HIV InfectionsPhase 4NCT00885664

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

A Phase 4 study testing Truvada (tenofovir/emtricitabine) and Kaletra (lopinavir/ritonavir) in people with HIV Infections, run by University of Cincinnati at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: HIV Infections
What is being tested?: Truvada (tenofovir/emtricitabine) and Kaletra (lopinavir/ritonavir)
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 60 participants
Where: 1 siteUnited States
Study dates: Oct 2005to Mar 2010
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

Blinded drug treatment.
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.
Known resistance to proposed new HIV regimen or components of regimen.
Requirement for drug therapy with known contraindication with proposed new antiretroviral therapy (see Prohibited and Precautionary Medications below)
Pregnancy or breast feeding.
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.
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.
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.

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Cincinnati AIDS Clinical Trials Unit
Cincinnati, Ohio, 45267

Other trials in United States

About this study

The purposes of this study are:

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

Read the detailed description

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.
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.
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.
To determine the relationship between adverse events and immunological status as evidenced by lymphocyte counts and activation marker cytokine levels.
To determine the relationship between clinical events and immunological status as evidenced by lymphocyte counts and activation marker cytokine levels.

Conditions: HIV Infections
Being tested: Truvada (tenofovir/emtricitabine), Kaletra (lopinavir/ritonavir)
Keywords: HIV, immune reconstitution, treatment naive
Medical subject headings: HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT00885664
Study group	Role	What they receive
Truvada/Kaletra CD4<100	Other	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 Receives: Drug: Truvada (tenofovir/emtricitabine); Drug: Kaletra (lopinavir/ritonavir)
Truvada/Kaletra CD4>/=100	Other	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 Receives: Drug: Truvada (tenofovir/emtricitabine); Drug: Kaletra (lopinavir/ritonavir)

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Week 4

Secondary outcomes (10)

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 2005Mar 2010

First posted22 Apr 2009 (estimated)
Study startOct 2005
Primary completionSep 2009
Study completionMar 2010

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for HIV InfectionsStudies of the same condition, open and under way.
More trials run by University of CincinnatiThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Model description: All participants received truvada and kaletra in this trial
Masking: None (open label)
Enrolment: 60 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00885664
Sponsor's protocol ID: IDC 30
Status last verified: Jul 2022
First submitted: 20 Apr 2009
Last updated: 10 Aug 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All HIV Infections trials

Study at a glance

From the registry record, last updated by the sponsor on 10 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Immune Reconstitution as a Determinant of Adverse Effects to New Antiretroviral Therapy in Persons With Advanced HIV Infection
ClinicalTrials.gov ID: NCT00885664
Acronym / sponsor ID: IDC 30
Conditions: HIV Infections
Keywords: HIV, immune reconstitution, treatment naive
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 60 participants (actual)
Lead sponsor: University of CincinnatiUniversity, hospital or other
Collaborators: Abbott, Gilead Sciences
Study start: Oct 2005
Primary completion: Sep 2009 (actual)
Study completion: Mar 2010 (actual)
First posted: 22 Apr 2009 (estimated)
Results: Posted 10 Aug 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The purposes of this study are:

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

Detailed description

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.
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.
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.
To determine the relationship between adverse events and immunological status as evidenced by lymphocyte counts and activation marker cytokine levels.
To determine the relationship between clinical events and immunological status as evidenced by lymphocyte counts and activation marker cytokine levels.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 2
Model description: All participants received truvada and kaletra in this trial

Arm	Type	Receives
Truvada/Kaletra CD4<100	Other	Drug: Truvada (tenofovir/emtricitabine), Drug: 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	Other	Drug: Truvada (tenofovir/emtricitabine), Drug: 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

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

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

Key exclusion criteria (8 listed)

Blinded drug treatment.
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.
Known resistance to proposed new HIV regimen or components of regimen.
Requirement for drug therapy with known contraindication with proposed new antiretroviral therapy (see Prohibited and Precautionary Medications below)
Pregnancy or breast feeding.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Truvada (tenofovir/emtricitabine)Also: TruvadaTenofovir/emtricitabine fixed dose combination once daily	Drug	Truvada/Kaletra CD4<100, Truvada/Kaletra CD4>/=100
Kaletra (lopinavir/ritonavir)Also: KaletraLopinavir/ritonavir 400/100 mg twice daily	Drug	Truvada/Kaletra CD4<100, Truvada/Kaletra CD4>/=100

Primary outcome

Symptom Score
Time frame: 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.

10 secondary outcomes

SF-12 Physical Capacity Score
Time frame: 4 weeks
SF-12 Mental Capacity Score
Time frame: 4 weeks
IL-1 Beta
Time frame: 4 weeks
IL-4
Time frame: 4 weeks
IL-6
Time frame: 4 weeks
IL-7
Time frame: 4 weeks
IL-8
Time frame: 4 weeks
IL-10
Time frame: 4 weeks
TNF Alpha
Time frame: 4 weeks
INF Gamma
Time frame: 4 weeks

Results and safety

Results posted to the registry on 10 Aug 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Truvada/Kaletra	60	48

Primary outcome: Symptom Score

Time frame: Week 4. Median (Inter-Quartile Range). Unit: units on a scale

Measure	CD4<100 n = 26	CD4>/=100 n = 34
Value	10 (5 to 17)	8 (6 to 13)

CD4<100 vs CD4>/=100: p = 0.45, Wilcoxon (Mann-Whitney)

10 secondary outcomes are reported in the full results.

Adverse events

Time frame: 6 months. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Truvada/Kaletra CD4<100	1 of 26 (3.8%)	26 of 26 (100%)	0 of 26
Truvada/Kaletra CD4>/=100	0 of 34 (0%)	34 of 34 (100%)	0 of 34

Limitations and caveats (from the sponsor): Small study of 60 subjects. Some subjects did not complete all study visits limiting data available for each time point.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Carl J Fichtenbaum, MD principal investigator

University of Cincinnati

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Truvada (tenofovir/emtricitabine) and Kaletra (lopinavir/ritonavir) in people with HIV Infections, run by University of Cincinnati at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Aug 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Symptom Score (time frame: Week 4). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00885664.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Aug 2022.