Clinical trial NCT00096824: A Study of Dementia and Neurological Problems in HIV Infected Patients Who Are Participating in ACTG A5175
Official title: International Neurological Study: A Stand Alone Study for Participants of A5175 (A Phase IV, Randomized, Open-Label Evaluation of the Efficacy of Once-Daily Protease Inhibitor and Once-Daily Non-Nucleoside Reverse Transcriptase Inhibitor-Containing Therapy Combination for Initial Treatment of HIV-1 Infected Individuals From Diverse Areas of the World)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV Infections
Keywords: Acute Infection
Treatment Naive
Lead sponsor: Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
Sponsor class: NETWORK
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
name: National Institute of Mental Health (NIMH)
First posted: 2004-11-16
Enrollment: 860
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All participants who enrolled in ACTG study 5175

Brief summary: The purpose of this study is to determine how often dementia and other neurological problems occur in people with HIV. Participants of ACTG A5175 will enroll in this study.

Detailed description: Both the central and peripheral nervous systems (CNS and PNS) are affected by HIV; however, the causes of neurotoxicity in HIV infected patients are unknown. Initial data indicate that as many as 40% of patients with HIV develop some form of dementia. Other common neurological problems observed in HIV patients are peripheral neuropathy and opportunistic infections of the CNS. Most antiretroviral drugs used in the treatment of HIV have poor penetration into the CNS, which may explain how HIV persists in the CNS and contributes to the prevalence of dementia and other neurological disorders in HIV infected patients. This study will examine the prevalence of dementia and other neurological disorders in participants in ACTG A5175, "Once-Daily PI/NNRTI Therapy Combinations for Treatment Naive, HIV Infected Patients in Resource-limited Conditions."

The study will last approximately 2.5 to 3 years. Participants will undergo neurological examinations and neuropsychological assessments at entry to both steps of ACTG A5175 and before the administration of the new antiretroviral regimen, then every 24 weeks until they discontinue ACTG A5175. Physicians will make targeted diagnoses at each study visit.

Eligibility criteria: Inclusion Criteria:

* HIV-1 infected
* Prior antiretroviral therapy for less than 7 days any time prior to study entry
* CD4 count less than 300 cells/mm3
* Willing to use acceptable means of contraception
* Plans to stay in the area for the duration of study participation
* Willing to adhere to study follow-up schedule for ACTG A5175 and this study
* Have not begun ACTG A5175 antiretroviral therapy, but planning to start therapy after enrolling in this study

Exclusion Criteria:

* Any active severe psychiatric illness (e.g., schizophrenia, severe depression, severe bipolar affective disorder) that, in the opinion of the site investigator, may interfere with the study results
* Current drug or alcohol abuse that, in the opinion of the site investigator, would interfere with study requirements
* Serious illness or hospitalization that, in the opinion of the site investigator, may interfere with the study results
* Any condition that, in the opinion of the site investigator, would interfere with study requirements

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Porto Alegre
country: Brazil
facility: Hospital Nossa Senhora da Conceicao
state: RS
city: Rio de Janeiro
country: Brazil
facility: Instituto de Pesquisa Clinica Evandro Chagas-Fiocruz
city: Chennai
country: India
facility: YRG Center for AIDS Research and Education
city: Pune
country: India
facility: Dr. Kotnis Dispensary
city: Pune
country: India
facility: National AIDS Research Institute (NARI) ICMR
city: Pune
country: India
facility: National Institute of Virology (NARI)
city: Blantyre
country: Malawi
facility: The Johns Hopkins-Malawi College of Medicine Project
city: Lilongwe
country: Malawi
facility: University of North Carolina Project (UNC Project)
city: Durban
country: South Africa
facility: University of KwaZulu Natal
state: KZN
city: Johannesburg
country: South Africa
facility: University of Witwatersrand
city: Harare
country: Zimbabwe
facility: University of Zimbabwe
Study officials:
affiliation: Department of Neurology, University of North Carolina at Chapel Hill
name: Kevin Robertson, PhD
role: STUDY_CHAIR
affiliation: Internal Medicine, Johns Hopkins Project
name: Johnstone Kumwenda, MD, MBBS, MMED
role: STUDY_CHAIR
affiliation: Research Institute for Health Sciences, Chiang Mai University
name: Khuanchai Supparatpinyo, MD
role: STUDY_CHAIR
References:
citation: Albright AV, Soldan SS, Gonzalez-Scarano F. Pathogenesis of human immunodeficiency virus-induced neurological disease. J Neurovirol. 2003 Apr;9(2):222-7. doi: 10.1080/13550280390194073.
citation: McArthur JC, Haughey N, Gartner S, Conant K, Pardo C, Nath A, Sacktor N. Human immunodeficiency virus-associated dementia: an evolving disease. J Neurovirol. 2003 Apr;9(2):205-21. doi: 10.1080/13550280390194109.
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: Sacktor N, McDermott MP, Marder K, Schifitto G, Selnes OA, McArthur JC, Stern Y, Albert S, Palumbo D, Kieburtz K, De Marcaida JA, Cohen B, Epstein L. HIV-associated cognitive impairment before and after the advent of combination therapy. J Neurovirol. 2002 Apr;8(2):136-42. doi: 10.1080/13550280290049615.
citation: Robertson KR, Jiang H, Kumwenda J, Supparatpinyo K, Marra CM, Berzins B, Hakim J, Sacktor N, Campbell TB, Schouten J, Mollan K, Tripathy S, Kumarasamy N, La Rosa A, Santos B, Silva MT, Kanyama C, Firhnhaber C, Murphy R, Hall C, Marcus C, Naini L, Masih R, Hosseinipour MC, Mngqibisa R, Badal-Faesen S, Yosief S, Vecchio A, Nair A; AIDS Clinical Trials Group. Human Immunodeficiency Virus-associated Neurocognitive Impairment in Diverse Resource-limited Settings. Clin Infect Dis. 2019 May 2;68(10):1733-1738. doi: 10.1093/cid/ciy767.
citation: Robertson KR, Oladeji B, Jiang H, Kumwenda J, Supparatpinyo K, Campbell TB, Hakim J, Tripathy S, Hosseinipour MC, Marra CM, Kumarasamy N, Evans S, Vecchio A, La Rosa A, Santos B, Silva MT, Montano S, Kanyama C, Firnhaber C, Price R, Marcus C, Berzins B, Masih R, Lalloo U, Sanne I, Yosief S, Walawander A, Nair A, Sacktor N, Hall C; 5199 Study Team; and the AIDS Clinical Trials Group. Human Immunodeficiency Virus Type 1 and Tuberculosis Coinfection in Multinational, Resource-limited Settings: Increased Neurological Dysfunction. Clin Infect Dis. 2019 May 2;68(10):1739-1746. doi: 10.1093/cid/ciy718.
citation: Robertson K, Jiang H, Kumwenda J, Supparatpinyo K, Evans S, Campbell TB, Price R, Tripathy S, Kumarasamy N, La Rosa A, Santos B; 5199 study team; Silva MT, Montano S, Kanyama C, Faesen S, Murphy R, Hall C, Marra CM, Marcus C, Berzins B, Allen R, Housseinipour M, Amod F, Sanne I, Hakim J, Walawander A, Nair A; AIDS Clinical Trials Group. Improved neuropsychological and neurological functioning across three antiretroviral regimens in diverse resource-limited settings: AIDS Clinical Trials Group study a5199, the International Neurological Study. Clin Infect Dis. 2012 Sep;55(6):868-76. doi: 10.1093/cid/cis507. Epub 2012 Jun 1.