Financial incentives for reduced alcohol use and increased isoniazid adherence during tuberculosis preventive therapy among people with HIV in Uganda: an open-label, factorial randomised controlled trial.

BACKGROUND: Alcohol use is common among people with HIV and is a risk factor for tuberculosis disease and non-adherence to isoniazid preventive therapy (IPT). Few interventions exist to reduce alcohol use and increase IPT adherence in sub-Saharan Africa. The aim of this study was to test the hypothesis that financial incentives conditional on point-of-care negative urine alcohol biomarker testing and positive urine isoniazid testing would reduce alcohol use and increase isoniazid adherence, respectively, in people with HIV who have latent tuberculosis infection and hazardous alcohol use. METHODS: We conducted an open-label, 2×2 factorial randomised controlled trial in Uganda. Eligible for the study were non-pregnant HIV-positive adults (aged ≥18 years) prescribed antiretroviral therapy for at least 6 months, with current heavy alcohol use confirmed by urine ethyl glucuronide (biomarker of recent alcohol use) and a positive Alcohol Use Disorders Identification Test-Consumption (AUDIT-C; ≥3 for women, ≥4 for men) for the past 3 months' drinking, no history of active tuberculosis, tuberculosis treatment, or tuberculosis preventive therapy, and a positive tuberculin skin test. We randomly assigned participants (1:1:1:1) initiating 6 months of IPT to: no incentives (group 1); or incentives for recent alcohol abstinence (group 2), isoniazid adherence (group 3), or both (group 4). Escalating incentives were contingent on monthly point-of-care urine tests negative for ethyl glucuronide (groups 2 and 4), or positive on IsoScreen (biomarker of recent isoniazid use; groups 3 and 4). The primary alcohol outcome was non-hazardous use by self-report (AUDIT-C <3 for women, <4 for men) and phosphatidylethanol (PEth; past-month alcohol biomarker) <35 ng/mL at 3 months and 6 months. The primary isoniazid adherence outcome was more than 90% bottle opening of days prescribed. We performed intention-to-treat analyses. This trial is registered with ClinicalTrials.gov (NCT03492216), and is complete. FINDINGS: From April 16, 2018, to Aug 2, 2021, 5508 people were screened, of whom 680 were randomly assigned: 169 to group 1, 169 to group 2, 170 to group 3, and 172 to group 4. The median age of participants was 39 years (IQR 32-47), 470 (69%) were male, 598 (90%) of 663 had HIV RNA viral loads of less than 40 copies per mL, median AUDIT-C score was 6 (IQR 4-8), and median PEth was 252 ng/mL (IQR 87-579). Among 636 participants who completed the trial with alcohol use endpoint measures (group 1: 152, group 2: 159, group 3: 161, group 4: 164), non-hazardous alcohol use was more likely in the groups with incentives for alcohol abstinence (groups 2 and 4) versus no alcohol incentives (groups 1 and 3): 57 (17·6%) of 323 versus 31 (9·9%) of 313, respectively; adjusted risk difference (aRD) 7·6% (95% CI 2·7 to 12·5, p=0·0025). Among 656 participants who completed the trial with isoniazid adherence endpoint measures (group 1: 158, group 2: 163, group 3: 168, group 4: 167), incentives for isoniazid adherence did not increase adherence: 244 (72·8%) of 335 in the isoniazid incentive groups (groups 3 and 4) versus 234 (72·9%) of 321 in the no isoniazid incentive groups (groups 1 and 2); aRD -0·2% (95% CI -7·0 to 6·5, p=0·94). Overall, 53 (8%) of 680 participants discontinued isoniazid due to grade 3 or higher adverse events. There was no significant association between randomisation group and hepatotoxicity resulting in isoniazid discontinuation, after adjusting for sex and site. INTERPRETATION: Escalating financial incentives contingent on recent alcohol abstinence led to significantly lower biomarker-confirmed alcohol use versus control, but incentives for recent isoniazid adherence did not lead to changes in adherence. The alcohol intervention was efficacious despite less intensive frequency of incentives and clinic visits than traditional programmes for substance use, suggesting that pragmatic modifications of contingency management for resource-limited settings can have efficacy and that further evaluation of implementation is merited. FUNDING: National Institute on Alcohol Abuse and Alcoholism. TRANSLATION: For the Runyankole translation of the abstract see Supplementary Materials section.

Using value of information methods to determine the optimal sample size for effectiveness trials of alcohol interventions for HIV-infected patients in East Africa.

BACKGROUND: Unhealthy alcohol consumption exacerbates the HIV epidemic in East Africa. Potential benefits of new trials that test the effectiveness of alcohol interventions could not be evaluated by traditional sampling methods. Given the competition for health care resources in East Africa, this study aims to determine the optimal sample size given the opportunity cost of potentially re-allocating trial funds towards cost-effective alcohol treatments. METHODS: We used value of information methods to determine the optimal sample size by maximizing the expected net benefit of sampling for a hypothetical 2-arm intervention vs. control randomized trial, across ranges of policymaker's willingness-to-pay for the health benefit of an intervention. Probability distributions describing the relative likelihood of alternative trial results were imputed based on prior studies. In the base case, policymaker's willingness-to-pay was based on a simultaneously resource-constrained priority (routine HIV virological testing). Sensitivity analysis was performed for various willingness-to-pay thresholds and intervention durations. RESULTS: A new effectiveness trial accounting for the benefit of more precise decision-making on alcohol intervention implementation would benefit East Africa $67,000 with the optimal sample size of 100 persons per arm under the base case willingness-to-pay threshold and intervention duration of 20 years. At both a conservative willingness-to-pay of 1 x GDP/capita and a high willingness-to-pay of 3 x GDP/capita for an additional health gain added by an alcohol intervention, a new trial was not recommended due to limited decision uncertainty. When intervention duration was 10 or 5 years, there was no return on investment across suggested willingness-to-pay thresholds. CONCLUSIONS: Value of information methods could be used as an alternative approach to assist the efficient design of alcohol trials. If reducing unhealthy alcohol use is a long-term goal for HIV programs in East Africa, additional new trials with optimal sample sizes ranging from 100 to 250 persons per arm could save the opportunity cost of implementing less cost-effective alcohol strategies in HIV prevention. Otherwise, conducting a new trial is not recommended.

Betting on the fastest horse: Using computer simulation to design a combination HIV intervention for future projects in Maharashtra, India.

OBJECTIVE: To inform the design of a combination intervention strategy targeting HIV-infected unhealthy alcohol users in Maharashtra, India, that could be tested in future randomized control trials. METHODS: Using probabilistic compartmental simulation modeling we compared intervention strategies targeting HIV-infected unhealthy alcohol users on antiretroviral therapy (ART) in Maharashtra, India. We tested interventions targeting four behaviors (unhealthy alcohol consumption, risky sexual behavior, depression and antiretroviral adherence), in three formats (individual, group based, community) and two durations (shorter versus longer). A total of 5,386 possible intervention combinations were tested across the population for a 20-year time horizon and intervention bundles were narrowed down based on incremental cost-effectiveness analysis using a two-step probabilistic uncertainty analysis approach. RESULTS: Taking into account uncertainty in transmission variables and intervention cost and effectiveness values, we were able to reduce the number of possible intervention combinations to be used in a randomized control trial from over 5,000 to less than 5. The most robust intervention bundle identified was a combination of three interventions: long individual alcohol counseling; weekly Short Message Service (SMS) adherence counseling; and brief sex risk group counseling. CONCLUSIONS: In addition to guiding policy design, simulation modeling of HIV transmission can be used as a preparatory step to trial design, offering a method for intervention pre-selection at a reduced cost.

Quality of HIV Care and Mortality Rates in HIV-Infected Patients.

BACKGROUND: The Patient Protection and Affordable Care Act encourages healthcare systems to track quality-of-care measures; little is known about their impact on mortality rates. The objective of this study was to assess associations between HIV quality of care and mortality rates. METHODS: A longitudinal survival analysis of the Veterans Aging Cohort Study included 3038 human immunodeficiency virus (HIV)-infected patients enrolled between June 2002 and July 2008. The independent variable was receipt of ≥80% of 9 HIV quality indicators (QIs) abstracted from medical records in the 12 months after enrollment. Overall mortality rates through 2014 were assessed from the Veterans Health Administration, Medicare, and Social Security National Death Index records. We assessed associations between receiving ≥80% of HIV QIs and mortality rates using Kaplan-Meier survival analysis and adjusted Cox proportional hazards models. Results were stratified by unhealthy alcohol and illicit drug use. RESULTS: The majority of participants were male (97.5%) and black (66.8%), with a mean (standard deviation) age of 49.0 (8.8) years. Overall, 25.9% reported past-year unhealthy alcohol use and 28.4% reported past-year illicit drug use. During 24 805 person-years of follow-up (mean [standard deviation], 8.2 [3.3] years), those who received ≥80% of QIs experienced lower age-adjusted mortality rates (adjusted hazard ratio, 0.75; 95% confidence interval, .65-.86). Adjustment for disease severity attenuated the association. CONCLUSIONS: Receipt of ≥80% of select HIV QIs is associated with improved survival in a sample of predominantly male, black, HIV-infected patients but was insufficient to overcome adjustment for disease severity. Interventions to ensure high-quality care and address underlying chronic illness may improve survival in HIV-infected patients.

Systematic review of interventions to reduce problematic alcohol use in men who have sex with men.

ISSUES: Rates of heavy drinking, alcohol problems and alcohol-related disorders are high among men who have sex with men (MSM) and are an important public health issue. Associations between heavy drinking and human immunodeficiency virus (HIV) acquisition among MSM also suggest that drinking may have more severe and chronic consequences for this population relative to others. Consequently, effective interventions to reduce heavy drinking and alcohol-related risk factors among MSM are needed. APPROACH: We conducted a systematic review of randomised controlled trials of interventions to reduce heavy drinking and/or alcohol-related problems among MSM. We searched five electronic databases, screened 3722 records and identified 5 studies involving 1022 participants that satisfied inclusion criteria, which included having: (i) incorporated a comparison condition; (ii) randomised participants to groups; and (iii) reported quantitative outcomes. KEY FINDINGS: The methodological quality of studies varied, and meta-analysis was not conducted because of heterogeneity in intervention approaches and outcomes. Studies provided preliminary support for the use of motivational interviewing/motivational enhancement-based interventions (MI) and hybrid MI and cognitive behavioural therapy treatments for heavy drinking among MSM over no treatment. Perhaps the most important conclusion of this review, however, is that well-designed, theoretically informed research focused on establishing the efficacy of interventions for hazardous drinking and alcohol use disorders among MSM is alarmingly scarce. CONCLUSIONS: Effective interventions to reduce hazardous drinking among MSM and prevent key alcohol-related outcomes, including risk for HIV transmission and health problems among HIV-positive MSM, are needed to mitigate health disparities in this population.

The epidemiology of substance use disorders in US Veterans: A systematic review and analysis of assessment methods.

BACKGROUND: Substance use disorders (SUDs), which encompass alcohol and drug use disorders (AUDs, DUDs), constitute a major public health challenge among US veterans. SUDs are among the most common and costly of all health conditions among veterans. OBJECTIVES: This study sought to examine the epidemiology of SUDs among US veterans, compare the prevalence of SUDs in studies using diagnostic and administrative criteria assessment methods, and summarize trends in the prevalence of SUDs reported in studies sampling US veterans over time. METHODS: Comprehensive electronic database searches were conducted. A total of 3,490 studies were identified. We analyzed studies sampling US veterans and reporting prevalence, distribution, and examining AUDs and DUDs. RESULTS: Of the studies identified, 72 met inclusion criteria. The studies were published between 1995 and 2013. Studies using diagnostic criteria reported higher prevalence of AUDs (32% vs. 10%) and DUDs (20% vs. 5%) than administrative criteria, respectively. Regardless of assessment method, both the lifetime and past year prevalence of AUDs in studies sampling US veterans has declined gradually over time. CONCLUSION: The prevalence of SUDs reported in studies sampling US veterans are affected by assessment method. Given the significant public health problems of SUDs among US veterans, improved guidelines for clinical screening using validated diagnostic criteria to assess AUDs and DUDs in US veteran populations are needed. SCIENTIFIC SIGNIFICANCE: These findings may inform VA and other healthcare systems in prevention, diagnosis, and intervention for SUDs among US veterans.

Targeting an alcohol intervention cost-effectively to persons living with HIV/AIDS in East Africa.

BACKGROUND: In the current report, we ask if targeting a cognitive behavioral therapy (CBT)-based intervention aimed at reducing hazardous alcohol consumption to HIV-infected persons in East Africa would have a favorable value at costs that are feasible for scale-up. METHODS: Using a computer simulation to inform HIV prevention decisions in East Africa, we compared 4 different strategies for targeting a CBT intervention-(i) all HIV-infected persons attending clinic; (ii) only those patients in the pre-antiretroviral therapy (ART) stages of care; (iii) only those patients receiving ART; and (iv) only those patients with detectable viral loads (VLs) regardless of disease stage. We define targeting as screening for hazardous alcohol consumption (e.g., using the Alcohol Use Disorders Identification Test and offering the CBT intervention to those who screen positive). We compared these targeting strategies to a null strategy (no intervention) or a hypothetical scenario where an alcohol intervention was delivered to all adults regardless of HIV status. RESULTS: An intervention targeted to HIV-infected patients could prevent 18,000 new infections, add 46,000 quality-adjusted life years (QALYs), and yield an incremental cost-effectiveness ratio of $600/QALY compared to the null scenario. Narrowing the prioritized population to only HIV-infected patients in pre-ART phases of care results in 15,000 infections averted, the addition of 21,000 QALYs and would be cost-saving, while prioritizing based on an unsuppressed HIV-1 VL test results in 8,300 new infections averted, adds 6,000 additional QALYs, and would be cost-saving as well. CONCLUSIONS: Our results suggest that targeting a cognitive-based treatment aimed at reducing hazardous alcohol consumption to subgroups of HIV-infected patients provides favorable value in comparison with other beneficial strategies for HIV prevention and control in this region. It may even be cost-saving under certain circumstances.

Evaluating interventions to improve antiretroviral adherence: how much of an effect is required for favorable value?

OBJECTIVE: Uncertainty about the value of antiretroviral therapy (ARV) adherence interventions may be a barrier to implementation and evaluation. Our objective is to estimate the minimum effectiveness required for ARV adherence interventions to deliver acceptable value. METHODS: We used a validated HIV computer simulation to estimate the impact of ARV adherence interventions on incremental costs and life expectancy. Across a wide range of intervention costs ($1000-10,000, one time or per year), we estimated the smallest effect size compatible with acceptable value (incremental cost-effective ratio < or =$100,000 per life-year). Effect sizes were measured using relative risk (RR) and absolute risk reduction (ARR), and these metrics were applied to nonadherence and nonadherence risk factors. Costs were estimated from a societal perspective ($2003) discounted at 3%. RESULTS: To give acceptable value, a one-time $1000 intervention must reduce ARV nonadherence by RR < or = 0.82 (ARR > or = 0.04) for moderately nonadherent patients (20% of ARV doses missed) and RR < or = 0.90 (ARR > or = 0.05) for severely nonadherent patients (50% of ARV doses missed). A one-time $5000 intervention has an unacceptable value regardless of effect size for moderately nonadherent patients, and must reduce ARV nonadherence by RR or = 0.69) for severely nonadherent patients. Interventions aimed at behavioral risk factors (e.g., unhealthy alcohol use) may confer acceptable value (e.g., if < or = $2000 and effect RR < or = 0.71 [ARR > or = 0.29]). CONCLUSIONS: ARV adherence interventions with plausible effect sizes may offer favorable value if they cost <$5000 one time or per year. ARV adherence interventions with a favorable value should become more integral components of HIV care.

Estimating alcohol content of traditional brew in Western Kenya using culturally relevant methods: the case for cost over volume.

Traditional homemade brew is believed to represent the highest proportion of alcohol use in sub-Saharan Africa. In Eldoret, Kenya, two types of brew are common: chang'aa, spirits, and busaa, maize beer. Local residents refer to the amount of brew consumed by the amount of money spent, suggesting a culturally relevant estimation method. The purposes of this study were to analyze ethanol content of chang'aa and busaa; and to compare two methods of alcohol estimation: use by cost, and use by volume, the latter the current international standard. Laboratory results showed mean ethanol content was 34% (SD = 14%) for chang'aa and 4% (SD = 1%) for busaa. Standard drink unit equivalents for chang'aa and busaa, respectively, were 2 and 1.3 (US) and 3.5 and 2.3 (Great Britain). Using a computational approach, both methods demonstrated comparable results. We conclude that cost estimation of alcohol content is more culturally relevant and does not differ in accuracy from the international standard.