Seronegatives and Metabolic Abnormalities Protocol 2 (SAMA002): Study to Compare the Effect of Kaletra and Combivir® in HIV-Negative Healthy Subjects

Condition(s) targeted: HIV Infections; Dyslipidemias; Glucose Metabolism Disorders; Metabolic Diseases; Lipodystrophy; Cardiovascular Disease

Intervention: Combivir (zidovudine [AZT] / lamivudine [3TC]) (Drug); Kaletra (lopinavir [LPVr]) (Drug)

Phase: Phase 4

Status: Active, not recruiting

Sponsored by: The National Centre in HIV Epidemiology and Clinical Research

Official(s) and/or principal investigator(s):
Andrew D Carr, MD FRACP FRCPA, Principal Investigator, Affiliation: National Centre in HIV Epidemiology and Clinical Research
David A Cooper, MD, Study Director, Affiliation: National Centre in HIV Epidemiology and Clinical Research

This is a randomised study of the effect of treatment with Combivir (zidovudine [AZT] and lamivudine [3TC]) and Kaletra (lopinavir [LPVr]), alone and in combination, on the development of abnormalities in lipid and glucose metabolism in HIV negative healthy subjects.

Official title: A 3 Arm, Prospective Study to Compare the Effect of 6 Weeks Exposure to the Combination of Lopinavir (LPVr)/Combivir® (AZT/3TC) Versus Lopinavir Alone or Combivir® Alone in HIV-Negative Healthy Subjects on the Development of Abnormalities of Lipid and Glucose Metabolism

Study design: Diagnostic, Randomized, Open Label, Dose Comparison, Parallel Assignment, Safety Study

Primary outcome: To determine effect of 6 wks ART with LPVr and CBV, alone and in combination, in HIV negative healthy subjects with respect to changes from baseline in genes related to mitochondrial and lipid metabolism in adipocytes

Secondary outcome: includes: To determine the effect of 6 wks of ART with LPVr and CBV in HIV negative subjects with respect to: changes from baseline in genes related to mitochondrial and lipid and glucose metabolism in monocytes.

Detailed description: Antiretroviral medications, used to treat HIV infection, cause side effects. These include changes in the way that fat is laid down on the body. This results in fat loss from some parts of the body, with fat deposits at other sites, giving a characteristic look known as "HIV associated lipodystrophy" or HIVLD. With these changes, there are also abnormalities in glucose and fat metabolism (collectively termed metabolic abnormalities). In HIV negative populations, these metabolic changes are associated with an increased risk of developing cardiovascular disease (CVD). The aim of this study is to investigate if changes in the body's handling of fats and glucose occur with a short course of treatment in HIV negative subjects and if these correlate to an increased risk of CVD.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Age >18

- Be able to provide written consent to perform in the trial.

- HIV antibody negative and HIV DNA negative at time of entry to the study.

Exclusion Criteria:

- Any history of, or ongoing, mental or physical condition (including suspected or known

diagnosis of ischaemic heart disease), which, in the opinion of the investigator, would impede the subject's ability to participate in the trial.

- History of type I or type II diabetes mellitus or previous treatment with antidiabetic

medication.

- Prior use of testosterone, oestrogen, growth hormone or other oral glucocorticoid or

anabolic steroid products within the previous six months.

- Alcohol or substance abuse which in the opinion of the investigator would affect the

subject's ability to participate in the trial.

- Prior use of anti-retroviral agents (including protease inhibitors, nucleoside or

non-nucleoside reverse transcriptase inhibitors, investigational antiretroviral agents or fusion inhibitors either in a previous study, as treatment or as part of post-exposure prophylaxis).

- Prior use of any retinoid-containing compound within the previous six months.

- Abnormal coagulation.

- Previous allergic reaction or known allergy to local anaesthetic.

- Previous use of psychotropic medications.

- Concomitant use of medications, including those metabolised by CYP3A4 enzyme system,

which, in the opinion of the investigator, would affect the subject's ability to participate in all activities involved in the trial.

- Any grade-three laboratory abnormality recorded from screening bloods.

- Any grade-two laboratory abnormality recorded from screening bloods, which, in the

opinion of the investigator, would impede the subject's ability to safely complete all study requirements.

- Gastrointestinal disorders, which may affect drug absorption.

- Any finding on screening clinical examination, which, in the opinion of the

investigator, would impede the subject's ability to participate in the rest of the trial.

- Pregnancy

- Evidence of acute or chronic active hepatitis B virus infection by serology performed

at baseline.

- Evidence of hepatitis C infection by serology performed at baseline.

St Vincents Hospital, Sydney, New South Wales 2010, Australia

National Centre in HIV Epidemiology and Clinical Research Homepage

Starting date: November 2004
Ending date: December 2006
Last updated: August 15, 2007