Reactivation of herpesviruses and cardiovascular and cerebrovascular risk factors in an African ART population

• Register: ISRCTN
• Last refreshed on: 23 May 2022
• Main ID: ISRCTN42862937
• Date of registration: 15/05/2018
• Prospective Registration: No
• Primary sponsor: GlaxoSmithKline
• Public title: Reactivation of herpesviruses and cardiovascular and cerebrovascular risk factors in an African ART population
• Scientific title: Protocol for a longitudinal, cohort study to evaluate Reactivation of Herpesviruses and Inflammation as Cardiovascular and Cerebrovascular risk factors in Antiretroviral initiators, in an African HIV population (RHICCA)
• Date of first enrolment: 17/05/2017
• Target sample size: 1090
• Recruitment status: Completed
• URL: https://www.isrctn.com/ISRCTN42862937
• Study type: Observational
• Study design: Single-centre 36-month observational prospective cohort study (Treatment)
• Phase: Not Applicable

Countries of recruitment

Malawi

Contacts

• Name: Ingrid Peterson

• Name: Laura Benjamin

Key inclusion & exclusion criteria

Inclusion criteria:
1. Aged => 35 years
2. Resident in Blantyre
3. HIV-infected patients must further be ART-naïve or initiated ART <10 days prior to enrolment
4. Initiating standard first-line ART (in Malawi this is: TDF/3TC/EFV)
5. Adult controls must further be HIV uninfected

Exclusion criteria:
1. Clinical history of CVD/CBD
2. Pregnant
3. Critically ill or have symptomatic anaemia at enrolment
4. Enrolled in an intervention study


Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Cardiovascular and cerebrovascular disease
Circulatory System
Cardiovascular and cerebrovascular disease

Intervention(s)

The primary study exposures are HIV infection, CMV reactivation, and markers of inflammation and endothelial dysfunction. HIV tested at baseline in all participants (ART patient and HIV uninfected community controls). HIV status will be assessed yearly by rapid test in HIV-uninfected participants to detect sero-conversion. Reactivated latent herpes viral infections will be assessed by quantification of IgG VZV, CMV and HHV-8 antibodies at baseline in HIV uninfected controls and at baseline and 6 months in HIV infected participants. In all participants, at baseline, 6, 12, 24 and 36 months we will measure soluble markers in plasma , which are associated with systemic inflammation (plasma IL-6, hsCRP), and activation of coagulatory pathways (D-Dimers) and endothelial activation (sICAM-1 and sVCAM-1).

Primary Outcome(s)

1. Carotid intima media thickness (cIMT) is assessed by ultrasonography at baseline and 24 months
2. Carotid femoral pulse wave velocity (PWV) is assessed using a Vicorder at baseline, 6, 12, 18, 24, 30 and 26 months

Secondary Outcome(s)

All secondary outcomes are reviewed by an Endpoint Review Committee, comprised of medical experts. Retrospective assessment of outcomes deceased cases is done by medical record review, or by verbal autopsy if the individual died > 4 weeks after hospital discharge (or with no hospital admission). Verbal autopsy is conducted using a standardized WHO assessment tool
1. Stroke is measured at all occurrences by clinical assessment with standard protocols with MRI confirmation
2. Myocardial infarction (MI) is measured at all occurrences by clinical assessment with standard protocols, and ECG confirmation
3. Unstable angina is measured at all occurrences by clinical assessment with standard protocols, and ECG confirmation
4. Peripheral vascular disease (PVD) is measured at baseline, 6, 12, 18, 24, 30 and 36 months by calculation of ankle brachial pressure index (ABPI), which is assessed by sphygmomanometer and doppler ultrasound. A change of >0.15 ABPI from baseline is considered clinically significant PVD
5. All cause death or vascular death is measured at all occurrences. For deaths occurring within 4 weeks of hospital admissions, cause of death will be assessed by medical record review using standardized protocols. Deaths occurring >4 week post hospital discharge (or with no hospital admission) will be assessed by verbal autopsy
6. Immune Reconstitution Syndrome [IRIS] vasculopathy is measured at all occurrences within 6 months of the baseline visit. It is defined as a vascular event (ex. stroke, MI or unstable angina) accompanied by a decrease in viral load >1 log10 copies from baseline

Secondary ID(s)

P02161874

Source(s) of Monetary Support

GlaxoSmithKline

Ethics review

Status:
Approval date:
Contact:

1. University of Malawi College of Medicine Ethics Committee, 05/30/2016, ref: P02/16/1874 2. Liverpool School of Tropical Medicine Research Ethics Committee, 08/10/2016, ref: 16-014

Results

• Results available: Yes
• Date Completed: 30/11/2021