Clinical trial NCT00432003: Effects of Anti-HIV Therapy on Nervous System Function
Official title: Neurology: A Substudy of a Large, Simple Trial Comparing Two Strategies for Management of Anti-Retroviral Therapy (SMART) to Determine the Impact of the Strategies Upon Central and Peripheral Nervous System Function
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV Infections
Keywords: Treatment Experienced
HIV
Antiretroviral Therapy, Highly Active
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2007-02-06
Enrollment: 297
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Time perspective: PROSPECTIVE

Brief summary: The purpose of this study is to observe the way two different anti-HIV treatment strategies affect nerve and brain function in adults with HIV.

Detailed description: AIDS dementia complex (ADC) is a condition characterized by cognitive impairment, psychomotor slowing, and behavioral change. A milder form of ADC, called HIV minor cognitive/motor disorder (MCMD), is characterized by similar symptoms but has less of an impact on daily functioning. The neurocognitive impairment that results from ADC and MCMD carries an increased risk of poor drug adherence, morbidity, and mortality. It is unclear if highly active antiretroviral therapy (HAART) is effective in preserving neurocognitive function or in preventing or treating neurocognitive impairment. Distal symmetric sensory polyneuropathy (DSPN) and nucleoside-related neuropathy are two other serious conditions that HIV patients are at high risk for. DSPN is thought to be caused by active HIV infection; nucleoside-related neuropathy is thought to be caused by mitochondrial toxicity related to the use of certain antiretrovirals. These 2 conditions may lead to severe pain and discomfort in the feet. It is unknown what connection, if any, there is between DSPN and nucleoside-related neuropathy and the use of HAART. More data are needed on the natural history of these conditions.

This trial is a substudy of a study of management of antiretroviral therapy (SMART). In the SMART study, patients will participate in one of two strategies: a drug conservation (DC) strategy and a viral suppression (VS) strategy. Participants in the DC group will stop or defer HAART, then receive episodic HAART treatment for the minimum time needed to maintain a CD4 cell count of at least 250 cells/mm3. Participants in the VS group will receive HAART to maintain a viral load as low as possible, regardless of CD4 count. The purpose of this study is to compare changes in neurocognitive functioning and peripheral neuropathy symptoms between the 2 strategies of the SMART study.

Patients will participate in this substudy and the main SMART study at the same time. Within 45 days prior to randomization into the main SMART study, participants will have baseline data collected for this substudy. This data will include peripheral neuropathy assessments, treatments for symptoms of peripheral neuropathy. At selected study sites, additional measures will assess neurocognitive function, depression, alcohol and drug use, and education. At 6 months, 12 months, and every 12 months thereafter, peripheral neuropathy symptoms and treatment for the symptoms will be assessed; a pain questionnaire will also be completed. Participants will be followed until the SMART study ends.

Eligibility criteria: Inclusion Criteria:

* Coenrollment in the SMART study

Exclusion Criteria:

* Unable to comply with all study requirements

Primary outcomes:
measure: Change in QNPZ-5 scores
measure: time to development of symptomatic peripheral neuropathy
measure: change in peripheral neuropathy symptoms
Secondary outcomes:
measure: Time to neurocognitive impairment
measure: time to development of ADC, stage 2 or greater
measure: chage in peripheral neuropathy symptoms
measure: time to development of asymptomatic or symptomatic peripheral neuropathy
measure: time to resolution of symptomatic peripheral neuropathy
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Castro-Mission Health Ctr. CRS
state: California
city: Denver
country: United States
facility: Kaiser Permanente of Denver CRS
state: Colorado
city: Denver
country: United States
facility: Univ. of Colorado Health Science Ctr. CRS
state: Colorado
city: Denver
country: United States
facility: Denver Public Health CRS
state: Colorado
city: Denver
country: United States
facility: Eastside Family Health Ctr. CRS
state: Colorado
city: Wheat Ridge
country: United States
facility: Western Infectious Disease Consultants CRS
state: Colorado
city: Washington
country: United States
facility: Washington DC VAMC, Washington Regional AIDS Program, Infectious Diseases CRS
state: District of Columbia
city: Jacksonville
country: United States
facility: Univ. of Florida, Div. of Infectious Diseases CRS
state: Florida
city: Baton Rouge
country: United States
facility: Earl K. Long Med. Ctr., LSU - Mid City EIC Clinic CRS
state: Louisiana
city: Detroit
country: United States
facility: Wayne State Univ. CRS
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hosp. CRS
state: Michigan
city: Lansing
country: United States
facility: Michigan State Univ., Infectious Disease Clinic CRS
state: Michigan
city: Bronx
country: United States
facility: Bronx-Lebanon Hosp. Ctr. CRS
state: New York
city: Bronx
country: United States
facility: Jacobi Med. Ctr., Ambulatory Care Pavillion CRS
state: New York
city: Bronx
country: United States
facility: Montefiore Med. Ctr., AIDS Ctr. CRS
state: New York
city: Bronx
country: United States
facility: Bronx VAMC CRS
state: New York
city: Brooklyn
country: United States
facility: SUNY Downstate Med. Ctr., HIV Ctr. for Women & Children CRS
state: New York
city: New York
country: United States
facility: Harlem Hospital Ctr./Columbia University CRS (Gordin CTU)
state: New York
city: Oklahoma City
country: United States
facility: Univ. of Oklahoma Health Sciences Ctr., Div. of Infectious Diseases CRS
state: Oklahoma
city: Portland
country: United States
facility: The Research & Education Group-Portland CRS
state: Oregon
city: Portland
country: United States
facility: Kaiser Immune Deficiency Clinic of Portland CRS
state: Oregon
city: Portland
country: United States
facility: Legacy Clinic Emanuel CRS
state: Oregon
city: Portland
country: United States
facility: Oregon Health & Sciences Univ. Internal Medicine (L-475) CRS
state: Oregon
city: Philadelphia
country: United States
facility: Temple Univ. School of Medicine CRS
state: Pennsylvania
city: Fredericksburg
country: United States
facility: MediCorp, Infectious Disease Associates CRS
state: Virginia
city: Richmond
country: United States
facility: Vernon Harris East End Community Health Ctr. CRS
state: Virginia
city: Richmond
country: United States
facility: CrossOver Health Ctr. CRS
state: Virginia
city: Richmond
country: United States
facility: VCU Health Systems, Infectious Disease Clinic CRS
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth Univ. Medical Ctr. CRS
state: Virginia
city: Milwaukee
country: United States
facility: Med. College of Wisconsin, Infectious Disease Clinic CRS
state: Wisconsin
city: Burwood
country: Australia
facility: Burwood Road Gen. Practice CRS
state: New South Wales
city: Darlinghurst
country: Australia
facility: St. Vincent's Hospital CRS
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital CRS
state: New South Wales
city: Carlton,
country: Australia
facility: Melbourne Sexual Health Ctr. CRS
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hosp., Clinical Research - Infectious Diseases Unit CRS
state: Victoria
city: Melbourne
country: Australia
facility: Prahran Market Clinic CRS
state: Victoria
city: Salvador
country: Brazil
facility: Hosp. Universitario Prof. Edgard SantosCRS
state: Bahia
city: Sao Paulo
country: Brazil
facility: Instituto de Infectologia Emilio Ribas CRS
city: Halifax
country: Canada
facility: Q.E. II Health Sciences Ctr., Captial District Authority, Victoria Gen. Hosp. CRS
state: Nova Scotia
city: Windsor
country: Canada
facility: Windsor Regional Hosp., HIV Care Program CRS
state: Ontario
city: Muang
country: Thailand
facility: Bamrasnaradura Institute CRS
state: Nonthaburi
city: Bangkok
country: Thailand
facility: Chulalongkorn University Hospital CRS
state: Ratchathewi
city: Bangkok
country: Thailand
facility: Mahidol Univ., Ramathibodi Hosp., Div of Infectious Disease CRS
state: Ratchathewi
city: Chiang Mai
country: Thailand
facility: Sanpatong Hosp. CRS
city: Khon Kaen
country: Thailand
facility: Khon Kaen Univ., Srinagarind Hosp., Div. of Infectious Diseases & Tropical Medicine, Dept. of Medici
Study officials:
affiliation: Infectious Disease Unit, the Alfred Hospital
name: Edwina Wright, MBBS, FRACP
role: STUDY_CHAIR
References:
citation: Antunes F. Central nervous system AIDS--related diseases. Acta Neurochir (Wien). 2004 Oct;146(10):1071-4. doi: 10.1007/s00701-004-0334-0.
citation: Morgello S, Estanislao L, Simpson D, Geraci A, DiRocco A, Gerits P, Ryan E, Yakoushina T, Khan S, Mahboob R, Naseer M, Dorfman D, Sharp V; Manhattan HIV Brain Bank. HIV-associated distal sensory polyneuropathy in the era of highly active antiretroviral therapy: the Manhattan HIV Brain Bank. Arch Neurol. 2004 Apr;61(4):546-51. doi: 10.1001/archneur.61.4.546.
citation: Sacktor N. The epidemiology of human immunodeficiency virus-associated neurological disease in the era of highly active antiretroviral therapy. J Neurovirol. 2002 Dec;8 Suppl 2:115-21. doi: 10.1080/13550280290101094.
citation: Verma S, Estanislao L, Simpson D. HIV-associated neuropathic pain: epidemiology, pathophysiology and management. CNS Drugs. 2005;19(4):325-34. doi: 10.2165/00023210-200519040-00005.