HIVPhase 3NCT00339456
Intermittent Versus Continuous HAART (Highly Active Antiretroviral Therapy) for Treating Chronic HIV Infected Patients in Uganda
A Phase 3 study testing HAART in people with HIV, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in Uganda.
Trial summary
Although highly active antiretroviral therapy (HAART) has been successful in suppressing plasma HIV RNA levels and providing significant clinical benefit in infected patients, it does not eradicate HIV infection. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV
- What is being tested?
- HAART
- How many people
- 155 participants
- Where
- 1 siteUganda
- Study dates
- 21 Aug 2002to 1 Feb 2008
- Phase
- Phase 3
- 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
- Documentation of HIV-1 infection by licensed ELISA test kit and confirmed by a second method (e.g. Western Blot).
- Absolute CD4+ T-cell count of greater than or equal to 125/mm(3) within 30 days before randomization (For patients who are status post-splenectomy, also CD4+ T-cell greater than 20%).
- If the CD4+ T cell count is less than or equal to 200 cells/mm(3), the patient must be receiving PCP prophylaxis.
- Receiving at least 3-drug HAART with the most recent viral load test prior to screening less than 500 copies/ml. Patients must be receiving 3 drug HAART containing an NNRTI, abacavir or PI for at least 90 days prior to enrollment and at least 1 PI or efavirenz for 30 days prior to enrollment.
- A viral load of less than 50 copies/ml prior to enrollment.
- Age at least 18 years and above.
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- For women of childbearing potential, a negative pregnancy test (serum or urine) is required within 14 days prior to randomization.
- Laboratory values (within 30 days prior to randomization):
- AST no more than 5 X the upper limit of normal (ULN).
- Total or direct bilirubin no more than 2 X ULN unless there is a pattern consistent with Gilbert s syndrome or the patient is receiving indinavir.
- Creatinine no more than 2.0 mg/dL.
- Platelet count at least 50,000/microliters.
- Written consent to participate in the trial.
- Patient financially capable of purchasing the drugs uninterrupted for at least 72 weeks (the duration of the study).
Who cannot join
- Concurrent malignancy, or any other disease state, requiring cytotoxic chemotherapy.
- Symptomatic for significant HIV-related illnesses, such as opportunistic infections and malignancies other than mucocutaneous Kaposi s sarcoma. A history of AIDS defining opportunistic infections other than mucocutaneous Kaposi s sarcoma or candida or treated tuberculosis.
- Use of experimental antiretroviral less than or equal to 6 months prior to enrollment. An exception may be made for hydroxeurea according to the judgment of the Principal Investigator.
- Pregnancy or breastfeeding.
- Significant cardiac, pulmonary, kidney, rheumatologic, gastrointestinal, or CNS disease as detectable on routine history, physical examination, or screening laboratory studies. If an abnormality is a contraindication to a specific drug, an alternative drug within the same class may be used.
- Psychiatric illness that, in the opinion of the PI, might interfere with study compliance.
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- Active substance abuse or history of prior substance abuse that may interfere with protocol compliance or compromise patient safety.
- Refusal to practice safe sex or use precautions against pregnancy (effective birth control with barrier contraceptives or abstinence).
- Known history or laboratory evidence of chronic hepatitis B infection including surface antigen positivity.
- Receiving salvage HAART, i.e. evidence of clinical resistance to licensed anti-retrovirals as indicated by clinical progression, an elevated viral load or declining CD4+ T cell count while receiving antiretroviral therapy, or receiving sub-optimal antiretroviral therapy prior to HAART.
- Patients currently receiving nevirapine or abacavir are excluded.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Controlled Trial of Short Cycle Intermittent Versus Continuous HAART for the Treatment of Chronic HIV Infection in Uganda
Although highly active antiretroviral therapy (HAART) has been successful in suppressing plasma HIV RNA levels and providing significant clinical benefit in infected patients, it does not eradicate HIV infection. It is now clear that virus replication persists despite undetectable plasma viremia in individuals receiving HAART. In this regard, withdrawing HAART, even after prolonged periods of virus suppression, leads almost invariably to a rapid rebound of plasma viremia. It is also now clear that prolonged, continuous HAART carries a risk of significant toxicity and side effects. In addition, the monetary cost of HAART is prohibitive for many individuals and countries. In terms of cost, 95% of the HIV-infected individuals in the world are beyond the reach of therapy as a direct consequence of the cost of therapy. These observations may argue for a different approach to HAART with the goals of: 1) durable suppression of virus replication, without an attempt at eradication, 2) minimization of toxicity and side effects and improvement in patient life-style, and 3) a reduction in cost. Preliminary data from a pilot study conducted at the National Institutes of Allergy and Infectious Diseases, USA, have demonstrated that short cycle structured intermittent therapy, 7 days HAART drug followed by 7 days off HAART has maintained suppression of plasma HIV RNA while preserving CD4+ T cell counts for up to 80 weeks. In addition, there was no evidence for increased HIV in reservoir sites; nor was there evidence for the development of resistance to antiretroviral drugs. Finally, there was a decrease in parameters of toxicity. This approach may have particular applicability for the treatment of HIV in the Southern Hemisphere. Therefore, we propose to study the virologic and immunologic effects of short cycle intermittent versus continuous HAART in HIV-infected individuals from the JCRC (Kampala, Uganda) in a randomized, controlled, intent-to-treat trial. We shall evaluate both the 7 days on-HAART/7 days off-HAART as well as a 2 days off-HAART/5 days on-HAART approach. In December, 2004, the 7/7 arm was discontinued....
Read the detailed description
Although highly active antiretroviral therapy (HAART) has been successful in suppressing plasma HIV RNA levels and providing significant clinical benefit in infected patients, it does not eradicate HIV infection. It is now clear that virus replication persists despite undetectable plasma viremia in individuals receiving HAART. In this regard, withdrawing HAART, even after prolonged periods of virus suppression, leads almost invariably to a rapid rebound of plasma viremia. It is also now clear that prolonged, continuous HAART carries a risk of significant toxicity and side effects. In addition, the monetary cost of HAART is prohibitive for many individuals and countries. In terms of cost, 95 percent of the HIV-infected individuals in the world are beyond the reach of therapy as a direct consequence of the cost of therapy. These observations may argue for a different approach to HAART with the goals of: 1) durable suppression of virus replication, without an attempt at eradication, 2) minimization of toxicity and side effects and improvement in patient life-style, and 3) a reduction in cost. Preliminary data from a pilot study conducted at the National Institutes of Allergy and Infectious Diseases, USA, have demonstrated that short cycle structured intermittent therapy, 7 days HAART drug followed by 7 days off HAART has maintained suppression of plasma HIV RNA while preserving CD4+ T cell counts for up to 80 weeks. In addition, there was no evidence for increased HIV in reservoir sites; nor was there evidence for the development of resistance to antiretroviral drugs. Finally, there was a decrease in parameters of toxicity. This approach may have particular applicability for the treatment of HIV in the Southern Hemisphere. Therefore, we propose to study the virologic and immunologic effects of short cycle intermittent versus continuous HAART in HIV-infected individuals from the JCRC (Kampala, Uganda) in a randomized, controlled, intent-to-treat trial. We shall evaluate both the 7 days on-HAART/7 days off-HAART as well as a 2 days off-HAART/5 days on-HAART approach. In December, 2004, the 7/7 arm was discontinued.
- Conditions
- HIV
- Being tested
- HAART
- Keywords
- Therapy, Africa, Structured, Interruption, Antiretroviral, HIV
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HAARTDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the effects of short cycle intermittent versus continuous HAART on viral load.
Secondary outcomes (1)
To evaluate change in CD4 T-cell counts, change in virus patterns, toxicity and side effects, Quality of Life, and adherence.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2006 (estimated)
- Study start21 Aug 2002
- Primary completion1 Feb 2008
- Study completion1 Feb 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for HIVStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Enrolment
- 155 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Thomas C Quinn, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00339456
- Sponsor's protocol ID
- 999902288
- Other IDs
- 02-I-N288
- Status last verified
- 20 May 2014
- First submitted
- 19 Jun 2006
- Last updated
- 17 Dec 2019
- Results posted
- No
Publications
Natarajan V, Bosche M, Metcalf JA, Ward DJ, Lane HC, Kovacs JA. HIV-1 replication in patients with undetectable plasma virus receiving HAART. Highly active antiretroviral therapy. Lancet. 1999 Jan 9;353(9147):119-20. doi: 10.1016/s0140-6736(05)76156-0. No abstract available.
PubMed 10023903Furtado MR, Callaway DS, Phair JP, Kunstman KJ, Stanton JL, Macken CA, Perelson AS, Wolinsky SM. Persistence of HIV-1 transcription in peripheral-blood mononuclear cells in patients receiving potent antiretroviral therapy. N Engl J Med. 1999 May 27;340(21):1614-22. doi: 10.1056/NEJM199905273402102.
PubMed 10341273Zhang L, Ramratnam B, Tenner-Racz K, He Y, Vesanen M, Lewin S, Talal A, Racz P, Perelson AS, Korber BT, Markowitz M, Ho DD. Quantifying residual HIV-1 replication in patients receiving combination antiretroviral therapy. N Engl J Med. 1999 May 27;340(21):1605-13. doi: 10.1056/NEJM199905273402101.
PubMed 10341272Reynolds SJ, Kityo C, Hallahan CW, Kabuye G, Atwiine D, Mbamanya F, Ssali F, Dewar R, Daucher M, Davey RT Jr, Mugyenyi P, Fauci AS, Quinn TC, Dybul MR. A randomized, controlled, trial of short cycle intermittent compared to continuous antiretroviral therapy for the treatment of HIV infection in Uganda. PLoS One. 2010 Apr 22;5(4):e10307. doi: 10.1371/journal.pone.0010307.
PubMed 20442758
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Controlled Trial of Short Cycle Intermittent Versus Continuous HAART for the Treatment of Chronic HIV Infection in Uganda
- ClinicalTrials.gov ID
- NCT00339456
- Acronym / sponsor ID
- 999902288
- Conditions
- HIV
- Keywords
- Therapy, Africa, Structured, Interruption, Antiretroviral, HIV
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 155 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 21 Aug 2002
- Primary completion
- 1 Feb 2008 (actual)
- Study completion
- 1 Feb 2008 (actual)
- First posted
- 21 Jun 2006 (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.
Although highly active antiretroviral therapy (HAART) has been successful in suppressing plasma HIV RNA levels and providing significant clinical benefit in infected patients, it does not eradicate HIV infection. It is now clear that virus replication persists despite undetectable plasma viremia in individuals receiving HAART. In this regard, withdrawing HAART, even after prolonged periods of virus suppression, leads almost invariably to a rapid rebound of plasma viremia. It is also now clear that prolonged, continuous HAART carries a risk of significant toxicity and side effects. In addition, the monetary cost of HAART is prohibitive for many individuals and countries. In terms of cost, 95% of the HIV-infected individuals in the world are beyond the reach of therapy as a direct consequence of the cost of therapy. These observations may argue for a different approach to HAART with the goals of: 1) durable suppression of virus replication, without an attempt at eradication, 2) minimization of toxicity and side effects and improvement in patient life-style, and 3) a reduction in cost. Preliminary data from a pilot study conducted at the National Institutes of Allergy and Infectious Diseases, USA, have demonstrated that short cycle structured intermittent therapy, 7 days HAART drug followed by 7 days off HAART has maintained suppression of plasma HIV RNA while preserving CD4+ T cell counts for up to 80 weeks. In addition, there was no evidence for increased HIV in reservoir sites; nor was there evidence for the development of resistance to antiretroviral drugs. Finally, there was a decrease in parameters of toxicity. This approach may have particular applicability for the treatment of HIV in the Southern Hemisphere. Therefore, we propose to study the virologic and immunologic effects of short cycle intermittent versus continuous HAART in HIV-infected individuals from the JCRC (Kampala, Uganda) in a randomized, controlled, intent-to-treat trial. We shall evaluate both the 7 days on-HAART/7 days off-HAART as well as a 2 days off-HAART/5 days on-HAART approach. In December, 2004, the 7/7 arm was discontinued....
Detailed description
Although highly active antiretroviral therapy (HAART) has been successful in suppressing plasma HIV RNA levels and providing significant clinical benefit in infected patients, it does not eradicate HIV infection. It is now clear that virus replication persists despite undetectable plasma viremia in individuals receiving HAART. In this regard, withdrawing HAART, even after prolonged periods of virus suppression, leads almost invariably to a rapid rebound of plasma viremia. It is also now clear that prolonged, continuous HAART carries a risk of significant toxicity and side effects. In addition, the monetary cost of HAART is prohibitive for many individuals and countries. In terms of cost, 95 percent of the HIV-infected individuals in the world are beyond the reach of therapy as a direct consequence of the cost of therapy. These observations may argue for a different approach to HAART with the goals of: 1) durable suppression of virus replication, without an attempt at eradication, 2) minimization of toxicity and side effects and improvement in patient life-style, and 3) a reduction in cost. Preliminary data from a pilot study conducted at the National Institutes of Allergy and Infectious Diseases, USA, have demonstrated that short cycle structured intermittent therapy, 7 days HAART drug followed by 7 days off HAART has maintained suppression of plasma HIV RNA while preserving CD4+ T cell counts for up to 80 weeks. In addition, there was no evidence for increased HIV in reservoir sites; nor was there evidence for the development of resistance to antiretroviral drugs. Finally, there was a decrease in parameters of toxicity. This approach may have particular applicability for the treatment of HIV in the Southern Hemisphere. Therefore, we propose to study the virologic and immunologic effects of short cycle intermittent versus continuous HAART in HIV-infected individuals from the JCRC (Kampala, Uganda) in a randomized, controlled, intent-to-treat trial. We shall evaluate both the 7 days on-HAART/7 days off-HAART as well as a 2 days off-HAART/5 days on-HAART approach. In December, 2004, the 7/7 arm was discontinued.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Documentation of HIV-1 infection by licensed ELISA test kit and confirmed by a second method (e.g. Western Blot).
- Absolute CD4+ T-cell count of greater than or equal to 125/mm(3) within 30 days before randomization (For patients who are status post-splenectomy, also CD4+ T-cell greater than 20%).
- If the CD4+ T cell count is less than or equal to 200 cells/mm(3), the patient must be receiving PCP prophylaxis.
- Receiving at least 3-drug HAART with the most recent viral load test prior to screening less than 500 copies/ml. Patients must be receiving 3 drug HAART containing an NNRTI, abacavir or PI for at least 90 days prior to enrollment and at least 1 PI or efavirenz for 30 days prior to enrollment.
- A viral load of less than 50 copies/ml prior to enrollment.
Key exclusion criteria (11 listed)
- Concurrent malignancy, or any other disease state, requiring cytotoxic chemotherapy.
- Symptomatic for significant HIV-related illnesses, such as opportunistic infections and malignancies other than mucocutaneous Kaposi s sarcoma. A history of AIDS defining opportunistic infections other than mucocutaneous Kaposi s sarcoma or candida or treated tuberculosis.
- Use of experimental antiretroviral less than or equal to 6 months prior to enrollment. An exception may be made for hydroxeurea according to the judgment of the Principal Investigator.
- Pregnancy or breastfeeding.
- Significant cardiac, pulmonary, kidney, rheumatologic, gastrointestinal, or CNS disease as detectable on routine history, physical examination, or screening laboratory studies. If an abnormality is a contraindication to a specific drug, an alternative drug within the same class may be used.
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 |
|---|---|---|
| HAART | Drug | – |
Primary outcome
To evaluate the effects of short cycle intermittent versus continuous HAART on viral load.
1 secondary outcome
To evaluate change in CD4 T-cell counts, change in virus patterns, toxicity and side effects, Quality of Life, and adherence.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2019.
- Background: PubMed 10023903Natarajan V, Bosche M, Metcalf JA, Ward DJ, Lane HC, Kovacs JA. HIV-1 replication in patients with undetectable plasma virus receiving HAART. Highly active antiretroviral therapy. Lancet. 1999 Jan 9;353(9147):119-20. doi: 10.1016/s0140-6736(05)76156-0. No abstract available.
- Background: PubMed 10341273Furtado MR, Callaway DS, Phair JP, Kunstman KJ, Stanton JL, Macken CA, Perelson AS, Wolinsky SM. Persistence of HIV-1 transcription in peripheral-blood mononuclear cells in patients receiving potent antiretroviral therapy. N Engl J Med. 1999 May 27;340(21):1614-22. doi: 10.1056/NEJM199905273402102.
- Background: PubMed 10341272Zhang L, Ramratnam B, Tenner-Racz K, He Y, Vesanen M, Lewin S, Talal A, Racz P, Perelson AS, Korber BT, Markowitz M, Ho DD. Quantifying residual HIV-1 replication in patients receiving combination antiretroviral therapy. N Engl J Med. 1999 May 27;340(21):1605-13. doi: 10.1056/NEJM199905273402101.
- Derived from this study: PubMed 20442758Reynolds SJ, Kityo C, Hallahan CW, Kabuye G, Atwiine D, Mbamanya F, Ssali F, Dewar R, Daucher M, Davey RT Jr, Mugyenyi P, Fauci AS, Quinn TC, Dybul MR. A randomized, controlled, trial of short cycle intermittent compared to continuous antiretroviral therapy for the treatment of HIV infection in Uganda. PLoS One. 2010 Apr 22;5(4):e10307. doi: 10.1371/journal.pone.0010307.
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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.
Thomas C Quinn, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing HAART in people with HIV, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in Uganda.
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 14 inclusion and 11 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: finished, as of the sponsor's last update on 17 Dec 2019. 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 Uganda. 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To evaluate the effects of short cycle intermittent versus continuous HAART on viral load.. 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 NCT00339456, which also lists 4 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 17 Dec 2019.