2020CROI_1235;
We recently reported that, in vitro, HIV-1 can acquire resistance to the potent IN inhibitor, dolutegravir (DTG), by acquiring mutations in the envelope (Env) glycoprotein that enhance viral spread via cell-to-cell transmission...To examine possible in vivo relevance of Env-mediated drug resistance, we performed single-genome sequencing using plasma from 5 patients failing a raltegravir (RTG)-containing regimen (La Rosa et al., 2016)...Moreover, we established a relationship between Env stability, drug resistance, and the efficiency of viral cell-to-cell transmission. These findings offer mechanistic insights into Env-mediated drug resistance in culture, and suggest, preliminarily, that Env-mediated drug resistance may also occur in vivo.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare, Vitekta (elvitegravir) / Japan Tobacco, Gilead
[VIRTUAL] INVESTIGATION OF INTEGRASE-INHIBITOR RESISTANCE MUTATIONS IN gp41 IN CLINICAL SAMPLES ([VIRTUAL]) - Mar 2, 2020 - Abstract #CROI2020CROI_1226;
Differences in gp41 amino acid frequencies in INSTI-experienced vs. -nave individuals were observed only at highly polymorphic positions. No substitutions in gp41 previously associated with INSTI resistance in vitro were identified, suggesting that these may arise rarely in vivo.
- |||||||||| Prezcobix (darunavir/cobicistat) / Gilead, J&J, Tivicay (dolutegravir) / ViiV Healthcare, abacavir / Generic mfg.
[VIRTUAL] CLINICAL FEATURES AND OUTCOMES OF PATIENTS STOPPING DTG FOR NEUROPSYCHIATRIC SYMPTOMS ([VIRTUAL]) - Mar 2, 2020 - Abstract #CROI2020CROI_1212;
In several, but not all, cohorts a high rate of discontinuation for neuropsychological side effects (NPS) has been reported: age, female gender, older age and abacavir co-administration have been suggested as potential risk factors while pharmacological and genetic features are still under study...Patients were switched to raltegravir (30.3%), elvitegravir/cobicistat (28.8%), darunavir/cobicistat (25.8%) or rilpivirine (12.1%)-containing regimens...In our cohort study 11.7% of participants stopped DTG due to NPS: they were mostly sleep disorders and headache and a full regression of both was observed after switching to other drugs. In most cases a complete resolution of symptoms was observed; the incomplete resolution in almost one third of participants suggests alternative reasons.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare, Vitekta (elvitegravir) / Japan Tobacco, Gilead
[VIRTUAL] INTEGRASE INHIBITOR START OR SWITCH IMPACTS LEARNING IN WOMEN WITH HIV ([VIRTUAL]) - Mar 2, 2020 - Abstract #CROI2020CROI_1208;
Switching or starting an INSTI was primarily associated with poorer performance in learning among WWH. These changes were mainly observed in EVG and DTG users, and not with RAL, indicating that the impact of INSTI on cognition in WWH may not be a class effect.
- |||||||||| lamivudine / Generic mfg., Tivicay (dolutegravir) / ViiV Healthcare
[VIRTUAL] DOLUTEGRAVIR INCREASES B CELLS AND RESTING MEMORY B CELLS IN RV254 ([VIRTUAL]) - Mar 2, 2020 - Abstract #CROI2020CROI_1168;
Further, 2NRTI+DTG treated participants had fewer AM and TLM B cells, the latter of which have an exhausted phenotype. These data suggest that switching from EFV to DTG may be beneficial to limit activation and exhaustion in the B cell compartment of participants who initiated treatment in AHI.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
[VIRTUAL] HARNESSING ORIGINAL ANTIGENIC SIN FOR PREVENTING MTCT OF HIV ([VIRTUAL]) - Mar 2, 2020 - Abstract #CROI2020CROI_1163;
Twelve female RMs were infected intravenously with SHIV.C.CH505.375H.dCT, and began a daily ART (TDF, FTC, dolutegravir) regimen at 12 weeks post-infection (wpi)...In conclusion, vaccination of SHIV-infected RMs in the setting of ART can boost IgG responses against the original infecting antigen, SHIV.C.CH505, and Env-specific antibody responses previously associated with low risk of MTCT. Our results suggest that a vaccine regimen administered to HIV-infected pregnant women could boost previously identified humoral correlates of reduced MTCT risk in humans.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
[VIRTUAL] EFFECT OF INTEGRASE INHIBITORS ON WEIGHT GAIN IN CHILDREN AND ADOLESCENTS WITH HIV ([VIRTUAL]) - Mar 2, 2020 - Abstract #CROI2020CROI_999;
We enrolled 51 YPLWH (median age 18 years (IQR 15-21), 47% male, 94% black, 72% perinatally infected, 59% initiated dolutegravir, 57% had a history of AIDS)...Similar to adults, we report a greater rate of BMI and BMI-for-age z-score change following switch to INSTI in predominantly perinatally infected YPLWH. Although the final BMI remained in the normal range, our findings support the need for continued monitoring of BMI trends and potential cardiometabolic implications in YPLWH receiving INSTIs to assess if this represents more than a return to health phenomenon.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
[VIRTUAL] CHANGES IN DTG USE FOLLOWING THE NTD SAFETY SIGNAL IN BOTSWANA ([VIRTUAL]) - Mar 2, 2020 - Abstract #CROI2020CROI_991;
In May 2018 a preliminary safety signal for neural tube defects among women on dolutegravir (DTG) at conception led to in-country guidance for individualized counseling for pregnant women who had already conceived on DTG and women on DTG or starting antiretroviral treatment (ART) who desired pregnancy; DTG-based ART otherwise remained the recommended regimen for new ART starts...However, pregnant women frequently initiated non-DTG-based ART, or switched off DTG-based ART, despite being beyond the NTD risk period. Evaluation of clinician and patient perceptions of the NTD risk, and improvement in understanding pregnancy intention and barriers to pregnancy planning, will be critical for developing treatment guidelines within DTG-based ART programs.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
[VIRTUAL] OUTCOMES FOLLOWING PRENATAL EXPOSURE TO DOLUTEGRAVIR: THE DOLOMITE-EPPICC STUDY ([VIRTUAL]) - Mar 2, 2020 - Abstract #CROI2020CROI_990;
There were no vertical transmissions (106 infants still indeterminate) The birth defect rate and pattern add further support to current evidence on safety of periconception DTG use. This study is ongoing, in order to provide robust pharmacovigilance data in Europe.
- |||||||||| bictegravir (GS-9883) / Gilead, Tivicay (dolutegravir) / ViiV Healthcare, Vitekta (elvitegravir) / Japan Tobacco, Gilead
[VIRTUAL] ESTIMATES OF PERICONCEPTIONAL EXPOSURES TO INTEGRASE INHIBITORS UNITED STATES ([VIRTUAL]) - Mar 2, 2020 - Abstract #CROI2020CROI_989;
In 2018, an increased risk of neural tube defects among infants with periconceptional dolutegravir (DTG) exposure was reported from Botswana, triggering changes to global treatment guidelines for women and limiting access to DTG...Among 29,272-37,346 pregnancies conceived by women on ART, an estimated 6,727-8,583 (23%) had periconceptional INSTI exposure, of which 3,694-4,713 (55%) were exposed to raltegravir (RAL), 1,610-2,055 (24%) to DTG, 1,413-1,801 (21%) to elvitegravir (ELV) and none to bictegravir...INSTI use by U.S. women on ART at pregnancy conception has increased. This is the first U.S. national estimate, and ascertainment of exposures will be an important component of monitoring safety of new pharmacologic agents used in pregnancy.
- |||||||||| [VIRTUAL] TOXICITY OF INTEGRASE INHIBITORS IN A HUMAN EMBRYONIC STEM-CELL MODEL ([VIRTUAL]) - Mar 2, 2020 - Abstract #CROI2020CROI_988;
The Tsepamo study reported a signal for risk of neural tube defects in infants exposed to the InSTI dolutegravir (DTG) from conception...CA1S hESCs were cultured (n=5 independent experiments) in the presence of 0.1% DMSO or 1X Cmax of the following regimens: DTG, raltegravir (RAL), bictegravir (BIC), cobicistat-boosted elvitegravir (EVG/COBI), or efavirenz (EFV) on a TDF/FTC backbone; DTG, RAL, BIC, EVG/COBI, or rilpivirine (RPV) on a TAF/FTC backbone; DTG, RAL, or ritonavir-boosted darunavir (DRVr) on an ABC/3TC backbone; cabotegravir (CAB)/RPV...Our results further suggest that exposure to the InSTIs DTG and CAB can induce hESC differentiation. Given the increasing use of DTG and other InSTIs, it is imperative to investigate their long-term safety in the context of pregnancy and embryonic development.
- |||||||||| lamivudine / Generic mfg., Tivicay (dolutegravir) / ViiV Healthcare
[VIRTUAL] WEIGHT GAIN AT 18 MONTHS FOR ART-EXPERIENCED PATIENTS WHO SWITCHED TO DTG IN NIGERIA ([VIRTUAL]) - Mar 2, 2020 - Abstract #CROI2020CROI_954;
Weight gain has been associated with dolutegravir (DTG)...ART experienced adult patients with an intolerance to NNRTIs switched to TDF/3TC/DTG (TLD) over a 6-month period starting July 2017 at 3 pilot sites in Nigeria...Patients with above normal baseline BMI did not show a weight increase at 18m nor a gender association. While the original study was not designed to measure weight changes and has not been compared to a control group, the real world findings show that weight gain may be expected in ART experienced patients that were predominantly virally suppressed at time of switch in African patients.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare, Vemlidy (tenofovir alafenamide) / Gilead, Vitekta (elvitegravir) / Japan Tobacco, Gilead
[VIRTUAL] DIABETES, WEIGHT GAIN, AND INTEGRASE INHIBITOR USE IN NORTH AMERICAN HIV+ PERSONS ([VIRTUAL]) - Mar 2, 2020 - Abstract #CROI2020CROI_953;
Among INSTI initiators, 18% started dolutegravir (DTG), 30% raltegravir (RAL), and 52% elvitegravir (EVG)...Tenofovir alafenamide (TAF) was part of <1% of regimens...Initiating ART with INSTI- vs. NNRTI-based regimens may confer greater risk of incident DM, and this risk is likely only partially due to 12-month weight gain. Research to elucidate metabolic changes after INSTI initiation and identify interventions to mitigate them continues.
- |||||||||| [VIRTUAL] RACE IMPACT ON DOLUTEGRAVIR-ASSOCIATED WEIGHT GAIN AMONG PREVIOUSLY ART-NAIVE PLWH ([VIRTUAL]) - Mar 2, 2020 - Abstract #CROI2020CROI_951;
ART regimens included efavirenz, rilpivirine, atazanavir, darunavir, and DTG-based ≥3 drug regimens...We conducted sensitivity analyses including baseline HIV disease severity as measured by lowest CD4 count (cells/mm3) and limiting regimens to tenofovir (TDF) with emtricitabine/lamivudine backbones...Black PLWH had an increased risk of substantial weight gain compared to white PLWH in their first year after DTG initiation. Additional studies are needed to clarify reasons for racial disparities.
- |||||||||| lamivudine / Generic mfg., Tivicay (dolutegravir) / ViiV Healthcare
[VIRTUAL] DRUG CONCENTRATIONS AND BODY WEIGHT GAIN IN PLWH SWITCHED TO 3TC & DOLUTEGRAVIR (DTG) ([VIRTUAL]) - Mar 2, 2020 - Abstract #CROI2020CROI_950;
This effect was more important at initial phase of DTG administration when DTG was associated to a 2 NRTIs backbone, but persisted when DTG was combined with 3TC only, and was not related to trough plasma DTG concentrations. These results suggest that other factors than intensity of drug exposure are involved in weight increase under DTG.
- |||||||||| [VIRTUAL] EFFECTIVENESS OF DAA IN HIV-POSITIVE PATIENTS WITH HCV GENOTYPE 6 INFECTION ([VIRTUAL]) - Mar 2, 2020 - Abstract #CROI2020CROI_909;
At the time of DAA initiation, all had estimated glomerular filtration rate 30 ml/min/1.73m2, and combination antiretroviral therapy included regimens containing TAF in 27.3% of the patients, TDF 32.2%, non-TDF/TAF 40.5%, NNRTI 29.9%, PI 3.4%, and InSTI 68.6% (dolutegravir 55.8%, elvitegravir 39.8%, and raltegravir 4.4%), with 95.5% of the patients having CD4 counts 200 cells/mm3 and 96.6% plasma HIV RNA load <50 copies/mL...Overall, 98.3% achieved undetectable plasma HCV RNA load (<15 IU/mL) at EOT and 96.6% achieved SVR12 (97.2% in patients receiving SOF/LED, 96.0% in GP, and 100% in SOF/VEL). Similar to the observation in HIV-negative patients, SVR12 with DAAs is high in HIV-positive patients with HCV-6.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare, Vitekta (elvitegravir) / Japan Tobacco, Gilead
[VIRTUAL] EFFECTIVENESS OF LDV/SOF FOR HIV-POSITIVE PATIENTS WITH HCV GENOTYPE 2 INFECTION ([VIRTUAL]) - Mar 2, 2020 - Abstract #CROI2020CROI_908;
At the time of LDV/SOF initiation, all had estimated glomerular filtration rate (eGFR) 30 ml/min/1.73m2 and were receiving combination antiretroviral therapy (cART) with TAF-containing regimen in 38.6%, TDF 13.9%, non-TDF/TAF 47.5%, NNRTI 12.9%, PI 14.9%, and InSTI 72.3% (dolutegravir 46.6% and elvitegravir 53.4%%), with 98.0% having CD4 counts 200 cells/mm3 and 94.1% HIV RNA load <50 cp/mL...eGFR increased in 34.1% with a mean increase of 7.2 ml/min/1.73m2, while eGFR decreased in 65.9% with a mean decrease of 12.6 ml/min/1.73m2. Similar to the reported treatment response among HIV-negative patients, LDV/SOF is effective for HIV-positive patients infected with HCV-2.
- |||||||||| Prezista (darunavir) / J&J, Tivicay (dolutegravir) / ViiV Healthcare
[VIRTUAL] VIROLOGIC OUTCOMES BY RESISTANCE CATEGORY AND PRETREATMENT IN THE DUALIS STUDY ([VIRTUAL]) - Mar 2, 2020 - Abstract #CROI2020CROI_876;
No emergence of RAMs during follow-up was observed. As shown in the DUALIS study, dual therapy with DTG+bDRV tends to be an effective treatment option with no treatment-emergent resistance for PLWH on suppressive first- or further-line ART with or without evidence of pre-existing NRTI, NNRTI or PI RAMs.
- |||||||||| lamivudine / Generic mfg., Tivicay (dolutegravir) / ViiV Healthcare
[VIRTUAL] SHALL WE DANCE? EXTENDING TANGO’S RESULTS TO CLINICAL PRACTICE ([VIRTUAL]) - Mar 2, 2020 - Abstract #CROI2020CROI_875;
A significant increase in CD4 cell count (mean change at 96 weeks, +87 cell/L in TG and +40 cell/L in the non-TG) and CD4/CD8 ratio (mean change at 96 weeks, +0.05 in the TG and +0.07 in the other) was observed over time in both groups. Results from our multicenter study are in line with the results from the TANGO study and their applicability to everyday clinical practice.
- |||||||||| [VIRTUAL] DTG+3TC VS DTG+TDF/FTC (GEMINI 1&2): CONFIRMED VIROLOGIC WITHDRAWALS THROUGH WEEK 96 ([VIRTUAL]) - Mar 2, 2020 - Abstract #CROI2020CROI_866;
In GEMINI12, there were low and comparable numbers of participants meeting CVW through 96 weeks in the DTG+3TC and DTG+TDF/FTC arms without apparent predisposition by BL VL or CD4; no emergent genotypic/phenotypic resistance to INSTI/NRTIs was observed. These data further support the potency and durability of DTG+3TC.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
[VIRTUAL] ASSOCIATION BETWEEN INTEGRASE INHIBITOR HAIR CONCENTRATIONS AND WEIGHT GAIN IN WOMEN ([VIRTUAL]) - Mar 2, 2020 - Abstract #CROI2020CROI_856;
In virally-suppressed WLH, the effect of RAL and DTG cumulative drug exposure on body weight change over the short term appears to be limited. In addition to further pharmacologic assessments, other mechanisms to explain INSTI-associated weight gain should be explored.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
[VIRTUAL] EDITING OF SIV IN NONHUMAN PRIMATES BY CRISPR-CAS9 IN VIRAL RESERVOIRS ([VIRTUAL]) - Mar 2, 2020 - Abstract #CROI2020CROI_812;
Ten adult Indian rhesus macaques were i.v. infected with SIVmac239 then treated daily with a drug regimen of tenofovir, emtricitabine and dolutegravir (5.1/50/2.5mg/kg daily s.q.)...We observed biodistribution of AAV9-CRISPR-Cas9 in the blood in a dose and time dependent manner for the elimination of SIV DNA. These findings support the utilization of AAV9-CRISPR-Cas9 as a potential therapeutic strategy for in vivo gene editing of HIV proviral DNA from latent tissue reservoirs.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare, Vitekta (elvitegravir) / Japan Tobacco, Gilead
[VIRTUAL] START OR SWITCH OF INTEGRASE INHIBITORS ON DEPRESSIVE SYMPTOMS IN WOMEN WITH HIV ([VIRTUAL]) - Mar 2, 2020 - Abstract #CROI2020CROI_580;
Among WWH, switching to INSTI based therapy did not have an impact of depressive symptoms. Initiation of INSTIs did result in improvement in positive affect symptoms and this was predominantly driven by EVG use.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
[VIRTUAL] PRETREATMENT HIV DRUG RESISTANCE AND 48-WEEK VIROLOGIC OUTCOMES IN THE ADVANCE TRIAL ([VIRTUAL]) - Mar 2, 2020 - Abstract #CROI2020CROI_521;
PDR, primarily to NNRTIs, was associated with significantly diminished efficacy of EFV-based, but not DTG-based three drug ART in South Africa. These data support the use of integrase inhibitors as initial therapy in individuals with known drug resistance or in populations with a very high prevalence of circulating NNRTI PDR.
- |||||||||| lamivudine / Generic mfg., Tivicay (dolutegravir) / ViiV Healthcare, abacavir / Generic mfg.
[VIRTUAL] HIGH LEVELS OF DRUG RESISTANCE IN ART-NAIVE AND PLWH FAILING FIRST-LINE ART IN HAITI ([VIRTUAL]) - Mar 2, 2020 - Abstract #CROI2020CROI_520;
The high rate of abacavir resistance in children, and TDF cross-resistance, limits future treatment options in that age group. High levels of TDF and 3TC resistance in adults warrant caution in the implementation of new guidelines and roll out of TLD in patients failing NNRTI-based therapy
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
[VIRTUAL] COUNTRY-LEVEL DRIVERS OF NNRTI RESISTANCE IN SOUTHERN AFRICA ([VIRTUAL]) - Mar 2, 2020 - Abstract #CROI2020CROI_516;
Even with the introduction of dolutegravir, NNRTIs will remain a central component of first-line regimen in southern Africa...Our results suggest that the ability to control PDR is associated with features of the healthcare financing system at the national level. Additional data on NNRT PDR and ART management is urgently needed in some countries of southern Africa.
- |||||||||| Prezista (darunavir) / J&J, lamivudine / Generic mfg., Tivicay (dolutegravir) / ViiV Healthcare
[VIRTUAL] EMULATION OF AN RCT OF DOLUTEGRAVIR VS BOOSTED-DARUNAVIR IN ADVANCED ART NAIVE ([VIRTUAL]) - Mar 2, 2020 - Abstract #CROI2020CROI_507;
Calendar year of starting was a key factor but results were consistent across periods of ART initiation. Under the assumptions of no unmeasured confounding and correct model specification, our analysis suggests that a RCT conducted in the target population of ART-nave patients with CD4 count<200 or AIDS is likely to show a notable reduction in risk of treatment failure in people initiated with dolutegravir vs. boosted-darunavir based therapies.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare, Vitekta (elvitegravir) / Japan Tobacco, Gilead
[VIRTUAL] CD4/CD8 RECOVERY AND FIRST-LINE ART: GREATEST IMPROVEMENT WITH INTEGRASE INHIBITORS ([VIRTUAL]) - Mar 2, 2020 - Abstract #CROI2020CROI_501;
INSTI-based first line ART is associated with a greater CD4/CD8 ratio gain compared to NNRTI and PI-based ART. This study in real life indicates that ART initiation with INSTI improves immune recovery with respect to other ART classes, which could affect long-term mortality.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
[VIRTUAL] TOTAL DOLUTEGRAVIR LEVELS DECREASED BUT FREE FRACTION INCREASED BY VALPROIC ACID ([VIRTUAL]) - Mar 2, 2020 - Abstract #CROI2020CROI_498;
The decrease can be explained, at least partly, by displacement of DTG by VPA via competitive protein binding. Since unbound DTG levels remained sufficient this DDI should not be a reason to withhold DTG treatment to people living with HIV-1 who are also receiving VPA.
- |||||||||| rifampicin / Generic mfg., Tivicay (dolutegravir) / ViiV Healthcare
[VIRTUAL] HIGH-DOSE RIFAMPICIN FOR THE TREATMENT OF LEPROSY IN HIV PATIENTS TAKING DOLUTEGRAVIR ([VIRTUAL]) - Mar 2, 2020 - Abstract #CROI2020CROI_497;
Importantly, the return of DTG plasma concentrations to steady state Cmin was predicted to be considerably delayed after coadministration of both 600mg and 1200mg RIF QMT. These simulations could inform development of effective high-dose RIF strategies for special HIV populations with comorbidities such as Leprosy.
|
