HIV InfectionsNCT00817713
Can Presumptive Anthelminthic Treatment Delay the Progression of HIV in ART-naïve Patients in Rural Africa?
A study testing Praziquantel, Ivermectin, Albendazole in people with HIV Infections and Helminthiasis, run by Swiss Tropical & Public Health Institute at 1 site in Tanzania.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infections, Helminthiasis
- What is being tested?
- Praziquantel, Ivermectin, Albendazole
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 295 participants
- Where
- 1 siteTanzania
- Study dates
- Jan 2009to Sep 2010
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Tanzania1 site
Chronic Disease Clinic of St. Francis Designated District Hospital
Ifakara, Kilombero, P.O. Box 53
About this study
Official title: 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.
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.
Read the detailed description
- 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.
- Conditions
- HIV Infections, Helminthiasis
- Being tested
- Praziquantel, Ivermectin, Albendazole
- Keywords
- Human Immunodeficiency Virus, Helminthiasis, treatment naive, co-infection, immune modulation
- Medical subject headings
- HIV Infections, Helminthiasis, Acquired Immunodeficiency Syndrome, Coinfection
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Praziquantel, Ivermectin, AlbendazoleDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| anthelminthic treatment | Active comparator | Albendazol plus fix-dose Praziquantel plus Ivermectin Receives: Drug: Praziquantel, Ivermectin, Albendazole |
| HIV care, no anthelminthic treatment | No intervention | HIV care as per Tanzanian National AIDS Control Program (NACP) guidelines |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in HIV viral load between intervention and control arm
Measured: one year
Secondary outcomes (3)
Difference in CD4 counts between intervention and control arm
Measured: one year
Difference in time to meet criteria for the initiation of anti-retroviral treatment
Measured: one year
occurrence of severe adverse events
Measured: one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2009 (estimated)
- Study startJan 2009
- Primary completionSep 2010
- Study completionSep 2010
Why it stopped: Terminated prematurely due to recruitment difficulties. Expansion to more study sites not planned.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 295 participants (actual)
Sponsor and investigators
- Lead sponsor
- Swiss Tropical & Public Health Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Ifakara Health Research and Development Centre, Insel Gruppe AG, University Hospital Bern, Merck KGaA, Darmstadt, Germany
- Investigators
- Cornelia J. Staehelin, MD, Principal investigator, Swiss Tropical Institute, Ifakara Health InstituteChristoph F. Hatz, MD, Prof., Study director, Swiss Tropical & Public Health InstituteHansjakob Furrer, MD, Prof., Study chair, Infectious Disease Unit, Inselspital, University Hospital Berne, 3010 Berne, SwitzerlandHonorathy Urassa, MSc, Study chair, Ifakara Health InstituteBaraka Amuri, MD, Principal investigator, Ifakara Health InstituteSalim Hamis, MD, Study chair, Ifakara Health InstituteJuerg Utzinger, Prof., Study chair, Swiss Tropical & Public Health InstituteErik Mossdorf, MD, Study chair, Swiss Tropical & Public Health Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00817713
- Sponsor's protocol ID
- 257/08
- Status last verified
- Apr 2009
- First submitted
- 5 Jan 2009
- Last updated
- 16 Feb 2011
- Results posted
- No
- Data monitoring committee
- No
Publications
Walson JL, John-Stewart G. Treatment of helminth co-infection in HIV-1 infected individuals in resource-limited settings. Cochrane Database Syst Rev. 2008 Jan 23;(1):CD006419. doi: 10.1002/14651858.CD006419.pub2.
PubMed 18254104Walson JL, Otieno PA, Mbuchi M, Richardson BA, Lohman-Payne B, Macharia SW, Overbaugh J, Berkley J, Sanders EJ, Chung MH, John-Stewart GC. Albendazole treatment of HIV-1 and helminth co-infection: a randomized, double-blind, placebo-controlled trial. AIDS. 2008 Aug 20;22(13):1601-9. doi: 10.1097/QAD.0b013e32830a502e.
PubMed 18670219Gupta SB, Jacobson LP, Margolick JB, Rinaldo CR, Phair JP, Jamieson BD, Mehrotra DV, Robertson MN, Straus WL. Estimating the benefit of an HIV-1 vaccine that reduces viral load set point. J Infect Dis. 2007 Feb 15;195(4):546-50. doi: 10.1086/510909. Epub 2007 Jan 5.
PubMed 17230414Mohammed KA, Haji HJ, Gabrielli AF, Mubila L, Biswas G, Chitsulo L, Bradley MH, Engels D, Savioli L, Molyneux DH. Triple co-administration of ivermectin, albendazole and praziquantel in zanzibar: a safety study. PLoS Negl Trop Dis. 2008 Jan 23;2(1):e171. doi: 10.1371/journal.pntd.0000171.
PubMed 18235853Brown M, Mawa PA, Kaleebu P, Elliott AM. Helminths and HIV infection: epidemiological observations on immunological hypotheses. Parasite Immunol. 2006 Nov;28(11):613-23. doi: 10.1111/j.1365-3024.2006.00904.x.
PubMed 17042933Kallestrup P, Zinyama R, Gomo E, Butterworth AE, Mudenge B, van Dam GJ, Gerstoft J, Erikstrup C, Ullum H. Schistosomiasis and HIV-1 infection in rural Zimbabwe: effect of treatment of schistosomiasis on CD4 cell count and plasma HIV-1 RNA load. J Infect Dis. 2005 Dec 1;192(11):1956-61. doi: 10.1086/497696. Epub 2005 Oct 20.
PubMed 16267767Brown M, Kizza M, Watera C, Quigley MA, Rowland S, Hughes P, Whitworth JA, Elliott AM. Helminth infection is not associated with faster progression of HIV disease in coinfected adults in Uganda. J Infect Dis. 2004 Nov 15;190(10):1869-79. doi: 10.1086/425042. Epub 2004 Oct 20.
PubMed 15499545Elliott AM, Mawa PA, Joseph S, Namujju PB, Kizza M, Nakiyingi JS, Watera C, Dunne DW, Whitworth JA. Associations between helminth infection and CD4+ T cell count, viral load and cytokine responses in HIV-1-infected Ugandan adults. Trans R Soc Trop Med Hyg. 2003 Jan-Feb;97(1):103-8. doi: 10.1016/s0035-9203(03)90040-x.
PubMed 12886815Modjarrad K, Zulu I, Redden DT, Njobvu L, Lane HC, Bentwich Z, Vermund SH. Treatment of intestinal helminths does not reduce plasma concentrations of HIV-1 RNA in coinfected Zambian adults. J Infect Dis. 2005 Oct 1;192(7):1277-83. doi: 10.1086/444543. Epub 2005 Aug 25.
PubMed 16136473Wolday D, Mayaan S, Mariam ZG, Berhe N, Seboxa T, Britton S, Galai N, Landay A, Bentwich Z. Treatment of intestinal worms is associated with decreased HIV plasma viral load. J Acquir Immune Defic Syndr. 2002 Sep 1;31(1):56-62. doi: 10.1097/00126334-200209010-00008.
PubMed 12352151
Study at a glance
From the registry record, last updated by the sponsor on 16 Feb 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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.
- ClinicalTrials.gov ID
- NCT00817713
- Acronym / sponsor ID
- 257/08
- Conditions
- HIV Infections, Helminthiasis
- Keywords
- Human Immunodeficiency Virus, Helminthiasis, treatment naive, co-infection, immune modulation
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated prematurely due to recruitment difficulties. Expansion to more study sites not planned.
- Enrolment
- 295 participants (actual)
- Lead sponsor
- Swiss Tropical & Public Health InstituteUniversity, hospital or other
- Collaborators
- Ifakara Health Research and Development Centre, Insel Gruppe AG, University Hospital Bern, Merck KGaA, Darmstadt, Germany
- Study start
- Jan 2009
- Primary completion
- Sep 2010 (actual)
- Study completion
- Sep 2010 (actual)
- First posted
- 6 Jan 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| anthelminthic treatment | Active comparator | Drug: Praziquantel, Ivermectin, AlbendazoleAlbendazol plus fix-dose Praziquantel plus Ivermectin |
| HIV care, no anthelminthic treatment | No intervention | –HIV care as per Tanzanian National AIDS Control Program (NACP) guidelines |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Praziquantel, Ivermectin, AlbendazoleStandard 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. | Drug | anthelminthic treatment |
Primary outcome
Difference in HIV viral load between intervention and control arm
Time frame: one year
3 secondary outcomes
Difference in CD4 counts between intervention and control arm
Time frame: one year
Difference in time to meet criteria for the initiation of anti-retroviral treatment
Time frame: one year
occurrence of severe adverse events
Time frame: one year
Results and safety
The study was stopped early (reason given: Terminated prematurely due to recruitment difficulties. Expansion to more study sites not planned.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Feb 2011.
- Background: PubMed 18254104Walson JL, John-Stewart G. Treatment of helminth co-infection in HIV-1 infected individuals in resource-limited settings. Cochrane Database Syst Rev. 2008 Jan 23;(1):CD006419. doi: 10.1002/14651858.CD006419.pub2.
- Background: PubMed 18670219Walson JL, Otieno PA, Mbuchi M, Richardson BA, Lohman-Payne B, Macharia SW, Overbaugh J, Berkley J, Sanders EJ, Chung MH, John-Stewart GC. Albendazole treatment of HIV-1 and helminth co-infection: a randomized, double-blind, placebo-controlled trial. AIDS. 2008 Aug 20;22(13):1601-9. doi: 10.1097/QAD.0b013e32830a502e.
- Background: PubMed 17230414Gupta SB, Jacobson LP, Margolick JB, Rinaldo CR, Phair JP, Jamieson BD, Mehrotra DV, Robertson MN, Straus WL. Estimating the benefit of an HIV-1 vaccine that reduces viral load set point. J Infect Dis. 2007 Feb 15;195(4):546-50. doi: 10.1086/510909. Epub 2007 Jan 5.
- Background: PubMed 18235853Mohammed KA, Haji HJ, Gabrielli AF, Mubila L, Biswas G, Chitsulo L, Bradley MH, Engels D, Savioli L, Molyneux DH. Triple co-administration of ivermectin, albendazole and praziquantel in zanzibar: a safety study. PLoS Negl Trop Dis. 2008 Jan 23;2(1):e171. doi: 10.1371/journal.pntd.0000171.
- Background: PubMed 17042933Brown M, Mawa PA, Kaleebu P, Elliott AM. Helminths and HIV infection: epidemiological observations on immunological hypotheses. Parasite Immunol. 2006 Nov;28(11):613-23. doi: 10.1111/j.1365-3024.2006.00904.x.
- Background: PubMed 16267767Kallestrup P, Zinyama R, Gomo E, Butterworth AE, Mudenge B, van Dam GJ, Gerstoft J, Erikstrup C, Ullum H. Schistosomiasis and HIV-1 infection in rural Zimbabwe: effect of treatment of schistosomiasis on CD4 cell count and plasma HIV-1 RNA load. J Infect Dis. 2005 Dec 1;192(11):1956-61. doi: 10.1086/497696. Epub 2005 Oct 20.
- Background: PubMed 15499545Brown M, Kizza M, Watera C, Quigley MA, Rowland S, Hughes P, Whitworth JA, Elliott AM. Helminth infection is not associated with faster progression of HIV disease in coinfected adults in Uganda. J Infect Dis. 2004 Nov 15;190(10):1869-79. doi: 10.1086/425042. Epub 2004 Oct 20.
- Background: PubMed 12886815Elliott AM, Mawa PA, Joseph S, Namujju PB, Kizza M, Nakiyingi JS, Watera C, Dunne DW, Whitworth JA. Associations between helminth infection and CD4+ T cell count, viral load and cytokine responses in HIV-1-infected Ugandan adults. Trans R Soc Trop Med Hyg. 2003 Jan-Feb;97(1):103-8. doi: 10.1016/s0035-9203(03)90040-x.
- Background: PubMed 16136473Modjarrad K, Zulu I, Redden DT, Njobvu L, Lane HC, Bentwich Z, Vermund SH. Treatment of intestinal helminths does not reduce plasma concentrations of HIV-1 RNA in coinfected Zambian adults. J Infect Dis. 2005 Oct 1;192(7):1277-83. doi: 10.1086/444543. Epub 2005 Aug 25.
- Background: PubMed 12352151Wolday D, Mayaan S, Mariam ZG, Berhe N, Seboxa T, Britton S, Galai N, Landay A, Bentwich Z. Treatment of intestinal worms is associated with decreased HIV plasma viral load. J Acquir Immune Defic Syndr. 2002 Sep 1;31(1):56-62. doi: 10.1097/00126334-200209010-00008.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Cornelia J. Staehelin, MD principal investigator
Swiss Tropical Institute, Ifakara Health Institute
Christoph F. Hatz, MD, Prof. study director
Swiss Tropical & Public Health Institute
Hansjakob Furrer, MD, Prof. study chair
Infectious Disease Unit, Inselspital, University Hospital Berne, 3010 Berne, Switzerland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Praziquantel, Ivermectin, Albendazole in people with HIV Infections and Helminthiasis, run by Swiss Tropical & Public Health Institute at 1 site in Tanzania.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 16 Feb 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Tanzania. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Terminated prematurely due to recruitment difficulties. Expansion to more study sites not planned.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in HIV viral load between intervention and control arm (time frame: one year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00817713, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Feb 2011.