Comparing a Nucleoside-Analogue-Sparing Regimen and a Protease-Inhibitor-Sparing Regimen in HIV Infected Patients

• Changes in peripheral fat mass, determined by DEXA-changes
• Changes in body composition from baseline, determined by patient and physician in a standardized questionnaire and by standardized clinical examination
• Change from baseline in fasting lipids and subsets hereof
• Development of impaired glucose tolerance and insulin resistance

• Changes in peripheral fat mass, determined by DEXA-Changes Changes in body composition from baseline, determined by patient and physician in a standardized questionnaire and by standardized clinical examination.
• Change from baseline in fasting lipids and subsets hereof
• Development of impaired glucose tolerance and insulin resistance

• Proportion of patients with HIV-RNA < 20 copies after 24, 48, 72 and 96 weeks
• Change in CD4 cell count from baseline after 24, 48, 72 and 96 weeks
• Incidence of adverse events
• Incidence of clinical disease progression
• Proportion of patients who have virological, immunological or clinical failure or treatment-limiting adverse events at week 24, 48 and 96
• Change in plasma lactate from baseline
• Time to discontinuation of the randomized therapy and reasons for this
• Incidence of genotypical and virological resistance
• Development of osteopenia, judged by DEXA-scan
• Compliance – proportion of patients who report to take 90%, respectively 95% of their medications at week 4, 48 and 96

• Proportion of patients with HIV-RNA < 20 copies after 24, 48, 72 and 96 weeks.
• Change in CD4 cell count from baseline after 24, 48, 72 and 96 weeks.
• Incidence of adverse events.
• Incidence of clinical disease progression.
• Proportion of patients who have virological, immunological or clinical failure or treatment-limiting adverse events at week 24,48 and 96.
• Change in plasma lactate from baseline.
• Time to discontinuation of the randomized therapy and reasons for this.
• Incidence of genotypical and virological resistance.
• Development of osteopenia, judged by DEXA-scan.
• Compliance – proportion of patients who report to take 90%, respectively 95% of their medications at week 4, 48 and 96.

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.

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).

• Rigshospitalet, Denmark
• Hvidovre University Hospital
• Odense University Hospital
• Aarhus University Hospital
• Aalborg Universityhospital
• Abbott