HIVNCT01125228
Effectiveness of Zidovudine vs. Zidovudine Plus Alpha Interferon vs. Interferon for Treatment of HIV
An observational study of HIV, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
This study will compare the effectiveness of zidovudine (AZT) alone vs. zidovudine plus interferon (IFN) vs. interferon alone in reducing HIV viral load, lessening immune system deterioration, and increasing the time to development of the first opportunistic infection in HIV-infected patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV
- What is being tested?
- Ziodovudine and Alpha Interferon
- Type of treatment
- Pill or oral medicine
- How many people
- 180 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Oct 1988to not given
- Phase
- Observational
- 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
Study population: Individuals infected with HIV during the 1980s and living throughout the US
Who may be able to join
- Over 18 years of age.
- T4 lymphocyte count greater than or equal to 500/mm3.
- Infection with HIV as documented by positive ELISA and Western blot and positive HIV culture or positive p24 antigen or positive polymerase chain reaction.
- Absence of current opportunistic infection (defined for purposes of this study as: candidiasis, cryptosporidiosis, mycobacterial infection, persistent herpes simplex infection, isosporiasis, cytomegalovirus infection, toxoplasmosis, pneumocystosis, salmonellosis, and cryptococcosis). Routine clinical methods and observations were performed to exclude such patients.
- Afebrile (Temperature less the 38 degrees Centigrade orally) without antipyretics for at least 72 hours prior to enrollment.
- Performance status 0, 1, or 2.
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- Relatively stable clinical condition, with no deterioration of performance status in the month prior to enrollment.
- Ability to give informed consent and willing to comply with all procedures and visits scheduled.
- Suitability of I.V. access for the scheduled blood tests.
- Normal renal function as defined by BUN less than or equal to 30 and creatinine less than or equal to 1.5.
- Normal hepatic function with transaminases and alkaline phosphatase less than 5 times the upper limit of normal range.
- Hemoglobin greater than or equal to 10 gm/dl, total granulocyte count greater than or equal to 1250/mm(3), platelet count greater than or equal to 125,000/mm(3).
- No previous therapy for KS within the month prior to enrollment, and no prior exposure to investigational agents. Prior exposure to AZT did not disqualify a patient; however patients were stratified on this basis.
Who cannot join
- Patients with malignancy other than Kaposi's sarcoma were specifically excluded from this study.
- Pregnant women, nursing mothers, or women of childbearing potential who were not employing effective means of contraception or abstinence.
- Patients actively using illicit drugs.
- Patients receiving systemically and potentially myelosuppressive drugs (such as TMP/SMX, pyrimethamine-sulfa or DHPG), nephrotoxic agents (such as amphotericin B or aminoglycosides), or cytotoxic or experimental chemotherapy.
- Patients with a history of significant depressive disorder.
- Patients with a history of an AIDS-defining opportunistic infection.
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- Subsequent Exclusion Criteria (Post Enrollment)
- After enrollment, a patient was excluded from further participation in the study for any of the following reasons:
- Serious infection not cleared by antibiotic therapy. The occurrence of a life-threatening infection, whether or not considered to be opportunistic, will prompt a discontinuation of therapy during the infection and for 2 weeks following its successful resolution. Therapy was re-initiated unless (1) in the investigator's judgment re-treatment with either or both of the study medications would be contraindicated for other reasons or (2) therapy had been held for more than 6 weeks.
- Decrease in percent CD4 to less than 20 percent or in absolute CD4 count to less than 200/mm(3) on 3 consecutive blood tests.
- Systemic allergic reaction to either study medication, characterized by angioedema, bronchial constriction, or anaphylaxis.
- It was the principal investigator's judgment that the patient was too ill to continue in the trial.
- Toxicity necessitating withdrawal.
- Patient non-compliance: A patient not taking medication as directed or not keeping appointments was not allowed to continue on this study.
- Rapid or life-threatening progression of KS such that the principal investigator believed other therapies would be in the patient's best interest.
- Voluntary withdrawal: A patient could remove himself from study at any time. The patient was allowed to withdraw without prejudice.
- Termination of the study by the principal investigator, sponsor, or the FDA.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: A Phase III Study With Long-Term Follow-Up of Zidovudine Versus Zidovudine and Alpha-Interferon Versus Alpha-Interferon in Patients With Early HIV Infection
This study will compare the effectiveness of zidovudine (AZT) alone vs. zidovudine plus interferon (IFN) vs. interferon alone in reducing HIV viral load, lessening immune system deterioration, and increasing the time to development of the first opportunistic infection in HIV-infected patients.
HIV-infected persons 18 years of age and older with a T4 lymphocyte count of 500/mm3 or more and no current opportunistic infections may be eligible for this study. Candidates will be screened with a medical history, physical examination, blood tests, chest X-ray, electrocardiogram, urinalysis, and, for patients with Kaposi s sarcoma lesions, measurement, photographs, and biopsy of lesions.
Read more
Patients will be assigned to receive treatment with either zidovudine alone, zidovudine plus interferon or interferon alone. They will continue treatment until one of the following occurs:
- Unacceptable side effects, despite dose modifications
- Development of an opportunistic infection
- Decrease in CD4 count by 20 percent or to an absolute count of less than 200/mm3
- Rapid progression of Kaposi s sarcoma lesions, requiring alternative therapy
- A decision is made to terminate the study
Patients will be followed long term for viral load, immune function, development of opportunistic infections, disease progression, and survival.
Read the detailed description
Initial Study: THREE ARM (INTERVENTIONAL) STUDY
This randomized, controlled phase III protocol, initiated in 1988, was the first study to examine intervention with antiretroviral therapy and alpha interferon in patients with HIV infection. It evaluated the relative efficacy of zidovudine (AZT) vs. AZT + alpha interferon (IFN) vs. IFN in increasing time to first opportunistic infection, reducing HIV viremia, and lessening immune system deterioration in HIV-infected persons.
For the AZT alone arm, AZT dosing consisted of the standard regimen of 200 mg q4h. Persons on the AZT + IFN combination arm received AZT 100 mg q4h with IFN beginning at 1 million units qd, escalating up to 2.5 million units at 2 weeks, then in increments of 2.5 million units every 2 weeks. Patients on the IFN-alone arm began therapy at 5 million units qd and escalated in 2.5 million unit increments every 2 weeks, unless escalations were precluded by toxicity. Patients who had evidence of HIV infection and a CD4 countgreater than or equal to 500 were randomized to one of the three treatment groups. Patients were treated with their assigned medication until intolerable toxicity, opportunistic infection, or progressive Kaposi's sarcoma developed, or CD4 count declined to less than 200/mm(3).
Our statistically significant findings during this pre-HAART era study showed that interferon-alpha decreased HIV RNA viral load levels, both alone and in combination with AZT.
Long-Term Follow-up: EXTENSION PHASE (NATURAL HISTORY STUDY)
Once the intervention phase was completed, this protocol entered a long-term follow-up phase and evolved into a longitudinal natural history study. As of 2013, this work earned the distinction of following a cohort for 25 years or more. It continues to serve as an important source of data regarding the long-term outcomes of patients receiving anti-HIV treatment, and to provide information on the long-term consequences of therapy. In addition, stored blood and cells enable the study of cutting edge research questions, such as those related to immune activation, with new state-of-the-art laboratory assays.
- Conditions
- HIV
- Being tested
- Ziodovudine and Alpha Interferon
- Keywords
- HIV, Natural History
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ziodovudine and Alpha InterferonDrug
| Study group | Role | What they receive |
|---|---|---|
| AZT Alone | Zidovudine 200mg by mouth every 4hr Receives: Drug: Ziodovudine and Alpha Interferon | |
| AZT plus IFN | -Zidovudine 200mg by mouth every 4hr -Alpha Interferon 1 million units once a day, escalating Receives: Drug: Ziodovudine and Alpha Interferon | |
| IFN Alone | -Alpha Interferon 1 million units once a day, escalating |
What is being measured
The primary outcome is the main question the study is designed to answer.
Long term follow up
long-term follow-up of the medical and treatment outcomes of patients who received anti-HIV treatment and alpha-IFN in the pre-HAART era
Measured: ongoing
sample collection
Ongoing prospective research plasma and cell collection as new lab assays and study questions continue to emerge (especially regarding immune activation and the pathways that drive it).
Measured: ongoing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2010 (estimated)
- Study start19 Oct 1988
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 180 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Mary E Wright, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01125228
- Sponsor's protocol ID
- 880172
- Other IDs
- 88-I-0172
- Status last verified
- 5 Aug 2026
- First submitted
- 15 May 2010
- Last updated
- 2 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data related to the intervention phase of the study was already shared in published form in 2011: Tavel et al. https://www.liebertpub.com/doi/10.1089/jir.2009.0090 ). For the long-term observational follow-up phase of the study, individual data continues to be located in CRIMSON, CRIS, and Clinic 8 s Stored sample repository in Frederick. Participants signed consents allowing stored blood for future research for the duration of the protocol.
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Study With Long-Term Follow-Up of Zidovudine Versus Zidovudine and Alpha-Interferon Versus Alpha-Interferon in Patients With Early HIV Infection
- ClinicalTrials.gov ID
- NCT01125228
- Acronym / sponsor ID
- 880172
- Conditions
- HIV
- Keywords
- HIV, Natural History
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 180 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 19 Oct 1988 (actual)
- First posted
- 18 May 2010 (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 will compare the effectiveness of zidovudine (AZT) alone vs. zidovudine plus interferon (IFN) vs. interferon alone in reducing HIV viral load, lessening immune system deterioration, and increasing the time to development of the first opportunistic infection in HIV-infected patients.
HIV-infected persons 18 years of age and older with a T4 lymphocyte count of 500/mm3 or more and no current opportunistic infections may be eligible for this study. Candidates will be screened with a medical history, physical examination, blood tests, chest X-ray, electrocardiogram, urinalysis, and, for patients with Kaposi s sarcoma lesions, measurement, photographs, and biopsy of lesions.
Patients will be assigned to receive treatment with either zidovudine alone, zidovudine plus interferon or interferon alone. They will continue treatment until one of the following occurs:
- Unacceptable side effects, despite dose modifications
- Development of an opportunistic infection
- Decrease in CD4 count by 20 percent or to an absolute count of less than 200/mm3
- Rapid progression of Kaposi s sarcoma lesions, requiring alternative therapy
- A decision is made to terminate the study
Patients will be followed long term for viral load, immune function, development of opportunistic infections, disease progression, and survival.
Detailed description
Initial Study: THREE ARM (INTERVENTIONAL) STUDY
This randomized, controlled phase III protocol, initiated in 1988, was the first study to examine intervention with antiretroviral therapy and alpha interferon in patients with HIV infection. It evaluated the relative efficacy of zidovudine (AZT) vs. AZT + alpha interferon (IFN) vs. IFN in increasing time to first opportunistic infection, reducing HIV viremia, and lessening immune system deterioration in HIV-infected persons.
For the AZT alone arm, AZT dosing consisted of the standard regimen of 200 mg q4h. Persons on the AZT + IFN combination arm received AZT 100 mg q4h with IFN beginning at 1 million units qd, escalating up to 2.5 million units at 2 weeks, then in increments of 2.5 million units every 2 weeks. Patients on the IFN-alone arm began therapy at 5 million units qd and escalated in 2.5 million unit increments every 2 weeks, unless escalations were precluded by toxicity. Patients who had evidence of HIV infection and a CD4 countgreater than or equal to 500 were randomized to one of the three treatment groups. Patients were treated with their assigned medication until intolerable toxicity, opportunistic infection, or progressive Kaposi's sarcoma developed, or CD4 count declined to less than 200/mm(3).
Our statistically significant findings during this pre-HAART era study showed that interferon-alpha decreased HIV RNA viral load levels, both alone and in combination with AZT.
Long-Term Follow-up: EXTENSION PHASE (NATURAL HISTORY STUDY)
Once the intervention phase was completed, this protocol entered a long-term follow-up phase and evolved into a longitudinal natural history study. As of 2013, this work earned the distinction of following a cohort for 25 years or more. It continues to serve as an important source of data regarding the long-term outcomes of patients receiving anti-HIV treatment, and to provide information on the long-term consequences of therapy. In addition, stored blood and cells enable the study of cutting edge research questions, such as those related to immune activation, with new state-of-the-art laboratory assays.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| AZT Alone | – | Drug: Ziodovudine and Alpha InterferonZidovudine 200mg by mouth every 4hr |
| AZT plus IFN | – | Drug: Ziodovudine and Alpha Interferon-Zidovudine 200mg by mouth every 4hr -Alpha Interferon 1 million units once a day, escalating |
| IFN Alone | – | –-Alpha Interferon 1 million units once a day, escalating |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Individuals infected with HIV during the 1980s and living throughout the US
Key inclusion criteria (13 listed)
- Over 18 years of age.
- T4 lymphocyte count greater than or equal to 500/mm3.
- Infection with HIV as documented by positive ELISA and Western blot and positive HIV culture or positive p24 antigen or positive polymerase chain reaction.
- Absence of current opportunistic infection (defined for purposes of this study as: candidiasis, cryptosporidiosis, mycobacterial infection, persistent herpes simplex infection, isosporiasis, cytomegalovirus infection, toxoplasmosis, pneumocystosis, salmonellosis, and cryptococcosis). Routine clinical methods and observations were performed to exclude such patients.
- Afebrile (Temperature less the 38 degrees Centigrade orally) without antipyretics for at least 72 hours prior to enrollment.
Key exclusion criteria (17 listed)
- Patients with malignancy other than Kaposi's sarcoma were specifically excluded from this study.
- Pregnant women, nursing mothers, or women of childbearing potential who were not employing effective means of contraception or abstinence.
- Patients actively using illicit drugs.
- Patients receiving systemically and potentially myelosuppressive drugs (such as TMP/SMX, pyrimethamine-sulfa or DHPG), nephrotoxic agents (such as amphotericin B or aminoglycosides), or cytotoxic or experimental chemotherapy.
- Patients with a history of significant depressive disorder.
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 |
|---|---|---|
| Ziodovudine and Alpha Interferon | Drug | AZT Alone, AZT plus IFN |
Primary outcome
Long term follow up
Time frame: ongoing
long-term follow-up of the medical and treatment outcomes of patients who received anti-HIV treatment and alpha-IFN in the pre-HAART era
sample collection
Time frame: ongoing
Ongoing prospective research plasma and cell collection as new lab assays and study questions continue to emerge (especially regarding immune activation and the pathways that drive it).
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 2 Oct 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Data related to the intervention phase of the study was already shared in published form in 2011: Tavel et al. https://www.liebertpub.com/doi/10.1089/jir.2009.0090 ). For the long-term observational follow-up phase of the study, individual data continues to be located in CRIMSON, CRIS, and Clinic 8 s Stored sample repository in Frederick. Participants signed consents allowing stored blood for future research for the duration of the protocol.
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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.
Mary E Wright, 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?
An observational study of HIV, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site 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 13 inclusion and 17 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 2 Oct 2026. 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 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.
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?
Long term follow up (time frame: ongoing). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Oct 2026; AzTrials last refreshed its copy on 7 Nov 2026.