Interventions for tobacco use cessation in people living with HIV.

BACKGROUND: The prevalence of tobacco use among people living with HIV (PLWH) is up to four times higher than in the general population. Unfortunately, tobacco use increases the risk of progression to AIDS and death. Individual- and group-level interventions, and system-change interventions that are effective in helping PLWH stop using tobacco can markedly improve the health and quality of life of this population. However, clear evidence to guide policy and practice is lacking, which hinders the integration of tobacco use cessation interventions into routine HIV care. This is an update of a review that was published in 2016. We include 11 new studies. OBJECTIVES: To assess the benefits, harms and tolerability of interventions for tobacco use cessation among people living with HIV. To compare the benefits, harms and tolerability of interventions for tobacco use cessation that are tailored to the needs of people living with HIV with that of non-tailored cessation interventions. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group's Specialised Register, CENTRAL, MEDLINE, Embase, and PsycINFO in December 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of individual-/group-level behavioural or pharmacological interventions, or both, for tobacco use cessation, delivered directly to PLWH aged 18 years and over, who use tobacco. We also included RCTs, quasi-RCTs, other non-randomised controlled studies (e.g. controlled before and after studies), and interrupted time series studies of system-change interventions for tobacco use cessation among PLWH. For system-change interventions, participants could be PLWH receiving care, or staff working in healthcare settings and providing care to PLWH; but studies where intervention delivery was by research personnel were excluded. For both individual-/group-level interventions, and system-change interventions, any comparator was eligible. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods, and used GRADE to assess certainty of the evidence. The primary measure of benefit was tobacco use cessation at a minimum of six months. Primary measures for harm were adverse events (AEs) and serious adverse events (SAEs). We also measured quit attempts or quit episodes, the receipt of a tobacco use cessation intervention, quality of life, HIV viral load, CD4 count, and the incidence of opportunistic infections. MAIN RESULTS: We identified 17 studies (16 RCTs and one non-randomised study) with a total of 9959 participants; 11 studies are new to this update. Nine studies contributed to meta-analyses (2741 participants). Fifteen studies evaluated individual-/group-level interventions, and two evaluated system-change interventions. Twelve studies were from the USA, two from Switzerland, and there were single studies for France, Russia and South Africa. All studies focused on cigarette smoking cessation. All studies received funding from independent national- or institutional-level funding. Three studies received study medication free of charge from a pharmaceutical company. Of the 16 RCTs, three were at low risk of bias overall, five were at high risk, and eight were at unclear risk. Behavioural support or system-change interventions versus no or less intensive behavioural support Low-certainty evidence (7 studies, 2314 participants) did not demonstrate a clear benefit for tobacco use cessation rates in PLWH randomised to receive behavioural support compared with brief advice or no intervention: risk ratio (RR) 1.11, 95% confidence interval (CI) 0.87 to 1.42, with no evidence of heterogeneity. Abstinence at six months or more was 10% (n = 108/1121) in the control group and 11% (n = 127/1193) in the intervention group. There was no evidence of an effect on tobacco use cessation on system-change interventions: calling the quitline and transferring the call to the patient whilst they are still in hospital ('warm handoff') versus fax referral (RR 3.18, 95% CI 0.76 to 13.99; 1 study, 25 participants; very low-certainty evidence). None of the studies in this comparison assessed SAE. Pharmacological interventions versus placebo, no intervention, or another pharmacotherapy Moderate-certainty evidence (2 studies, 427 participants) suggested that varenicline may help more PLWH to quit smoking than placebo (RR 1.95, 95% CI 1.05 to 3.62) with no evidence of heterogeneity. Abstinence at six months or more was 7% (n = 14/215) in the placebo control group and 13% (n = 27/212) in the varenicline group. There was no evidence of intervention effects from individual studies on behavioural support plus nicotine replacement therapy (NRT) versus brief advice (RR 8.00, 95% CI 0.51 to 126.67; 15 participants; very low-certainty evidence), behavioural support plus NRT versus behavioural support alone (RR 1.47, 95% CI 0.92 to 2.36; 560 participants; low-certainty evidence), varenicline versus NRT (RR 0.93, 95% CI 0.48 to 1.83; 200 participants; very low-certainty evidence), and cytisine versus NRT (RR 1.18, 95% CI 0.66 to 2.11; 200 participants; very low-certainty evidence). Low-certainty evidence (2 studies, 427 participants) did not detect a difference between varenicline and placebo in the proportion of participants experiencing SAEs (8% (n = 17/212) versus 7% (n = 15/215), respectively; RR 1.14, 95% CI 0.58 to 2.22) with no evidence of heterogeneity. Low-certainty evidence from one study indicated similar SAE rates between behavioural support plus NRT and behavioural support only (1.8% (n = 5/279) versus 1.4% (n = 4/281), respectively; RR 1.26, 95% CI 0.34 to 4.64). No studies assessed SAEs for the following: behavioural support plus NRT versus brief advice; varenicline versus NRT and cytisine versus NRT. AUTHORS' CONCLUSIONS: There is no clear evidence to support or refute the use of behavioural support over brief advice, one type of behavioural support over another, behavioural support plus NRT over behavioural support alone or brief advice, varenicline over NRT, or cytisine over NRT for tobacco use cessation for six months or more among PLWH. Nor is there clear evidence to support or refute the use of system-change interventions such as warm handoff over fax referral, to increase tobacco use cessation or receipt of cessation interventions among PLWH who use tobacco. However, the results must be considered in the context of the small number of studies included. Varenicline likely helps PLWH to quit smoking for six months or more compared to control. We did not find evidence of difference in SAE rates between varenicline and placebo, although the certainty of the evidence is low.

MAVMET trial: maraviroc and/or metformin for metabolic dysfunction associated fatty liver disease in adults with suppressed HIV.

OBJECTIVE: Metabolic dysfunction associated fatty liver disease (MAFLD) is over-represented in people with HIV (PWH). Maraviroc (MVC) and/or metformin (MET) may reduce MAFLD by influencing inflammatory pathways and fatty acid metabolism. DESIGN: Open-label, 48-week randomized trial with a 2 x 2 factorial design. SETTING: Multicenter HIV clinics. PARTICIPANTS: Nondiabetic, virologically suppressed PLWH, aged at least 35 years, with confirmed/suspected MAFLD (≥1 biochemical/anthropometric/radiological/histological features). INTERVENTION: Adjunctive MVC; MET; MVC+MET vs. antiretroviral therapy (ART) alone. PRIMARY OUTCOME: Change in liver fat fraction (LFF) between baseline and week-48 using magnetic resonance proton density fat fraction (MR PDFF). RESULTS: Six sites enrolled 90 participants (93% male; 81% white; median age 52 [interquartile range, IQR 47-57] years) between March 19, 2018, and November 11, 2019. Seventy percent had imaging/biopsy and at least one 1 MAFLD criteria. The analysis included 82/90 with week-0 and week-48 scans. Median baseline MR PDFF was 8.9 (4.6-17.1); 40, 38, 8, and 14% had grade zero, one, two, and three steatosis, respectively. Mean LFF increased slightly between baseline and follow-up scans: 2.22% MVC, 1.26% MET, 0.81% MVC+MET, and 1.39% ART alone. Prolonged intervention exposure (delayed week-48 scans) exhibited greater increases in MR PDFF (estimated difference 4.23% [95% confidence interval, 95% CI 2.97-5.48], P  < 0.001). There were no differences in predicted change for any intervention compared to ART alone: MVC (-0.42% [95% CI -1.53 to 0.68, P  = 0.45]), MET (-0.62 [-1.81 to 0.56, P  = 0.30]), and MVC+MET (-1.04 [-2.74 to 0.65, P  = 0.23]). Steatosis grade remained unchanged in 55% and increased in 24%. CONCLUSION: Baseline levels of liver fat were lower than predicted. Contrary to our hypothesis, neither MVC, MET, or the combination significantly reduced liver fat as measured by MRPDFF compared to ART alone.

Interventions for tobacco use cessation in people living with HIV and AIDS.

BACKGROUND: Tobacco use is highly prevalent amongst people living with HIV/AIDS (PLWHA) and has a substantial impact on morbidity and mortality. OBJECTIVES: To assess the effectiveness of interventions to motivate and assist tobacco use cessation for people living with HIV/AIDS (PLWHA), and to evaluate the risks of any harms associated with those interventions. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group's Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and PsycINFO in June 2015. We also searched EThOS, ProQuest, four clinical trial registries, reference lists of articles, and searched for conference abstracts using Web of Science and handsearched speciality conference databases. SELECTION CRITERIA: Controlled trials of behavioural or pharmacological interventions for tobacco cessation for PLWHA. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted all data using a standardised electronic data collection form. They extracted data on the nature of the intervention, participants, and proportion achieving abstinence and they contacted study authors to obtain missing information. We collected data on long-term (greater than or equal to six months) and short-term (less than six months) outcomes. Where appropriate, we performed meta-analysis and estimated the pooled effects using the Mantel-Haenszel fixed-effect method. Two authors independently assessed and reported the risk of bias according to prespecified criteria. MAIN RESULTS: We identified 14 studies relevant to this review, of which we included 12 in a meta-analysis (n = 2087). All studies provided an intervention combining behavioural support and pharmacotherapy, and in most studies this was compared to a less intensive control, typically comprising a brief behavioural intervention plus pharmacotherapy.There was moderate quality evidence from six studies for the long-term abstinence outcome, which showed no evidence of effect for more intense cessation interventions: (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.72 to 1.39) with no evidence of heterogeneity (I(2) = 0%). The pooled long-term abstinence was 8% in both intervention and control conditions. There was very low quality evidence from 11 studies that more intense tobacco cessation interventions were effective in achieving short-term abstinence (RR 1.51, 95% CI 1.15 to 2.00); there was moderate heterogeneity (I(2) = 42%). Abstinence in the control group at short-term follow-up was 8% (n = 67/848) and in the intervention group was 13% (n = 118/937). The effect of tailoring the intervention for PLWHA was unclear. We further investigated the effect of intensity of behavioural intervention via number of sessions and total duration of contact. We failed to detect evidence of a difference in effect according to either measure of intensity, although there were few studies in each subgroup. It was not possible to perform the planned analysis of adverse events or HIV outcomes since these were not reported in more than one study. AUTHORS' CONCLUSIONS: There is moderate quality evidence that combined tobacco cessation interventions provide similar outcomes to controls in PLWHA in the long-term. There is very low quality evidence that combined tobacco cessation interventions were effective in helping PLWHA achieve short-term abstinence. Despite this, tobacco cessation interventions should be offered to PLWHA, since even non-sustained periods of abstinence have proven benefits. Further large, well designed studies of cessation interventions for PLWHA are needed.