HIV And Parasitic Infection (HAPI) Study

NCT05323396 | Completed Results

• 2 other identifiers: 21-2553D43TW009340
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HIV Coinfection

Keywords

parasitic infection; chronic immune activation; HIV coinfection; Malawi; sCD14; sCD163; I-FABP; intestinal damage

Outcome Measures

Primary Outcomes (7)

• Number of Participants With and Without Intestinal Parasitic Infection

  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

  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

  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

  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

  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

  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

  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

Study Arms (2)

Parasite-positive arm

ACTIVE COMPARATOR

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

Parasite-negative arm

NO INTERVENTION

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.

Interventions

Antiparasitic medication DRUG

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.

Also known as: Albendazole, Praziquantel, Metronidazole

Parasite-positive arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• Fogarty International Center of the National Institute of Health: collaborator

Study Sites (1)

Lighthouse Clinic

Lilongwe, Malawi

Location

Related Publications (3)

• Sandler NG, Wand H, Roque A, Law M, Nason MC, Nixon DE, Pedersen C, Ruxrungtham K, Lewin SR, Emery S, Neaton JD, Brenchley JM, Deeks SG, Sereti I, Douek DC; INSIGHT SMART Study Group. Plasma levels of soluble CD14 independently predict mortality in HIV infection. J Infect Dis. 2011 Mar 15;203(6):780-90. doi: 10.1093/infdis/jiq118. Epub 2011 Jan 20.

  PMID: 21252259 BACKGROUND

• Knudsen TB, Ertner G, Petersen J, Moller HJ, Moestrup SK, Eugen-Olsen J, Kronborg G, Benfield T. Plasma Soluble CD163 Level Independently Predicts All-Cause Mortality in HIV-1-Infected Individuals. J Infect Dis. 2016 Oct 15;214(8):1198-204. doi: 10.1093/infdis/jiw263. Epub 2016 Jun 28.

  PMID: 27354366 BACKGROUND

• Cheru LT, Park EA, Saylor CF, Burdo TH, Fitch KV, Looby S, Weiner J, Robinson JA, Hubbard J, Torriani M, Lo J. I-FABP Is Higher in People With Chronic HIV Than Elite Controllers, Related to Sugar and Fatty Acid Intake and Inversely Related to Body Fat in People With HIV. Open Forum Infect Dis. 2018 Nov 5;5(11):ofy288. doi: 10.1093/ofid/ofy288. eCollection 2018 Nov.

  PMID: 30515430 BACKGROUND

MeSH Terms

Conditions

HIV Infections; Parasitic Diseases

Interventions

Albendazole; Praziquantel; Metronidazole

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Isoquinolines; Nitroimidazoles; Nitro Compounds; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Melisa Reimer-McAtee, MD
• Organization: University of North Carolina at Chapel Hill

melissa_reimer-mcatee@med.unc.edu

265 175 5056

Study Officials

• Melissa Reimer-McAtee, MD

  University of North Carolina

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: The participants and the study team will know the results of the tests, and thus will know the groups that the participants are in, since only the "parasite-positive" participants will receive treatment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This trial is closest to a parallel trial, but different from most clinical trials in that the participants will not be randomized by the study team. The two groups will be determined based on the results of the initial sample collection. Those with a result positive for intestinal parasitic infection (by either stool microscopy or stool PCR) will be in the "parasite-positive" group for the remainder of the study. Those negative for all of these will be in the "parasite-negative" group. The markers sCD14, sCD163, and I-FABP will be compared between the two groups. Additionally a comparison will be made between the pre-treatment and post-treatment levels of the "parasite-positive" participants.

Study Record Dates

• First Submitted: April 4, 2022
• First Posted: April 12, 2022
• Study Start: May 2, 2022
• Primary Completion: August 4, 2023
• Study Completion: August 4, 2023
• Last Updated: July 16, 2025
• Results First Posted: July 16, 2024

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: beginning 9 and continuing 36 months following publication
• Access Criteria: Investigator has approved IRB, IEC, or REB and an executed data use/sharing agreement with UNC.

Locations

MA (1)