Staccato: A Trial of CD4 Guided Treatment Interruption, Compared to Continuous Treatment, for HIV Infection - Full Text View

Purpose

Treatment of HIV repairs the immune system, but continuous treatment is expensive and causes side effects. Would it not be better to treat intermittently, e.g. stop treatment when the immune system has recovered, and start again only when damage reappears? That is the question which STACCATO proposes to answer.

Approximately 500 patients were recruited for this trial from 2002 to 2004. One third were treated continuously; in two thirds, the treatment was interrupted whenever the CD4 count, a measure of immune recovery, exceeded 350. At the end of 2005, the two treatment groups will be compared in order to see which fared better regarding amount of drugs used, side effects, CD4 counts, and development of resistance to treatment.

Condition	Intervention
HIV Infection AIDS	Drug: Treatment interruption

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Randomized Trial of CD4 Guided Treatment Interruption, Compared to Continuous Treatment, for HIV Infection

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: HIV/AIDS

U.S. FDA Resources

Further study details as provided by University Hospital, Geneva:

Primary Outcome Measures:

Amounts of drugs used
Response of viral load to retreatment after interruption

Secondary Outcome Measures:

Opportunistic infections and deaths
Adverse effects
CD4 counts
Resistance development

Estimated Enrollment:	526
Study Start Date:	January 2002
Estimated Study Completion Date:	October 2005

Detailed Description:

Continuous treatment has been very successful in diminishing the diseases and deaths caused by HIV. However, continuous treatment is expensive. Intermittent treatment will always cost less than continuous treatment, and therefore has the potential to facilitate access to highly active antiretroviral therapy (HAART) in developing countries. HAART also causes many undesirable effects. Intermittent treatment decreases exposure to drugs and is therefore expected to decrease side effects.

STACCATO is a randomised trial of intermittent versus continuous anti-retroviral treatment. At least 600 patients on HAART, with viremia below 50 copies/ml and CD4 count above 350 cells/ml were randomised to one of two arms, in 1:2 proportions:

Arm 1: Continuation (control) arm: Drugs are continued or changed according to current guidelines and good clinical practice.
Arm 2: CD4-guided arm: Drugs discontinued and reintroduced according to CD4 counts, with HAART being administered only if CD4 count is < 350 cells/ml.

Randomized treatment will continue during an average of approximately 2 years, and will be followed by a period of 12 to 24 weeks’ continuous treatment, for patients in both arms.

Endpoints: The amount of drugs used, side effects, viremia and CD4 counts, number of clinical events, at the end of the randomized treatment period, and again 12 to 24 weeks later. A subproject will study the effect of treatment interruption on resistance development, mutations in proviral DNA and proviral DNA levels.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

CD4 lymphocyte count above 350/microliter and viral HIV1-RNA below 50 copies/ml on antiretroviral treatment.

Exclusion Criteria:

Virologic failure of treatment. Failure of treatment defined as a treatment switch motivated by high viral loads on treatment.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00113126

Locations

Switzerland
Infectious Diseases Unit - University Hospital
Geneva, Switzerland, 1205

Sponsors and Collaborators

University Hospital, Geneva

Investigators

Study Chair:

Bernard Hirschel, MD

Infectious Diseases Unit - University Hospital

More Information

Publications:

Ananworanich J, Gayet-Ageron A, Le Braz M, Prasithsirikul W, Chetchotisakd P, Kiertiburanakul S, Munsakul W, Raksakulkarn P, Tansuphasawasdikul S, Sirivichayakul S, Cavassini M, Karrer U, Genne D, Nuesch R, Vernazza P, Bernasconi E, Leduc D, Satchell C, Yerly S, Perrin L, Hill A, Perneger T, Phanuphak P, Furrer H, Cooper D, Ruxrungtham K, Hirschel B; Staccato Study Group; Swiss HIV Cohort Study. CD4-guided scheduled treatment interruptions compared with continuous therapy for patients infected with HIV-1: results of the Staccato randomised trial. Lancet. 2006 Aug 5;368(9534):459-65.

Ananworanich J, Nuesch R, Le Braz M, Chetchotisakd P, Vibhagool A, Wicharuk S, Ruxrungtham K, Furrer H, Cooper D, Hirschel B, Bernasconi E, Cavassini M, Ebnother C, Fagard C, Genne D, Khanna N, Perrin L, Phanupak P, Ubolyam S, Vernazza P, Yerly S; Swiss HIV Cohort Study. Failures of 1 week on, 1 week off antiretroviral therapies in a randomized trial. AIDS. 2003 Oct 17;17(15):F33-7.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Calmy A, Gayet-Ageron A, Montecucco F, Nguyen A, Mach F, Burger F, Ubolyam S, Carr A, Ruxungtham K, Hirschel B, Ananworanich J; STACCATO Study Group. HIV increases markers of cardiovascular risk: results from a randomized, treatment interruption trial. AIDS. 2009 May 15;23(8):929-39.

Ananworanich J, Nuesch R, Côté HC, Kerr SJ, Hill A, Jupimai T, Laopraynak N, Saenawat S, Ruxrungtham K, Hirschel B. Changes in metabolic toxicity after switching from stavudine/didanosine to tenofovir/lamivudine--a Staccato trial substudy. J Antimicrob Chemother. 2008 Jun;61(6):1340-3. Epub 2008 Mar 12.

ClinicalTrials.gov Identifier:	NCT00113126 History of Changes
Other Study ID Numbers:	SHCS # 356
Study First Received:	June 3, 2005
Last Updated:	November 28, 2006
Health Authority:	Switzerland: Swissmedic

Keywords provided by University Hospital, Geneva:

Scheduled treatment interruptions
STI

Additional relevant MeSH terms:

HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases

Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases

ClinicalTrials.gov processed this record on June 17, 2013