Treatment of Helminth co-Infection: Short-Term Effects on HIV-1 Progression Markers and Immune Activation

November 13, 2007 updated by: University of Washington

Randomized, Double Blind, Placebo Controlled Trial of Albendazole in Soil-Transmitted Helminth and HIV-1 co-Infected Kenyan Individuals to Determine the Effect of Such Treatment on HIV-1 Disease Progression and Genital Shedding.

Identifying methods to slow disease progression in patients with HIV-1 infection remains a top priority in many regions of the world. In many countries, medications known to slow progression are not readily affordable or available. Many of the individuals living in these countries are also co-infected with a variety of other diseases such as tuberculosis, malaria and soil-transmitted helminths. There are data to suggest that infection with these agents may activate the immune system in HIV-1 co-infected individuals and may lead to more rapid HIV disease progression. This study will evaluate the potential impact of treating helminths in HIV-1 seropositive individuals. Markers of disease progression and immune activation will be assessed. We will also measure the amount of virus in genital secretions to determine if treatment of co-infection can reduce the infectiousness of HIV in these individuals.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Many HIV infected individuals live in crowded urban settings. These conditions are associated with repeated intestinal parasite infections (helminths), which may alter the immune system in individuals with HIV and AIDS. This alteration in the immune system may increase both the susceptibility to other infections and the severity of these infections in these individuals. Prior studies have shown that in HIV infected individuals, intestinal parasites are associated with increased levels of the HIV virus circulating in the blood. Studies have also clearly shown that in individuals with HIV, progression to AIDS can be predicted by the quantity of HIV virus detectable within the blood. It is important to determine whether treating helminth co-infection in patients with HIV will help individuals control HIV infection and slow disease progression.

The investigators propose a study to characterize the short-term effect of antihelminth therapy on HIV disease progression, markers of immune activation and levels of HIV in genital secretions. They also plan to determine the prevalence of helminth infection in individuals with HIV. This study will examine factors that might affect an individual's risk of helminth infection, such as CD4 count, viral load, age, gender and duration of time spent in an urban setting. In addition, the investigators will conduct a randomized clinical trial to determine the effect of treating helminth infection on markers of immune activation, HIV disease progression and risk of transmission as measured by HIV-1 RNA in genital secretions. The study will be conducted in a group of HIV infected individuals in and around Nairobi, Kenya who do not yet meet criteria for highly active antiretroviral therapy (HAART).

Identifying inexpensive and practical methods to delay HIV progression offers tremendous public health benefits. At the present time, highly active antiretroviral therapy is being rapidly scaled up in resource poor settings. The demand for these drugs currently far outweighs the capacity for such services to be provided in many regions. For the millions of people infected by HIV in resource poor settings, delaying immunosuppression for months to years could allow important developments in infrastructure which would permit the maximum number of individuals to benefit from highly active antiretroviral therapy.

HIV-1 infected adults will be invited to participate in the trial. Women whose pregnancy test is positive will be excluded from the study. A physical examination will be conducted on all prospective clients, and those found to have clinical pallor, or signs and symptoms of active tuberculosis, malaria or malignancy will be excluded from the study. Individuals with CD4 counts greater than 250 cells/mm3 will be enrolled in the study following written informed consent.

HIV-1 infected patients who meet inclusion and exclusion criteria will be enrolled for screening. Stool samples will be collected at enrollment and evaluated for ova and parasites. All patients who are found to have positive stool parasite examinations and who consent to participate will be enrolled in the treatment phase of the study. Those who are found to have negative stool specimens will not continue to the treatment phase. Baseline demographic and socio-economic data will be collected from these patients in order to evaluate the prevalence and correlates of helminth infection among HIV-1 infected individuals. Those who are found to be infected with helminths but who decline to participate in the treatment phase will be treated at no charge with a three day course of albendazole (400 mg/day) by the study investigators. Those patients who are enrolled in the treatment phase will have blood collected for baseline plasma HIV-1 RNA levels. Computer-generated random number allocation will be used to assign treatment group. The pharmacy at the Kenya Medical Research Institute will be responsible for the determination of randomization group and distribution of albendazole and placebo. The pharmacy will also be responsible for maintaining records regarding treatment group. Treatment will be provided in the form of a six 200 mg pills of albendazole or six placebo pills identical in appearance. Both placebo and albendazole will be provided in an identical appearing envelope. Treatment arms consist of either initial therapy with albendazole (400 mg per day for three days) or two placebo pills per day initially. All patients will be required to visit the clinic twelve weeks after enrollment. At this twelve week visit, stool samples will again be collected for evaluation of helminth infection. Plasma CD4 count and HIV-1 RNA level measurements will be repeated at this twelve week visit. All patients who received placebo initially as well as all patients with evidence of helminth infection will be treated with open-label albendazole therapy regardless of initial treatment arm. At enrollment and the twelve week visit, lymphocytes will also be isolated from serum samples for assessment of immune activation markers. Genital HIV-1 RNA levels will be compared in 100 individuals randomized to immediate versus deferred antihelminthics at baseline and at the 3-month visit (prior to receiving deferred therapy). This will provide data quantifying the potential effect of anti-helminthic treatment on genital HIV-1 RNA. Consenting adults will have genital swabs collected (semen or cervical/vaginal) and placed in freezing media prior to cryopreservation and transport to Fred Hutchinson Cancer Research Center for HIV-1 RNA assays.

Patients who do not follow-up as directed will be contacted by the administrative support team at their homes in order to determine the reason for each loss to follow up. Any adverse events during the treatment period will be reported and managed accordingly at the treatment clinic.

Study Type

Interventional

Enrollment (Actual)

234

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

  • Kenya
      • Nairobi, Kenya
        • Kenya Medical Research Institute

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

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Participants must not be or have been on highly active antiretroviral therapy.
  • Participants must have a CD4 count greater than 250 cells/mm3.
  • Participants must be at least 18 years of age.
  • Participants must be able and willing to participate and give written informed consent.
  • Participants must be able and willing to return for the scheduled follow-up visits.
  • In addition, in order to be included in the treatment phase of the study, patients must have at least one stool specimen positive for a soil transmitted helminth.

Exclusion Criteria:

  • Participants who have received treatment for helminth infection in the past 6 months (by self report or chart review).
  • Participants must not be pregnant at the time of treatment (by urine HCG testing).
  • Participants who present with other serious co-morbidities such as severe anaemia, malaria or tuberculosis.

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: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
PLACEBO_COMPARATOR: 2
Drug: Placebo
Albendazole Placebo 400mg x 3 first dose observed
EXPERIMENTAL: 1
Albendazole
Drug: Albendazole
Albendazole 400mg x 3 first dose observed
Other Names:
  • Zentel

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change in markers of HIV-1 disease progression
Time Frame: 12 weeks
12 weeks
CD4 count
Time Frame: 12 weeks
12 weeks
HIV-1 RNA level
Time Frame: 12 weeks
12 weeks
Genital HIV-1 RNA levels
Time Frame: 12 weeks
12 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Immune activation markers of global T cell activation
Time Frame: 12 weeks
12 weeks
Numbers of CD4+ and CD8+ T cells expressing Ki67
Time Frame: 12 weeks
12 weeks
Naïve and memory T cell subsets
Time Frame: 12 weeks
12 weeks
Type and number of helminth co-infections
Time Frame: 12 weeks
12 weeks

Collaborators and Investigators

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

Sponsor

University of Washington

Collaborators

University of Nairobi
Kenyatta National Hospital
Kenya Medical Research Institute

Investigators

  • Study Director: Judd L Walson, MD, MPH, University of Washington
  • Principal Investigator: Grace C. John-Stewart, MD, PhD, MPH, University of Washington

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

March 1, 2006

Study Completion (ACTUAL)

June 1, 2007

Study Registration Dates

First Submitted

August 12, 2005

First Submitted That Met QC Criteria

August 15, 2005

First Posted (ESTIMATE)

August 16, 2005

Study Record Updates

Last Update Posted (ESTIMATE)

November 15, 2007

Last Update Submitted That Met QC Criteria

November 13, 2007

Last Verified

November 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 06-1127-D03
  • NIH 5 P30 AI027757-19
  • UW Royalty Research Fund #3335

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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