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 Acquired Immunodeficiency Syndrome	Procedure: Antiretroviral Drug Combination Switching Criteria	Phase III

Further Study Details: 

Primary Outcomes: Proportion of “clinical failures” defined as confirmed CD4 count below 50/mm3, first or new AIDS-defining event, or death
Secondary Outcomes: The number of therapeutic options left taking into account drugs exhausted cross-resistance mutations and shared toxicities
Expected Total Enrollment:  700

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 (5 years for the first enrollee, three years for the last enrollee).

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

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.

Please refer to this study by ClinicalTrials.gov identifier  NCT00162682

Marc Lallemant, MD      +66 53 814633  Ext. 0    marc@phpt.org
Gonzague Jourdain, MD      +66 53 814633  Ext. 0    gonzague@phpt.org

Thailand
      Buddhachinaraj Hospital, Bangkok,  10220,  Thailand; Recruiting
      Chacheongsao Hospital, Chacheongsao,  24000,  Thailand; Recruiting
      Regional Health Promotion Centre 6,, Khon Kaen,  40000,  Thailand; Recruiting
      Rayong Hospital, Rayong,  21000,  Thailand; Recruiting
      Samutprakarn Hospital, Samutprakarn,  10280,  Thailand; Recruiting
Thailand, Chantaburi
      Prapokklao Hospital, Prapokklao, Muang,  Chantaburi,  22000,  Thailand; Recruiting
Thailand, Chiang Mai
      Nakornping Hospital, Mae Rim,  Chiang Mai,  50180,  Thailand; Recruiting
      Sanpatong Hospital, Sanpatong,  Chiang Mai,  50120,  Thailand; Recruiting
Thailand, Chiang Rai
      Mae Chan Hospital, Mae Chan,  Chiang Rai,  57110,  Thailand; Recruiting
Thailand, Chiangrai
      Chiangrai Prachanukroh Hospital, Muang, Chiangrai,  Chiangrai,  57000,  Thailand; Recruiting
Thailand, Chonburi
      Chonburi Hospital, Muang, Chonburi,  Chonburi,  20000,  Thailand; Recruiting
Thailand, Lampang
      Lampang Hospital, Muang, Lampang,  Lampang,  52000,  Thailand; Recruiting
Thailand, Lamphun
      Lamphun Hospital, Muang, Lamphun,  Lamphun,  51000,  Thailand; Recruiting
Thailand, Mahasarakam
      Mahasarakam Hospital, Munag, Mahasarakam,  Mahasarakam,  44000,  Thailand; Recruiting
Thailand, Nakornratchasrima
      Maharaj Nakornratchasrima Hospital, Muang, Nakornratchasrima,  Nakornratchasrima,  30000,  Thailand; Recruiting
Thailand, Nong Khai
      Nong Khai Hospital, Muang, Nong Khai,  Nong Khai,  43000,  Thailand; Recruiting
Thailand, Phayao
      Phayao Provincial Hospital, Muang, Phayao,  Phayao,  56000,  Thailand; Recruiting
Thailand, Ratchaburi
      Ratchaburi Hospital, Muang, Ratchaburi,  Ratchaburi,  70000,  Thailand; Recruiting
Thailand, Samutsakorn
      Samutsakorn Hospital, Muang, Samutsakorn,  Samutsakorn,  74000,  Thailand; Recruiting
Thailand, Songkla
      Hat Yai Hospital, Hat Yai,  Songkla,  90110,  Thailand; Recruiting

Study chairs or principal investigators

Marc Lallemant, MD,  Principal Investigator,  Institut de Recherche pour le Developpement & Harvard School of Public Health   

Study ID Numbers:  R01-HD042964
Last Updated:  September 12, 2005
Record first received:  September 7, 2005
ClinicalTrials.gov Identifier:  NCT00162682
Health Authority: Thailand: Ministry of Public Health
ClinicalTrials.gov processed this record on 2005-09-13