Clinical trial NCT00885664: Immune Reconstitution as a Determinant of Adverse Effects to New Antiretroviral Therapy in Persons With Advanced HIV Infection
Official title: Immune Reconstitution as a Determinant of Adverse Effects to New Antiretroviral Therapy in Persons With Advanced HIV Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV Infections
Keywords: HIV
immune reconstitution
treatment naive
Lead sponsor: University of Cincinnati
Sponsor class: OTHER
Collaborators: name: Abbott
name: Gilead Sciences
First posted: 2009-04-22
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: All participants received truvada and kaletra in this trial
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Symptom Score
timeFrame: Week 4
Secondary outcomes:
measure: SF-12 Physical Capacity Score
timeFrame: 4 weeks
measure: SF-12 Mental Capacity Score
timeFrame: 4 weeks
measure: IL-1 Beta
timeFrame: 4 weeks
measure: IL-4
timeFrame: 4 weeks
measure: IL-6
timeFrame: 4 weeks
measure: IL-7
timeFrame: 4 weeks
measure: IL-8
timeFrame: 4 weeks
measure: IL-10
timeFrame: 4 weeks
measure: TNF Alpha
timeFrame: 4 weeks
measure: INF Gamma
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: University of Cincinnati AIDS Clinical Trials Unit
state: Ohio
Study officials:
affiliation: University of Cincinnati
name: Carl J Fichtenbaum, MD
role: PRINCIPAL_INVESTIGATOR
References: