High adherence to antiretroviral therapy is crucial to the success of HIV treatment. We evaluated comparative effectiveness of adherence interventions with the aim of informing the WHO's global ...guidance on interventions to increase adherence.
For this systematic review and network meta-analysis, we searched for randomised controlled trials of interventions that aimed to improve adherence to antiretroviral therapy regimens in populations with HIV. We searched Cochrane Central Register of Controlled Trials, Embase, and MEDLINE for reports published up to July 16, 2015, and searched major conference abstracts from Jan 1, 2013, to July 16, 2015. We extracted data from eligible studies for study characteristics, interventions, patients' characteristics at baseline, and outcomes for the study populations of interest. We used network meta-analyses to compare adherence and viral suppression for all study settings (global network) and for studies in low-income and middle-income countries only (LMIC network).
We obtained data from 85 trials with 16 271 participants. Short message service (SMS; text message) interventions were superior to standard of care in improving adherence in both the global network (odds ratio OR 1·48, 95% credible interval CrI 1·00-2·16) and in the LMIC network (1·49, 1·04-2·09). Multiple interventions showed generally superior adherence to single interventions, indicating additive effects. For viral suppression, only cognitive behavioural therapy (1·46, 1·05-2·12) and supporter interventions (1·28, 1·01-1·71) were superior to standard of care in the global network; none of the interventions improved viral response in the LMIC network. For the global network, the time discrepancy (whether the study outcome was measured during or after intervention was withdrawn) was an effect modifier for both adherence to antiretroviral therapy (coefficient estimate -0·43, 95% CrI -0·75 to -0·11) and viral suppression (-0·48; -0·84 to -0·12), suggesting that the effects of interventions wane over time.
Several interventions can improve adherence and viral suppression; generally, their estimated effects were modest and waned over time.
WHO.
New antiretroviral therapy (ART) regimens for HIV could improve clinical outcomes for patients. To inform global guidelines, we aimed to assess the comparative effectiveness of recommended ART ...regimens for HIV in ART-naive patients.
For this systematic review and network meta-analysis, we searched for randomised clinical trials published up to July 5, 2015, comparing recommended antiretroviral regimens in treatment-naive adults and adolescents (aged 12 years or older) with HIV. We extracted data on trial and patient characteristics, and the following primary outcomes: viral suppression, mortality, AIDS defining illnesses, discontinuations, discontinuations due to adverse events, and serious adverse events. We synthesised data using network meta-analyses in a Bayesian framework and included older treatments, such as indinavir, to serve as connecting nodes. We defined network nodes in terms of specific antivirals rather than specific ART regimens. We categorised backbone regimens and adjusted for them through group-specific meta-regression. We used the GRADE framework to interpret the strength of inference.
We identified 5865 citations through database searches and other sources, of which, 126 articles related to 71 unique trials were included in the network analysis, including 34 032 patients randomly assigned to 161 treatment groups. For viral suppression at 48 weeks, compared with efavirenz, the odds ratio (OR) for viral suppression was 1·87 (95% credible interval CrI 1·34-2·64) with dolutegravir and 1·40 (1·02-1·96) with raltegravir; with respect to viral suppression, low-dose efavirenz was similar to all other treatments. Both low-dose efavirenz and integrase strand transfer inhibitors tended to be protective of discontinuations due to adverse events relative to normal-dose efavirenz. The most protective effect relative to efavirenz in network meta-analyses was that of dolutegravir (OR 0·26, 95% CrI 0·14-0·47), followed by low-dose efavirenz (0·39, 0·16-0·92). Owing to insufficient data, we could make no conclusions about serious adverse events. Low event rates also limited the quality of evidence with regard to mortality and AIDS defining illnesses.
The efficacy and safety of ART has substantially improved with the introduction of newer drug classes of antiretrovirals that are now available to patients and HIV care providers. Their improved tolerance could be part of a larger solution to improve retention, which is a challenge, particularly in low-income and middle-income country settings.
The World Health Organization.
Background and Aims
Cannabis use is common among people on opioid agonist treatment (OAT), causing concern for some care providers. However, there is limited and conflicting evidence on the impact of ...cannabis use on OAT outcomes. Given the critical role of retention in OAT in reducing opioid‐related morbidity and mortality, we aimed to estimate the association of at least daily cannabis use on the likelihood of retention in treatment among people initiating OAT. As a secondary aim we tested the impacts of less frequent cannabis use.
Design
Data were drawn from two community‐recruited prospective cohorts of people who use illicit drugs (PWUD). Participants were followed for a median of 81 months (interquartile range = 37–130).
Setting
Vancouver, Canada.
Participants
This study comprised a total of 820 PWUD (57.8% men, 59.4% of Caucasian ethnicity, 32.2% HIV‐positive) initiating OAT between December 1996 and May 2016. The proportion of women was higher among HIV‐negative participants, with no other significant differences.
Measurements
The primary outcome was retention in OAT, defined as remaining in OAT (methadone or buprenorphine/naloxone‐based) for two consecutive 6‐month follow‐up periods. The primary explanatory variable was cannabis use (at least daily versus less than daily) during the same 6‐month period. Confounders assessed included: socio‐demographic characteristics, substance use patterns and social–structural exposures.
Findings
In adjusted analysis, at least daily cannabis use was positively associated with retention in OAT adjusted odds ratio (aOR) = 1.21, 95% confidence interval (CI) = 1.04–1.41. Our secondary analysis showed that compared with non‐cannabis users, at least daily users had increased odds of retention in OAT (aOR = 1.20, 95% CI = 1.02–1.43), but not less than daily users (aOR = 1.00, 95% CI = 0.87–1.14).
Conclusions
Among people who use illicit drugs initiating opioid agonist treatment in Vancouver, at least daily cannabis use was associated with approximately 21% greater odds of retention in treatment compared with less than daily consumption.
Background. People living with hepatitis C infection (HCV) have a significant impact on the global healthcare system, with high rates of inpatient service use. Direct-acting antivirals (DAAs) have ...the potential to alleviate this burden; however, the evidence on the impact of HCV infection and hospital outcomes is undetermined. This systematic review aims to assess this research gap, including how DAAs may modify the relationship between HCV infection and hospital-related outcomes. Methods. We searched five databases up to August 2022 to identify relevant studies evaluating the impact of HCV infection on hospital-related outcomes. We created an electronic database of potentially eligible articles, removed duplicates, and then independently screened titles, abstracts, and full-text articles. Results. A total of 57 studies were included. Analysis of the included studies found an association between HCV infection and increased number of hospitalizations, length of stay, and readmissions. There was less consistent evidence of a relationship between HCV and in-hospital mortality. Only four studies examined the impact of DAAs, which showed that DAAs were associated with a reduction in hospitalizations and mortality. In the 14 studies available among people living with HIV, HCV coinfection similarly increased hospitalization, but there was less evidence for the other hospital-related outcomes. Conclusions. There is good to high-quality evidence that HCV negatively impacts hospital-related outcomes, primarily through increased hospitalizations, length of stay, and readmissions. Given the paucity of studies on the effect of DAAs on hospital outcomes, future research is needed to understand their impact on hospital-related outcomes.
Abstract
We sought to evaluate the rates and predictors of SARS-CoV-2 vaccination among members of a structurally-marginalized population of people who use drugs (PWUD) during a targeted, ...community-wide, vaccination campaign in Vancouver, Canada. Interviewer-administered data were collected from study participants between June 2021 and March 2022. Generalized estimating equation analysis was used to identify factors associated with SARS-CoV-2 vaccine uptake, ascertained through a province-wide vaccine registry. Among 223 PWUD, 107 (48.0%) reported receipt of at least two SARS-CoV-2 vaccine doses at baseline and this increased to 151 (67.7%) by the end of the study period. Using social media as a source of vaccine information was negatively associated with SARS-CoV-2 vaccine uptake (Adjusted odds ratio AOR 0.27, 95% confidence interval CI 0.09–0.81) and HIV seropositivity (AOR 2.68, 95% CI 1.12–6.39) and older age (AOR 1.27, 95% CI 1.07–1.51) were positively associated with SARS-CoV-2 vaccine uptake. These findings suggest that the targeted vaccination campaign in Vancouver may be an effective model to promote SARS-CoV-2 vaccination in other jurisdictions. However, using social media as a source of vaccine information likely reduced SARS-CoV-2 vaccine uptake in PWUD arguing for further efforts to promote accessible and evidence-based vaccine information among marginalized populations.
Objectives
There is limited evidence on how opioid agonist treatment (OAT) may affect psychoactive non-opioid substance use in prescription-type opioid use disorder (POUD) and whether this effect ...might explain OAT outcomes. We aimed to assess the effect of methadone on non-opioid substance use compared to buprenorphine/naloxone (BUP/NX), to explore whether non-opioid substance use is associated with opioid use and retention in treatment, and to test non-opioid use as a moderator of associations between methadone with retention in OAT and opioid use compared to BUP/NX.
Methods
This is a secondary analysis of data from the OPTIMA trial, an open-label, pragmatic, parallel, two-arm, pan-Canadian, multicentre, randomized-controlled trial to compare standard methadone model of care and flexible take-home dosing BUP/NX for POUD treatment. We studied the effect of methadone and BUP/NX on non-opioid substance use evaluated by urine drug screen (UDS) and by classes of non-opioid substances (i.e., tetrahydrocannabinol THC, benzodiazepines, stimulants) (weeks 2–24) using adjusted generalized estimation equation (GEE). We studied the association between non-opioid substance-positive UDS and opioid-positive UDS and retention in treatment, using adjusted GEE and logistic regressions.
Results
Overall, methadone was not associated with non-opioid substance-positive UDS compared to BUP/NX (OR: 0.78; 95%CI, 0.41 to 1.48). When non-opioid substances were studied separately, methadone was associated with lower odds of benzodiazepine-positive UDS (OR: 0.63; 95% CI: 0.40 to 0.98) and THC-positive UDS (OR: 0.47; 95% CI: 0.28 to 0.77), but not with different odds of stimulant-positive UDS (OR: 1.29; 95% CI: 0.78 to 2.16) compared to BUP/NX. Substance-positive UDS, overall and separate classes, were not associated with opioid-positive UDS or retention in treatment.
Conclusion
Methadone did not show a significant effect on overall non-opioid substance use in POUD compared to BUP/NX treatment but was associated with lower odds of benzodiazepine and THC use in particular. Non-opioid substance use did not predict OAT outcomes. Further research is needed to ascertain whether specific patterns of polysubstance use (quantity and frequency) may affect treatment outcomes.
High levels of morbidity and mortality associated with injection drug use continue to represent a significant public health challenge in many settings worldwide. Previous studies have shown an ...association between cannabis use and decreased risk of some drug-related harms. We sought to evaluate the association between high-intensity cannabis use and the frequency of injection drug use among people who inject drugs (PWID).
The data for this analysis were collected from three prospective cohorts of PWID in Vancouver, Canada, between September 2005 and May 2018. Generalized linear mixed-effects models were used to analyze the association between daily cannabis use and the frequency of injecting illegal drugs (i.e., self-reported average number of injections per month).
Among the 2,619 active PWID, the frequency of injection drug use was significantly lower among people who use cannabis daily compared with people who use it less than daily (adjusted odds ratio AOR=0.84, 95% confidence interval CI: 0.73-0.95). Sub-analyses indicated that this effect was restricted to the frequency of illegal opioid injection (AOR=0.78, 95% CI: 0.68-0.90); the association between daily cannabis use and the frequency of illegal stimulant injection was not significant (AOR=1.08, 95% CI 0.93-1.25).
The findings from these prospective cohorts suggest that people who use cannabis daily were less likely to report daily injection of illegal drugs compared with people who use it less than daily. These results suggest the potential value of conducting experimental research to test whether controlled administration of cannabinoids impacts the frequency of illegal opioid injection among PWID.
Although factors associated with completion of medical detoxification treatment for substance use disorders (SUD) are well described, there is limited information on barriers and facilitators to ...subsequent linkage to SUD treatment in the community. This study aimed to evaluate correlates of successful linkage to community SUD treatment on discharge.
Data were drawn from 2 prospective cohorts of people who use unregulated drugs in Vancouver, Canada between December 2012 and May 2018. Multivariable generalized estimating equations were used to investigate factors associated with linkage to community SUD treatment in the 6-month period after attending detoxification treatment.
Of the 264 detoxification treatment encounters contributed by 178 people who use unregulated drugs, these were most often (n = 104, 39%) related to polysubstance use, and the majority (n = 174, 66%) resulted in subsequent linkage to community treatment. In the multivariable analysis, compared to attending detoxification treatment for opioid use, attending detoxification treatment for stimulants (adjusted odds ratio AOR = 0.23, 95% confidence interval CI : 0.10-0.51) and alcohol (AOR = 0.17, 95% CI: 0.06-0.54) were associated with lower odds of subsequent linkage to community treatment. Conversely, later calendar year of detoxification treatment remained associated with higher odds (AOR = 1.23, 95% CI: 1.06-1.42).
Only two-thirds of detoxification treatment encounters in Vancouver were subsequently linked to community SUD treatment, with those related to nonopioid substances being less likely. Findings suggest the need for tailored interventions for specific substances to improve linkage to SUD treatment in the community on discharge.
Selection of optimal second-line antiretroviral therapy (ART) has important clinical and programmatic implications. To inform the 2016 revision of the WHO ART guidelines, we assessed the comparative ...effectiveness and safety of available second-line ART regimens for adults and adolescents in whom first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens have failed.
In this systematic review and network meta-analysis, we searched for randomised controlled trials and prospective and retrospective cohort studies that evaluated outcomes in treatment-experienced adults living with HIV who switched ART regimen after failure of a WHO-recommended first-line NNRTI-based regimen. We searched Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials for reports published from Jan 1, 1996, to Aug 8, 2016, and searched conference abstracts published from Jan 1, 2014, to Aug 8, 2016. Outcomes of interest were viral suppression, mortality, AIDS-defining illnesses or WHO stage 3-4 disease, discontinuations, discontinuations due to adverse events, and serious adverse events. We assessed comparative efficacy and safety in a network meta-analysis, using Bayesian hierarchical models.
We identified 12 papers pertaining to eight studies, including 4778 participants. The network was centred on ritonavir-boosted lopinavir plus two nucleoside or nucleotide reverse transcriptase inhibitors. Ritonavir-boosted lopinavir monotherapy was the only regimen inferior to others. With the lower estimate of the 95% credible interval (CrI) not exceeding the predefined threshold of 15%, evidence at 48 weeks supported the non-inferiority of ritonavir-boosted lopinavir plus raltegravir to regimens including ritonavir-boosted protease inhibitor plus two NRTIs with respect to viral suppression (odds ratio 1·09, 95% CrI 0·88-1·35). Estimated efficacy of ritonavir-boosted darunavir (800 mg once daily) was too imprecise to determine non-inferiority. Overall, regimens did not differ significantly with respect to continuations, AIDS-defining illnesses or WHO stage 3-4 disease, or mortality.
With the exception of ritonavir-boosted lopinavir plus raltegravir, the evidence base is unable to provide strong support to alternative second-line options to ritonavir-boosted protease inhibitor plus two NRTIs, and thus more trials are warranted.
WHO.
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