NRTI-Sparing Pilot Study

Study Overview
=================
Brief Summary
-----------------
This study will compare a nucleoside reverse transcriptase inhibitor-sparing (NRTI-sparing) regimen (Kaletra + nevirapine) to two nucleoside reverse transcriptase inhibitor-based regimens (Combivir + nevirapine and Combivir + Kaletra). Participants will be randomly assigned to receive one of the following drug combinations: lopinavir/ritonavir (Kaletra) and nevirapine (Viramune) twice a day; Combivir (Zidovudine (AZT) plus lamivudine (3TC)) and nevirapine twice a day; Combivir and lopinavir/ritonavir twice a day.

Official Title
-----------------
A Pilot Study of a Nucleoside Analogue Reverse Transcriptase Inhibitor Sparing Regimen in Antiretroviral-Naïve, HIV-infected Patients

Conditions
-----------------
HIV, Mitochondrial Toxicity

Intervention / Treatment
-----------------
* Drug: lopinavir/ritonavir; nevirapine; Zidovudine; Lamivudine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Be HIV-positive Be at least18 years of age Have viral load above 5 000 copies/ml Be likely to comply with the study protocol Agree not to take, for the duration of the study, any drug that is contraindicated with the study drugs Agree not to take any medication, including over-the-counter medicine, alcohol, or street drugs without the knowledge and permission of the principal investigator Exclusion Criteria: Have ever received antiretroviral therapy Pregnancy or breastfeeding Have abnormal laboratory tests (see investigator) Have received an investigational drug within 30 days of study drugs administration Be receiving systemic chemotherapy Have an acute illness

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lopinavir/ritonavir, Zidovudine, Lamivudine<br>Participants will be randomly assigned to receive one of the following drug combinations: lopinavir/ritonavir (Kaletra) and nevirapine (Viramune) twice a day; Combivir (Zidovudine (AZT) plus lamivudine (3TC)) and nevirapine twice a day; Combivir and lopinavir/ritonavir twice a day. | Drug: lopinavir/ritonavir; nevirapine; Zidovudine; Lamivudine<br>* See Detailed Description.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in mitochondrial DNA/Nuclear DNA (mtDNA/nDNA) ratio at 48 weeks, as a marker of mitochondrial toxicity. |  | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in mitochondrial DNA/Nuclear DNA (mtDNA/nDNA) ratio at 96 weeks |  | 96 weeks | 
| Proportions of patients with viral load below 50 and below 400 copies/mL |  |  | 
| Viral load changes from baseline |  |  | 
| Rates and extent of immune reconstitution (CD4 count increase) |  |  | 
| Rates and severity of dyslipidemia and insuline resistance/diabetes |  |  |