HIV And Parasitic Infection (HAPI) Study

NCT ID: NCT05323396

Last Updated: 2025-07-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-02
• Study Completion Date: 2023-08-04

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.

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.

Conditions

HIV Coinfection

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Antiparasitic medication

Intervention Type: 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.

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Albendazole; Praziquantel; Metronidazole

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Fogarty International Center of the National Institute of Health

NIH

Sponsor Role: collaborator

University of North Carolina, Chapel Hill

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Melissa Reimer-McAtee, MD

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina

Locations

Lighthouse Clinic

Lilongwe, , Malawi

Countries

Malawi

References

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.

Reference Type: BACKGROUND

PMID: 21252259 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 27354366 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 30515430 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

D43TW009340

Identifier Type: NIH

Identifier Source: secondary_id

View Link

21-2553

Identifier Type: -

Identifier Source: org_study_id