The Safety, Pharmacokinetic Profile and Efficacy of Raltegravir in HIV-infected Patients at Least 60 Years of Age

Study Overview
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Brief Summary
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This is a phase IV, open label, prospective, one phase pharmacokinetic and observational study. Twenty HIV-1 infected subjects will be recruited, subjects will switch antiretroviral therapy to: tenofovir/emtricitabine 245/200 mg daily (Truvada™) plus raltegravir 400 mg twice daily On day 28, all subjects will attend for an intensive 24 hour pharmacokinetic visit.

Detailed Description
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This is a phase IV, open label, prospective, one phase pharmacokinetic and observational study. Twenty HIV-1 infected subjects will be recruited. Eligible subjects will currently be receiving stable antiretroviral therapy with undetectable plasma HIV RNA and have no evidence of previous HIV- resistance mutations on genotypic resistance testing. At baseline, subjects will switch antiretroviral therapy to: tenofovir/emtricitabine 245/200 mg daily (Truvada™) plus raltegravir 400 mg twice daily On day 28, all subjects will attend for an intensive 24 hour pharmacokinetic visit. Follow up over 6 months, subjects will attend on days 14, 90 and 180 for follow up visits that will include standard safety parameters. Assessment of cardiac biomarkers at baseline and on days 90 and 180 and assessment of neurocognitive function at screening, baseline and on day 180 will also be undertaken. Following completion of this study, subjects will recommence their usual antiretroviral treatment regimen and attend for a study follow up visit.

Official Title
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An Open Label Study to Investigate the Safety, Pharmacokinetic Profile and Efficacy of Raltegravir in HIV-infected Patients at Least 60 Years of Age

Conditions
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HIV

Intervention / Treatment
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* Drug: Raltegravir
* Drug: Tenofovir
* Drug: Emtricitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-1 infected males or females 60 years of age or greater* signed informed consent willing to switch therapy as per study protocol no previous exposure to raltegravir or HIV-1 integrase inhibitors plasma HIV RNA < 50 copies/mL at screening and on at least one other occasion over the last 3 months currently receiving a stable antiretroviral regimen with no antiretroviral drug switches for at least 3 months no previous clinically-significant resistance documented on HIV-1 genotypic resistance subjects in good health upon medical history, physical exam, and laboratory testing BMI above or equal to 18 and below 32 Male subjects who are heterosexually active must use two forms of barrier contraception (e.g., condom with spermicide) during heterosexual intercourse, from screening through completion of the study. Have local screening laboratory results (haematology and chemistry that fall within the normal range of the central laboratory's reference ranges unless the results have been determined by the Investigator to have no clinical significance * 50% of total enrolled cohort will be 65 years of age or over. Subsequent to 10 subjects aged between 60 and 64 recruited, only subjects aged 65 or over will be eligible. Exclusion Criteria: current alcohol abuse or drug dependence positive urine drug of abuse screening active opportunistic infection or significant co-morbidities current disallowed concomitant medication

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: HIV affected over 60 years old
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Tenofovir/Emtricitabine and Raltegravir<br>Single arm study tenofovir/emtricitabine 245/200 mg once daily and raltegravir 400 mg twice daily | Drug: Raltegravir<br>* 400 mg twice daily<br>* Other names: Isentress;Drug: Tenofovir<br>* 245 mg once daily<br>Drug: Emtricitabine<br>* 200mg once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Drug Levels in Blood | rategravir concentration | Day 28 | 
| Changes in Haematology, Biochemistry and Virology Tests | full blood count, electrolytes and blood lipids will be measured at all visits to assess for changes through out the study. HIV viral load will also be measured to assess the efficacy of the medication at controlling the virus | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiovascular Disease Markers | • To investigate cardiovascular disease markers before and after a switch in antiretroviral therapy to raltegravir. | 6 months | 
| Cerebral Function; Changes in Global Cognitive Z-score | Cerebral function via cognitive testing before and after a switch in antiretroviral therapy to raltegravir. Mean Scores from the eight tasks (NPZ-8) assessed were used to derive a global composite measure of neurocognitive function. The result shows the change before and after switch, an increase in z-score represents an improvement in cognitive function assessed by CogState battery, required approximately 10-15 min for completion. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Pharmatokinetic, 60 years old, Raltegravir