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

Phase 4

Completed

Brief Summary: 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: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Tenofovir/Emtricitabine and Raltegravir	Emtricitabine	Single arm study tenofovir/emtricitabine 245/200 mg once daily and raltegravir 400 mg twice daily
Tenofovir/Emtricitabine and Raltegravir	Tenofovir	Single arm study tenofovir/emtricitabine 245/200 mg once daily and raltegravir 400 mg twice daily
Tenofovir/Emtricitabine and Raltegravir	Raltegravir	Single arm study tenofovir/emtricitabine 245/200 mg once daily and raltegravir 400 mg twice daily

Primary Outcome Measures

Name	Time	Method
Drug Levels in Blood	Day 28	rategravir concentration
Changes in Haematology, Biochemistry and Virology Tests	6 months	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

Secondary Outcome Measures

Name	Time	Method
Cerebral Function; Changes in Global Cognitive Z-score	6 months	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.
Cardiovascular Disease Markers	6 months	• To investigate cardiovascular disease markers before and after a switch in antiretroviral therapy to raltegravir.