Harm Reduction for Smoking in People With HIV

Recruiting at 1 trial location

Overseen By Jonathan Shuter, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Montefiore Medical Center

Must be taking: Varenicline

Must not be taking: Other cessation treatments

Disqualifiers: Pregnancy, Lack of insurance, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

400 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to help people with HIV who smoke by exploring a harm reduction approach instead of the traditional "quit or nothing" strategy. Researchers seek to determine if reducing smoking, screening for lung cancer, and managing blood pressure and cholesterol can improve health outcomes. Participants will be divided into groups testing different treatments, including a standard care option and a new experimental approach (EX+). Individuals who currently smoke, have HIV, and are interested in web-based tobacco treatment may be a good fit for this trial.

As an unphased trial, this study provides a unique opportunity to explore innovative strategies for improving health outcomes.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, you cannot be receiving other smoking cessation treatments while participating in this study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that varenicline, one of the treatments in this trial, has undergone thorough study. Previous studies found it to be as safe for people with HIV as for those without. However, some participants experienced side effects that sometimes led them to stop using the medication. These side effects included serious mental health issues, which are noted in safety warnings. Despite these concerns, varenicline has significantly improved the chances of quitting smoking compared to a placebo.

For the harm reduction approach, which includes strategies like cutting down on smoking and managing health factors, less direct safety data exists. This approach focuses more on reducing risks rather than quitting smoking entirely. Since this trial is labeled "Not Applicable" for phases, it likely emphasizes strategies rather than testing new drugs, suggesting a different safety profile than drug trials. Always consult a healthcare provider about any concerns before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the harm reduction strategies being explored for smoking cessation in people with HIV because they focus on innovative approaches rather than traditional methods. Unlike standard treatments like nicotine replacement therapy or counseling, the EX+/HR approach combines exercise with harm reduction techniques, which aim to reduce smoking-related harm without requiring immediate cessation. This method acknowledges the challenges specific to people with HIV, offering a more personalized and potentially more effective pathway to reducing smoking's health impacts. By integrating exercise, this treatment not only targets smoking habits but also promotes overall wellness, making it a promising alternative to conventional smoking cessation methods.

What evidence suggests that this trial's treatments could be effective for smoking reduction in people with HIV?

Research has shown that combining behavioral support and medication can help people with HIV reduce smoking. In this trial, participants in the EX+/HR arm will receive a harm reduction approach, which may include varenicline. One study found that 42% of HIV-positive smokers who used varenicline quit smoking. Another study revealed that after 12 weeks, 34.3% of people using varenicline stopped smoking, compared to only 12.6% who took a placebo. These results suggest that varenicline, along with other methods, could help people with HIV smoke less. Reducing the number of cigarettes smoked and managing health risks may also be beneficial. ^{6 7 8 9 10}

Who Is on the Research Team?

Jonathan Shuter, MD

Principal Investigator

Montefiore Medical Center

Are You a Good Fit for This Trial?

This trial is for people aged 40-79 with lab-confirmed HIV who smoke cigarettes and are interested in a web-based tobacco treatment. Participants must have smoked over 100 cigarettes in their lifetime, currently smoke, have internet access, and can read at a 7th-grade level or higher.

Inclusion Criteria

Lab-confirmed HIV

I am between 40 and 79 years old.

Current cigarette smoking with exhaled carbon monoxide (ECO) level ≥6ppm

Exclusion Criteria

Pregnancy

I have had a low-dose CT scan or been evaluated in a CM Clinic before.

Spouses, partners, or roommates of participants

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Enrollment and Initial Treatment

Participants are enrolled and offered intensive cessation treatment including the BecomeAnEX+ program and a 12-week supply of varenicline

12 weeks

1 visit (in-person) for enrollment, ongoing virtual support

Randomization and Harm Reduction Strategy

Participants are randomized to either the harm reduction (EX+/HR) or treatment as usual (EX+/TAU) arm. EX+/HR participants receive harm reduction counseling and support for lung cancer screening and cardiometabolic health

9 months

Regular virtual check-ins, in-person visits as needed for screenings

Follow-up

Participants are monitored for changes in smoking behavior, lung cancer screening, blood pressure, cholesterol, and cardiovascular risk

9 months

Follow-up assessments at 3, 6, and 9 months

What Are the Treatments Tested in This Trial?

Interventions

• EX+
• HR
• TAU
• Varenicline

Trial Overview The study tests a harm reduction strategy for smokers with HIV. It includes cutting down on smoking, lung cancer screening, blood pressure and cholesterol control (HR), usual care (TAU), an online cessation program (EX+), plus the offer of Varenicline—a medication to help quit smoking.

How Is the Trial Designed?

Group I: EX+/HR Experimental Treatment 3 Interventions

The harm reduction arm (described in detail elsewhere)

Group II: EX+/TAU Active Control 3 Interventions

The treatment as usual arm

EX+ is already approved in United States, European Union for the following indications:

Approved in United States as Chantix for:

• Smoking cessation

Approved in European Union as Champix for:

• Smoking cessation

Who Is Running the Clinical Trial?

Montefiore Medical Center

Lead Sponsor

Trials

468

Recruited

599,000+

Westat

Collaborator

Trials

49

Recruited

39,700+

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+

Truth Initiative

Collaborator

Trials

20

Recruited

32,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Antiretroviral therapy is effective in suppressing HIV replication, but the complex pharmacokinetics of these drugs can lead to significant drug-drug interactions, especially when combined with common medications like opioids and hormonal contraceptives.

The review summarizes thirteen FDA-approved antiretroviral drugs and their interactions with drug metabolism enzymes and transporters, aiming to enhance the safe clinical use of these medications in HIV treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic Drug-Drug Interactions Involving Antiretroviral Agents: An Update. Yu, X., Zhao, L., Yuan, Z., et al.[2023]

In a study of 179 people living with HIV/AIDS, quitting smoking did not negatively impact adherence to anti-retroviral therapy (ART), which remained above 98% for all participants.

Participants who successfully quit smoking reported significant reductions in depression and anxiety symptoms, along with increased life satisfaction, suggesting that smoking cessation can have positive psychological effects for individuals with HIV/AIDS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved clinical outcomes among persons with HIV who quit smoking. Lubitz, SF., Flitter, A., Ashare, RL., et al.[2021]

In a study involving 7 opioid-dependent volunteers, the nonnucleoside reverse transcriptase inhibitor nevirapine was found to significantly reduce the overall exposure to buprenorphine and its metabolites, suggesting a drug interaction.

Despite this interaction, no clinically significant effects were observed, indicating that dose adjustments for buprenorphine or nevirapine are not necessary when these medications are used together.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lack of clinically significant drug interactions between nevirapine and buprenorphine. McCance-Katz, EF., Moody, DE., Morse, GD., et al.[2022]

In a pilot study involving 36 HIV-infected smokers, varenicline was found to be safe and effective for smoking cessation, with a 42% rate of verified continuous abstinence over 4 weeks.

The treatment did not adversely affect HIV viral load, and CD4 counts increased significantly, indicating that varenicline can be a viable option for smoking cessation in this population, despite common side effects like nausea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of varenicline tartrate (Champix(®)/Chantix(®)) for smoking cessation in HIV-infected subjects: a pilot open-label study. Cui, Q., Robinson, L., Elston, D., et al.[2021]

In a study involving 18 HIV-negative volunteers, coadministering etravirine with fluconazole or voriconazole increased etravirine levels in the body, but these interactions are not clinically significant, meaning no dose adjustments are needed.

The combination treatments were well tolerated, with only mild adverse effects reported, such as headaches and blurred vision, indicating a good safety profile for etravirine when used with these antifungal medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and short-term safety of etravirine in combination with fluconazole or voriconazole in HIV-negative volunteers. Kakuda, TN., Van Solingen-Ristea, R., Aharchi, F., et al.[2020]

Rilpivirine, a next-generation NNRTI, shows high antiviral activity against HIV-1, including strains resistant to other NNRTIs, and has similar rates of virological suppression compared to efavirenz after 96 weeks in therapy-naive individuals.

Rilpivirine is generally well tolerated with fewer CNS side effects than efavirenz, but caution is needed due to potential interactions with acid suppressant medications, which could affect its effectiveness in clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rilpivirine: a novel non-nucleoside reverse transcriptase inhibitor. Garvey, L., Winston, A.[2016]

In a study involving 248 people living with HIV, varenicline combined with counseling significantly increased the rate of smoking cessation compared to placebo, with 15% of participants in the varenicline group achieving continuous abstinence from weeks 9 to 48.

The safety profile of varenicline was favorable, showing a lower incidence of depression in the varenicline group (2%) compared to the placebo group (10%), indicating that varenicline is a safe and effective option for smoking cessation in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of varenicline for smoking cessation in people living with HIV in France (ANRS 144 Inter-ACTIV): a randomised controlled phase 3 clinical trial. Mercié, P., Arsandaux, J., Katlama, C., et al.[2018]

Varenicline, when used for smoking cessation in HIV-infected individuals, has a safety profile similar to that observed in non-HIV smokers, with common side effects including nausea and sleep problems, but no significant cardiovascular issues reported.

Preliminary results indicate that varenicline is more effective than nicotine replacement therapy (NRT) for promoting smoking abstinence, with a confirmed abstinence rate of 25.6% in the varenicline group compared to 11.8% in the NRT group, suggesting that varenicline could be a preferred treatment option for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of varenicline among smokers enrolled in the lung HIV study. Ferketich, AK., Diaz, P., Browning, KK., et al.[2021]

In a clinical trial involving 179 people living with HIV/AIDS, varenicline significantly increased smoking cessation rates at Week 12 compared to placebo, with 28.1% of participants quitting versus 12.1%.

Varenicline was found to be safe, with no significant differences in treatment-related side effects or adverse events compared to placebo, making it a viable option for short-term smoking cessation in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo-controlled randomized clinical trial testing the efficacy and safety of varenicline for smokers with HIV. Ashare, RL., Thompson, M., Serrano, K., et al.[2023]

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) like delavirdine, efavirenz, and nevirapine effectively inhibit HIV Type 1 reverse transcriptase, but they differ in their structural and pharmacokinetic properties.

NNRTIs are metabolized by the cytochrome P450 enzyme system, leading to significant drug interactions with other medications, which is crucial to consider when creating combination treatment regimens for HIV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic drug interactions with non-nucleoside reverse transcriptase inhibitors. Ma, Q., Okusanya, OO., Smith, PF., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8607828/

Effectiveness of a Smoking Cessation Algorithm Integrated ... A smoking cessation pharmacotherapy recommendation algorithm integrated into HIV primary care may increase treatment utilization and smoking abstinence.

2. withpower.com withpower.com/trial/phase-hiv-3-2023-f5871

Harm Reduction for Smoking in People With HIV In a pilot study involving 36 HIV-infected smokers, varenicline was found to be safe and effective for smoking cessation, with a 42% rate of verified continuous ...

3. aidsmap.com aidsmap.com/news/mar-2015/varenicline-helps-people-hiv-stop-smoking-success-rate-remains-low

Varenicline helps people with HIV stop smoking, but ... By the end of treatment at 12 weeks, 34.3% of varenicline recipients were not smoking compared to 12.6% of placebo recipients. By 48 weeks, ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2352301821001569

Harm reduction for smokers living with HIV Combinations of behavioural and pharmacological cessation therapies in people living with HIV have yielded increases in short-term quit rates, but few have ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05642715

Trial of a Harm Reduction Strategy for People With HIV ... The main outcomes to be compared between the two groups will be (1) change in (Δ) # cigarettes smoked per day (CPD), (2) % completing LDCT lung cancer screening ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3242617/

Safety and Tolerability of Varenicline Tartrate (Champix®/ ... In summary, varenicline was as safe in HIV-infected smokers as in HIV-negative smokers, although AEs were common and occasionally resulted in drug cessation.

7. thennt.com thennt.com/nnt/varenicline-smoking-cessation/

Varenicline for Smoking Cessation Varenicline adminstered at the standard dosage (1 mg twice daily) more than doubled the chances of quitting compared with placebo, with a pooled risk ratio [RR] ...

8. fda.gov fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-safety-review-update-chantix-varenicline-and-risk-neuropsychiatric

Safety review update of Chantix (varenicline) and risk ... The risk of serious neuropsychiatric events with Chantix is currently highlighted in the Boxed Warning and Warnings and Precautions section of the physician ...

9. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2785264

Effects of Combined Varenicline With Nicotine Patch and of ... Research suggests that combining varenicline with the nicotine patch, extending the duration of varenicline treatment, or both, may increase cessation ...

10. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(23)00493-5/fulltext

Varenicline for smoking cessation in individuals who ... Safety reporting. Safety data were summarised for both treatment groups and summary statistics reported. Any events documented in the period ...