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

Primary Purpose

HIV Infections

Status
Completed
Phase
Phase 3
Locations
Thailand
Study Type
Interventional
Intervention
Antiretroviral Drug Combination Switching Criteria
Antiretroviral Drug Combination Switching Criteria
Sponsored by
Institut de Recherche pour le Developpement
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring HIV, Highly Active Antiretroviral Therapy, Monitoring, Viral load, CD4, Thailand, Future Drug Options, Resistance, Developing Country, Acquired Immunodeficiency Syndrome

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Prapokklao Hospital
  • Nakornping Hospital
  • Sanpatong Hospital
  • Mae Chan Hospital
  • Chiangrai Prachanukroh Hospital
  • Chonburi Hospital
  • Lampang Hospital
  • Lamphun Hospital
  • Mahasarakam Hospital
  • Maharaj Nakornratchasrima Hospital
  • Nong Khai Hospital
  • Phayao Provincial Hospital
  • Ratchaburi Hospital
  • Samutsakorn Hospital
  • Hat Yai Hospital
  • Buddhachinaraj Hospital
  • Chacheongsao Hospital
  • Regional Health Promotion Centre 6,
  • Rayong Hospital
  • Samutprakarn Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

1

2

Arm Description

* 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.

Outcomes

Primary Outcome Measures

Proportion of "clinical failures" defined as confirmed CD4 count below 50/mm3, first or new AIDS-defining event, or death

Secondary Outcome Measures

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

Full Information

First Posted
September 7, 2005
Last Updated
January 4, 2012
Sponsor
Institut de Recherche pour le Developpement
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Harvard School of Public Health (HSPH)
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1. Study Identification

Unique Protocol Identification Number
NCT00162682
Brief Title
Monitoring Highly Active Antiretroviral Therapy in HIV-infected Parents in Thailand
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2012
Overall Recruitment Status
Completed
Study Start Date
May 2005 (undefined)
Primary Completion Date
April 2010 (Actual)
Study Completion Date
December 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Institut de Recherche pour le Developpement
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Harvard School of Public Health (HSPH)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
HIV, Highly Active Antiretroviral Therapy, Monitoring, Viral load, CD4, Thailand, Future Drug Options, Resistance, Developing Country, Acquired Immunodeficiency Syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
716 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Active Comparator
Arm Description
* 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.
Arm Title
2
Arm Type
Experimental
Arm Description
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.
Intervention Type
Procedure
Intervention Name(s)
Antiretroviral Drug Combination Switching Criteria
Intervention Description
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
Intervention Name(s)
Antiretroviral Drug Combination Switching Criteria
Intervention Description
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.
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
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
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marc Lallemant, MD
Organizational Affiliation
Institut de Recherche pour le Developpement & Harvard School of Public Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
Prapokklao Hospital
City
Prapokklao, Muang
State/Province
Chantaburi
ZIP/Postal Code
22000
Country
Thailand
Facility Name
Nakornping Hospital
City
Mae Rim
State/Province
Chiang Mai
ZIP/Postal Code
50180
Country
Thailand
Facility Name
Sanpatong Hospital
City
Sanpatong
State/Province
Chiang Mai
ZIP/Postal Code
50120
Country
Thailand
Facility Name
Mae Chan Hospital
City
Mae Chan
State/Province
Chiang Rai
ZIP/Postal Code
57110
Country
Thailand
Facility Name
Chiangrai Prachanukroh Hospital
City
Muang, Chiangrai
State/Province
Chiangrai
ZIP/Postal Code
57000
Country
Thailand
Facility Name
Chonburi Hospital
City
Muang, Chonburi
State/Province
Chonburi
ZIP/Postal Code
20000
Country
Thailand
Facility Name
Lampang Hospital
City
Muang, Lampang
State/Province
Lampang
ZIP/Postal Code
52000
Country
Thailand
Facility Name
Lamphun Hospital
City
Muang
State/Province
Lamphun
ZIP/Postal Code
51000
Country
Thailand
Facility Name
Mahasarakam Hospital
City
Muang
State/Province
Mahasarakam
ZIP/Postal Code
44000
Country
Thailand
Facility Name
Maharaj Nakornratchasrima Hospital
City
Muang, Nakornratchasrima
State/Province
Nakornratchasrima
ZIP/Postal Code
30000
Country
Thailand
Facility Name
Nong Khai Hospital
City
Muang, Nong Khai
State/Province
Nong Khai
ZIP/Postal Code
43000
Country
Thailand
Facility Name
Phayao Provincial Hospital
City
Muang
State/Province
Phayao
ZIP/Postal Code
56000
Country
Thailand
Facility Name
Ratchaburi Hospital
City
Muang, Ratchaburi
State/Province
Ratchaburi
ZIP/Postal Code
70000
Country
Thailand
Facility Name
Samutsakorn Hospital
City
Muang, Samutsakorn
State/Province
Samutsakorn
ZIP/Postal Code
74000
Country
Thailand
Facility Name
Hat Yai Hospital
City
Hat Yai
State/Province
Songkla
ZIP/Postal Code
90110
Country
Thailand
Facility Name
Buddhachinaraj Hospital
City
Bangkok
ZIP/Postal Code
10220
Country
Thailand
Facility Name
Chacheongsao Hospital
City
Chacheongsao
ZIP/Postal Code
24000
Country
Thailand
Facility Name
Regional Health Promotion Centre 6,
City
Khon Kaen
ZIP/Postal Code
40000
Country
Thailand
Facility Name
Rayong Hospital
City
Rayong
ZIP/Postal Code
21000
Country
Thailand
Facility Name
Samutprakarn Hospital
City
Samutprakarn
ZIP/Postal Code
10280
Country
Thailand

12. IPD Sharing Statement

Citations:
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) Antiretroviral Therapy Monitoring/Switching Strategies in Thailand. 18th Conference on Retroviruses and Opportunistic Infections, 27 February-2 March, 2011,Boston, USA. Oral Presentation #44.
Results Reference
result
PubMed Identifier
21233689
Citation
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.
Results Reference
result
PubMed Identifier
23940461
Citation
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.
Results Reference
derived
Links:
URL
http://www.phpt.org
Description
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Monitoring Highly Active Antiretroviral Therapy in HIV-infected Parents in Thailand

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