Immune Reconstitution as a Determinant of Adverse Effects to New Antiretroviral Therapy in Persons With Advanced HIV Infection

The purposes of this study are:

1. To understand whether the use of HIV therapy in persons with more advanced HIV disease results in greater side effects.
2. To determine whether these side effects can be related to greater activation of the immune system.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Truvada (tenofovir/emtricitabine); Drug: Kaletra (lopinavir/ritonavir)

Detailed Description

1. To compare the incidence and severity of self-reported symptoms in persons with CD4 counts <100 cells/mm3 versus those with CD4 counts ≥ 100 cells/mm3 who are initiating antiretroviral therapy.
2. To determine the relationship between self-reported symptoms and levels of T cells, HIV RNA, activation marker cytokines including TNF-α, IFN-γ, IL-2, IL-4, IL-6, IL-10 and other cytokines as measured before and after the initiation of antiretroviral therapy.
3. To determine the relationship between antiretroviral drug trough levels (estimated drug concentrations) and the incidence and severity of self-reported symptoms in persons initiating antiretroviral therapy.
4. To determine the relationship between adverse events and immunological status as evidenced by lymphocyte counts and activation marker cytokine levels.
5. To determine the relationship between clinical events and immunological status as evidenced by lymphocyte counts and activation marker cytokine levels.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati AIDS Clinical Trials Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age > 18 years
2. Diagnosis of HIV infection.
3. Naive to antiretroviral therapy OR no use of antiretrovirals for ≥ 6 months.

Exclusion Criteria:

1. Blinded drug treatment.
2. Active untreated serious infection within 14 days of enrollment that in the opinion of the investigator would affect the subject's participation and/or safety in the study.
3. Known resistance to proposed new HIV regimen or components of regimen.
4. Requirement for drug therapy with known contraindication with proposed new antiretroviral therapy (see Prohibited and Precautionary Medications below)
5. Pregnancy or breast feeding.
6. Liver enzyme abnormalities on screening. Patients who have symptomatic Grade 3 elevations of total bilirubin, AST, ALT, or alkaline phosphatase or Grade > 3 elevations of total bilirubin, AST, ALT, or alkaline phosphatase will be excluded. Patients who have asymptomatic grade 3 elevations of total bilirubin, AST, ALT, or alkaline phosphatase may be included in the study at the discretion of the primary physician in consultation with the principal or senior investigator. Patients with grade 3 elevations of liver function tests who are co-infected with hepatitis B or hepatitis C may be included in the study at the discretion of the primary care physician in consultation with the primary or senior investigator provided that they do not have signs or symptoms of clinical hepatitis. Signs of clinical hepatitis include: icterus, abdominal tenderness and hepatosplenomegaly. Symptoms of clinical hepatitis include: fever, abdominal pain, anorexia, nausea, vomiting, fatigue, malaise, and myalgia.
7. Decreased creatinine clearance at the time of screening. Patients with a creatinine clearance of <50mL/min as calculated by the Cockcroft-Gault method should be excluded from study entry. The Cockcroft-Gault method is defined on page 33.
8. Other Grade ≥3 lab abnormalities. For any other laboratory abnormalities of grade 3 or higher, patients may be included or excluded from the study at the discretion of the primary care physician in consultation with the primary or senior investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Truvada/Kaletra CD4<100; All participants were treated but at baseline by design were divided based upon their CD4 count at baseline measurement. Group with CD4<100 cells/cu mm	Drug: Truvada (tenofovir/emtricitabine); Tenofovir/emtricitabine fixed dose combination once daily; Other Names: Truvada; Drug: Kaletra (lopinavir/ritonavir); Lopinavir/ritonavir 400/100 mg twice daily; Other Names: Kaletra
Other: Truvada/Kaletra CD4>/=100; All participants were treated but at baseline by design were divided based upon their CD4 count at baseline measurement. Group with CD4>/=100 cells/cu mm	Drug: Truvada (tenofovir/emtricitabine); Tenofovir/emtricitabine fixed dose combination once daily; Other Names: Truvada; Drug: Kaletra (lopinavir/ritonavir); Lopinavir/ritonavir 400/100 mg twice daily; Other Names: Kaletra

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptom Score	AIDS Clinical Trials Group Symptom Summary Score (20 item scale with severity from 0-4); Severity scale, 0=absent, 1=is least severe and 4 is most severe. Minimum score = 0 units on scale. Maximum score = 80 units on scale.	Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SF-12 Physical Capacity Score	Measure of physical function out of 100. Lower score means less physical capacity.	4 weeks
SF-12 Mental Capacity Score	Measure of mental functioning where lower is better out of a scale of 100.	4 weeks
IL-1 Beta	Cytokine IL-1 beta measurement by Luminex multiplex assay in picograms/mL, dynamic range 0.13-2000 pg/mL	4 weeks
IL-4	Interleukin-4 measured by Luminex multiplex assay in picograms/mL, dynamic range 0.13-2000 pg/mL	4 weeks
IL-6	Interleukin 6 measured by Luminex multiplex assay in picograms/mL, dynamic range 0.13-2000 pg/mL	4 weeks
IL-7	Interleukin 7 measured by Luminex multiplex assay in picograms/mL, dynamic range 0.13-2000 pg/mL	4 weeks
IL-8	Interleukin 8 measured by Luminex multiplex assay in picograms/mL, dynamic range 0.13-2000 pg/mL	4 weeks
IL-10	Interleukin 10 measured by Luminex multiplex assay in picograms/mL, dynamic range 0.13-2000 pg/mL	4 weeks
TNF Alpha	Tumor Necrosis Factor Alpha - measured by Luminex multiplex assay in picograms/mL, dynamic range 0.13-2000 pg/mL	4 weeks
INF Gamma	Interferon gamma measured by Luminex multiplex assay in picograms/mL, dynamic range 0.13-2000 pg/mL	4 weeks

Collaborators and Investigators

• Sponsor: University of Cincinnati
• Collaborators: Gilead Sciences; Abbott
• Investigators: Principal Investigator: Carl J Fichtenbaum, MD, University of Cincinnati

Study record dates

Study Major Dates

• Study Start: October 1, 2005
• Primary Completion (Actual): September 1, 2009
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: April 20, 2009
• First Submitted That Met QC Criteria: April 21, 2009
• First Posted (Estimate): April 22, 2009

Study Record Updates

• Last Update Posted (Actual): August 10, 2022
• Last Update Submitted That Met QC Criteria: July 14, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: HIV; immune reconstitution; treatment naive
• Additional Relevant MeSH Terms: Pathologic Processes; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Disease Attributes; Slow Virus Diseases; HIV Infections; Infections; Communicable Diseases; Acquired Immunodeficiency Syndrome; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Tenofovir; Emtricitabine; Ritonavir; Lopinavir; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
• Other Study ID Numbers: IDC 30