A Study of Dementia and Neurological Problems in HIV Infected Patients Who Are Participating in ACTG A5175

NCT ID: NCT00096824

Last Updated: 2015-03-18

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 860 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2006-02-28
• Study Completion Date: 2010-05-31

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.

Conditions

HIV Infections

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

1

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.

Neurological assessment

Intervention Type: BEHAVIORAL

All participants will undergo neurological examinations and neuropsychological assessments.

Interventions

Neurological assessment

All participants will undergo neurological examinations and neuropsychological assessments.

Intervention Type: BEHAVIORAL

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kevin Robertson, PhD

Role: STUDY_CHAIR

Department of Neurology, University of North Carolina at Chapel Hill

Johnstone Kumwenda, MD, MBBS, MMED

Role: STUDY_CHAIR

Internal Medicine, Johns Hopkins Project

Khuanchai Supparatpinyo, MD

Role: STUDY_CHAIR

Research Institute for Health Sciences, Chiang Mai University

Locations

Hospital Nossa Senhora da Conceicao

Porto Alegre, Rio Grande do Sul, Brazil

Instituto de Pesquisa Clinica Evandro Chagas-Fiocruz

Rio de Janeiro, , Brazil

YRG Center for AIDS Research and Education

Chennai, , India

Dr. Kotnis Dispensary

Pune, , India

National AIDS Research Institute (NARI) ICMR

Pune, , India

National Institute of Virology (NARI)

Pune, , India

The Johns Hopkins-Malawi College of Medicine Project

Blantyre, , Malawi

University of North Carolina Project (UNC Project)

Lilongwe, , Malawi

University of KwaZulu Natal

Durban, KwaZulu-Natal, South Africa

University of Witwatersrand

Johannesburg, , South Africa

University of Zimbabwe

Harare, , Zimbabwe

Countries

Brazil; India; Malawi; South Africa; Zimbabwe

References

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.

Reference Type: BACKGROUND

PMID: 12707852 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 12707851 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 12491162 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 11935465 (View on PubMed)

Michael H, Rapulana A, Smit T, Xulu N, Danaviah S, Ramlall S, Oosthuizen F. Dual Trajectories of Serum Brain-Derived Neurotrophic Factor and Cognitive Function in People Living with HIV. Res Sq [Preprint]. 2025 Apr 14:rs.3.rs-4307577. doi: 10.21203/rs.3.rs-4307577/v1.

Reference Type: DERIVED

PMID: 40321763 (View on PubMed)

Michael HU, Rapulana AM, Smit T, Xulu N, Danaviah S, Ramlall S, Oosthuizen F. Dual trajectories of serum brain-derived neurotrophic factor and cognitive function in people living with HIV. Sci Rep. 2025 May 3;15(1):15520. doi: 10.1038/s41598-025-99569-6.

Reference Type: DERIVED

PMID: 40319152 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30219843 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30137250 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 22661489 (View on PubMed)

Related Links

http://clinicaltrials.gov/ct/show/NCT00084136

Click here for more information about the ACTG A5175 study

Other Identifiers

1U01AI068636

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ACTG A5199

Identifier Type: -

Identifier Source: org_study_id