Monitoring Highly Active Antiretroviral Therapy in HIV-infected Parents in Thailand

Phase 3

Completed

• Conditions: HIV Infections
• Interventions: Procedure: Antiretroviral Drug Combination Switching Criteria

• Registration Number: NCT00162682
• Lead Sponsor: Institut de Recherche pour le Developpement

Brief Summary

The purpose of this study is to determine if a decision to switch to a subsequent antiretroviral regimen based upon the CD4 cell count rather than the standard switching strategy based on viral load could ensure the same immunological and clinical outcome and preserve future treatment options in AIDS patients

Detailed Description

Implementation of highly active antiretroviral therapy (HAART) has led to a substantial decrease in HIV-related mortality and morbidity. Current guidelines emphasize maximal and durable viral load suppression. However, while the goal of therapy is the restoration of immunity, treatment failure is usually defined as the inability to maintain undetectable viral load, without regard to immune function. This situation often leads to a rapid sequence of therapeutic switches, thus narrowing therapeutic options over time. A monitoring strategy driven primarily by the patient's immune restoration would most likely be as effective in preventing disease progression, would lead to fewer changes in HAART regimens and would be considerably simpler and cost effective.

Subjects will be randomly assigned to one of two switching strategies:

* VL-S, the standard viral load (VL) based monitoring strategy, where switching is performed when VL is confirmed (within one month) above 400 copies per mL.

* CD4-S, the alternative CD4 based monitoring strategy where switching is performed when a confirmed (within one month) relative decline in CD4 count of more than 30% from peak values is observed within 200 cells from baseline.

The initial HAART regimen will be a NNRTI+NRTI containing regimen and the second line regimen will be a PI containing regimen, subsequent regimens will be chosen individually based on tolerance, previous drugs used, resistance profile, and drugs available. Patients will be followed until the end of the study (maximum of 5 years for the first enrollee, three years for the last enrollee).

Study Timeline

• Study Start: 2005-05
• Study First Submitted: 2005-09-07
• Study First Submitted QC: 2005-09-07
• Study First Posted: 2005-09-13
• Primary Completion: 2010-04
• Study Completion: 2011-12
• Status Verified: 2012-01
• Last Update Submitted: 2012-01-04
• Last Update Posted: 2012-01-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 716

Inclusion Criteria

Eligible patients fulfilling the following criteria can be enrolled in the study:

• Meeting all eligibility criteria
• Two CD4+ cell counts between 50 and 250 cells/mm3 performed within the last six months before enrolment (CD4 cell count should be assessed at least 2 weeks apart from any acute infection)
• Willingness to modify antiretroviral therapy in accordance with the randomized switching scheme assignment
• Subject understands that study drugs will be supplied for free by the study only during participation in the study. After discontinuation of the study, patients will be taken care of in the National ARV Access Program.

Exclusion Criteria

• For women, pregnancy
• For women of child bearing potential, lack of willingness to follow an effective method of contraception (in case, during the study, a woman wants to become pregnant or becomes pregnant, she should inform the physician immediately for best therapeutic decision)
• Chronic hepatitis B or C
• Acute hepatitis within 30 days of study entry.
• Acute HIV infection, as it can be established with the date of last negative serology less than one year before enrollment and the history of the patient disease
• Co-enrollment in another study without prior written agreement of the study team
• Psycho-social environment or condition which, in the physician's opinion, makes adherence to the protocol highly unlikely.
• Pre-existing diabetes mellitus (prior gestational diabetes is allowed).
• The following laboratory values: hemoglobin < 8.0 mg/dl, absolute neutrophil count < 1000 cells/mm3, ALT, AST or total bilirubin value > 5.0 x ULN, serum creatinine > 1.0 x ULN, platelet count < 50,000/mm3, pancreatic amylase >2.0 x ULN or lipase > 2.0 X ULN, or total amylase > 2.0 X ULN plus symptoms of pancreatitis.
• Severe illness, grade 3 or 4 laboratory exam values not resolved within one month of enrollment without previous agreement of the PHPT attending physician
• Any clinically significant condition (other than HIV infection) which, in the investigator's opinion, would interfere with the conduct of the study.
• Current active substance or alcohol abuse that would interfere with participation in the study.
• Condition(s) that contraindicate all the first line regimens proposed in this study.
• Chemotherapy for active malignancy.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Antiretroviral Drug Combination Switching Criteria	\* VL-S, the standard viral load (VL) based monitoring strategy, where switching is performed when VL is confirmed (within one month) above 400 copies per mL.
2	Antiretroviral Drug Combination Switching Criteria	CD4-S, the alternative CD4 based monitoring strategy where switching is performed when a confirmed (within one month) relative decline in CD4 count of more than 30% from peak values is observed within 200 cells from baseline.

Primary Outcome Measures

Name	Time	Method
Proportion of "clinical failures" defined as confirmed CD4 count below 50/mm3, first or new AIDS-defining event, or death	After 3 years of follow-up

Secondary Outcome Measures

Name	Time	Method
The number of therapeutic options left taking into account drugs exhausted cross-resistance mutations and shared toxicities	After 3 years of follow-up
The secondary endpoint related to safety will be time to the first development of grade 3 or grade 4 sign, symptom, and laboratory abnormality.	During 3 years of follow-up

Trial Locations

Locations (20)

Mahasarakam Hospital; 🇹🇭 Muang, Mahasarakam, Thailand

Lamphun Hospital; 🇹🇭 Muang, Lamphun, Thailand

Prapokklao Hospital; 🇹🇭 Prapokklao, Muang, Chantaburi, Thailand

Sanpatong Hospital; 🇹🇭 Sanpatong, Chiang Mai, Thailand

Chiangrai Prachanukroh Hospital; 🇹🇭 Muang, Chiangrai, Chiangrai, Thailand

Chonburi Hospital; 🇹🇭 Muang, Chonburi, Chonburi, Thailand

Mae Chan Hospital; 🇹🇭 Mae Chan, Chiang Rai, Thailand

Maharaj Nakornratchasrima Hospital; 🇹🇭 Muang, Nakornratchasrima, Nakornratchasrima, Thailand

Nong Khai Hospital; 🇹🇭 Muang, Nong Khai, Nong Khai, Thailand

Phayao Provincial Hospital; 🇹🇭 Muang, Phayao, Thailand

Ratchaburi Hospital; 🇹🇭 Muang, Ratchaburi, Ratchaburi, Thailand

Samutsakorn Hospital; 🇹🇭 Muang, Samutsakorn, Samutsakorn, Thailand

Buddhachinaraj Hospital; 🇹🇭 Bangkok, Thailand

Chacheongsao Hospital; 🇹🇭 Chacheongsao, Thailand

Lampang Hospital; 🇹🇭 Muang, Lampang, Lampang, Thailand

Rayong Hospital; 🇹🇭 Rayong, Thailand

Nakornping Hospital; 🇹🇭 Mae Rim, Chiang Mai, Thailand

Regional Health Promotion Centre 6,; 🇹🇭 Khon Kaen, Thailand

Samutprakarn Hospital; 🇹🇭 Samutprakarn, Thailand

Hat Yai Hospital; 🇹🇭 Hat Yai, Songkla, Thailand