Comparing the Safety, Effectiveness, and Tolerability of Three Anti-HIV Drug Regimens for Treatment-Naive Patients

National Institute of Allergy and Infectious Diseases (NIAID)775 enrolled

Overview

With new strategies and drugs available, many different regimens exist for the treatment of HIV. The purpose of this study is to compare three different anti-HIV drug regimens as first-time treatments for HIV infection.

Numerous treatment options are available to HIV infected patients who are antiretroviral (ARV) therapy naive, but an optimal regimen has not yet been established. This study will compare a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen, a ritonavir (RTV)-enhanced protease inhibitor (PI)-based regimen, and a nucleoside reverse transcriptase inhibitor (NRTI)-sparing regimen for the initial treatment of HIV infection. Patients will be randomly assigned to one of three study arms. In Arm A, patients will receive lopinavir/ritonavir (LPV/r) twice daily and efavirenz (EFV) once daily before bed. Arm B patients will receive LPV/r twice daily, lamivudine (3TC) once daily, plus either stavudine extended release (d4T XR) once daily, zidovudine (ZDV) twice daily, or tenofovir disoproxil fumarate (TDF) once daily. Patients in Arm C will receive EFV once daily before bed and 3TC plus either d4T XR once daily before bed, ZDV twice daily, or TDF once daily before bed. Study visits will occur every 4 weeks until Week 24, then every 8 weeks thereafter for a maximum of 96 weeks. Blood will be drawn at every visit and a urine sample will be collected every 8 weeks. Body measurements will be taken at Weeks 24, 48, 72, and 96. Whole body dual-energy x-ray absorptiometry (DEXA) scans will be done at Weeks 48 and 96. Patients must fast before study visits at Weeks 12, 24, 48, 72, and 96. Women in the study will have gynecological assessments every 24 weeks.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

775

Conditions

HIV Infections

Interventions

Lopinavir/ritonavirDRUG

EfavirenzDRUG

StavudineDRUG

ZidovudineDRUG

Eligibility

Sex: ALLMin age: 13 Years

Medical Language ↔ Plain English

Inclusion Criteria for Step 1: * HIV infected * HIV viral load of 2000 copies/ml or greater within 60 days prior to study entry * Willing to use acceptable means of contraception * d4T XR, TDF, or ZDV chosen as part of an initial regimen prior to randomization to a study arm * Coenrolled in ACTG A5152s Exclusion Criteria for Step 1: * On ARV therapy for 7 days or more any time prior to study entry * NNRTIs or 3TC at any time prior to study entry * Current peripheral neuropathy of Grade 2 or higher * Pregnancy or breastfeeding * Immunomodulators, vaccines, or investigational therapies within 30 days of study entry. Patients taking a stable or tapering dose of prednisone at less than 10 mg are not excluded. * Human growth hormone within 30 days prior to study entry * Initiation of testosterone or anabolic steroids within 30 days prior to study entry * Certain other medications within 30 days of study entry * Hypersensitivity to components of the study drug formulations * Drug or alcohol use or dependence that would interfere with adherence to study requirements * Acute therapy for serious medical illnesses requiring systemic treatment and/or hospitalization within 14 days prior to study entry * Recent infection with drug-resistant HIV

Locations (60)

Outcomes

Primary Outcomes

Time from study entry to virologic failure

time from study entry to regimen completion

Secondary Outcomes

20 % or more loss in peripheral fat

increase in lactic acid levels at least 2-4old above the upper limit of normal (ULN)

20 % or more increase in truncal fat accumulation

fasting cholesterol level equal to or greater than 240 mg/dl

Grade 3 or greater elevation in fasting triglyceride levels

change from baseline in insulin resistance

Time frame: at Weeks 24, 48 and 96

change from baseline of whole-body bone density and whole-body bone mineral content

Time frame: at Weeks 48 and 96

time to confirmed virologic failure while on Steps I (initial randomized regimen) or II (within class substitutes for initial regimen toxicity) OR treatment-limiting toxicity on Steps I or II

number of antiretroviral classes with resistance mutations at virologic failure

number of missed medication doses

Time frame: 4 days prior

change from baseline in self-reported symptoms OR occurrence of reporting an increase in symptoms

Time frame: at Weeks 4, 48, 72 and 96

Data from ClinicalTrials.gov

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