The Effect of Aspirin on HIV Disease Progression Among HIV- Infected Individuals Initiating Anti- Retroviral Therapy

August 30, 2022 updated by: Tosi Michael Mwakyandile, Muhimbili University of Health and Allied Sciences

Introduction An increase in cardiovascular disease (CVD) among people living with HIV infection is linked to platelet and immune activation, a phenomenon unabolished by antiretroviral (ARV) drugs alone. In small studies, aspirin (acetylsalicylic acid [ASA]) has been shown to control immune activation, increase CD4+ count, halt HIV disease progression and reduce HIV viral load (HVL). The investigators present a protocol for a larger suspended randomised placebo controlled trial on the effect of an addition of ASA to ARV drugs on HIV disease progression.

Methods and analysis A single-centre phase IIA double-blind, parallel-group randomised controlled trial intended to recruit 454 consenting ARV drug-naïve, HIV-infected adults initiating ART. Participants were randomised in blocks of 10 in a 1:1 ratio to receive, in addition to ARV drugs, 75 mg ASA or placebo for 6 months. The primary outcome is the proportion of participants attaining HVL of <50 copies/mL by 8, 12 and 24 weeks. Secondary outcomes include proportions of participants with HVL of >1000 copies/mL at week 24, attaining a >30% rise of CD4 count from baseline value at week 12, experiencing adverse events, with normal levels of biomarkers of platelet and immune activation at weeks 12 and 24 and rates of morbidity and all-cause mortality. Intention-to-treat analysis will be done for all study outcomes.

Study Overview

Status

Suspended

Conditions

Intervention / Treatment

Detailed Description

Despite the introduction of antiretroviral (ARV) therapy, HIV is still a public health problem in Eastern and Southern Africa. The wide spread use of the ARV drugs has improved the life expectancy of people living with HIV and/ or acquired immunodeficiency syndrome (AIDS). As a result, there has been an increase in the prevalence of and mortality from non - AIDS complications such as non - AIDS defining cancers, liver, pulmonary and cardiovascular diseases. The increase in the non - AIDS complications especially the cardiovascular disease risk is linked to platelet and immune activation. Antiretroviral therapy (ART) does not completely abolish the immune activation and the platelet activation making it a necessity to find additional therapy to the conventional ART therapy, that will decrease the occurrence of these non- AIDS complications and their associated morbidities. Aspirin or acetyl salicylic acid (ASA) has shown promise as such an additional drug. In addition, ASA appears to have an array of beneficial effects in the HIV infected individuals. ASA is reported to possibly cause a reduction in HIV load, increase CD4 counts and halt the clinical HIV disease progression. Literature shows that additional therapy to ARV drugs may compromise adherence to ART among HIV- infected individuals. However, when addition of a pill is associated with significant benefit, the addition of a pill or pills may be justifiable. For example, addition of medication for opportunistic infection, methadone maintenance therapy and antidepressants has been reported to improve adherence to ART among HIV- infected patients in some studies. Therefore, considering the reported benefits of ASA in the HIV- infected population, it is important to study the effect of the addition of ASA on both the HIV disease progression and the adherence to ARV drugs. The project aims at investigating the effects of low dose aspirin on immunological, virologic and clinical outcomes among HIV- infected individuals initiating ART.

The investigators hypothesize that addition of ASA to ART in the newly recruited HIV- infected patients will be associated with earlier and sustained virologic suppression, better immunological and clinical responses and improved quality of life. And also that addition of ASA to ART in the newly recruited HIV- infected patients will not compromise adherence to ARV therapy.

b. The objectives of the research project: Broad objective: To determine the effect of low dose of ASA on HIV disease progression and adherence to anti- retroviral therapy among HIV-infected individuals initiating ARV therapy.

Specific Objectives i. To compare the HIV viral loads measured at 2, 3 and 6 months among HIV- infected individuals after initiating ARV therapy alone or ARV therapy and 75mg ASA.

ii. To compare the CD4 counts measured at 3 and 6 months among HIV- infected individuals after initiating ARV therapy alone or ARV therapy and 75mg ASA.

iii. To compare the plasma levels of immune activation biomarker (sCD14) measured at 3 and 6 months among HIV- infected individuals after initiating ARV therapy alone or ARV therapy and 75mg ASA.

iv. To compare the plasma levels of platelet activation biomarker (P- selectin) measured at 3 and 6 months among HIV- infected individuals after initiating ARV therapy alone or ARV therapy and 75mg ASA.

v. To compare percentage of activated T cells (CD38 positive and HLA-DR positive T cells) measured at 3 and 6 months among HIV- infected individuals after initiating ARV therapy alone or ARV therapy and 75mg ASA.

vi. To compare percentages of exhausted T cells (PD1 positive T cells) measured at 3 and 6 months among HIV- infected individuals after initiating ARV therapy alone or ARV therapy and 75mg ASA.

vii. To compare morbidity among HIV- infected individuals initiating ARV therapy alone or ARV therapy and 75mg ASA.

viii. To compare all-cause-mortality among HIV- infected individuals initiating ARV therapy alone or ARV therapy and 75mg ASA.

ix. To determine level of adherence to ARV therapy among HIV- infected individuals initiating ARV therapy and ASA or placebo.

Study Type

Interventional

Enrollment (Anticipated)

454

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Tanzania
      • Dar Es Salaam, Tanzania
        • Mwananyamala Regional Referral Hospital, Mbagala Rangi Tatu Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Consenting newly recruited male or female HIV-infected patients
  • Antiretroviral drug-naïve initiating on antiretroviral drugs
  • Age 18 years or older
  • Willingness to stay in Dar es Salaam for at least 6 consecutive months
  • Willingness to attend HIV clinics at Temeke or Mbagala Rangi Tatu or Mwananyamala hospital for at least six consecutive months

Exclusion Criteria:

  • Previous intolerance or allergy to aspirin or any aspirin products
  • Asthmatics
  • Predisposition to bleeding (increased chance of bleeding due to being on antiplatelets and/or anticoagulants and/or having history of or active diagnosis of bleeding disorder)
  • Antithrombotic therapy
  • Therapy with protocol prohibited drugs
  • Active or history of peptic ulcer disease
  • Pregnancy
  • Severe renal disease (eGFR <30 mil/min/1.73 m2)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Aspirin arm
In addition to their antiretroviral regimen, participants self administer blister packaged enteric coated tablet of 75 mg aspirin (Cardisprin 75, Cosmos, Nairobi, Kenya) for 24 weeks at a dose of one tablet per day at evening times swallowed wholly with a glass of clean drinking water, preferably after a meal. All adults initiating antiretroviral therapy are prescribed the default combination of tenofovir (TDF) +lamivudine (3TC)+dolutegravir (DTG). Those with contraindications are alternatively prescribed abacavir+3TC+DTG or TDF +3TC+efavirenz and in special situations zidovudine+3TC+DTG
Drug: aspirin enteric coated tablet 75 mg
blister packaged enteric coated tablet of 75 mg aspirin taken once daily for 24 weeks in addition to the conventional antiretroviral drugs
Other Names:
  • antiretroviral drugs
Placebo Comparator: Placebo arm
In addition to their antiretroviral regimen, participants self administer blister packaged placebo (Cardisprin 75, Cosmos, Nairobi, Kenya) for 24 weeks at a dose of one tablet per day at evening times swallowed wholly with a glass of clean drinking water, preferably after a meal. The placebo has colour, shape and size similar to aspirin
Drug: aspirin enteric coated tablet 75 mg
blister packaged enteric coated tablet of 75 mg aspirin taken once daily for 24 weeks in addition to the conventional antiretroviral drugs
Other Names:
  • antiretroviral drugs

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Virologic suppression
Time Frame: 8 weeks
The primary outcome is the proportion of participants attaining viral load of <50 copies/mL at the end of 8, 12 and 24 weeks. I
8 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Virologic failure, safety, immunological and clinical responses
Time Frame: up to 24 weeks for safety, 12 and 24 weeks
Secondary outcomes include proportion of participants with viral load of >1000 copies/mL at the end of 24 weeks, proportion of participants attaining a >30% rise of CD4 count from baseline value at the end of 12 weeks, and prevalence of morbidity and all-cause mortality. Other secondary outcomes are proportion of participants with normal levels of the assessed biomarkers of platelet and immune activation at the end of 12 and 24 weeks, proportion of participants experiencing adverse events, mean percentage adherence to antiretroviral drugs and mean percentage compliance to the study drugs.
up to 24 weeks for safety, 12 and 24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Muhimbili University of Health and Allied Sciences

Collaborators

Fogarty International Center of the National Institute of Health
Kumamoto University

Investigators

  • Principal Investigator: Eligius F Lyamuya, MD, MMed, PhD, FTAAS, FCPath, Muhimbili University of Health and Allied Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 2, 2020

Primary Completion (Actual)

June 22, 2022

Study Completion (Anticipated)

June 22, 2023

Study Registration Dates

First Submitted

August 28, 2022

First Submitted That Met QC Criteria

August 30, 2022

First Posted (Actual)

September 1, 2022

Study Record Updates

Last Update Posted (Actual)

September 1, 2022

Last Update Submitted That Met QC Criteria

August 30, 2022

Last Verified

August 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DA.282/298/01 /C
  • PACTR202003522049711 (Registry Identifier: Pan African Clinical Trial Registry)
  • R25TW011227 (U.S. NIH Grant/Contract)
  • 5D43TW009775-03 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Individual participant data that underlie the results reported in the respective article, after deidentification (text, tables, figures and appendices).

IPD Sharing Time Frame

From 9 months and to 36 months after article publication

IPD Sharing Access Criteria

Investigators with approval by an independent review committee for proposed use of data. Data will be shared for individual participant data meta analysis The mechanism by which data will be made available is that proposals may be submitted up to 36 months after respective article publication. after this period data will be made available at MUHAS data warehouse but without investigator support other than deposited metadata.

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Informed Consent Form (ICF)
  • Clinical Study Report (CSR)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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