Estudio primario

No clasificado

HIV-1 reverse transcriptase and protease resistance mutations selected during 16-72 weeks of therapy in isolates from antiretroviral therapy-experienced patients receiving abacavir/efavirenz/amprenavir in the CNA2007 study.

Año 2003
Revista Antiviral therapy
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OBJECTIVE:

To determine HIV-1 reverse transcriptase (RT) and protease (PRO) mutations selected in isolates from antiretroviral therapy (ART)-experienced patients receiving an efavirenz/abacavir/amprenavir salvage regimen.

METHODS:

Open-label, single arm of abacavir, 300 mg twice daily, amprenavir, 1200 mg twice daily and efavirenz, 600 mg once daily, in ART-experienced patients of which 42% were non-nucleoside reverse transcriptase inhibitor-naive. The virology population examined consisted of all patients who took at least 16 weeks of study drugs (n=74). Plasma population sequencing was carried out at baseline and last time point at which patients were still taking the three study drugs + other ART. The median follow-up was 48 weeks (range week 16-72).

RESULTS:

Baseline (n=73) and on-therapy (n=49) genotypes were obtained. By 48 weeks, 51% of isolates had > or = 3 non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations. NNRTI mutations selected on therapy were K103N (51%), substitutions at position 190 (17/49, 35%): G to A (n=11) / S (n=4) / E (n=1) and T (n=1); L100I (37%) and V1081 (20%) mutations. P225H was not observed in this study. L100I and G190A/S/E/T mutations were rarely detected in the same viral population and baseline Y181C favoured the G190 mutations (OR=8.9, P<0.001), rather than the L100I. The NRTI mutations selected were in accordance with abacavir known resistance profile, no new TAMs were observed, new L74V or I mutations developed in 39 and 16% of isolates, respectively, however, new M184V mutations were only detected in isolates from two patients, one of whom had added lamivudine + didanosine. M184V was common at baseline (55%) and maintained in 22/27 (81%) isolates (five of these 22 added lamivudine or didanosine, or both). The PRO mutations selected were in accordance with the distinct resistance profile of amprenavir compared with other protease inhibitors. Mutations D30N, G48V, N88D/S, L90M and 154V were de-selected, and mutations I50V, I or V to 54M/L, I84V, M46I/L, L33F, I47V as well mutations at position 10 were observed in 20/49 (41%) isolates.

CONCLUSION:

Prior NNRTI and NRTI therapy influences the pathway of resistance to efavirenz. In this study, the prevalence of mutations selected by efavirenz were different from those described in less ART-experienced patients. Baseline Y181C was associated with the development of mutations at position 190, but not L100I or K103N. In this patient population, abacavir with efavirenz preferentially selected for L74V but not for thymidine analogue mutations. M184V was rarely selected and was maintained in only 77% of patients who did not add lamivudine or didanosine. Finally, amprenavir-specific mutations were selected in the background of other primary protease inhibitor mutations, confirming the distinct resistance profile of amprenavir.

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Pharmacokinetics of [(14)C]abacavir, a human immunodeficiency virus type 1 (HIV-1) reverse transcriptase inhibitor, administered in a single oral dose to HIV-1-infected adults: a mass balance study.

Año 1999
Revista Antimicrobial agents and chemotherapy
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Abacavir (1592U89) ((-)-(1S, 4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene- 1-m ethanol) is a 2'-deoxyguanosine analogue with potent activity against human immunodeficiency virus (HIV) type 1. To determine the metabolic profile, routes of elimination, and total recovery of abacavir and metabolites in humans, we undertook a phase I mass balance study in which six HIV-infected male volunteers ingested a single 600-mg oral dose of abacavir including 100 microCi of [(14)C]abacavir. The metabolic disposition of the drug was determined through analyses of whole-blood, plasma, urine, and stool samples, collected for a period of up to 10 days postdosing, and of cerebrospinal fluid (CSF), collected up to 6 h postdosing. The radioactivity from abacavir and its two major metabolites, a 5'-carboxylate (2269W93) and a 5'-glucuronide (361W94), accounted for the majority (92%) of radioactivity detected in plasma. Virtually all of the administered dose of radioactivity (99%) was recovered, with 83% eliminated in urine and 16% eliminated in feces. Of the 83% radioactivity dose eliminated in the urine, 36% was identified as 361W94, 30% was identified as 2269W93, and 1.2% was identified as abacavir; the remaining 15.8% was attributed to numerous trace metabolites, of which <1% of the administered radioactivity was 1144U88, a minor metabolite. The peak concentration of abacavir in CSF ranged from 0.6 to 1.4 microg/ml, which is 8 to 20 times the mean 50% inhibitory concentration for HIV clinical isolates in vitro (0.07 microg/ml). In conclusion, the main route of elimination for oral abacavir in humans is metabolism, with <2% of a dose recovered in urine as unchanged drug. The main route of metabolite excretion is renal, with 83% of a dose recovered in urine. Two major metabolites, the 5'-carboxylate and the 5'-glucuronide, were identified in urine and, combined, accounted for 66% of the dose. Abacavir showed significant penetration into CSF.

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Quadruple nucleos(t)ide reverse transcriptase inhibitors-only regimen of tenofovir plus zidovudine/lamivudine/abacavir in heavily pre-treated HIV-1 infected patients: salvage therapy or backbone only?

Año 2009
Revista Current HIV research
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BACKGROUND:

We investigated the virologic and immunologic responses to a mono-class, nucleoside/nucleotide reverse transcriptase inhibitor - combination therapy consisting of tenofovir and zidovudine/lamivudine/abacavir in therapy experienced patients.

METHODS:

Retrospective study of 122 patients. Primary analysis was performed at 48 weeks. Virologic response was defined as viral load levels less than 400 copies/ml.

RESULTS:

About half of the patients had switched to tenofovir+ zidovudine/lamivudine/abacavir for simplification purposes or toxicity while the other half had experienced virologic failure. 80/122 (66%) responded. Median viral load decreased to 78 copies/ml at week 48; median CD4 count increased to 321 cells/mm(3). Of the 42 virologic failures, only 3 patients failed after week 24. 24/35 patients who had been on a non-suppressive zidovudine/lamivudine/abacavir-only regimen at baseline and added tenofovir to intensify, responded. 41/53 patients who switched from any nucleoside reverse transcriptase inhibitor-only regimen improved or maintained suppression. Genotypes were available for 85/122 patients. The only predictor of virologic failure was the combination 41L+210W+215Y/F mutational pattern. 16 of the patients who failed on tenofovir+ zidovudine/lamivudine/abacavir therapy selected new primary nucleoside reverse transcriptase inhibitor resistance mutations that they previously did not have. 48/85 (56%) patients with genotype tests had at least 3 (3-10; median 4) nucleoside reverse transcriptase inhibitor resistance-associated mutations in the past.

CONCLUSIONS:

Patients heavily pre-treated with nucleoside analogues may show response to mono-class tenofovir+ zidovudine/lamivudine/abacavir therapy despite having a history of failure with nucleoside reverse transcriptase inhibitors. Lower baseline viral load, higher baseline CD4 count were significant predictors for response. Archived 41L+210W+215Y/F mutational pattern was significantly associated with non-response.

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HLA-B*57:01 allele prevalence in HIV-infected North American subjects and the impact of allele testing on the incidence of abacavir-associated hypersensitivity reaction in HLA-B*57:01-negative subjects.

Año 2017
Autores Small CB , Margolis DA , Shaefer MS , Ross LL
Revista BMC infectious diseases
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BACKGROUND:

The presence of the HLA-B*57:01 allele in HIV-infected subjects is associated with a higher risk of abacavir-associated hypersensitivity reaction (ABC HSR). HLA-B*57:01 allele prevalence varies in different populations, but HLA-B*57:01 testing with immunological confirmation has had a negative predictive value for ABC HSR between 97 and 100%.

METHODS:

In the ASSURE study (EPZ113734), the HLA-B*57:01 prevalence in virologically suppressed, antiretroviral treatment-experienced, HIV-infected subjects from the United States, including Puerto Rico, was assessed.

RESULTS:

Three hundred eighty-five subjects were screened; 13 were HLA-B*57:01 positive and 372 were negative. Only HLA-B*57:01-negative, abacavir-naive subjects were eligible to enroll into the ASSURE trial. Eleven of the 13 subjects who possessed the HLA-B*57:01 allele were white, the other 2 were African-American. There was no geographic clustering of HLA-B*57:01-positive subjects, and the incidence correlated roughly with those states with the greatest numbers of subjects screened. Similarly, there was no statistically significant correlation between subjects who possessed or lacked the allele and age, gender, ethnicity or CD4+ T-cell numbers. The incidence of ABC HSR following abacavir initiation was also evaluated. Only 1 of 199 HLA-B*57:01-negative subjects (an African-American male) randomized to receive abacavir-containing treatment developed symptoms consistent with suspected ABC HSR; ABC HSR was not immunologically confirmed.

CONCLUSIONS:

These findings confirm the utility of HLA-B*57:01 allele testing to reduce the frequency of ABC HSR. The prevalence of HLA-B*57:01 positivity was higher in white than in African-American subjects. In HLA-B*57:01-negative subjects, suspected ABC HSR is very rare, but should lead to discontinuation of abacavir when ABC HSR cannot be definitively excluded from the differential diagnosis.

TRIAL REGISTRATION:

The ASSURE (EPZ113734) study was registered on ClinicalTrials.gov registration on April 8th 2010 and the registration number is NCT01102972.

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Estudio primario

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A randomized, double-blind study of triple nucleoside therapy of abacavir, lamivudine, and zidovudine versus lamivudine and zidovudine in previously treated human immunodeficiency virus type 1-infected children. The CNAA3006 Study Team

Año 2001
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OBJECTIVES:

Abacavir (ABC) is a potent inhibitor of human immunodeficiency virus type 1 (HIV‐1) reverse transcriptase. We compared the efficacy, safety, and tolerability of combination therapy with ABC, lamivudine (3TC), and zidovudine (ZDV) versus 3TC and ZDV in antiretroviral experienced HIV‐1‐infected children over 48 weeks.

METHODS:

Two hundred five HIV‐1‐infected children who had received previous antiretroviral therapy and had CD4(+) cell counts >/=100 cells/mm(3) were stratified by age and by previous treatment. Participants were randomly assigned to receive ABC (8 mg/kg twice daily [BID]) plus 3TC (4 mg/kg BID) and ZDV (180 mg/m(2) BID; ABC/3TC/ZDV group) or ABC placebo plus 3TC (4 mg/kg BID) and ZDV (180 mg/m(2); 3TC/ZDV group). Participants who met a protocol‐defined switch criteria (plasma HIV‐1 RNA >0.5 log(10) copies/mL above baseline at week 8 or >10 000 copies/mL after week 16) had the option to switch to open‐label ABC plus any antiretroviral combination or continue randomized therapy or withdraw from the study.

RESULTS:

The Kaplan‐Meier estimates (95% confidence interval) of the proportion of participants who maintained HIV‐1 RNA levels </=10 000 copies/mL for 48 weeks or more was significantly better in the ABC/3TC/ZDV group compared with the 3TC/ZDV group: 33% (23%‐42%) versus 21% (13%‐29%). At week 48, the proportions of participants with HIV‐1 RNA </=10 000 copies/mL were 36% versus 26% for the ABC/3TC/ZDV and 3TC/ZDV groups, respectively, by intent‐to‐treat analysis. For the subgroup of participants with baseline HIV‐1 RNA >10 000 copies/mL, a significantly higher proportion of participants in the ABC/3TC/ZDV group had HIV‐1 RNA </=10 000 copies/mL compared with the 3TC/ZDV group (29% vs 12%) but no difference was observed in the subgroup of participants with baseline HIV‐1 RNA </=10 000 copies/mL (78% vs 72%). The median changes from baseline in CD4(+) cell counts were greater in the ABC/3TC/ZDV group than in the 3TC/ZDV group. Few participants (3%) experienced abacavir‐related hypersensitivity reaction.

CONCLUSIONS:

ABC, in combination with 3TC and ZDV, provides additional antiretroviral activity over 48 weeks, compared with combination therapy with 3TC and ZDV in antiretroviral experienced HIV‐1‐infected children. ABC was safe and generally well‐tolerated and should be considered an active component of combination antiretroviral therapy in this pediatric population.

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Estudio primario

No clasificado

Plasma pharmacokinetic study of once versus twice daily abacavir as part of combination antiretroviral therapy in children with human immunodeficiency virus-1 infection aged 3 months to less than 36 months

Año 2005
Autores Giaquinto, Carlo
Registro de estudios ISRCTN registry
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INTERVENTION:

1. At week 0, while children enrolled in the study are on a twice‐daily regimen containing ABC or ABC and 3TC, serial pharmacokinetic samples will be collected 2. Following collection of these samples, children will cross over and begin a regimen of ABC 16 mg/kg once‐daily (and 3TC 8 mg/kg once‐daily if applicable) for at least 12 weeks, with the second pharmacokinetic sample collected at week 4 3. The same daily dose will be maintained within 25% (allowing for dose adjustment for growth as appropriate)

CONDITION:

Paediatric HIV ; Infections and Infestations ; Paediatric

HIV PRIMARY OUTCOME:

Area under curve (AUC), Cmin and Cmax values of ABC after once and twice daily dosing

SECONDARY OUTCOME:

1. AUC, Cmin and Cmax values of 3TC after once and twice daily dosing; 2. Assessment of adherence and satisfaction with twice and once daily dosage regimens, using questionnaires

INCLUSION CRITERIA:

1. Infants and children with confirmed presence of human immunodeficiency virus (HIV‐1) infection 2. Infants and children aged 3 to less than 36 months 3. Parents able/willing to give consent 4. Currently on combination anti‐retroviral therapy (ART) including ABC oral solution or a combination of ABC and 3TC, for at least 12 weeks, and expected to stay on this regimen for at least a further 12 weeks 5. HIV‐1 ribonucleic acid (RNA) viral load ‐ either suppressed HIV‐1 RNA viral load (i.e. less than 400 copies/ml) or non‐suppressed but low HIV‐1 RNA viral load (i.e. 400 ‐ 20,000 copies/ml). The non‐suppressed children should have had a stable or decreasing HIV‐1 RNA viral load prior to study entry and should be considered to still be gaining benefit from the current regimen. 6. Children should have stable or rising cluster of differentiation‐4 (CD4+) cell percentage prior to study entry and their CD4+ cell percentage should not be expected to fall with

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Nevirapine/zidovudine/lamivudine has superior immunological and virological responses not reflected in clinical outcomes in a 48-week randomized comparison with abacavir/zidovudine/lamivudine in HIV-infected Ugandan adults with low CD4 cell counts.

Año 2010
Revista HIV medicine
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Background: Triple nucleoside reverse transcriptase inhibitor regimens have advantages as first-line antiretroviral therapy (ART), avoiding hepatotoxicity and interactions with anti-tuberculosis therapy, and sparing two drug classes for second-line ART. Concerns exist about virological potency; efficacy has not been assessed in Africa. Methods:A safety trial comparing nevirapine with abacavir was conducted in two Ugandan Development of Antiretroviral Therapy in Africa (DART) centres: 600 symptomatic antiretroviral-naïve HIV-infected adults with CD4 counts <200 cells/μL were randomized to zidovudine/lamivudine plus abacavir or nevirapine (placebo-controlled to 24-week primary toxicity endpoint, and then open-label). Documented World Health Organization (WHO) stage 4 events were independently reviewed and plasma HIV-1 RNA assayed retrospectively. Exploratory efficacy analyses are intention-to-treat. Results:The median pre-ART CD4 count was 99 cells/μL, and the median pre-ART viral load was 284 600 HIV-1 RNA copies/mL. A total of 563 participants (94%) completed 48 weeks of follow-up, 25 (4%) died and 12 (2%) were lost to follow-up. The randomized drug was substituted in 21 participants (7%) receiving abacavir vs. 34 (11%) receiving nevirapine (P=0.09). At 48 weeks, 62% of participants receiving abacavir vs. 77% of those receiving nevirapine had viral loads <50 copies/mL (P<0.001), and mean CD4 count increases from baseline were +147 vs. +173 cells/μL, respectively (P=0.006). Nine participants (3%) receiving abacavir vs. 16 (5%) receiving nevirapine died [hazard ratio (HR) 0.55; 95% confidence interval (CI) 0.24-1.25; P=0.15]; 20 receiving abacavir vs. 32 receiving nevirapine developed new or recurrent WHO 4 events or died (HR=0.60; 95% CI 0.34-1.05; P=0.07) and 48 receiving abacavir vs. 68 receiving nevirapine developed new or recurrent WHO 3 or 4 events or died (HR=0.67; 95% CI 0.46-0.96; P=0.03). Seventy-one participants (24%) receiving abacavir experienced 91 grade 4 adverse events compared with 130 events in 109 participants (36%) on nevirapine (P<0.001). Conclusions:The clear virological/immunological superiority of nevirapine over abacavir was not reflected in clinical outcomes over 48 weeks. The inability of CD4 cell count/viral load to predict initial clinical treatment efficacy is unexplained and requires further evaluation. © 2010 British HIV Association.

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Pharmacokinetics, safety, and tolerability of dispersible and immediate-release abacavir, dolutegravir, and lamivudine tablets in children with HIV (IMPAACT 2019): week 24 results of an open-label, multicentre, phase 1-2 dose-confirmation study.

Año 2023
Revista The lancet. HIV
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BACKGROUND:

Child-friendly fixed-dose combination (FDC) antiretroviral therapy (ART) options are limited. We evaluated the pharmacokinetics, safety, and tolerability of dispersible and immediate-release FDC abacavir, dolutegravir, and lamivudine taken once per day in children younger than 12 years with HIV.

METHODS:

IMPAACT 2019 was an international, phase 1-2, multisite, open-label, non-comparative dose-confirmation study of abacavir, dolutegravir, and lamivudine in children younger than 12 years. Participants were enrolled across five weight bands: those weighing 6 kg to less than 25 kg received abacavir (60 mg), dolutegravir (5 mg), and lamivudine (30 mg) dispersible tablets (three to six tablets depending on body weight), and those weighing 25 kg to less than 40 kg received abacavir (600 mg), dolutegravir (50 mg), and lamivudine (300 mg) in an immediate-release tablet. At entry, participants were ART naive or ART experienced and virologically suppressed on stable ART for 6 months or more. Dose confirmation was based on pharmacokinetic and safety criteria in the first five to seven participants in each weight band to week 4; all participants were followed up to week 48. We present the results for the primary objectives to assess pharmacokinetics, confirm dosing, and evaluate safety through 24 weeks across all weight bands. The trial is registered with ClinicalTrials.gov (NCT03760458).

FINDINGS:

57 children were enrolled and initiated study drug (26 [46%] female and 31 [54%] male; 37 [65%] Black, 18 [32%] Asian, and 1 [2%] had race reported as unknown). Within each weight band, 6 kg to less than 10 kg, 10 kg to less than 14 kg, 14 kg to less than 20 kg, 20 kg to less than 25 kg, and 25 kg or higher: the geometric mean dolutegravir area under the concentration time curve over the 24 h dosing interval (AUC0-24 h) was 75·9 h·μg/mL (33·7%), 91·0 h·μg/mL (36·5%), 71·4 h·μg/mL (23·5%), 84·4 h·μg/mL (26·3%), and 71·8 h·μg/mL (13·9%); dolutegravir concentrations 24 h after dosage (C24 h) were 0·91 μg/mL (67·6%), 1·22 μg/mL (77·5%), 0·79 μg/mL (44·2%), 1·35 μg/mL (95·5%), and 0·98 μg/mL (27·9%); abacavir AUC0-24 h was 17·7 h·μg/mL (38·8%), 19·8 h·μg/mL (50·6%), 15·1 h·μg/mL (40·3%), 17·4 h·μg/mL (19·4%), and 25·7 h·μg/mL (14·6%); lamivudine AUC0-24 h was 10·7 h·μg/mL (46·0%), 14·2 h·μg/mL (23·9%), 13·0 h·μg/mL (15·6%), 14·5 h·μg/mL (16·6%), and 21·7 h·μg/mL (26·2%), respectively. Pharmacokinetic targets and safety criteria were met within each weight band, and thus dosing of abacavir, dolutegravir, and lamivudine was confirmed at the originally selected doses. 54 (95%) of participants were treatment experienced and all who continued taking the study drug remained virologically suppressed (<200 copies per mL) through week 24. Virological suppression was achieved in two of three participants who were ART naive by week 24. There were no grade 3 or higher adverse events related to abacavir, dolutegravir, and lamivudine and no discontinuations because of toxicity to week 24. Both formulations were well tolerated.

INTERPRETATION:

Dosing of abacavir, dolutegravir, and lamivudine was confirmed in children weighing 6 kg to less than 40 kg, and both FDC formulations were safe, well tolerated, and efficacious through 24 weeks of treatment. These findings support global efforts to expand the availability of FDC abacavir, dolutegravir, and lamivudine to children with HIV.

FUNDING:

National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Mental Health, ViiV Healthcare, and GlaxoSmithKline.

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Virological Outcomes After Switching to Abacavir/Lamivudine/Dolutegravir Combined with Adherence Support in People Living with HIV with Poor Adherence: A Phase IV, Multicentre Randomized Prospective Open Label Study (TriiADD-CTN 286)

Año 2022
Revista Patient preference and adherence
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BACKGROUND:

Many people living with HIV struggle to consistently adhere to antiretroviral therapy, fail to achieve long-term virologic control and remain at risk for HIV-related disease progression, development of resistance and may transmit HIV infection to others.

OBJECTIVE:

To determine if switching from current multi-tablet (curART) to single-tablet antiretroviral therapy (abacavir/lamivudine/dolutegravir; ABC/3TC/DTG), both combined with individualized adherence support, would improve HIV suppression in non-adherent vulnerable populations.

METHODS:

TriiADD was an investigator-initiated randomized, multicentre, open label study. HIV+ adults with documented non-adherence on curART were randomized in a 1:1 ratio to immediately switch to ABC/3TC/DTG or to continue curART. Both arms received adherence support. The primary outcome was the proportion of participants in each arm with HIV RNA < 50 copies/mL 24 weeks after randomization.

RESULTS:

In total, 50 people were screened and 27 randomized from 11 sites across Canada before the trial was stopped early due to slow recruitment. Participants were predominantly from ethnocultural communities, Indigenous people and/or had a history of injection drug use. The proportion achieving HIV RNA < 50 copies/mL at week 24 was 4/12 (33%) in the curART arm vs 7/13 (54%) in the ABC/3TC/DTG arm; median Bayesian risk difference, 5% (95% CrI, -17 to 28%) higher for those randomized to ABC/3TC/DTG. We encountered difficulties with recruitment of participants without prior drug resistance, retention despite intensive support, reliably measuring adherence and in overcoming entrenched adherence barriers.

CONCLUSION:

Results of our trial are consistent with a slight improvement in viral suppression in a vulnerable population when a single tablet regimen is combined with patient-level adherence support. Beyond treatment simplicity and tolerability, tailored interventions addressing stigma and social determinants of health are still needed. The numerous challenges we encountered illustrate how randomised trials may not be the best approach for assessing adherence interventions in vulnerable populations.

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A phase IV open- label, randomized and pilot clinical trial, designed to evaluate the potential neurotoxicity of dolutegravir/lamivudine/abacavir in neurosymptomatic HIV patients and their reversibility after switching to elvitegravir/cobicistat/emtricitabina/tenofovir alafenamide

Año 2017
Registro de estudios EU Clinical Trials Register
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INTERVENTION:

Trade Name: Triumeq Product Name: Triumeq Pharmaceutical Form: Tablet INN or Proposed

INN:

DOLUTEGRAVIR CAS Number: 1051375‐16‐6 Other descriptive name: DOLUTEGRAVIR SODIUM Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 50‐ INN or Proposed

INN:

LAMIVUDINE CAS Number: 134678‐17‐4 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 300‐ INN or Proposed

INN:

ABACAVIR CAS Number: 188062‐50‐2 Other descriptive name: ABACAVIR SULFATE Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 600‐ Trade Name: Genvoya Product Name: Genvoya Pharmaceutical Form: Tablet INN or Proposed

INN:

ELVITEGRAVIR CAS Number: 697761‐98‐1 Other descriptive name: ELVITEGRAVIR Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 150‐ INN or Proposed

INN:

COBICISTAT CAS Number: 1004316‐88‐4 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 150‐ INN or Proposed

INN:

EMTRICITABINE CAS Number: 143491‐57‐0 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 200‐ INN or Proposed

INN:

TENOFOVIR CAS Number: 379270‐37‐8 Other descriptive name: TENOFOVIR ALAFENAMIDE FUMARATE Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 10‐

CONDITION:

HIV ; MedDRA version: 19.1 Level: LLT Classification code 10001509 Term: AIDS System Organ Class: 100000004862 Therapeutic area: Diseases [C] ‐ Virus Diseases [C02]

PRIMARY OUTCOME:

Main Objective: To compare changes in the severity of neuropsychiatric symptoms potentially associated with the use of DTG/3TC/ABC, perceived by patients randomised to begin isolated symptomatic treatment or treatment associated with switching antiretroviral therapy Primary end point(s): The ACTG adverse effects scale, the Pittsburg sleep quality index and the hospital anxiety and depression scale. Secondary Objective: ‐ To evaluate changes in the severity of neuropsychiatric symptoms potentially associated with the use of DTG/3TC/ABC after switching to ELV/COBI/FTC/TAF; ‐To evaluate changes in neurocognitive function and volumetric, spectroscopic, tractographic and cerebral perfusion markers, acquired by Magnetic Resonance Imaging, after switching from DTG/3TC/ABC to ELV/COBI/FTC/TAF; ‐ To evaluate the percentages of virologic failure after switching antiretroviral therapy from DTG/3TC/ABC to ELV/COBI/FTC/TAF Timepoint(s) of evaluation of this end point: Basal visit and week 4

SECONDARY OUTCOME:

Secondary end point(s): ‐The ACTG adverse effects scale, the Pittsburg sleep quality index and the hospital anxiety and depression scale.; ‐ Volumes of the different structures of the brain ; the Change in levels of neuronal integrity, the change in the level of white matter integrity, and change in levels of brain inflammation.; ‐ Viral load Timepoint(s) of evaluation of this end point: ‐Weeks 4, 12 and 24 after the change.

INCLUSION CRITERIA:

•Patient > 18 years of age diagnosed with HIV using normal serology techniques. •Current antiretroviral therapy with DTG/3TC/ABC. •HIV viral load < 50 copies/mL for at least 12 weeks prior to signing the consent form [(]confirmed by two assays at least 12 weeks apart with viremia < 50 copies/mL between both •Appearance or worsening of the following symptoms compared to when DTG/3TC/ABC was started: ‐ Symptoms of anxiety or depression ‐ Insomnia or other sleep disturbances ‐ Headache ‐ Cognitive complaints (attention, concentration or memory) ‐ Alterations in behaviour (irritability, aggressiveness or agitation) ‐ Dizziness of neurological or neurologically‐mediated origin Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 64 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range

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