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

NCT ID: NCT00162682

Last Updated: 2012-01-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 716 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-05-31
• Study Completion Date: 2011-12-31

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).

Conditions

HIV Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Antiretroviral Drug Combination Switching Criteria

Intervention Type: PROCEDURE

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.

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.

Group Type: EXPERIMENTAL

Antiretroviral Drug Combination Switching Criteria

Intervention Type: PROCEDURE

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• 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)

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

Harvard School of Public Health (HSPH)

OTHER

Sponsor Role: collaborator

Institut de Recherche pour le Developpement

OTHER_GOV

Sponsor Role: lead

Responsible Party

Marc Lallemant

Senior Researcher

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Marc Lallemant, MD

Role: PRINCIPAL_INVESTIGATOR

Institut de Recherche pour le Developpement & Harvard School of Public Health

Locations

Buddhachinaraj Hospital

Bangkok, Bangkok, Thailand

Chacheongsao Hospital

Chacheongsao, Chacheongsao, Thailand

Prapokklao Hospital

Prapokklao, Muang, Changwat Chanthaburi, Thailand

Mae Chan Hospital

Mae Chan, Changwat Chiang Rai, Thailand

Chonburi Hospital

Muang, Chonburi, Changwat Chon Buri, Thailand

Regional Health Promotion Centre 6,

Khon Kaen, Changwat Khon Kaen, Thailand

Lampang Hospital

Lampang, Changwat Lampang, Thailand

Lamphun Hospital

Muang, Changwat Lamphun, Thailand

Nong Khai Hospital

Muang, Nong Khai, Changwat Nong Khai, Thailand

Phayao Provincial Hospital

Muang, Changwat Phayao, Thailand

Ratchaburi Hospital

Muang, Ratchaburi, Changwat Ratchaburi, Thailand

Rayong Hospital

Rayong, Changwat Rayong, Thailand

Hat Yai Hospital

Hat Yai, Changwat Songkhla, Thailand

Nakornping Hospital

Mae Rim, Chiang Mai, Thailand

Sanpatong Hospital

Sanpatong, Chiang Mai, Thailand

Chiangrai Prachanukroh Hospital

Muang, Chiangrai, Chiangrai, Thailand

Mahasarakam Hospital

Muang, Mahasarakam, Thailand

Maharaj Nakornratchasrima Hospital

Muang, Nakornratchasrima, Nakornratchasrima, Thailand

Samutprakarn Hospital

Samutprakarn, Samutprakarn, Thailand

Samutsakorn Hospital

Muang, Samutsakorn, Samutsakorn, Thailand

Countries

Thailand

References

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) Antiretroviral Therapy Monitoring/Switching Strategies in Thailand. 18th Conference on Retroviruses and Opportunistic Infections, 27 February-2 March, 2011,Boston, USA. Oral Presentation #44.

Reference Type: RESULT

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 Thai patients receiving indinavir boosted with ritonavir. Ther Drug Monit. 2011 Feb;33(1):25-31. doi: 10.1097/FTD.0b013e3182057f6f.

Reference Type: RESULT

PMID: 21233689 (View on PubMed)

Jourdain G, Le Coeur S, Ngo-Giang-Huong N, Traisathit P, Cressey TR, Fregonese F, Leurent B, Collins IJ, Techapornroong M, Banchongkit S, Buranabanjasatean S, Halue G, Nilmanat A, Luekamlung N, Klinbuayaem V, Chutanunta A, Kantipong P, Bowonwatanuwong C, Lertkoonalak R, Leenasirimakul P, Tansuphasawasdikul S, Sang-A-Gad P, Pathipvanich P, Thongbuaban S, Wittayapraparat P, Eiamsirikit N, Buranawanitchakorn Y, Yutthakasemsunt N, Winiyakul N, Decker L, Barbier S, Koetsawang S, Sirirungsi W, McIntosh K, Thanprasertsuk S, Lallemant M; PHPT-3 study team. Switching HIV treatment in adults based on CD4 count versus viral load monitoring: a randomized, non-inferiority trial in Thailand. PLoS Med. 2013 Aug;10(8):e1001494. doi: 10.1371/journal.pmed.1001494. Epub 2013 Aug 6.

Reference Type: DERIVED

PMID: 23940461 (View on PubMed)

Related Links

http://www.phpt.org

Related Info

Other Identifiers

R01HD042964

Identifier Type: NIH

Identifier Source: org_study_id

View Link

NCT00197626

Identifier Type: -

Identifier Source: nct_alias