Changes in Triglyceride and Other Lipids (Levels of Fats Found in Blood) When Taking Darunavir Compared to Atazanavir in HIV-infected Patients That Have Never Received Treatment

The purpose of this study is to expand our understanding of the metabolic effects of
darunavir/ritonavir (DRV/r) in HIV-infected patients. This is a phase 4, multicenter,
open-label, randomized (study drug assigned by chance), comparative study designed to
compare changes in lipid, glucose, and insulin parameters in HIV-infected, anti-retroviral
(ARV) naive patients treated with DRV/r 800/100 mg once daily (QD) versus
atazanavir/ritonavir (ATV/r) 300/100 mg QD in combination with a common background of
emtricitabine (FTC)/ tenofovir (TDF) 200/300 mg QD. In addition, changes in inflammatory
markers will be measured. A substudy of the parent study TMC114HIV4023 will evaluate insulin
sensitivity and endothelial function in a subset of patients. The study will be conducted at
approximately 16 study sites in the United States. Approximately 60 HIV-1 infected,
treatment-naive adult patients will be enrolled in the study. Screening will take place
during a 4-week period. At the baseline visit, eligible patients will be randomized in a 1:1
ratio to receive DRV/r 800/100 mg QD or ATV/r 300/100 mg QD administered in combination with
a fixed-dose background regimen consisting of emtricitabine (FTC)/tenofovir (TDF) 200/300 mg
once daily. The treatment period is 48 weeks. Study assessments will be performed at clinic
visits at the end of weeks 4, 8, 12, 24, 36, and 48. The primary endpoint will be assessed
at week 12. All patients will return for follow up visits 1 week and 4 weeks after the
completion of study treatment. During the treatment period, the patient will be seen at
regular visits during which the investigator will assess the patient's medical condition,
any Adverse Events and study drug compliance. Laboratory evaluations for efficacy and safety
will be done at regular visits as well as blood pressure monitoring. Up to twenty patients
(evenly randomized to receive DRV/r or ATV/r) who meet additional entry criteria will be
enrolled in the substudy. The study hypothesis is the change in triglycerides and other
lipids from baseline to week 12 will be similar in the DRV/r arm versus the ATV/r arm. The
substudy hypothesis is that DRV/r will not adversely affect insulin sensitivity or
endothelial function during 12 weeks of therapy, and the change from baseline in insulin
sensitivity and endothelial function will be similar in the DRV/r arm versus the ATV/r arm.
During the treatment period, the patient will be seen at regular visits during which the
investigator will assess the patient's medical condition, any Adverse Events and study drug
compliance. Laboratory evaluations for efficacy and safety will be done at regular visits as
well as blood pressure monitoring. Patients will be randomized in a 1:1 ratio to receive
darunavir/ritonavir 800/100 mg once daily (QD) plus emtricitabine (FTC)/tenofovir (TDF)
200/300 mg QD or atazanavir/ritonavir 300/100 mg QD plus emtricitabine (FTC)/tenofovir (TDF)
for 48 weeks.

Inclusion Criteria:

- HIV-1 RNA of 1000 copies/mL or more

- No previous treatment with antiretroviral drugs for more than 10 days

- Demonstrated sensitivity [Fold Change (FC) = lower Clinical Cut Off (CCO)] to
tenofovir, darunavir and atazanavir

- Demonstrated sensitivity to emtricitabine defined as absence of M184V/I mutation

- Any CD4 (Cluster of Differentiation 4) cell count

Exclusion Criteria:

- Body mass index >30 kg/m2

- Laboratory parameters as follows: fasting glucose >110 mg/dL, Low-Density Lipoprotein
(LDL) cholesterol >130 mg/dL, triglycerides >200 mg/dL

- Presence of any currently active AIDS-defining illness

- Treatment for primary HIV infection or postexposure prophylaxis for HIV

- Patients with acute or chronic hepatitis A, B or C infection