HIV Infections
Conditions
Keywords
HIV, immune reconstitution, treatment naive
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.
Interventions
Tenofovir/emtricitabine fixed dose combination once daily
Lopinavir/ritonavir 400/100 mg twice daily
Sponsors
Abbott
Gilead Sciences
University of Cincinnati
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
All participants received truvada and kaletra in this trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| SF-12 Physical Capacity Score | 4 weeks | Measure of physical function out of 100. Lower score means less physical capacity. |
| 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 |
| IL-7 | 4 weeks | Interleukin 7 measured by Luminex multiplex assay in picograms/mL, dynamic range 0.13-2000 pg/mL |
Countries
United States
Participant flow
Recruitment details
Patients were recruited from Academic HIV practice from October 2005 through March 2009.
Participants by arm
| Arm | Count |
|---|---|
| Truvada/Kaletra CD4<100 Group with CD4 lymphocyte count less than 100 cell/cu mm treated with truvada/kaletra | 26 |
| Truvada/Kaletra CD4>/=100 Group with CD4 lymphocyte count greater than or equal to 100 cell/cu mm | 34 |
| Total | 60 |
Baseline characteristics
| Characteristic | Truvada/Kaletra CD4<100 | Truvada/Kaletra CD4>/=100 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 26 Participants | 34 Participants | 60 Participants |
| Age, Continuous | 42 years | 37 years | 39.5 years |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 5 Participants |
| Sex: Female, Male Male | 24 Participants | 31 Participants | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 0 / 34 |
| other Total, other adverse events | 26 / 26 | 34 / 34 |
| serious Total, serious adverse events | 1 / 26 | 0 / 34 |
Outcome results
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.
Time frame: Week 4
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CD4<100 | Symptom Score | 10 units on a scale |
| CD4>/=100 | Symptom Score | 8 units on a scale |
p-value: 0.45Wilcoxon (Mann-Whitney)
Secondary
IL-10
Interleukin 10 measured by Luminex multiplex assay in picograms/mL, dynamic range 0.13-2000 pg/mL
Time frame: 4 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CD4<100 | IL-10 | 21.32 pg/mL |
| CD4>/=100 | IL-10 | 10.30 pg/mL |
p-value: 0.05Wilcoxon (Mann-Whitney)
Secondary
IL-1 Beta
Cytokine IL-1 beta measurement by Luminex multiplex assay in picograms/mL, dynamic range 0.13-2000 pg/mL
Time frame: 4 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CD4<100 | IL-1 Beta | 0.03 pg/mL |
| CD4>/=100 | IL-1 Beta | 0.03 pg/mL |
p-value: 0.81Wilcoxon (Mann-Whitney)
Secondary
IL-4
Interleukin-4 measured by Luminex multiplex assay in picograms/mL, dynamic range 0.13-2000 pg/mL
Time frame: 4 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CD4<100 | IL-4 | 0.07 pg/mL |
| CD4>/=100 | IL-4 | 0.07 pg/mL |
p-value: 0.99Wilcoxon (Mann-Whitney)
Secondary
IL-6
Interleukin 6 measured by Luminex multiplex assay in picograms/mL, dynamic range 0.13-2000 pg/mL
Time frame: 4 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CD4<100 | IL-6 | 4.41 pg/mL |
| CD4>/=100 | IL-6 | 4.01 pg/mL |
p-value: 0.95Wilcoxon (Mann-Whitney)
Secondary
IL-7
Interleukin 7 measured by Luminex multiplex assay in picograms/mL, dynamic range 0.13-2000 pg/mL
Time frame: 4 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CD4<100 | IL-7 | 17.50 pg/mL |
| CD4>/=100 | IL-7 | 10.53 pg/mL |
p-value: 0.01Wilcoxon (Mann-Whitney)
Secondary
IL-8
Interleukin 8 measured by Luminex multiplex assay in picograms/mL, dynamic range 0.13-2000 pg/mL
Time frame: 4 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CD4<100 | IL-8 | 7.58 pg/mL |
| CD4>/=100 | IL-8 | 5.18 pg/mL |
p-value: 0.002Wilcoxon (Mann-Whitney)
Secondary
INF Gamma
Interferon gamma measured by Luminex multiplex assay in picograms/mL, dynamic range 0.13-2000 pg/mL
Time frame: 4 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CD4<100 | INF Gamma | 2.24 pg/mL |
| CD4>/=100 | INF Gamma | 1.06 pg/mL |
p-value: 0.33Wilcoxon (Mann-Whitney)
Secondary
SF-12 Mental Capacity Score
Measure of mental functioning where lower is better out of a scale of 100.
Time frame: 4 weeks
Population: lower CD4 count at baseline compared to higher CD4 counts
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CD4<100 | SF-12 Mental Capacity Score | 46 score on a scale |
| CD4>/=100 | SF-12 Mental Capacity Score | 50 score on a scale |
p-value: 0.91Wilcoxon (Mann-Whitney)
Secondary
SF-12 Physical Capacity Score
Measure of physical function out of 100. Lower score means less physical capacity.
Time frame: 4 weeks
Population: Those with lower CD4 at baseline compared to those with a higher CD4 count.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CD4<100 | SF-12 Physical Capacity Score | 43 units on a scale |
| CD4>/=100 | SF-12 Physical Capacity Score | 54 units on a scale |
p-value: 0.003Wilcoxon (Mann-Whitney)
Secondary
TNF Alpha
Tumor Necrosis Factor Alpha - measured by Luminex multiplex assay in picograms/mL, dynamic range 0.13-2000 pg/mL
Time frame: 4 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CD4<100 | TNF Alpha | 13.07 pg/mL |
| CD4>/=100 | TNF Alpha | 9.07 pg/mL |
p-value: 0.06Wilcoxon (Mann-Whitney)