Tenofovir DF (Disoproxil Fumarate) in Combination With Emtricitabine in HIV-1 Patients

A Phase 4, Single-Arm Study to Evaluate the Safety, Antiviral Activity and Pharmacokinetics of Tenofovir Disoproxil Fumarate in Combination With Emtricitabine in HIV-1 Infected Patients Experiencing Various Degrees of Renal Impairment

The purpose of this study is to provide long-term clinical safety and efficacy data for tenofovir disoproxil fumarate and emtricitabine in HIV-infected patients experiencing various degrees of renal impairment.

The primary objective of this study is as follows:

• To evaluate the safety and tolerability of tenofovir following administration of tenofovir disoproxil fumarate 300 mg for 48 weeks in HIV-infected patients experiencing various degrees of renal impairment.

The secondary objectives of this study are as follows:

• To evaluate the safety and tolerability of emtricitabine following administration of emtricitabine 200 mg for 48 weeks in HIV-infected patients experiencing various degrees of renal impairment.
• To evaluate the efficacy of tenofovir disoproxil fumarate in combination with emtricitabine in renally-impaired HIV-infected patients.
• To evaluate the pharmacokinetics of tenofovir and emtricitabine in renally-impaired HIV-infected patients.

Inclusion Criteria:

Patients must meet all of the following inclusion criteria to be eligible for participation in the study.

• HIV-1 infection
• Either antiretroviral therapy-naive requiring antiretroviral treatment with HIV-1 RNA greater than 400 copies/mL or antiretroviral therapy-experienced on a stable antiretroviral regimen for at least 3 mos. with HIV-1 RNA less than or equal to 50 copies/mL at screening.
• No active opportunistic infection within 45 days prior to baseline.
• Able to understand and sign the informed consent form and comply with the study.
• Stable renal impairment within the four defined groups for at least 3 mos., based on creatinine clearance (Cockcroft-Gault method).

Exclusion Criteria:

Patients who meet any of the following are not to be enrolled in this study.

• Women who are pregnant or breastfeeding
• Fanconi syndrome or multiple myeloma, tertiary hyperparathyroidism, malignancy (with the exception of basocellular carcinoma) or myeloproliferative disorder.
• Women of childbearing potential who are unwilling to use an effective contraceptive method during the study
• Contraindications to tenofovir DF, emtricitabine or efavirenz
• Undergoing treatment for tuberculosis
• Using atazanavir
• Prior history of mutation M184V, K65R or T69 insertion
• Z-score on pre-baseline DEXA scan less than -2.5
• The following laboratory values within 30 days prior to study entry: *absolute neutrophil count (ANC) less than 750/mm3, *hemoglobin less than 9.0 g/dL, *platelet count less than 50,000/mm3, *AST (SGOT) or ALT (SGPT) less than 5 x ULN and *CD4 cell count less than 100/mm3.
• Use of nephrotoxic agents or competitors with renal excretions, including aminoglycoside antibiotics, intravenous amphotericin B, cidofovir, cisplatin, foscarnet, intravenous pentamidine, probenecid or other agents with significant nephrotoxic potential
• Clinically significant cardiac, pulmonary or gastrointestinal disorder
• Alcohol or drug abuse that could hinder compliance with the study