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

HIV Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00885664
• Other study ID #: IDC 30
• Status: Completed
• Phase: Phase 4
• Start date: October 2005
• Est. completion date: March 2010

Study information

• Verified date: July 2022
• Source: University of Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: March 2010
• Est. primary completion date: September 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Communicable Diseases
• HIV Infections
• Infections

Intervention

Drug:
• Truvada (tenofovir/emtricitabine)
Tenofovir/emtricitabine fixed dose combination once daily
• Kaletra (lopinavir/ritonavir)
Lopinavir/ritonavir 400/100 mg twice daily

Locations

Country	Name	City	State
United States	University of Cincinnati AIDS Clinical Trials Unit	Cincinnati	Ohio

Sponsors (3)

Lead Sponsor	Collaborator
University of Cincinnati	Abbott, Gilead Sciences

Country where clinical trial is conducted

United States, 

Outcome

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