Harm Reduction for Smoking in People With HIV
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Montefiore Medical Center
Must be taking: Varenicline
Must not be taking: Other cessation treatments
Disqualifiers: Pregnancy, Lack of insurance, others
No Placebo Group
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.
12345Eligibility 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
+3 more
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
+3 more
Trial 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Active Control
Group I: EX+/HRExperimental Treatment3 Interventions
The harm reduction arm (described in detail elsewhere)
Group II: EX+/TAUActive Control3 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Montefiore Medical CenterBronx, NY
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Who Is Running the Clinical Trial?
Montefiore Medical CenterLead Sponsor
WestatCollaborator
Massachusetts General HospitalCollaborator
Truth InitiativeCollaborator
National Cancer Institute (NCI)Collaborator
References
Safety and tolerability of varenicline tartrate (Champix(®)/Chantix(®)) for smoking cessation in HIV-infected subjects: a pilot open-label study. [2021]The prevalence of smoking in HIV-infected subjects is high. As a smoking cessation aid, varenicline (Champix(®), Pfizer, Saint-Laurent, QC, Canada or Chantix(®), Pfizer, Mission, KS) has not been previously evaluated in HIV-infected smokers. In this multicenter pilot open label study, varenicline 1.0 mg was used twice daily for 12 weeks with dose titration in the first week. Adverse events (AEs) during the treatment period were recorded. Changes from baseline in laboratory tests, vital signs, daily cigarette consumption, nicotine dependence, and withdrawal were measured through week 24. Self-reported abstinence was validated by serum cotinine at week 12. We enrolled 36 subjects with a mean of 29 pack-years of smoking and a minimum of 4 cigarettes per day. All but 1 were male, 33 (92%) were white. The most frequently reported AEs were nausea (33%), abnormal dreams (31%), affect lability (19%), and insomnia (19%). Six (17%) subjects discontinued varenicline due to AEs. No grade 3/4 laboratory abnormalities or serious AEs occurred during the study. There was no significant change in HIV viral load. CD4 counts increased by 69 cells/mm3 (p = 0.001) at week 24. Serum cotinine-verified 4-week continuous abstinence rate through weeks 9-12 was 42% (95% confidence interval [CI]: 26-58%). AEs and abstinence rates were comparable to those in published randomized controlled trials conducted in generally healthy HIV-negative smokers. Varenicline was safe and appears effective among HIV-infected smokers in this exploratory study, although AEs were common. The most common AE was nausea, with no adverse effect on HIV treatment outcome. Close monitoring of liver enzymes and blood pressure is recommended for HIV-positive smokers taking varenicline.
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]Tobacco smoking is common in people living with HIV, but high-quality evidence on interventions for smoking cessation is not available in this population. We aimed to assess the efficacy and safety of varenicline with counselling to aid smoking cessation in people living with HIV.
Improved clinical outcomes among persons with HIV who quit smoking. [2021]Quitting smoking among people living with HIV/AIDS (PLWHA) is a priority. However, PLWHA and clinicians working with PLWHA are reluctant to use tobacco use treatments out of concern that smoking cessation can diminish anti-retroviral therapy (ART) adherence and quality of life (QoL) and increase psychiatric symptoms. This secondary analysis from a placebo-controlled varenicline trial for tobacco dependence among PLWHA (N = 179) examined if smoking cessation at the end of treatment (EOT) was associated with changes in ART adherence, QoL, anxiety and depression symptoms, and varenicline side effects. ART adherence was not affected by smoking cessation (p > 0.05), remaining ≥98% for all participants. Across 8 QoL subscales, 7 remained unchanged over time across smokers and abstainers; side effects were not associated with cessation. Controlling for baseline smoking rate, adherence to varenicline/placebo and counseling, and treatment arm, participants who had quit smoking at EOT reported a significant reduction in depression (β = -1.657, 95% CI: -2.893, -0.422, p = .009) and anxiety (β = -1.434, 95% CI: -2.812, -0.56, p = .041) and increased life satisfaction (β = 0.88, 95% CI: 0.21, 3.275, p = .027). When PLWHA quit smoking they may not experience adverse clinical outcomes including ART non-adherence and may experience beneficial psychological effects, supporting the use of FDA-approved smoking cessation treatments among PLWHA.
Placebo-controlled randomized clinical trial testing the efficacy and safety of varenicline for smokers with HIV. [2023]People living with HIV/AIDS (PLWH) smoke tobacco at higher rates and have more difficulty quitting than the general population, which contributes to significant life-years lost. The effectiveness of varenicline, one of the most effective tobacco dependence treatments, is understudied in HIV. We evaluated the safety and efficacy of varenicline for smoking cessation among PLWH.
Safety of varenicline among smokers enrolled in the lung HIV study. [2021]The prevalence of smoking is high among the human immunodeficiency virus (HIV)-infected population, yet there are few studies of tobacco dependence treatment in this population. This paper reports the safety of varenicline versus nicotine replacement therapy (NRT) and describes preliminary results about the effectiveness of varenicline versus NRT in HIV-infected smokers.
Pharmacokinetics and short-term safety of etravirine in combination with fluconazole or voriconazole in HIV-negative volunteers. [2020]The nonnucleoside reverse transcriptase inhibitor etravirine, approved for use in treatment-experienced, HIV-1-infected patients, is a substrate and inducer of cytochrome P450 (CYP) 3A4 and a substrate and inhibitor of CYP2C9/CYP2C19. Pharmacokinetic interactions and safety of etravirine 200 mg twice daily coadministered with fluconazole 200 mg daily or voriconazole 200 mg twice daily, both inhibitors of CYP3A4, CYP2C9, and CYP2C19, were evaluated in an open-label, randomized, 3-period crossover trial in 18 HIV-negative volunteers. Based on least squares means (LSM) ratios, coadministration of etravirine with fluconazole or voriconazole resulted in higher etravirine exposures (area under plasma concentration-time curve from 0-12 hours [AUC(12) (h) ] 1.86- and 1.36-fold, respectively). Fluconazole pharmacokinetics were unchanged with etravirine coadministration (AUC(12) (h) LSM ratio: 0.94), and voriconazole plasma concentrations were slightly raised (AUC(12) (h) LSM ratio: 1.14). All treatments and combinations were well tolerated, with no grade 3 or 4 adverse events observed during treatment. There was 1 adverse event-related trial withdrawal during treatment with fluconazole alone (leukocyturia). The most frequent adverse events were headache and blurred vision (11 and 8 volunteers, respectively), with blurred vision occurring exclusively during voriconazole-alone treatment. Pharmacokinetic interactions between etravirine and fluconazole or voriconazole are not expected to be clinically relevant; no dose adjustments are required during coadministration.
Pharmacokinetic Drug-Drug Interactions Involving Antiretroviral Agents: An Update. [2023]Antiretroviral therapy is the recognized treatment for human immunodeficiency virus (HIV) infection involving several antiviral agents. Even though highly active antiretroviral therapy has been proven to be very effective in suppressing HIV replication, the antiretroviral drugs, belonging to different pharmacological classes, present quite complex pharmacokinetic properties such as extensive drug metabolism and transport by membrane-associated drug carriers. Moreover, due to uncomplications or complications in HIV-infected populations, an antiretroviralbased multiple-drug coadministration therapy strategy is usually applied for treatment effect, thus raising the possibility of drug-drug interactions between antiretroviral drugs and common drugs such as opioids, stains, and hormonal contraceptives. Herein, thirteen classical antiretroviral drugs approved by US Food and Drug Administration were summarized. Besides, relative drug metabolism enzymes and transporters known to interact with those antiretroviral drugs were detailed and described. Furthermore, one after the summarized antiretroviral drugs, the drug-drug interactions between two antiretroviral drugs or antiretroviral drug - conventional medical drugs of the past decade were discussed and summarized. This review is intended to deepen the pharmacological understanding of antiretroviral drugs and promote more secure clinical applications for antiretroviral drugs to treat HIV.
Lack of clinically significant drug interactions between nevirapine and buprenorphine. [2022]This study was conducted to determine whether drug interactions of clinical importance occur between buprenorphine, an opioid partial agonist medication used in treatment of opioid dependence, and the nonnucleoside reverse transcriptase inhibitor (NNRTI) nevirapine. Opioid-dependent, buprenorphine/naloxone-maintained, HIV-negative volunteers (n = 7) participated in 24-hour sessions to determine the pharmacokinetics of buprenorphine alone and of buprenorphine and nevirapine following administration of 200 mg nevirapine daily for 15 days. Opiate withdrawal symptoms, cognitive effects, and adverse events were determined prior to and following nevirapine administration. Modest decreases were observed for AUC for buprenorphine and its metabolites. There was a trend for more rapid clearance of both buprenorphine (p = .08) and buprenorphine-3-glucuronide (p = .08). While no single effect reached statistical significance, the joint probability that the consistent declines in all measures of exposure were due to chance was extremely low, indicating that nevirapine significantly reduces overall exposure to buprenorphine and buprenorphine metabolites. Clinically significant consequences of the interaction were not observed. Buprenorphine did not alter nevirapine pharmacokinetics. Dose adjustments of either buprenorphine or nevirapine are not likely to be necessary when these drugs are coadministered for the treatment of opiate dependence and HIV disease.
Rilpivirine: a novel non-nucleoside reverse transcriptase inhibitor. [2016]Combination antiretroviral therapy has transformed the prognosis and life expectancy of HIV-1 infected individuals in resource-rich settings. British guidelines currently recommend the non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz as part of first-line treatment in therapy-naive HIV-1 infected individuals. However, efavirenz is limited by its low genetic barrier to the development of resistance, together with its potential for CNS toxicities. To overcome these obstacles, several 'next-generation' NNRTIs are in various stages of clinical development. Here, we review the journey of rilpivirine (also known as TMC278, Tibotec), from the discovery of the chemical compound, through successful Phase I and II development, to its current position of being studied in international Phase III trials for the treatment of therapy-naive HIV-1 infected subjects using a 25 mg daily dose. Pharmacokinetic findings and food and drug interactions are discussed, together with safety profile. Rilpivirine has demonstrated high antiviral activity (including against NNRTI-resistant isolates) in vitro, with similar rates of virological suppression in therapy-naive individuals at 96 weeks when compared to efavirenz. Rilpivirine seems to be well tolerated with less CNS disturbance than efavirenz, and has non-teratogenic potential; however, unfavorable interactions with acid suppressant medications will require heightened vigilance when rilpivirine is used in widespread clinical practice.
Pharmacokinetic drug interactions with non-nucleoside reverse transcriptase inhibitors. [2019]Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are a diverse group of compounds that inhibit HIV Type 1 reverse transcriptase. Although possessing a common mechanism of action, the approved NNRTIs, delavirdine, efavirenz and nevirapine, differ in structural and pharmacokinetic characteristics. Each of the NNRTIs undergoes biotransformation by the cytochrome P450 (CYP) enzyme system, thus making them prone to clinically significant drug interactions when combined with other antiretrovirals. In addition, they interact with other concurrent medications and complementary/alternative medicines, acting as either inducers or inhibitors of drug-metabolising CYP enzymes. These drug interactions become an important consideration in the clinical use of these agents when designing combination regimens, as recommended by current guidelines. This review provides an updated summary of pharmacokinetic interactions with NNRTIs.