Can Presumptive Anthelminthic Treatment Delay the Progression of HIV in ART-naïve Patients in Rural Africa?

Study Overview
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Brief Summary
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This study focuses on one of the major health issues of Sub-Saharan Africa: multi-parasitism and co-infections. In particular this study aims to elucidate the interaction of helminths with HIV. There is good reason to suspect a detrimental effect of helminth infection on the course of HIV infection. We hypothesize, that treatment of helminths in HIV- and helminth co-infected individuals leads to a reduction of HIV viral load. With a lower HIV RNA level one would expect a slower decline of CD4 cells and hence also a slower progression of the disease. Ideally this would lead to a prolongation of the chronic phase of HIV infection and to a delay in the time when anti-retroviral treatment needs to be started.

Detailed Description
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* Background: On the basis of immunological considerations and in vitro trials on co-infections there is strong reason to suspect a detrimental effect of helminth infection on the course of HIV. The immunological answer very efficiently evoked by helminth infection is aimed at hijacking and suppressing the immune system in order to suit the requirements of the specific helminth. This permits helminths to cause chronic infection, often persisting over years and allowing some infecting worms to grow to several centimetres of length within their host. However, this immune modulation also affects non-related antigens (for example HIV) which would actually require a different line of immunological action. Some clinical trials have been able to confirm this detrimental effect of helminths on HIV infection, while other trials failed to do so. A recent Cochrane review on clinical trials with HIV and helminth co-infection found an overall slight reduction of HIV viral load if helminth infection was treated. However there was no measurable effect on CD4 count or clinical staging of HIV. This might be explained by the fact that these trials were very heterogeneous in their set-up and were run for too short a time (max 6 months) to allow sufficient answers to these questions. According to mathematical models, even a relatively modest reduction of HIV RNA by 0.5 log could delay the need to start combined antiretroviral therapy by about 3.5 years and potentially prolong the symptom-free phase of HIV-infection by nearly 1 year. On a population scale this could lead to substantial savings with regard to drug and clinical costs and on an individual level to an invaluable gain in drug-free and ideally also symptom-free life years. Objective: To assess the impact of presumptive anthelminthic treatment on HIV progression in patients infected with HIV in a rural setting with presumed high prevalence of helminth infection. Methods: Randomised open-label trial of presumptive triple anthelminthic treatment in HIV positive patients not yet requiring anti-retroviral treatment.

Official Title
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Can Anthelminthic Treatment Delay the Progression of HIV? Randomised Open-label Trial Testing Presumptive Anthelminthic Treatment on Progression of HIV in ART-naïve HIV-positive Patients in a Rural African Setting With Presumed High Prevalence of Helminth Infections.

Conditions
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HIV Infections, Helminthiasis

Intervention / Treatment
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* Drug: Praziquantel, Ivermectin, Albendazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-positive patients most recent CD4-count > 250 c/μl (latest within the previous 7 months) anti-retroviral treatment naïve age >18 years provide written informed consent Exclusion Criteria: Pregnant and lactating women in the first week of lactation Symptoms of severe anemia (or haemoglobin <5g/dl within the precious 3 months) Symptoms of chronic diarrhea (defined as >= 3 stools per day of loose consistency for more than 2 weeks) Patients on treatment for tuberculosis WHO clinical stage 3 disease and CD4-count <350 c/μl WHO clinical stage 4 disease

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: anthelminthic treatment<br>Albendazol plus fix-dose Praziquantel plus Ivermectin | Drug: Praziquantel, Ivermectin, Albendazole<br>* Standard HIV care plus triple anthelminthic treatment Praziquantel 2400mg single dose Ivermectin 12 mg, single dose Albendazole 400mg, 2 doses in 1 day All drugs given at baseline, after 6 months and after 12 months.<br>|
| No Intervention: HIV care, no anthelminthic treatment<br>HIV care as per Tanzanian National AIDS Control Program (NACP) guidelines | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in HIV viral load between intervention and control arm |  | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in CD4 counts between intervention and control arm |  | one year | 
| Difference in time to meet criteria for the initiation of anti-retroviral treatment |  | one year | 
| occurrence of severe adverse events |  | one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Human Immunodeficiency Virus, Helminthiasis, treatment naive, co-infection, immune modulation