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Clinical Trial Summary

This is a phase IV, open label, multicentre trial that will be taking place at 4 sites in the United Kingdom (UK). Efavirenz which is taken in combination with Kivexa® or as part of the combination pill, Atripla® is a recommended firstline regimen for the treatment of Human Immunodeficiency Virus-1 (HIV- 1) infection. Treatment against the HIV virus is also referred to as antiretroviral therapy.

Toxicity is the most common reason for modification of firstline therapy. Central Nervous System (CNS) side effects such as difficulty with sleeping & bad dreams are common side effect of Efavirenz based therapy and is one of the most frequent reasons for switching or discontinuing highly active antiretroviral therapy.

Dolutegravir is within a novel class of antiretroviral agents licensed in the UK for the treatment of HIV. In combination with Truvada®, it showed fewer side effects when compared to Efavirenz in other clinical studies, where patients were starting HIV treatment for the first time, or switching from other agents.

The purpose of the study is to investigate the benefits of switching away from Eefavirenz (in combination with Kivexa® or as part of the combination pill, Atripla®) to Dolutegravir in patients with CNS side effects (such as difficulty with sleeping, bad dreams etc).


Clinical Trial Description

The main aim of this study is to investigate the benefits of switching from Efavirenz (taken in combination with Kivexa®or as part of the combination pill, Atripla®) in patients with Central Nervous System (CNS) side effects (such as difficulty with sleeping, bad dreams etc). The study aims to investigate the effect of switching Efavirenz to Dolutegravir while continuing Truvada (tenofovir plus emtricitabine, two constituents of Atripla) or Kivexa. Dolutegravir will be the only new component of the combination.

In addition to the aims stated above, the study also aims:

To investigate whether switching to dolutegravir based combination Antiretroviral Therapy (cART) is associated with resolution of CNS toxicity (determined by CNS questionnaire) at 12 weeks post switch To investigate continued virological suppression at levels of <400 and <50 copies/ml in individuals switching to dolutegravircontaining cART at 4 and 12 weeks post switch To investigate changes in cluster of differentiation 4+ (CD4+) cell count in individuals switching to dolutegravircontaining cART over 12 weeks post switch To investigate the safety (laboratory and non CNS adverse events) of switching to dolutegravir based cART over 12 weeks post switch To investigate changes in quality of life in individuals switching to dolutegravir based cART as assessed by Quality of life (EuroQOL) questionnaires over 12 weeks post switch To investigate the impact of switching to dolutegravir based CART on anxiety and depression (as determined by Hospital Anxiety and Depression Score (HADS) over 12 weeks post switch To investigate changes in quality of sleep in individuals switching to dolutegravir based cART as per standardized sleep questionnaire at 4 and 12 weeks post switch To assess the impact of switching to dolutegravir based cART on adherence by standard questionnaire over 12 weeks post switch To investigate changes in neuropsychiatric function in individuals switching to dolutegravir based cART by CogState battery and Instrumental Activities of Daily Life (IADL) questionnaire over 12 weeks post switch To investigate changes in fasting cholesterol and triglycerides in individuals switching to dolutegravir based cART over 12 weekspost switch To investigate Efavirenz (EFV) plasma decay and its impact on Dolutegravir (DTG) concentrations following the switch (Maximum Concentration (Cmax), Minimum Concentration (Cmin), Area Under the concentration-time Curve (AUC) at weeks 1, 2 and 3 post switch) To investigate the association between genetic polymorphisms in drug disposition genes and drug exposure To assess changes in the levels of tryptophan, kynurenine, kynurenine/tryptophan ratio, neopterin, tumour necrosis factorα and interferonγ in plasma following treatment switch from efavirenz to dolutegravir.

To investigate the relationship between the immune activation biomarkers and the kynurenine/tryptophan ratio at baseline and post switch.

To investigate the relationship between the kynurenine/tryptophan ratio and measures of CNS toxicity and neurocognitive impairment at baseline and postswitch. ;


Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment


Related Conditions & MeSH terms


NCT number NCT02285374
Study type Interventional
Source St Stephens Aids Trust
Contact Nuno Morgado
Phone +44 (0)20 3315 3765
Email nuno.morgado@chelwest.nhs.uk
Status Not yet recruiting
Phase Phase 4
Start date November 2014
Completion date December 2015

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