Clinical trial NCT00135460: Comparing a Nucleoside-Analogue-Sparing Regimen and a Protease-Inhibitor-Sparing Regimen in HIV Infected Patients
Official title: Comparing a Nucleoside-Analogue-Sparing Regimen and a Protease-Inhibitor-Sparing Regimen in Patients With HIV. Influence on Morphological and Metabolic Disorders. A Randomized, Open-Label Multicenter Trial.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: HIV-Associated Lipodystrophy Syndrome
Keywords: HIV
Lipoatrophy
Lipodystrophy
Treatment Naive
HIV Infections
Hypercholesterolemia
Lead sponsor: Danish HIV Research Group
Sponsor class: OTHER
Collaborators: name: Rigshospitalet, Denmark
name: Hvidovre University Hospital
name: Odense University Hospital
name: Aarhus University Hospital
name: Aalborg University Hospital
name: Abbott
First posted: 2005-08-26
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Highly active antiretroviral therapy (HAART) has improved the long time survival of HIV infected individuals. However an increasing number of HIV-patients have developed metabolic and morphological alterations including peripheral lipoatrophy.

There is limited knowledge about lipodystrophic adverse events in nucleoside reverse transcriptase inhibitor (NRTI)-sparing regimens. The hypothesis is that nucleoside analogues are responsible for development of lipoatrophy, and, patients receiving an NRTI-sparing regimen will have little risk of peripheral lipoatrophy.

The researchers plan to perform a randomized study recruiting 100 antiretroviral naive patients that will be randomized to receive a nucleoside analogue sparing HAART regimen or a protease-inhibitor sparing regimen.

The main endpoint is changes in peripheral fat mass as determined by dual energy X-ray absortiometry (DEXA)-scanning.


Eligibility criteria: Inclusion Criteria:

* Antiretroviral naïve patients
* HIV-1 infection as documented by a licensed HIV-1 antibody ELISA.
* Fulfilling the criteria for starting antiretroviral therapy.
* Ability to understand and provide written informed consent.

Exclusion Criteria:

* Women being pregnant or breast-feeding.
* Fertile women using no safe contraception.
* Patients with active intravenous drug use.
* Abuse of alcohol, which in the opinion of the treating physician will reduce the patient´s ability to follow a therapeutic regimen and evaluations of the protocol.
* Ongoing medical treatment, which has a clinically significant interaction with lopinavir, ritonavir or efavirenz.
* Creatinine \> 200 mmol/l.
* ALT or AST \> 5 times upper normal value (200U/l).

Primary outcomes:
measure: Changes in peripheral fat mass, determined by DEXA-changes
measure: Changes in body composition from baseline, determined by patient and physician in a standardized questionnaire and by standardized clinical examination
measure: Change from baseline in fasting lipids and subsets hereof
measure: Development of impaired glucose tolerance and insulin resistance
Secondary outcomes:
measure: Proportion of patients with HIV-RNA < 20 copies after 24, 48, 72 and 96 weeks
measure: Change in CD4 cell count from baseline after 24, 48, 72 and 96 weeks
measure: Incidence of adverse events
measure: Incidence of clinical disease progression
measure: Proportion of patients who have virological, immunological or clinical failure or treatment-limiting adverse events at week 24, 48 and 96
measure: Change in plasma lactate from baseline
measure: Time to discontinuation of the randomized therapy and reasons for this
measure: Incidence of genotypical and virological resistance
measure: Development of osteopenia, judged by DEXA-scan
measure: Compliance - proportion of patients who report to take 90%, respectively 95% of their medications at week 4, 48 and 96
Other outcomes:
Locations:
city: Hvidovre
country: Denmark
facility: Department of Infectious Diseases, Hvidovre University Hospital
state: Copenhagen
city: Aalborg
country: Denmark
facility: Department of Infectious Diseases, Aalborg Hospital
city: Aarhus
country: Denmark
facility: Department of Infectious Diseases, Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: Department of Infectious Diseases, Rigshospitalet
city: Odense
country: Denmark
facility: Department of Infectious Diseases, Odense University Hospital
Study officials:
affiliation: Rigshospitalet, Denmark
name: Jan Gerstoft, M.D., DMSc
role: STUDY_CHAIR
affiliation: Odense University Hospital
name: Niels Obel, M.D., DMSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Odense University Hospital
name: Court Pedersen, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Hvidovre University Hospital
name: Lars Mathiesen, M.D.,DMSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Aalborg University Hospital
name: Henrik Nielsen, M.D.,DMSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Aarhus University City
name: Alex Laursen, M.D., DMSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Copenhagen University Hospital Rigshospitalet and Odense University Hospital
name: Ann-Brit E Hansen, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mathiesen IH, Salem M, Gerstoft J, Gaardbo JC, Obel N, Pedersen C, Ullum H, Nielsen SD, Hansen AE. Complete manuscript Title: Changes in RANKL during the first two years after cART initiation in HIV-infected cART naive adults. BMC Infect Dis. 2017 Apr 11;17(1):262. doi: 10.1186/s12879-017-2368-y.