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

This study has been completed.
Sponsor:
Collaborators:
Harvard School of Public Health
Information provided by (Responsible Party):
Marc Lallemant, Institut de Recherche pour le Developpement
ClinicalTrials.gov Identifier:
NCT00162682
First received: September 7, 2005
Last updated: January 4, 2012
Last verified: January 2012
  Purpose

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


Condition Intervention Phase
HIV Infections
Procedure: Antiretroviral Drug Combination Switching Criteria
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III, Randomized, Non-inferiority Trial Comparing the Standard Viral Load Based Antiretroviral Monitoring Strategy With a CD4 Based Monitoring Strategy Among Antiretroviral Naive Immunocompromised Adults in Thailand

Resource links provided by NLM:


Further study details as provided by Institut de Recherche pour le Developpement:

Primary Outcome Measures:
  • Proportion of "clinical failures" defined as confirmed CD4 count below 50/mm3, first or new AIDS-defining event, or death [ Time Frame: After 3 years of follow-up ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The number of therapeutic options left taking into account drugs exhausted cross-resistance mutations and shared toxicities [ Time Frame: After 3 years of follow-up ] [ Designated as safety issue: No ]
  • The secondary endpoint related to safety will be time to the first development of grade 3 or grade 4 sign, symptom, and laboratory abnormality. [ Time Frame: During 3 years of follow-up ] [ Designated as safety issue: Yes ]

Enrollment: 716
Study Start Date: May 2005
Study Completion Date: December 2011
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
* 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.
Procedure: Antiretroviral Drug Combination Switching Criteria
Antiretroviral treatment will use the standard viral load (VL) based monitoring strategy, where switching is performed when VL is confirmed (within one month) above 400 copies per mL.
Experimental: 2
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.
Procedure: Antiretroviral Drug Combination Switching Criteria
Antiretroviral treatment is monitored using a 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.

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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Eligibility Criteria:

Patients fulfilling the following criteria are eligible:

  • At least 18 years of age
  • Confirmed HIV infection: two positive serology results from two different blood draws are required for documentation of HIV infection.
  • Antiretroviral drug naïve with the exception of short course of antiretrovirals received in the context of the prevention of mother to child HIV transmission
  • Need for antiretroviral treatment
  • Willingness to receive a long-term treatment for the HIV infection, according to the study schedule at the participating site
  • Signed informed consent to participate in the study (the patient's legal guardian may give his/her consent if the patient cannot provide consent)
  • Does not present an exclusion criteria to the knowledge of the site investigator

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00162682

Locations
Thailand
Prapokklao Hospital
Prapokklao, Muang, Chantaburi, Thailand, 22000
Nakornping Hospital
Mae Rim, Chiang Mai, Thailand, 50180
Sanpatong Hospital
Sanpatong, Chiang Mai, Thailand, 50120
Mae Chan Hospital
Mae Chan, Chiang Rai, Thailand, 57110
Chiangrai Prachanukroh Hospital
Muang, Chiangrai, Chiangrai, Thailand, 57000
Chonburi Hospital
Muang, Chonburi, Chonburi, Thailand, 20000
Lampang Hospital
Muang, Lampang, Lampang, Thailand, 52000
Lamphun Hospital
Muang, Lamphun, Thailand, 51000
Mahasarakam Hospital
Muang, Mahasarakam, Thailand, 44000
Maharaj Nakornratchasrima Hospital
Muang, Nakornratchasrima, Nakornratchasrima, Thailand, 30000
Nong Khai Hospital
Muang, Nong Khai, Nong Khai, Thailand, 43000
Phayao Provincial Hospital
Muang, Phayao, Thailand, 56000
Ratchaburi Hospital
Muang, Ratchaburi, Ratchaburi, Thailand, 70000
Samutsakorn Hospital
Muang, Samutsakorn, Samutsakorn, Thailand, 74000
Hat Yai Hospital
Hat Yai, Songkla, Thailand, 90110
Buddhachinaraj Hospital
Bangkok, Thailand, 10220
Chacheongsao Hospital
Chacheongsao, Thailand, 24000
Regional Health Promotion Centre 6,
Khon Kaen, Thailand, 40000
Rayong Hospital
Rayong, Thailand, 21000
Samutprakarn Hospital
Samutprakarn, Thailand, 10280
Sponsors and Collaborators
Institut de Recherche pour le Developpement
Harvard School of Public Health
Investigators
Principal Investigator: Marc Lallemant, MD Institut de Recherche pour le Developpement & Harvard School of Public Health
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Marc Lallemant, Senior Researcher, Institut de Recherche pour le Developpement
ClinicalTrials.gov Identifier: NCT00162682     History of Changes
Obsolete Identifiers: NCT00197626
Other Study ID Numbers: R01-HD042964
Study First Received: September 7, 2005
Last Updated: January 4, 2012
Health Authority: Thailand: Ministry of Public Health

Keywords provided by Institut de Recherche pour le Developpement:
HIV
Highly Active Antiretroviral Therapy
Monitoring
Viral load
CD4
Thailand
Future Drug Options
Resistance
Developing Country
Acquired Immunodeficiency Syndrome

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases

ClinicalTrials.gov processed this record on April 22, 2014