HIV And Parasitic Infection (HAPI) Study (HAPI)

June 27, 2025 updated by: University of North Carolina, Chapel Hill

Impact of Parasitic Infections on Intestinal Epithelial Barrier and Immune Activation Among Persons Living With HIV in Lilongwe, Malawi

The overall goal of this study is to determine if periodic de-worming of persons living with HIV in intestinal parasite-endemic regions will lead to decreased morbidity and mortality associated with HIV by reducing immune activation and intestinal damage associated with these diseases. The hypothesis for this project is that intestinal parasitic infections contribute to a modifiable pro-inflammatory state in persons living with HIV (PLWH).

Aim 1: Determine the prevalence of intestinal parasitic infections in PLWH receiving care at an HIV-treatment center in Lilongwe, Malawi using a highly sensitive multi-parallel stool PCR test. Hypothesis: highly sensitive stool PCR testing will demonstrate that disease burden of parasitic infection in PLWH in Malawi is higher than historically reported based on stool microscopy.

Aim 2: Determine the impact of parasitic infection on intestinal damage and immune activation by measuring sCD14, sCD163, and intestinal fatty acid binding protein (I-FABP) in PLWH. Hypothesis: plasma biomarkers reflecting intestinal damage and immune activation are elevated in those with HIV and parasitic co-infection compared with parasite-negative participants with HIV.

Aim 3: Determine the impact of eradication of parasitic infection on intestinal damage and immune activation by measuring sCD14, sCD163, and intestinal fatty acid binding protein (I-FABP) in PLWH before and after treatment of parasitic co-infection. Hypothesis: plasma biomarkers reflecting intestinal damage and immune activation are elevated in those with HIV and parasitic co-infection, and these biomarkers decrease with anti-parasitic treatment.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a prospective study in which participants will be enrolled in outpatient HIV clinics associated with Kamuzu Central Hospital in Lilongwe, Malawi, where there are over 25,000 patients in care with over 90% virally suppressed on ART.

Any subject meeting inclusion criteria and lacking exclusion criteria who is currently receiving care at the clinics affiliated with Kamuzu Central Hospital or Bwaila Hospital will be eligible to participate in this study. After informed consent is signed, a total of 10ml of blood, 20g stool sample, and 20mL urine sample will be collected. Each participant will be asked a series of questions. Clinical variables including age, sex, CD4+ T-cell count, and CD4% will be collected from the participant's medical chart.

Stool samples will be processed by stool microscopy in the local UNC Project Malawi laboratory, and the remaining sample will be stored at -80 degrees Celsius (C) until transported to the Laboratory of Parasitology National School of Tropical Medicine Baylor College of Medicine in Houston, Texas for detection of 9 different parasites and quantification of parasite burden by stool qPCR. Blood samples will be collected in EDTA-blood collection tubes and centrifuged. Plasma will be frozen at -80 degrees C at UNC Project Malawi until transport to the National School of Tropical Medicine Baylor College of Medicine for determination of levels of immune activation and gut mucosal impairment (sCD14, sCD163, and I-FABP). Urine samples will be evaluated by microscopy to look for Schistosoma haematobium at UNC Project Malawi laboratory.

Multi-parallel real-time quantitative PCR (qPCR) performed on stool will evaluate for 9 different parasites including Ascaris lumbricoides, Ancylostoma duodenale, Necator americanus, Schistosoma mansonii, Strongyloides stercoralis, Taenia solium, Trichuris trichiura, Entamoeba histolytica, and Giardia lamblia.

Participants that test positive for parasitic infection will be contacted and appropriate treatment administered according to the local standard of care. Albendazole single 400mg dose will be given for infection with Ascaris lumbricoides, Ancylostoma duodenale, Necator americanus, Trichuris trichiura. Albendazole 400mg daily for 5 days will be given for Strongyloides stercoralis. Praziquantel single dose 40mg/kg will be given for infection with Schistosoma mansoni and Schistosoma haematobium. Praziquantel single dose 10mg/kg will be given to treat intestinal infection with Taenia solium. Metronidazole 500mg two times a day x5 days for Giardia lamblia and 500mg three times a day x7 days for Entamoeba histolytica.

Follow up appointments will be performed 8-12 weeks after treatment and will include repeated blood and stool sample collection.

The study team anticipates enrollment of 120 patients in a period of 8-12 weeks. With an estimated intestinal parasite prevalence of 30%, the study team predicts 30 cases and 70 controls will be enrolled. Participants found to be positive at both the initial and follow up visit will be considered reinfected rather than treatment failure. These will be included in the analysis of prevalence, but the change in markers of immune activation will not be measured in this group since parasite clearance not established. Using Student's unpaired t-test to compare mean values of biomarkers between study groups, there will be 80% power to detect a difference of 0.434 x106 pg/ml, 0.56 mg/l, and 598 pg/ml between groups for biomarkers sCD14, sCD163, and I-FABP, respectively with effect sizes within the range of prior studies. Using paired t-tests to compare pre- and post-treatment biomarker levels, there will be 80% power to detect post-treatment changes of 0.317 x106/ml, 0.41 mg/l, and 435 pg/ml in sCD14, CD163, and I-FABP respectively.

Clinical variables including age, sex, and most recent CD4 count will be recorded. Clinical predictors of parasitic infection (eg CD4%) will be determined using multivariable logistical regression. Univariable linear regression will be used to determine associations between markers of immune activation (continuous outcome variable) and predictors including the clinical variables above as well as presence of multiple parasitic infections.

Study Type

Interventional

Enrollment (Actual)

120

Phase

  • Not Applicable

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

  • Malawi
      • Lilongwe, Malawi
        • Lighthouse clinic

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Age ≥ 18 years
  • currently living in Malawi
  • HIV-1 infection
  • on ART ≥ 1 year with undetectable HIV RNA level at the last evaluation
  • willingness to be treated with anti-parasitic therapy if infection with intestinal parasite is identified.

Exclusion Criteria:

  • Use of antibiotics other than prophylaxis with trimethoprim-sulfamethoxazole within 60 days of screening
  • Use of antiparasitic medication (ex- albendazole, praziquantel, metronidazole) in the last year
  • Inflammatory bowel disease
  • Gastrointestinal tract malignancy
  • Major intestinal surgery during prior 2 years
  • Coinfection with Mycobacterium tuberculosis
  • Pregnancy, breastfeeding mother, or planning pregnancy.

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: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Parasite-positive arm
Participants will be evaluated for intestinal parasitic infection by stool microscopy or stool PCR. If positive by either of these, the participant will be treated for the detected parasitic infection. The biomarker levels of this parasite-positive group will be compared to the parasite-negative group. Additionally the parasite-positive pre-treatment biomarker levels will be compared to the parasite-positive post-treatment levels.
Drug: Antiparasitic medication

Participants in the "parasite-positive" group (based on positive result of either stool microscopy or stool PCR) will be administered antiparasitic treatment. Antiparasitic medication administered will be targeted to treat the parasite identified. See detailed description of protocol for medication, dose, and frequency that will be given for each parasitic infection identified.

Participants with negative stool microscopy and negative stool PCR will not be administered treatment, thus will serve as controls.

Other Names:
  • Metronidazole
  • Albendazole
  • Praziquantel
No Intervention: Parasite-negative arm
Participants will be evaluated for intestinal parasitic infection by stool microscopy or stool PCR. If negative by all of these tests on the initial sample collection, the participants will not receive treatment and will be in the "parasite-negative"/no intervention arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With and Without Intestinal Parasitic Infection
Time Frame: Baseline
The number of participants with and without parasitic infection was determined based on diagnostic tests utilized. Participants with a positive result by either stool microscopy or stool PCR were considered "parasite-positive". Participants negative by both diagnostic tests were considered "parasite-negative".
Baseline
Mean Soluble CD14 (sCD14) Levels
Time Frame: Baseline
The level of sCD14 detected in plasma will be measured in all patients at the baseline visit. The mean level of sCD14 of the parasite-positive group will be compared to the mean level of sCD14 of the parasite-negative group (µg/mL) using Student's unpaired t-test.
Baseline
Mean Soluble CD163 (sCD163) Levels
Time Frame: Baseline
The level of sCD163 detected in plasma will be measured in all patients at the baseline visit. The mean level of sCD163 of the parasite-positive group will be compared to the mean level of sCD163 of the parasite-negative group (ng/mL) using Student's unpaired t-test.
Baseline
Mean Intestinal Fatty-acid Binding Protein (I-FABP) Levels
Time Frame: Baseline
The level of I-FABP detected in plasma will be measured in all patients at the baseline visit. The mean level of I-FABP of the parasite-positive group will be compared to the mean level of I-FABP of the parasite-negative group (ng/mL) using Student's unpaired t-test.
Baseline
Percent Change of sCD14 Levels Pre- and Post-treatment
Time Frame: Baseline, 6 months after baseline visit
The level of sCD14 detected in plasma will be measured in all patients at the initial visit and the follow-up visit (µg/mL). The percent change of sCD14 from pre-treatment to post-treatment levels of the parasite-positive group will be compared to the percent change of sCD14 from pre- to post-treatment levels of the parasite-negative participants.
Baseline, 6 months after baseline visit
Percent Change of sCD163 Levels Pre- and Post-treatment
Time Frame: Baseline, 6 months after baseline visit
The level of sCD163 detected in plasma will be measured in all patients at the initial visit and the follow-up visit (ng/mL). The percent change of sCD163 from pre-treatment to post-treatment levels of the parasite-positive group will be compared to the percent change of sCD163 from pre- to post-treatment levels of the parasite-negative participants.
Baseline, 6 months after baseline visit
Percent Change of I-FABP Levels Pre- and Post-treatment
Time Frame: Baseline, 6 months after baseline visit
The level of I-FABP detected in plasma will be measured in all patients at the initial visit and the follow-up visit (ng/mL). The percent change of I-FABP levels from pre-treatment to post-treatment of the parasite-positive group will be compared to the percent change of I-FABP levels pre- and post-treatment of the parasite-negative participants.
Baseline, 6 months after baseline visit

Collaborators and Investigators

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

Sponsor

University of North Carolina, Chapel Hill

Collaborators

Fogarty International Center of the National Institute of Health

Investigators

  • Principal Investigator: Melissa Reimer-McAtee, MD, University of North Carolina

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

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)

May 2, 2022

Primary Completion (Actual)

August 4, 2023

Study Completion (Actual)

August 4, 2023

Study Registration Dates

First Submitted

April 4, 2022

First Submitted That Met QC Criteria

April 4, 2022

First Posted (Actual)

April 12, 2022

Study Record Updates

Last Update Posted (Actual)

July 16, 2025

Last Update Submitted That Met QC Criteria

June 27, 2025

Last Verified

April 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 21-2553
  • D43TW009340 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.

IPD Sharing Time Frame

beginning 9 and continuing 36 months following publication

IPD Sharing Access Criteria

Investigator has approved IRB, IEC, or REB and an executed data use/sharing agreement with UNC.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • 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

product manufactured in and exported from the U.S.

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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