Treatment of Early Hypertension Among Persons Living With HIV in Haiti

Study Overview
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Brief Summary
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The investigators are conducting an unblinded pilot randomized control trial of 250 persons living with HIV (PLWH), aged 18-65 years, who receive antiretroviral therapy care at Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic Infections (GHESKIO), are virally suppressed, and have pre-hypertension (systolic blood pressure (SBP) 120-139 or diastolic blood pressure (DBP) 80-89 mmHg) to be randomized to early hypertension (HTN) treatment versus standard of care (SOC). Participants will be recruited from GHESKIO's HIV clinic. Eligible individuals will complete informed consent and be randomized to early HTN treatment vs. SOC. Participants in early HTN treatment will initiate amlodipine immediately versus those in SOC will initiate amlodipine only if they meet the HTN threshold (SBP ≥140 or DBP ≥90 mmHg) during the study period. All participants will be followed for 12 months.

Detailed Description
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The investigators propose a pilot randomized controlled trial to evaluate antihypertensive treatment among people living with HIV (PLWH) with pre-hypertension (pre-HTN) at GHESKIO. This study will provide critical data on the feasibility, benefits and risks of antihypertensive treatment for cardiovascular disease (CVD) prevention among PLWH with pre-HTN that will inform a future definitive trial powered for incident CVD events. For the pilot study, the investigators will enroll 250 PLWH (18-65 years of age) who have been on antiretroviral therapy (ART) for ≥ 1 years with viral suppression within past 12 months and SBP 120-139 or DBP 80-89 mm Hg and no current antihypertensive treatment; randomize them to early HTN treatment or the current standard of care (SOC); and follow them for 12 months. Amlodipine is the recommended first-line anti-hypertensive medication according to Haiti's new primary care HTN guidelines. Participants in the early HTN treatment arm will initiate amlodipine 5 mg immediately, increasing to 10 mg if SBP >130 mm Hg after 1 month. Participants in the SOC arm will initiate amlodipine only if they develop HTN (SBP ≥140 or DBP ≥90 mm Hg). Participants that meet study eligibility criteria will proceed to study enrollment visit ( 90 min). Participants will be randomized to early HTN treatment vs. SOC in a 1:1 ratio using a computer-generated random assignment. The research nurse will collect demographic and clinical data, administer a baseline questionnaire, measure unobserved BP, and perform an ECG. The questionnaire includes a CVD medical history, family history, medications, CVD health behaviors (smoking, alcohol, physical activity, and diet) using validated questions that have been used at GHESKIO and are comparable to those used in US cohorts. Enrollment labs ( 15ml of venous blood) including HgbA1c, total cholesterol, high density cholesterol, CD4 (cluster of differentiation 4) cell count, and HIV viral load (unless available from electronic medical record in the past 6 months) will be collected. Samples of serum and plasma will be stored for future studies, with documented consent from participants. The study physician will interpret the ECG and perform an echocardiogram and vascular ultrasound. Study drug will be dispensed to participants randomized to the early treatment arm with appropriate education and counseling on adherence and potential side effects. Amlodipine will be started at 5mg at enrollment and increased to 10mg if SBP >130 mm Hg after 1 month for participants in the early treatment arm. Locator and contact information will be verified and follow up appointment given. After enrollment and randomization assignment (including amlodipine initiation), participants will have follow-up visits either at GHESKIO (months 0.5-1, 3, 6, 9, 12) or in the community / home with community health workers (months 2, 5, 8). All visits will include BP measurement, lifestyle counseling, adherence encouragement, and assessment of adverse events. The GHESKIO visits will also include a physical exam. Participants in the early intervention arm will receive monthly amlodipine refills. Participants in the SOC arm will initiate amlodipine only if they develop hypertension (SBP >140 or DBP >90 mm Hg). At the 12-month study visit, participants will also complete a brief questionnaire about changes in health behaviors and have viral load measured. Participants may return to the HIV clinic at any time for symptoms, questions, or other concerns, and a BP measurement will be taken at each of these encounters. Adverse events will be assessed at each visit. Medical record abstraction will be done by research staff for any hospitalization or death among a participant.

Official Title
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Treatment of Early Hypertension Among Persons Living With HIV in Haiti

Conditions
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HIV/AIDS, Pre Hypertension

Intervention / Treatment
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* Drug: Amlodipine 5mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: PLWH 18-65 years of age ART duration ≥ 1 year, stable regimen ≥ 6 months HIV 1-RNA < 1,000 copies/mL within past 12 months Pre-HTN (SBP 120-139 or DBP 80-89 mm Hg) No current antihypertensive treatment Receives HIV care at GHESKIO Willing to provide consent Exclusion Criteria: Pregnancy Kidney disease or diabetes On protease inhibitor/ritonavir Advanced illness with limited life expectancy Plans to move out of the area within the next year Clinician determination that patient is unstable on ART

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention (Early hypertension)<br>Participants randomized to the early HTN treatment arm will initiate 5mg daily of amlodipine immediately, increasing to 10 mg if SBP >130 mmHg after 1 month. | Drug: Amlodipine 5mg<br>* Amlodipine, Haiti's first-line antihypertensive medication, will be administered to the intervention group.<br>* Other names: Norvasc;|
| No Intervention: Standard of Care<br>Participants randomized to the SOC arm will not be initiated on any medications initially. They may be initiated on amlodipine only if they develop HTN (SBP ≥140 or DBP ≥90 mm Hg). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in change of mean systolic blood pressure (SBP) between study arms | Difference in change of mean systolic blood pressure (SBP) between intervention and control arms | Baseline, 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in number of participants with HIV viral suppression as measured by HIV-1 RNA viral loads < 1,000 copies/mL | Change in number of participants with HIV viral suppression as measured by HIV-1 RNA viral loads < 1,000 copies/mL | Baseline, 12 months | 
| Change in HIV medication adherence as measured by number of participants with > 90% adherence using 4-day pill recalls | Change in HIV medication adherence as measured by number of participants with > 90% adherence using 4-day pill recalls | Baseline, 6 months and 12 months | 
| Adverse Events | Number of subjects who have adverse events related to amlodipine, including dizziness, fainting, lower extremity edema, and any other symptoms which may be related. Symptoms will be categorized according to the Division of AIDS (DAIDS) severity score, with Grade III-IV considered adverse events. | Followup month 1 | 
| Adverse Events | Number of subjects who have adverse events related to amlodipine, including dizziness, fainting, lower extremity edema, and any other symptoms which may be related. Symptoms will be categorized according to the Division of AIDS (DAIDS) severity score, with Grade III-IV considered adverse events. | Followup month 2 | 
| Adverse Events | Number of subjects who have adverse events related to amlodipine, including dizziness, fainting, lower extremity edema, and any other symptoms which may be related. Symptoms will be categorized according to the Division of AIDS (DAIDS) severity score, with Grade III-IV considered adverse events. | Followup month 3 | 
| Adverse Events | Number of subjects who have adverse events related to amlodipine, including dizziness, fainting, lower extremity edema, and any other symptoms which may be related. Symptoms will be categorized according to the Division of AIDS (DAIDS) severity score, with Grade III-IV considered adverse events. | Followup month 5 | 
| Adverse Events | Number of subjects who have adverse events related to amlodipine, including dizziness, fainting, lower extremity edema, and any other symptoms which may be related. Symptoms will be categorized according to the Division of AIDS (DAIDS) severity score, with Grade III-IV considered adverse events. | Followup month 6 | 
| Adverse Events | Number of subjects who have adverse events related to amlodipine, including dizziness, fainting, lower extremity edema, and any other symptoms which may be related. Symptoms will be categorized according to the Division of AIDS (DAIDS) severity score, with Grade III-IV considered adverse events. | Followup month 8 | 
| Adverse Events | Number of subjects who have adverse events related to amlodipine, including dizziness, fainting, lower extremity edema, and any other symptoms which may be related. Symptoms will be categorized according to the Division of AIDS (DAIDS) severity score, with Grade III-IV considered adverse events. | Followup month 9 | 
| Adverse Events | Number of subjects who have adverse events related to amlodipine, including dizziness, fainting, lower extremity edema, and any other symptoms which may be related. Symptoms will be categorized according to the Division of AIDS (DAIDS) severity score, with Grade III-IV considered adverse events. | Followup month 12 | 
| Acceptability assessed by change in percent of participants at baseline and retained at 12 months | Percent of participants who are enrolled at baseline and remain in the study by 12 months | Baseline, 12 months | 
| Acceptability of study intervention assessed by qualitative interviews among participants and providers | Using semi-structured interview guides exploring topics including acceptability, side effects, perceived benefit, and perceived cost, in depth interviews will be conducted with 15-20 study participants in the intervention arm, and all healthcare providers involved in the study (nurses, doctors, social workers). | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, hypertension