HIV InfectionsPhase 2NCT00000891
Immunologic and Virologic Consequences of Long-Term Highly Active Antiretroviral Therapy (HAART) in Subjects With Moderately Advanced HIV-1 Disease: A Follow-Up Study to ACTG 315
A Phase 2 study testing Ritonavir, Saquinavir and Delavirdine mesylate in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 3 sites in United States.
Trial summary
To evaluate the relationship between viral suppression and changes in immune function, as measured by the restoration of delayed-type hypersensitivity (DTH) and lymphoproliferative (LP) responses, observed after 48 weeks of treatment with highly active antiretroviral therapy (HAART) in ACTG 315. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- HIV Infections
- What is being tested?
- Ritonavir, Saquinavir and Delavirdine mesylate
- How many people
- 34 participants
- Where
- 3 sitesUnited States
- Study dates
- Start not givento May 2004
- Phase
- Phase 2
- 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 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Concurrent Medication:
- Allowed:
- Protocol Chair-approved antiretroviral medications or research study treatment for an HIV complication.
- Treatment, maintenance, or chemoprophylaxis with approved medications for opportunistic infections.
- Antibiotics.
- Recombinant erythropoietin (rEPO) and granulocyte colony-stimulating factor (G-CSF, filgrastim).
Show all 12Show fewer
- Regularly prescribed medications, such as antipyretics, analgesics, allergy medications, antidepressants, sleep medications, oral contraceptives (not as a sole form of birth control), megestrol acetate, testosterone, or any other medication not explicitly excluded.
- Alternative therapies such as vitamins, acupuncture, and visualization techniques.
- Patients must have:
- HIV-positive status.
- Completion of 48 weeks of study treatment in ACTG 315 and maintenance in this regimen (on-study) until enrollment in this study.
- Signed, informed consent from parent or legal guardian for patients less than 18 years of age.
Who cannot join
- Co-existing Condition:
- Patients with the following conditions and symptoms are excluded:
- Documented or suspected pancreatitis or hepatitis within 2 weeks prior to study entry.
- Concurrent Medication:
- Excluded:
- Immunomodulators that affect immunologic or virologic indices (e.g., systemic corticosteroids, thalidomide, cytokines).
Show all 26Show fewer
- Ketoconazole, rifampin, and rifabutin.
- Amiodarone, astemizole, bepridil, bupropion, cisapride, clozapine, dihydroergotamine, encainide, ergotamine, flecainide, meperidine, pimozide, piroxicam, propafenone, propoxyphene, quinidine, terfenadine, alprazolam, clorazepate, diazepam, estazolam, flurazepam, midazolam, triazolam, zolpidem, phenytoin, phenobarbital, and carbamazepine.
- [AS PER AMENDMENT 3/5/01:
- Lovastatin and simvastatin.
- Excluded for patients who are pregnant:
- ddI or d4T.]
- Avoided:
- Herbal medications.
- [2. AS PER AMENDMENT 4/10/00:
- Use of ddI is contraindicated in patients who have serum amylase or lipase values over 1.5 times the ULN (Upper Limit of Normal), fasting triglycerides of 100 mg/dl or more, or a history of pancreatitis. Use ddI with extreme caution and only if clinically indicated in patients with known risk factors. Refer to package insert for more information.]
- Concurrent Treatment:
- Excluded:
- Systemic cytotoxic chemotherapy.
- Prior Medication:
- Excluded:
- Any antiretroviral medications other than the zidovudine, lamivudine, and ritonavir supplied in ACTG 315 or alternative antiretrovirals not approved by protocol chairs, 48 weeks prior to study entry.
- Immunomodulatory therapies within 30 days prior to study entry.
- Required:
- Zidovudine (200 mg tid or 300 mg bid) plus lamivudine (150 mg bid) plus ritonavir (500 or 600 mg bid, or 300 mg tid) for 48 weeks in ACTG 315.
- Active substance or alcohol abuse or dependence that would interfere with adherence to study requirements.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Rush Presbyterian - Saint Luke's Med Ctr
Chicago, Illinois, 60612
Case Western Reserve Univ
Cleveland, Ohio, 44106
Univ of Colorado Health Sciences Ctr
Denver, Colorado, 80262
About this study
To evaluate the relationship between viral suppression and changes in immune function, as measured by the restoration of delayed-type hypersensitivity (DTH) and lymphoproliferative (LP) responses, observed after 48 weeks of treatment with highly active antiretroviral therapy (HAART) in ACTG 315. To evaluate the durability of the antiviral and immunologic effects of long-term treatment with HAART.
Given the extensive immunologic and virologic data available from ACTG 315, follow-up studies of this advanced-disease population are indicated to primarily ascertain the impact of long-term suppression of viral replication on immunologic reconstitution or re-education and the durability of the antiviral effects of HAART.
Read the detailed description
Given the extensive immunologic and virologic data available from ACTG 315, follow-up studies of this advanced-disease population are indicated to primarily ascertain the impact of long-term suppression of viral replication on immunologic reconstitution or re-education and the durability of the antiviral effects of HAART.
Patients continue their current ACTG 315 regimen of zidovudine plus lamivudine plus ritonavir in an open-label fashion while undergoing 6 weeks of extensive evaluations. Treatment decisions are based on baseline viral load (mean of 2 viral load measurements taken during 6-week evaluations). Patients with HIV-1 RNA less than 100 copies/ml continue the ACTG 315 regimen. Patients with HIV-1 RNA 100-3000 copies/ml may continue the ACTG 315 regimen or initiate a new HAART regimen selected by the local investigator or primary care physician. Patients with HIV-1 RNA greater than 3000 copies/ml initiate a new HAART regimen selected by the local investigator or primary care physician. [AS PER AMENDMENT 4/10/00: Changes to regimens must be done in consultation with the study team. The team acknowledges that a viable regimen may not be available for a given patient when the plasma HIV RNA level is above 3,000 copies/ml. In this case, patients may remain on their failing regimen with evaluation every 8 weeks until a viable regimen becomes available to them.] All patients are required to maintain a HAART regimen that contains at least 3 drugs, 1 of which is a protease inhibitor. [AS PER AMENDMENT 3/5/01: All patients are required to maintain a HAART regimen that is approved by the protocol chairs.] Zidovudine (ZDV), lamivudine (3TC), stavudine (d4T), didanosine (ddI), delavirdine (DLV), ritonavir (RTV), and saquinavir soft gel capsules (SQV sgc) are provided on-study. [AS PER AMENDMENT 9/19/00: ZDV, 3TC, 3TC/ZDV combination tablet, d4T, ddI, DLV, RTV, and SQV sgc will be supplied by the protocol for 182 weeks.] [AS PER AMENDMENT 3/5/01: The following antiretroviral medications will be supplied by the protocol for Steps 1 and 2: ZDV, 3TC, 3TC/ZDV combination tablet, d4T, ddI, DLV, RTV, and SQV sgc.] Therapy is continued for 54 weeks. [AS PER AMENDMENT 10/6/98: The initial 54-week trial is followed by an additional 2 years of long-term evaluation. Also per this amendment, protocol therapy is initiated at Week 6.] [AS PER AMENDMENT 9/19/00: The initial 54-week trial is followed by an additional 2.5 years of long-term evaluation.] [AS PER AMENDMENT 3/5/01: Step 1 has an initial 54 weeks of treatment followed by 140 weeks of long-term follow-up. Step 2 has an additional 36 weeks of long-term follow-up. Patients who complete the final visit on Step 2 (Week 230) should return to the clinic 4 weeks after receiving the last dose of study-provided medication to complete the final evaluations.] [AS PER AMENDMENT 10/6/98: Patients may co-enroll in an immunology substudy.] [AS PER AMENDMENT 6/11/99: The immunology substudy is being piloted in 3 to 4 volunteers and may not proceed until the feasibility of the pilot project is reviewed.]
- Conditions
- HIV Infections
- Being tested
- Ritonavir, Saquinavir, Delavirdine mesylate, Lamivudine, Stavudine
- Keywords
- Drug Therapy, Combination, Hypersensitivity, Delayed, Follow-Up Studies, Anti-HIV Agents, Viral Load
- Medical subject headings
- HIV Infections, Hypersensitivity, Delayed
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RitonavirDrug
SaquinavirDrug
Delavirdine mesylateDrug
LamivudineDrug
StavudineDrug
ZidovudineDrug
DidanosineDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2001 (estimated)
- Study completionMay 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies 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 2
- Primary purpose
- Treatment
- Masking
- None (open label)
- Enrolment
- 34 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Hernan Valdez, Study chairKimberly Smith, Study chairMichael Lederman, Study chairHarold Kessler, Study chair
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00000891
- Sponsor's protocol ID
- ACTG 375
- Other IDs
- Substudy ACTG A5002s, 11336
- Status last verified
- Oct 2021
- First submitted
- 2 Nov 1999
- Last updated
- 4 Nov 2021
- Results posted
- No
Publications
Smith KY, Valdez H, Landay A, Spritzler J, Kessler HA, Connick E, Kuritzkes D, Gross B, Francis I, McCune JM, Lederman MM. Thymic size and lymphocyte restoration in patients with human immunodeficiency virus infection after 48 weeks of zidovudine, lamivudine, and ritonavir therapy. J Infect Dis. 2000 Jan;181(1):141-7. doi: 10.1086/315169.
PubMed 10608760Valdez H, Connick E, Lederman M, Smith K, Fox L, St. T-lymphocyte changes after 3 years of controlled viral replication. Clair M, Bosch R, Kim R, Blanchard M, Landay A. 8th Conf Retro and Opportun Infect 2001 Feb 4-8 (abstract no 372)
Valdez H, Smith KY, Landay A, Connick E, Kuritzkes DR, Kessler H, Fox L, Spritzler J, Roe J, Lederman MB, Lederman HM, Evans TG, Heath-Chiozzi M, Lederman MM. Response to immunization with recall and neoantigens after prolonged administration of an HIV-1 protease inhibitor-containing regimen. ACTG 375 team. AIDS Clinical Trials Group. AIDS. 2000 Jan 7;14(1):11-21. doi: 10.1097/00002030-200001070-00002.
PubMed 10714563Valdez H, Smith K, Lederman M, Landay A, Kessler H, Connick E, Kuritzkes D, Spritzler J, Fox L, Roe J, Lederman H, Lederman MB, Evans T. Response to immunization with recall and neoantigens after 48 weeks of HAART. Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4;6th:130 (abstract no 329)
Smith KY, Valdez H, Landay A, Connick E, Gross B, Wade M, Lederman M. Correlations between immunologic indices and thymic mass in HIV infected patients following 48 weeks of therapy with zidovudine, lamivudine and ritonavir (ZLR). Int Conf AIDS. 1998;12:264 (abstract no 21129)
Wu H, Connick E, Kuritzkes DR, Landay A, Spritzler J, Zhang B, Spear GT, Kessler H, Lederman MM; ACTG 315 Team. Multiple CD4+ cell kinetic patterns and their relationships with baseline factors and virological responses in HIV type 1 patients receiving highly active antiretroviral therapy. AIDS Res Hum Retroviruses. 2001 Sep 1;17(13):1231-40. doi: 10.1089/088922201750461285.
PubMed 11559422
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immunologic and Virologic Consequences of Long-Term Highly Active Antiretroviral Therapy (HAART) in Subjects With Moderately Advanced HIV-1 Disease: A Follow-Up Study to ACTG 315
- ClinicalTrials.gov ID
- NCT00000891
- Acronym / sponsor ID
- ACTG 375
- Conditions
- HIV Infections
- Keywords
- Drug Therapy, Combination, Hypersensitivity, Delayed, Follow-Up Studies, Anti-HIV Agents, Viral Load
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study completion
- May 2004 (actual)
- First posted
- 31 Aug 2001 (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.
To evaluate the relationship between viral suppression and changes in immune function, as measured by the restoration of delayed-type hypersensitivity (DTH) and lymphoproliferative (LP) responses, observed after 48 weeks of treatment with highly active antiretroviral therapy (HAART) in ACTG 315. To evaluate the durability of the antiviral and immunologic effects of long-term treatment with HAART.
Given the extensive immunologic and virologic data available from ACTG 315, follow-up studies of this advanced-disease population are indicated to primarily ascertain the impact of long-term suppression of viral replication on immunologic reconstitution or re-education and the durability of the antiviral effects of HAART.
Detailed description
Given the extensive immunologic and virologic data available from ACTG 315, follow-up studies of this advanced-disease population are indicated to primarily ascertain the impact of long-term suppression of viral replication on immunologic reconstitution or re-education and the durability of the antiviral effects of HAART.
Patients continue their current ACTG 315 regimen of zidovudine plus lamivudine plus ritonavir in an open-label fashion while undergoing 6 weeks of extensive evaluations. Treatment decisions are based on baseline viral load (mean of 2 viral load measurements taken during 6-week evaluations). Patients with HIV-1 RNA less than 100 copies/ml continue the ACTG 315 regimen. Patients with HIV-1 RNA 100-3000 copies/ml may continue the ACTG 315 regimen or initiate a new HAART regimen selected by the local investigator or primary care physician. Patients with HIV-1 RNA greater than 3000 copies/ml initiate a new HAART regimen selected by the local investigator or primary care physician. [AS PER AMENDMENT 4/10/00: Changes to regimens must be done in consultation with the study team. The team acknowledges that a viable regimen may not be available for a given patient when the plasma HIV RNA level is above 3,000 copies/ml. In this case, patients may remain on their failing regimen with evaluation every 8 weeks until a viable regimen becomes available to them.] All patients are required to maintain a HAART regimen that contains at least 3 drugs, 1 of which is a protease inhibitor. [AS PER AMENDMENT 3/5/01: All patients are required to maintain a HAART regimen that is approved by the protocol chairs.] Zidovudine (ZDV), lamivudine (3TC), stavudine (d4T), didanosine (ddI), delavirdine (DLV), ritonavir (RTV), and saquinavir soft gel capsules (SQV sgc) are provided on-study. [AS PER AMENDMENT 9/19/00: ZDV, 3TC, 3TC/ZDV combination tablet, d4T, ddI, DLV, RTV, and SQV sgc will be supplied by the protocol for 182 weeks.] [AS PER AMENDMENT 3/5/01: The following antiretroviral medications will be supplied by the protocol for Steps 1 and 2: ZDV, 3TC, 3TC/ZDV combination tablet, d4T, ddI, DLV, RTV, and SQV sgc.] Therapy is continued for 54 weeks. [AS PER AMENDMENT 10/6/98: The initial 54-week trial is followed by an additional 2 years of long-term evaluation. Also per this amendment, protocol therapy is initiated at Week 6.] [AS PER AMENDMENT 9/19/00: The initial 54-week trial is followed by an additional 2.5 years of long-term evaluation.] [AS PER AMENDMENT 3/5/01: Step 1 has an initial 54 weeks of treatment followed by 140 weeks of long-term follow-up. Step 2 has an additional 36 weeks of long-term follow-up. Patients who complete the final visit on Step 2 (Week 230) should return to the clinic 4 weeks after receiving the last dose of study-provided medication to complete the final evaluations.] [AS PER AMENDMENT 10/6/98: Patients may co-enroll in an immunology substudy.] [AS PER AMENDMENT 6/11/99: The immunology substudy is being piloted in 3 to 4 volunteers and may not proceed until the feasibility of the pilot project is reviewed.]
Study design
- Primary purpose
- Treatment
- Masking
- None (open label)
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (12 listed)
- Protocol Chair-approved antiretroviral medications or research study treatment for an HIV complication.
- Treatment, maintenance, or chemoprophylaxis with approved medications for opportunistic infections.
- Antibiotics.
- Recombinant erythropoietin (rEPO) and granulocyte colony-stimulating factor (G-CSF, filgrastim).
- Regularly prescribed medications, such as antipyretics, analgesics, allergy medications, antidepressants, sleep medications, oral contraceptives (not as a sole form of birth control), megestrol acetate, testosterone, or any other medication not explicitly excluded.
Key exclusion criteria (26 listed)
- Documented or suspected pancreatitis or hepatitis within 2 weeks prior to study entry.
- Immunomodulators that affect immunologic or virologic indices (e.g., systemic corticosteroids, thalidomide, cytokines).
- Ketoconazole, rifampin, and rifabutin.
- Amiodarone, astemizole, bepridil, bupropion, cisapride, clozapine, dihydroergotamine, encainide, ergotamine, flecainide, meperidine, pimozide, piroxicam, propafenone, propoxyphene, quinidine, terfenadine, alprazolam, clorazepate, diazepam, estazolam, flurazepam, midazolam, triazolam, zolpidem, phenytoin, phenobarbital, and carbamazepine.
- Lovastatin and simvastatin.
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 |
|---|---|---|
| Ritonavir | Drug | – |
| Saquinavir | Drug | – |
| Delavirdine mesylate | Drug | – |
| Lamivudine | Drug | – |
| Stavudine | Drug | – |
| Zidovudine | Drug | – |
| Didanosine | Drug | – |
Primary outcome
Not reported in the source record.
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 4 Nov 2021.
- Background: PubMed 10608760Smith KY, Valdez H, Landay A, Spritzler J, Kessler HA, Connick E, Kuritzkes D, Gross B, Francis I, McCune JM, Lederman MM. Thymic size and lymphocyte restoration in patients with human immunodeficiency virus infection after 48 weeks of zidovudine, lamivudine, and ritonavir therapy. J Infect Dis. 2000 Jan;181(1):141-7. doi: 10.1086/315169.
- BackgroundValdez H, Connick E, Lederman M, Smith K, Fox L, St. T-lymphocyte changes after 3 years of controlled viral replication. Clair M, Bosch R, Kim R, Blanchard M, Landay A. 8th Conf Retro and Opportun Infect 2001 Feb 4-8 (abstract no 372)
- Background: PubMed 10714563Valdez H, Smith KY, Landay A, Connick E, Kuritzkes DR, Kessler H, Fox L, Spritzler J, Roe J, Lederman MB, Lederman HM, Evans TG, Heath-Chiozzi M, Lederman MM. Response to immunization with recall and neoantigens after prolonged administration of an HIV-1 protease inhibitor-containing regimen. ACTG 375 team. AIDS Clinical Trials Group. AIDS. 2000 Jan 7;14(1):11-21. doi: 10.1097/00002030-200001070-00002.
- BackgroundValdez H, Smith K, Lederman M, Landay A, Kessler H, Connick E, Kuritzkes D, Spritzler J, Fox L, Roe J, Lederman H, Lederman MB, Evans T. Response to immunization with recall and neoantigens after 48 weeks of HAART. Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4;6th:130 (abstract no 329)
- BackgroundSmith KY, Valdez H, Landay A, Connick E, Gross B, Wade M, Lederman M. Correlations between immunologic indices and thymic mass in HIV infected patients following 48 weeks of therapy with zidovudine, lamivudine and ritonavir (ZLR). Int Conf AIDS. 1998;12:264 (abstract no 21129)
- Background: PubMed 11559422Wu H, Connick E, Kuritzkes DR, Landay A, Spritzler J, Zhang B, Spear GT, Kessler H, Lederman MM; ACTG 315 Team. Multiple CD4+ cell kinetic patterns and their relationships with baseline factors and virological responses in HIV type 1 patients receiving highly active antiretroviral therapy. AIDS Res Hum Retroviruses. 2001 Sep 1;17(13):1231-40. doi: 10.1089/088922201750461285.
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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.
Hernan Valdez study chair
Kimberly Smith study chair
Michael Lederman study chair
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ritonavir, Saquinavir and Delavirdine mesylate in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 3 sites in United States.
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 12 inclusion and 26 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 4 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00000891, which also lists 6 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 4 Nov 2021.