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

Phase 4

Completed

• Conditions: HIV Infections
• Interventions: Drug: Truvada (tenofovir/emtricitabine); Drug: Kaletra (lopinavir/ritonavir)

• Registration Number: NCT00885664
• Lead Sponsor: University of Cincinnati

Brief 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.

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 Timeline

• Study Start: 2005-10
• Study First Submitted: 2009-04-20
• Study First Submitted QC: 2009-04-21
• Study First Posted: 2009-04-22
• Primary Completion: 2009-09
• Study Completion: 2010-03
• Results First Submitted: 2021-12-20
• Status Verified: 2022-07
• Results First Submitted QC: 2022-07-14
• Last Update Submitted: 2022-07-14
• Results First Posted: 2022-08-10
• Last Update Posted: 2022-08-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Truvada/Kaletra CD4<100	Truvada (tenofovir/emtricitabine)	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
Truvada/Kaletra CD4<100	Kaletra (lopinavir/ritonavir)	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
Truvada/Kaletra CD4>/=100	Truvada (tenofovir/emtricitabine)	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
Truvada/Kaletra CD4>/=100	Kaletra (lopinavir/ritonavir)	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

Primary Outcome Measures

Name	Time	Method
Symptom Score	Week 4	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.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

University of Cincinnati AIDS Clinical Trials Unit; 🇺🇸 Cincinnati, Ohio, United States