Peripheral Reservoir of HIV DNA in Monocytes Pivotal to Cognition in HIV

Sixty HIV participants will be enrolled and stratified by PBMC HIV DNA levels, either high (greater than or equal to 5000 copies/106 cells) or low (less than 5000 copies/106 cells). Individuals will be enrolled into each group until filled. Screening PBMC HIV DNA levels will be performed at SEARCH in real-time with less than one-week turn around time. All individuals will intend to initiate ARV due to meeting MOPH guidelines for such. The protocol team will work with the primary care physician to facilitate initiation of standard ARV care; however, initiation of ARV is not a requirement of the study and ARV will not be provided by the study.

Study Overview

• Status: Completed
• Conditions: HIV Infections

• Study Type: Observational
• Enrollment (Actual): 60

Contacts and Locations

Study Locations

• Thailand
  • Bangkok, Thailand
    • SEARCH Thailand

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

HIV-infected individuals meeting MOPH criteria to initiate HAART and planning to initiate HAART within a month of screening. Consequently, all participants will have plasma CD4 counts at less than 250 cells.

Description

Inclusion Criteria:

• HIV-infected individuals meeting MOPH criteria to initiate HAART and planning to initiate HAART within a month of screening.
• Consequently, all participants will have plasma CD4 counts at less than 250 cells.

Exclusion Criteria:

• Head injury with loss of consciousness greater than 1 hour or cognitive sequela
• Current/past illicit drug use or positive drug screen for methamphetamines, amphetamines, or cocaine at screening or entry.

• Any of the following laboratory abnormalities:

  • PT/PTT > the upper limit of normal (ULN) or INR > 1.1
  • Hemoglobin < 9.0 mg/dL
  • ALT > 5x ULN
  • serum creatinine > 2x ULN or creatinine clearance < 30 cc per min by Cockroft-Gault formula
• Acute illness within 30 days prior, persistent and active AIDS-defining OI of any organ system or autoimmune disease.
• Current or recent fevers or meningeal signs suggestive of CNS opportunistic infection
• CNS opportunistic infection, past or present (Patients diagnosed with opportunistic infection after CSF examination will be excluded from further analysis. In such a situation, an additional patient will be enrolled)
• History of pre-existing neurologic disease to include stroke, multiple sclerosis or psychiatric illness including schizophrenia, bipolar disorder, anxiety disorder, panic attacks, major depression, or post traumatic stress disorder. Patients with past depression that is controlled and patients with or minor depressive symptoms will be allowed to enroll.
• Known learning disability including dyslexia or unable to read or write basic Thai
• Positive Hepatitis C serology (Hepatitis C Ab)
• Confusion or other signs and symptoms of metabolic encephalopathy or delirium
• Other conditions that could explain neurocognitive decline in the opinion of the investigator such as hypothyroidism, vitamin B12 deficiency or neurosyphilis
• Pregnancy or metal objects that would preclude MRI

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
1 HIV DNA will be stratified by high
2 HIV DNA will be stratified by low

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To determine the long-term relationship between cognition and HIV DNA in circulating PBMCs and monocytes (CD14+ PBMCs) among patients initiating HAART for the first time	After March 30, 2016

Collaborators and Investigators

• Sponsor: South East Asia Research Collaboration with Hawaii
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Principal Investigator: Victor Valcour, MD, University of Hawii

Publications and helpful links

General Publications

• Corley MJ, Sacdalan C, Pang APS, Chomchey N, Ratnaratorn N, Valcour V, Kroon E, Cho KS, Belden AC, Colby D, Robb M, Hsu D, Spudich S, Paul R, Vasan S, Ndhlovu LC; SEARCH010/RV254 and SEARCH013/RV304 study groups. Abrupt and altered cell-type specific DNA methylation profiles in blood during acute HIV infection persists despite prompt initiation of ART. PLoS Pathog. 2021 Aug 13;17(8):e1009785. doi: 10.1371/journal.ppat.1009785. eCollection 2021 Aug.

Helpful Links

• South East Asia Research Collaboration with Hawaii

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): January 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: October 29, 2008
• First Submitted That Met QC Criteria: October 29, 2008
• First Posted (Estimate): October 31, 2008

Study Record Updates

• Last Update Posted (Estimate): September 26, 2014
• Last Update Submitted That Met QC Criteria: September 25, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: HIV DNA in Monocytes
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections
• Other Study ID Numbers: SEARCH 011