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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00162682
• Other study ID #: R01HD042964
• Status: Completed
• Phase: Phase 3
• First received: September 7, 2005
• Last updated: January 4, 2012
• Start date: May 2005
• Est. completion date: December 2011

Study information

• Verified date: January 2012
• Source: Institut de Recherche pour le Developpement
• Contact: n/a
• Is FDA regulated: No
• Health authority: Thailand: Ministry of Public Health
• Study type: Interventional

Clinical Trial 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

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).

Other known NCT identifiers

• NCT00197626

Recruitment information / eligibility

• Status: Completed
• Enrollment: 716
• Est. completion date: December 2011
• Est. primary completion date: April 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections

Intervention

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.
• 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.

Locations

Country	Name	City	State
Thailand	Buddhachinaraj Hospital	Bangkok
Thailand	Chacheongsao Hospital	Chacheongsao
Thailand	Hat Yai Hospital	Hat Yai	Songkla
Thailand	Regional Health Promotion Centre 6,	Khon Kaen
Thailand	Mae Chan Hospital	Mae Chan	Chiang Rai
Thailand	Nakornping Hospital	Mae Rim	Chiang Mai
Thailand	Lamphun Hospital	Muang	Lamphun
Thailand	Mahasarakam Hospital	Muang	Mahasarakam
Thailand	Phayao Provincial Hospital	Muang	Phayao
Thailand	Chiangrai Prachanukroh Hospital	Muang, Chiangrai	Chiangrai
Thailand	Chonburi Hospital	Muang, Chonburi	Chonburi
Thailand	Lampang Hospital	Muang, Lampang	Lampang
Thailand	Maharaj Nakornratchasrima Hospital	Muang, Nakornratchasrima	Nakornratchasrima
Thailand	Nong Khai Hospital	Muang, Nong Khai	Nong Khai
Thailand	Ratchaburi Hospital	Muang, Ratchaburi	Ratchaburi
Thailand	Samutsakorn Hospital	Muang, Samutsakorn	Samutsakorn
Thailand	Prapokklao Hospital	Prapokklao, Muang	Chantaburi
Thailand	Rayong Hospital	Rayong
Thailand	Samutprakarn Hospital	Samutprakarn
Thailand	Sanpatong Hospital	Sanpatong	Chiang Mai

Sponsors (3)

Lead Sponsor	Collaborator
Institut de Recherche pour le Developpement	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Harvard School of Public Health

Country where clinical trial is conducted

Thailand, 

References & Publications (2)

Cressey TR, Urien S, Hirt D, Halue G, Techapornroong M, Bowonwatanuwong C, Leenasirimakul P, Treluyer JM, Jourdain G, Lallemant M; PHPT-3 Team. Influence of body weight on achieving indinavir concentrations within its therapeutic window in HIV-infected Th — View Citation

Jourdain G, Ngo-Giang-Huong Nicole, Le Coeur S, Traisaithit P, Barbier S, Techapornroong M, Banchongkit S, Buranabanjasatean S, Halue G, Lallemant M, and The PHPT-3 study group. PHPT-3: A Randomized Clinical Trial Comparing CD4 versus Viral Load (VL) Anti

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	The number of therapeutic options left taking into account drugs exhausted cross-resistance mutations and shared toxicities		After 3 years of follow-up	No
Secondary	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	Yes

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