HIV/AIDSPhase 3HTONCT04176172
Optimizing Tobacco Use Treatment for PLWHA
A Phase 3 study testing Varenicline, Nicotine patch and Standard treatment in people with HIV/AIDS and Nicotine Dependence, run by Abramson Cancer Center at Penn Medicine at 2 sites in United States.
Trial summary
The advent of anti-retroviral therapy (ART) for people living with HIV/AIDS (PLWHA) substantially improved life expectancy but has also led to the critical need to address modifiable risk factors associated with cancer and cardiovascular disease, such as tobacco smoking. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV/AIDS, Nicotine Dependence
- What is being tested?
- Varenicline, Nicotine patch and Standard treatment
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 340 participants
- Where
- 2 sitesUnited States
- Study dates
- 17 Feb 2020to 30 Nov 2026
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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
- >18 years, smoke daily for the past 30 days
- Confirmed HIV+ (exhibit viral load of <1000 copies/mL)
- Residing in the geographic area close to one of the sites for at least 7 months
- Able to use varenicline/TN patch safely
Who cannot join
- Current untreated and unstable diagnosis of substance abuse/dependence
- Current diagnosis of unstable and untreated major depression, psychosis or bipolar disorder
- Suicide risk as measured by the C-SSRS
- Current use or discontinuation within last 14 days of quit smoking medications
- Cancer, heart disease, stroke or MI within the past 6 months requires study physician approval
- Uncontrolled hypertension
Show all 12Show fewer
- History of epilepsy or seizure disorder requires study physician approval
- Women who are pregnant, planning a pregnancy, or lactating
- Use of e-cigarettes, chewing tobacco, snuff or snus
- Generalized eczema or psoriasis
- A reaction or sensitivity to a nicotine patch or any other transdermal medication requires study physician approval
- Currently participating in a smoking cessation program
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Northwestern University
Chicago, Illinois, 60611
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: Testing Novel Pharmacogenetic and Adherence Optimization Treatments to Improve the Effectiveness of Smoking Cessation Treatments for Smokers With HIV
The advent of anti-retroviral therapy (ART) for people living with HIV/AIDS (PLWHA) substantially improved life expectancy but has also led to the critical need to address modifiable risk factors associated with cancer and cardiovascular disease, such as tobacco smoking. HIV-infected smokers lose more life-years due to tobacco use than they do to their HIV infection.
There have been relatively few studies of tobacco use treatments for PLWHA and systematic reviews show that there are insufficient data to conclude that tobacco dependence interventions that are efficacious in the general population are efficacious for PLWHA. Further, many studies in this area have lacked randomization and a control group, infrequently used an intent-to-treat (ITT) approach and biological verification of tobacco abstinence, and lacked post-treatment follow-up.10 What investigators do know thus far is that behavioral interventions and the nicotine patch yield moderate effects on cessation; and 2 recent placebo-controlled trials - one in France and one by this lab - found that varenicline is safe and effective for treating tobacco use among PLWHA, but yield quit rates that are substantially lower than those reported in the general population. Thus, there is a critical need to rigorously test novel ways to optimize tobacco cessation treatment for smokers with HIV.
Read the detailed description
Smoking among PLWHA is a critical public health issue, with the rate of smoking 2-3 times greater than it is in the general population and the health risks of smoking outweighing those associated with the virus itself. Unfortunately, remarkably few studies have evaluated smoking cessation interventions for PLWHA and the available literature indicates that both behavioral and pharmacological smoking cessation interventions yield modest effect sizes and quit rates that are considerably lower than in the general population. A sizable literature, including studies by our research team, indicates that using the nicotine metabolite ratio (NMR) to personalize the selection of medications for tobacco use and the MAPS intervention to augment adherence to these medications can optimize treatments for tobacco use among PLWHA. The NCI recognized the potential for clinicians to use the NMR to individualize cessation treatment in order to improve effectiveness (https://www.cancer.gov/about-nci/budget/plan/public-health) and the Centers for Disease Control and Prevention (CDC) has endorsed MAPS as an evidence-based approach to increasing medication adherence among PLWHA. As such, this trial will test these intervention optimization strategies to determine if individually or together they can represent an effective approach to treating tobacco use in this under-served population of smokers. As a major advance for this area of work, the investigators will use rigorous methodology to evaluate these optimization strategies (i.e., a randomized design, biological verification, an ITT approach, and 6-month outcome assessments) and, overall, our approach is consistent with the multiphase optimization strategy (MOST) framework, which has been used to identify intervention components that maximize cessation outcomes. This trial will also assess theoretically derived and empirically based mechanisms through which these optimization strategies affect cessation and explore sub-groups who are more or less responsive to these strategies. In the end, this trial, which is consistent with the Office of AIDS Research trans-NIH Strategic Plan for HIV and HIV-Related Research (https://www.oar.nih.gov/hiv-policy-and-research/research-priorities), will determine if getting the right medication to the right person and making sure they adequately use the medication optimizes tobacco cessation treatments among PLWHA as a critical way to improve health outcomes for this population.
- Conditions
- HIV/AIDS, Nicotine Dependence
- Being tested
- Varenicline, Nicotine patch, Standard treatment, Standard treatment + Managed Problem Solving (MAPS) adherence intervention
- Keywords
- Smoking Cessation, Nicotine Dependence, HIV/AIDS, Varenicline, Nicotine Patch, Cigarette Smoking, Managed Problem Solving
- Medical subject headings
- Acquired Immunodeficiency Syndrome, Tobacco Use Disorder, Smoking Cessation, Cigarette Smoking
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VareniclineDrug
Also called Chantix or Apo-Varenicline
Participants will receive open-label varenicline for 12 weeks.
Nicotine patchDrug
Also called NicoDerm
Participants will receive open-label nicotine patch for 12 weeks. (Participants in the NMR-tailored treatment arms will receive either varenicline OR patch; they will not receive both)
Standard treatmentBehavioural
Also called Standard Therapy
Standard behavioral smoking cessation treatment is an effective treatment for nicotine dependence. Treatment focuses on self-monitoring of smoking behavior, identifying smoking triggers and alternative trigger management strategies, relaxation, social support for non-smoking, and relapse prevention. Participants will receive up to 5 therapy sessions (2 in person, 3 over the phone) over 8 weeks.
Standard treatment + Managed Problem Solving (MAPS) adherence interventionBehavioural
Also called Standard treatment + MAPS
Standard behavioral smoking cessation treatment is an effective treatment for nicotine dependence. Treatment focuses on self-monitoring of smoking behavior, identifying smoking triggers and alternative trigger management strategies, relaxation, social support for non-smoking, and relapse prevention. Managed Problem Solving (MAPS) is a therapeutic process that involves the systematic delineation of a participant's medication adherence problems and construction of a series of individualized solutions that therapists and participants explore together. Participants will receive up to 5 therapy sessions (2 in person, 3 over the phone) over 8 weeks. The first session will directly address potential medication adherence barriers, and therapist and participant will collaboratively brainstorm ways to overcome these barriers.
| Study group | Role | What they receive |
|---|---|---|
| Varenicline & Standard Cessation Counseling | Active comparator | varenicline plus standard behavioral smoking cessation treatment Receives: Drug: Varenicline; Behavioral: Standard treatment |
| NMR-Tailored Medication & Standard Cessation Counseling + MAPS | Experimental | varenicline or nicotine patch plus standard behavioral smoking cessation treatment with Managed Problem Solving adherence intervention Receives: Drug: Varenicline; Drug: Nicotine patch; Behavioral: Standard treatment + Managed Problem Solving (MAPS) adherence intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Point-prevalence abstinence
Participants will be considered abstinent if they report abstinence, not even a puff of a cigarette, for >7 days prior to week 26 (24 weeks post target quit date) and have an expired carbon monoxide reading of ≤8 parts per million at week 26.
Measured: 26 weeks (24 weeks post target quit date)
Secondary outcomes (4)
Six-month quit rate
The number of days in a six-month period of self-reported smoking
Measured: 6 months
Prolonged abstinence
<7 consecutive days of self-reported smoking after a 2-week grace period
Measured: 26 weeks (24 weeks post target quit date)
Continuous abstinence
No smoking between target quit date (week 2) and week 26
Measured: 26 weeks (24 weeks post target quit date)
Time to 7-day relapse
Time to relapse as defined by 7 or more consecutive days of self-reported smoking (no grace period)
Measured: 26 weeks (24 weeks post target quit date)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2019
- Study start17 Feb 2020
- Primary completion30 Nov 2026 (estimated)
- Study completion30 Nov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV/AIDSStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 340 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Abramson Cancer Center at Penn Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Robert Schnoll, PhD, University of Pennsylvania
- Investigators
- Robert Schnoll, PhD, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04176172
- Sponsor's protocol ID
- 834345
- Other IDs
- 1R01CA243914-01
- Acronym
- HTO
- Status last verified
- Sep 2026
- First submitted
- 21 Nov 2019
- Last updated
- 4 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Testing Novel Pharmacogenetic and Adherence Optimization Treatments to Improve the Effectiveness of Smoking Cessation Treatments for Smokers With HIV
- ClinicalTrials.gov ID
- NCT04176172
- Acronym / sponsor ID
- HTO / 834345
- Conditions
- HIV/AIDS, Nicotine Dependence
- Keywords
- Smoking Cessation, Nicotine Dependence, HIV/AIDS, Varenicline, Nicotine Patch, Cigarette Smoking, Managed Problem Solving
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 340 participants (estimated)
- Lead sponsor
- Abramson Cancer Center at Penn MedicineUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), Northwestern University, University of Pennsylvania
- Study start
- 17 Feb 2020 (actual)
- Primary completion
- 30 Nov 2026 (estimated)
- Study completion
- 30 Nov 2026 (estimated)
- First posted
- 25 Nov 2019 (actual)
- 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.
The advent of anti-retroviral therapy (ART) for people living with HIV/AIDS (PLWHA) substantially improved life expectancy but has also led to the critical need to address modifiable risk factors associated with cancer and cardiovascular disease, such as tobacco smoking. HIV-infected smokers lose more life-years due to tobacco use than they do to their HIV infection.
There have been relatively few studies of tobacco use treatments for PLWHA and systematic reviews show that there are insufficient data to conclude that tobacco dependence interventions that are efficacious in the general population are efficacious for PLWHA. Further, many studies in this area have lacked randomization and a control group, infrequently used an intent-to-treat (ITT) approach and biological verification of tobacco abstinence, and lacked post-treatment follow-up.10 What investigators do know thus far is that behavioral interventions and the nicotine patch yield moderate effects on cessation; and 2 recent placebo-controlled trials - one in France and one by this lab - found that varenicline is safe and effective for treating tobacco use among PLWHA, but yield quit rates that are substantially lower than those reported in the general population. Thus, there is a critical need to rigorously test novel ways to optimize tobacco cessation treatment for smokers with HIV.
Detailed description
Smoking among PLWHA is a critical public health issue, with the rate of smoking 2-3 times greater than it is in the general population and the health risks of smoking outweighing those associated with the virus itself. Unfortunately, remarkably few studies have evaluated smoking cessation interventions for PLWHA and the available literature indicates that both behavioral and pharmacological smoking cessation interventions yield modest effect sizes and quit rates that are considerably lower than in the general population. A sizable literature, including studies by our research team, indicates that using the nicotine metabolite ratio (NMR) to personalize the selection of medications for tobacco use and the MAPS intervention to augment adherence to these medications can optimize treatments for tobacco use among PLWHA. The NCI recognized the potential for clinicians to use the NMR to individualize cessation treatment in order to improve effectiveness (https://www.cancer.gov/about-nci/budget/plan/public-health) and the Centers for Disease Control and Prevention (CDC) has endorsed MAPS as an evidence-based approach to increasing medication adherence among PLWHA. As such, this trial will test these intervention optimization strategies to determine if individually or together they can represent an effective approach to treating tobacco use in this under-served population of smokers. As a major advance for this area of work, the investigators will use rigorous methodology to evaluate these optimization strategies (i.e., a randomized design, biological verification, an ITT approach, and 6-month outcome assessments) and, overall, our approach is consistent with the multiphase optimization strategy (MOST) framework, which has been used to identify intervention components that maximize cessation outcomes. This trial will also assess theoretically derived and empirically based mechanisms through which these optimization strategies affect cessation and explore sub-groups who are more or less responsive to these strategies. In the end, this trial, which is consistent with the Office of AIDS Research trans-NIH Strategic Plan for HIV and HIV-Related Research (https://www.oar.nih.gov/hiv-policy-and-research/research-priorities), will determine if getting the right medication to the right person and making sure they adequately use the medication optimizes tobacco cessation treatments among PLWHA as a critical way to improve health outcomes for this population.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Varenicline & Standard Cessation Counseling | Active comparator | Drug: Varenicline, Behavioral: Standard treatmentvarenicline plus standard behavioral smoking cessation treatment |
| NMR-Tailored Medication & Standard Cessation Counseling + MAPS | Experimental | Drug: Varenicline, Drug: Nicotine patch, Behavioral: Standard treatment + Managed Problem Solving (MAPS) adherence interventionvarenicline or nicotine patch plus standard behavioral smoking cessation treatment with Managed Problem Solving adherence intervention |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- >18 years, smoke daily for the past 30 days
- Confirmed HIV+ (exhibit viral load of <1000 copies/mL)
- Residing in the geographic area close to one of the sites for at least 7 months
- Able to use varenicline/TN patch safely
Key exclusion criteria (12 listed)
- Current untreated and unstable diagnosis of substance abuse/dependence
- Current diagnosis of unstable and untreated major depression, psychosis or bipolar disorder
- Suicide risk as measured by the C-SSRS
- Current use or discontinuation within last 14 days of quit smoking medications
- Cancer, heart disease, stroke or MI within the past 6 months requires study physician approval
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 |
|---|---|---|
| VareniclineAlso: Chantix or Apo-VareniclineParticipants will receive open-label varenicline for 12 weeks. | Drug | NMR-Tailored Medication & Standard Cessation Counseling + MAPS, Varenicline & Standard Cessation Counseling |
| Nicotine patchAlso: NicoDermParticipants will receive open-label nicotine patch for 12 weeks. (Participants in the NMR-tailored treatment arms will receive either varenicline OR patch; they will not receive both) | Drug | NMR-Tailored Medication & Standard Cessation Counseling + MAPS |
| Standard treatmentAlso: Standard TherapyStandard behavioral smoking cessation treatment is an effective treatment for nicotine dependence. Treatment focuses on self-monitoring of smoking behavior, identifying smoking triggers and alternative trigger management strategies, relaxation, social support for non-smoking, and relapse prevention. Participants will receive up to 5 therapy sessions (2 in person, 3 over the phone) over 8 weeks. | Behavioural | Varenicline & Standard Cessation Counseling |
| Standard treatment + Managed Problem Solving (MAPS) adherence interventionAlso: Standard treatment + MAPSStandard behavioral smoking cessation treatment is an effective treatment for nicotine dependence. Treatment focuses on self-monitoring of smoking behavior, identifying smoking triggers and alternative trigger management strategies, relaxation, social support for non-smoking, and relapse prevention. Managed Problem Solving (MAPS) is a therapeutic process that involves the systematic delineation of a participant's medication adherence problems and construction of a series of individualized solutions that therapists and participants explore together. Participants will receive up to 5 therapy sessions (2 in person, 3 over the phone) over 8 weeks. The first session will directly address potential medication adherence barriers, and therapist and participant will collaboratively brainstorm ways to overcome these barriers. | Behavioural | NMR-Tailored Medication & Standard Cessation Counseling + MAPS |
Primary outcome
Point-prevalence abstinence
Time frame: 26 weeks (24 weeks post target quit date)
Participants will be considered abstinent if they report abstinence, not even a puff of a cigarette, for >7 days prior to week 26 (24 weeks post target quit date) and have an expired carbon monoxide reading of ≤8 parts per million at week 26.
4 secondary outcomes
Six-month quit rate
Time frame: 6 months
Prolonged abstinence
Time frame: 26 weeks (24 weeks post target quit date)
Continuous abstinence
Time frame: 26 weeks (24 weeks post target quit date)
Time to 7-day relapse
Time frame: 26 weeks (24 weeks post target quit date)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2026.
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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.
Robert Schnoll, PhD principal investigator
University of Pennsylvania
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Varenicline, Nicotine patch and Standard treatment in people with HIV/AIDS and Nicotine Dependence, run by Abramson Cancer Center at Penn Medicine at 2 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 4 inclusion and 12 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: under way, not looking for participants, as of the sponsor's last update on 4 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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 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?
This study is still under way. Results are not available in the source record yet.
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?
Point-prevalence abstinence (time frame: 26 weeks (24 weeks post target quit date)). 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 4 Sep 2026.