HIV Infections
Conditions
Keywords
HIV, Highly Active Antiretroviral Therapy, Monitoring, Viral load, CD4, Thailand, Future Drug Options, Resistance, Developing Country, Acquired Immunodeficiency Syndrome
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).
Interventions
PROCEDUREAntiretroviral 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.
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Harvard School of Public Health (HSPH)
Institut de Recherche pour le Developpement
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 |
Secondary
| Measure | Time frame |
|---|---|
| The number of therapeutic options left taking into account drugs exhausted cross-resistance mutations and shared toxicities | After 3 years of follow-up |
| 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 |
Countries
Thailand
Outcome results
None listed