Harm Reduction for Smoking in People With HIV

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

Trial Summary

What is the purpose of this trial?

Cigarette smoking is now the leading killer of people with HIV (PWH) in the US, and most cessation strategies tried to date have failed to increase long-term quit rates. An "all or none" approach to smoking cessation in PWH offers little benefit to the large majority of PWH who are unable or unwilling to quit. In this proposal we argue that a harm reduction approach (i.e. cut down, get screened for lung cancer, control your blood pressure and cholesterol) has the potential to yield significant benefits in terms of the private and public health of PWH in the US.

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 the drug varenicline effective for helping people with HIV quit smoking?

Research shows that varenicline is effective for helping people with HIV quit smoking, with a 42% abstinence rate in one study. It also does not negatively impact HIV treatment and may improve mental health by reducing depression and anxiety. ^{1 2 3 4 5}

Is the treatment generally safe for humans?

The research articles provided do not contain relevant safety information about the treatment in question, such as Varenicline (also known as Chantix or Champix), for smoking harm reduction in people with HIV. ^{6 7 8 9 10}

How does the drug varenicline help people with HIV quit smoking?

Varenicline is a drug that helps people with HIV quit smoking by reducing cravings and withdrawal symptoms, and it has been shown to be safe and effective in this population without affecting HIV treatment outcomes. ^{1 2 3 4 5}

Research Team

Jonathan Shuter, MD

Principal Investigator

Montefiore Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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 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]

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 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]

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 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]

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]

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]

References

1. United States 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. [2021]

2. Netherlands 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. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Improved clinical outcomes among persons with HIV who quit smoking. [2021]

4. Ireland pubmed.ncbi.nlm.nih.gov

Placebo-controlled randomized clinical trial testing the efficacy and safety of varenicline for smokers with HIV. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Safety of varenicline among smokers enrolled in the lung HIV study. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and short-term safety of etravirine in combination with fluconazole or voriconazole in HIV-negative volunteers. [2020]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Pharmacokinetic Drug-Drug Interactions Involving Antiretroviral Agents: An Update. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Lack of clinically significant drug interactions between nevirapine and buprenorphine. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Rilpivirine: a novel non-nucleoside reverse transcriptase inhibitor. [2016]

10. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetic drug interactions with non-nucleoside reverse transcriptase inhibitors. [2019]