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Intentional Medication Non-Adherence Due to Interactive Toxicity Beliefs among HIV Positive Active Drug Users......."Results showed that 189 (35%) participants indicated that they intentionally miss their ART when they are using drugs"
 
 
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JAIDS July 28 2015
 
Kalichman, Seth C. PhD; Kalichman, Moira O. MSW; Cherry, Charsey PhD; Hoyt, Ginger BA; Washington, Christopher BA; Grebler, Tamar BA; Merely, Cindy BA; Welles, Brandi
 
"Unlike unintentional non-adherence, intentionally missing medications stems from beliefs about medication efficacy, necessity, and concerns"
 
"As noted in previous research, interactive toxicity beliefs may result in a sense of having to choose between continued drug use and HIV treatment. (12) Health care providers should assess patient understanding of ART and specifically assess beliefs regarding their medications in relation to substance use. Health care providers are uniquely positioned to counter interactive substance use toxicity beliefs and their associated concerns that impede adherence. Future research should test efficient and effective educational messages to correct interactive toxicity beliefs that contribute to intentional ART non-adherence and treatment failure"
 
"Our results are the first of which we are aware to examine interactive toxicity beliefs and intentional non-adherence among biologically confirmed active drug users.
 
Importantly, we observed a pattern of adherence that is strikingly similar to studies that have focused on self-reported alcohol use and interactive toxicity beliefs. (9, 22) We found significant overlap between intentional non-adherence when using drugs and intentional non-adherence when drinking."
 
"......active drug users demonstrated poor adherence to their HIV medications. The average monthly adherence was 83% of medications taken, with nearly one in five participants having less than 75% adherence over the six-week prospective observation period"
 
"Our results showed that it was common for active drug users with HIV to believe that ART and drugs should not be mixed, and the outcomes from treatment were worse for individuals who said that they do stop taking their medications when using drugs. Our prospective assessment of adherence found that one in four participants who claimed to be intentionally nonadherent indeed did miss their medications because they were either drinking or using drugs over the subsequent month. However, it should be noted that 18% of individuals who did not state they intentionally miss medications at baseline also did not take their medications over the next six weeks because they were drinking or using drugs. This is in addition to the 8% that indicated missing medications because they were intoxicated."
 
" there is emerging evidence that interactive toxicity beliefs regarding addictive drugs are associated with intentional non-adherence to ART. One study of patients in U.S. prison ambulatory HIV clinics found that 77% of patients believed ART is harmful when taken while using heroin, and 61% believed ART was harmful when taken with methadone. (12) In all, 67% of patients stated that they would not take ART if they were planning to get high on 'street drugs'. Results of this study suggest that interactive toxicity beliefs extend beyond alcohol use. However, we are not aware of studies that have examined interactive toxicity beliefs as predictors of ART adherence among active illicit drug users living with HIV infection."
 
"The current study was conducted to determine the degree to which active substance users living with HIV intentionally forego taking their ART when using or planning to use drugs. In a prospective study conducted in Atlanta, GA we tested the hypothesis that active substance users who state that they intentionally stop taking medications when using drugs (intentional non-adherence) would demonstrate greater non-adherence to ART, including missing medications because of the effects of substance use (unintentional non-adherence). We also predicted that intentional non adherence to ART would be directly related to poorer HIV viral suppression."
 
"Results of adjusted models showed that participants who reported intentional non-adherence at the initial assessment were significantly more likely to have poorer adherence over the subsequent six weeks; average of 79% of medications taken compared to 85% for persons who did not report intentionally missing ART.
 
In addition, 32% of intentionally non-adherent participants had detectable HIV viral loads compared to 22% of persons who were not intentionally non-adherent, a significant association. Results found that 25% of intentionally non-adherent participants had purposefully missed taking their medications when using substances over the prospective month of assessment, compared to 18% of individuals who did not state that they intentionally miss their ART
 
Abstract
 
Drug use poses significant challenges to medical management of HIV infection. While most research has focused on the influence of intoxication on unintentional adherence to HIV treatment, drug use may also lead to intentional non-adherence, particularly when individuals believe that mixing medications with drugs is harmful. This study examined whether interactive toxicity beliefs predict non-adherence to antiretroviral therapy (ART) over a prospective period of adherence monitoring. Men and women living with HIV who screened positive for drug use and were being treated with ART (N=530) completed computerized self-interviews, three prospective unannounced pill counts to measure ART adherence, provided urine specimens for drug screening, and HIV viral load results from medical records. Results showed that 189 (35%) participants indicated that they intentionally miss their ART when they are using drugs. These participants also reported common beliefs regarding the perceived hazards of mixing HIV medications with alcohol and other drugs. Multivariable models that controlled for demographic and health characteristics, as well as frequency of alcohol use, showed that intentional non-adherence predicted poorer ART adherence over the prospective month and also predicted poorer treatment outcomes as indexed by unsuppressed HIV viral load. These findings extend previous research to show that interactive toxicity beliefs and intentional non-adherence play a significant role in medication non-adherence for a substantial number of people living with HIV and should be actively addressed in HIV clinical care.
 
"The mean ART adherence for the sample was 83.2% (SD = 18.4, with 25% of participants taking less than 75% of their ART and 37% taking less than 85% of their ART. A total of 189 (35%) active substance users reported that they intentionally stop taking their HIV medications if they are using drugs.....Analyses showed that women were significantly more likely to intentionally miss their medications than men....In addition, intentional non-adherence was associated with lower income, less years of education, and a greater number of years since testing HIV positive"
 
Participants
 
Participants in the current study were men and women living with HIV in Atlanta, GA who were receiving ART and screened positive for active illicit drug use. Specifically, the study entry criteria were (a) 18 years of age or older, (b) HIV positive, (c) prescribed antiretroviral therapy, and (d) tested positive for at least one illicit drug in a urine screening test.
 
Introduction
 
Advances in the medical management of HIV infection have improved the health and increased the life expectancies of people living with HIV. To achieve optimal health outcomes, antiretroviral therapies (ART) demand considerably high-levels of adherence, with even the most forgiving regimens requiring at least 85% adherence to sustain HIV viral suppression. (1, 2) Among the most robust predictors of non-adherence in people living with HIV are alcohol and drug use, which can result in gaps in treatment and uncontrolled HIV replication. (3, 4)
 
The most studied effects of substance use on HIV treatment involve intoxication. (5, 6) However, beyond unintentional non-adherence caused by intoxication, individuals may intentionally forego taking their medications when using alcohol or illicit drugs because they believe that to do so would be harmful, known as interactive toxicity beliefs. Although the hazards of using alcohol and illicit drugs in combination with antiretroviral therapy are well established for individuals with co-morbid liver conditions, such as Hepatitis-C infection, interactive toxicity beliefs are prevalent among HIV patients not diagnosed with co-morbid liver conditions. (7) For example, one-in-four people living with HIV who drink alcohol stop taking their HIV medications when drinking to avoid mixing medications with alcohol. (8, 9) Intentional non-adherence when drinking is also associated with missing medications over and above other predictors of non-adherence, including HIV-related health status, ART side-effects and frequency of alcohol use itself. While interactive alcohol toxicity beliefs contribute to intentional non- adherence, there are few studies of intentional non-adherence in relation to illicit drug use. This study aims to fill this gap by focusing on intentional non-adherence and interactive toxicity beliefs in a sample of people living with HIV who are active illicit drug users.
 
Studies show that continued substance use is common among people living with HIV who have a history of illicit drug use.(10, 11) Like alcohol use, unintentional medication adherence in relation to drugs has primarily been considered a collateral effect of intoxication. (3) However, there is emerging evidence that interactive toxicity beliefs regarding addictive drugs are associated with intentional non-adherence to ART. One study of patients in U.S. prison ambulatory HIV clinics found that 77% of patients believed ART is harmful when taken while using heroin, and 61% believed ART was harmful when taken with methadone. (12) In all, 67% of patients stated that they would not take ART if they were planning to get high on 'street drugs'. Results of this study suggest that interactive toxicity beliefs extend beyond alcohol use. However, we are not aware of studies that have examined interactive toxicity beliefs as predictors of ART adherence among active illicit drug users living with HIV infection.
 
The current study was conducted to determine the degree to which active substance users living with HIV intentionally forego taking their ART when using or planning to use drugs. In a prospective study conducted in Atlanta, GA we tested the hypothesis that active substance users who state that they intentionally stop taking medications when using drugs (intentional non-adherence) would demonstrate greater non-adherence to ART, including missing medications because of the effects of substance use (unintentional non-adherence). We also predicted that intentional nonadherence to ART would be directly related to poorer HIV viral suppression.
 
Results
 
In this sample the most frequently detected drugs were THC (N = 314, 59%) and cocaine (N = 272, 51%). A total of 157 participants screened positive for two drugs and 43 screened positive for three or more drugs. The mean ART adherence for the sample was 83.2% (SD = 18.4, with 25% of participants taking less than 75% of their ART and 37% taking less than 85% of their ART. A total of 189 (35%) active substance users reported that they intentionally stop taking their HIV medications if they are using drugs. Table 1 shows the demographic and health characteristics of individuals who did not and those who did indicate that they intentionally miss their ART when using drugs.
 
Analyses showed that women were significantly more likely to intentionally miss their medications than men. In addition, intentional non-adherence was associated with lower income, less years of education, and a greater number of years since testing HIV positive. Intentional non-adherence was not associated with testing positive for Hepatitis-C virus, reporting a liver disease or other health-related characteristics. With respect to substance use, participants who intentionally miss their medications when using drugs reported greater frequency of alcohol use and more alcohol-related problems than their counterparts who do not intentionally miss their medications. (see Table 2) There were no associations between specific drugs detected and intentional non-adherence.
 
Interactive toxicity beliefs
 
Results showed that individuals who stated that they intentionally miss taking their ART when using drugs endorsed all of the interactive toxicity beliefs to a greater degree than those who are not intentionally non-adherent. (see Table 3) While it was common for both groups to endorse beliefs that substances and ART should not be mixed, only intentionally non-adherent participants indicated that people should stop taking ART when using substances. Overall more than half of individuals who were intentionally non-adherent endorsed all three of the interactive toxicity beliefs. In addition, 56% of those who were intentionally non-adherent when using drugs reported that they would also stop taking ART when drinking alcohol, compared to only 8% of participants who do not intentionally miss medications.
 
HIV treatment adherence and HIV suppression
 
Table 4 shows the results for the multivariable models that tested the association between intentionally not taking ART when using drugs and prospective HIV treatment adherence and HIV viral suppression. These analyses controlled for gender, education, income, CESD-depression scores, years since testing HIV positive, and frequency of alcohol use. Results of adjusted models showed that participants who reported intentional non-adherence at the initial assessment were significantly more likely to have poorer adherence over the subsequent six weeks; average of 79% of medications taken compared to 85% for persons who did not report intentionally missing ART. In addition, 32% of intentionally non-adherent participants had detectable HIV viral loads compared to 22% of persons who were not intentionally non-adherent, a significant association. Results found that 25% of intentionally non-adherent participants had purposefully missed taking their medications when using substances over the prospective month of assessment, compared to 18% of individuals who did not state that they intentionally miss their ART. In contrast, there were no differences between the two intentional non-adherence groups on prospectively missing medications attributed to intoxication.
 
DISCUSSION
 
Consistent with past research we found that active drug users demonstrated poor adherence to their HIV medications. The average monthly adherence was 83% of medications taken, with nearly one in five participants having less than 75% adherence over the six-week prospective observation period. Our results showed that it was common for active drug users with HIV to believe that ART and drugs should not be mixed, and the outcomes from treatment were worse for individuals who said that they do stop taking their medications when using drugs. Our prospective assessment of adherence found that one in four participants who claimed to be intentionally nonadherent indeed did miss their medications because they were either drinking or using drugs over the subsequent month. However, it should be noted that 18% of individuals who did not state they intentionally miss medications at baseline also did not take their medications over the next six weeks because they were drinking or using drugs. This is in addition to the 8% that indicated missing medications because they were intoxicated.
 
These findings again demonstrate the high-degree of variability in adherence behavior, a factor that should be taken into consideration when screening for adherence interventions. In addition, these results reflect the broad effects of substance use on adherence, including intentionally and unintentionally missing medications. These findings therefore demonstrate an urgent need to address interactive toxicity beliefs among active drug users who are intentionally non-adherent to ART.
 
Our results are the first of which we are aware to examine interactive toxicity beliefs and intentional non-adherence among biologically confirmed active drug users. Importantly, we observed a pattern of adherence that is strikingly similar to studies that have focused on self-reported alcohol use and interactive toxicity beliefs. (9, 22) We found significant overlap between intentional non-adherence when using drugs and intentional non-adherence when drinking. Although taking ART with alcohol and other drugs is hazardous for patients with co-morbid liver conditions, our results were not accounted for by co-occurring liver disease. Patients with healthy liver functions may do more harm by being non-adherent to ART than from taking ART with alcohol and drugs. The association between intentional non-adherence and treatment outcomes was significant in multivariable models that adjusted for alcohol use and other factors. These findings therefore build confidence in previous research to show that interactive toxicity beliefs are prevalent among people living with HIV and account for some degree of nonadherence and treatment failure among those who continue active substance use.
 
The current study should be interpreted in light of its methodological limitations.
 
First, the sample was one of convenience and cannot be considered representative of people living with HIV infection. Participants were recruited from multiple clinical services as well as through chain referrals. We cannot therefore know the range of care and clinical services that participants were receiving. In addition, participants in this study were taking a variety of ART regimens and we did not have information on their duration of treatment. The study also relied on self-report instruments to assess interactive toxicity beliefs and alcohol use. While each of these measures was collected using state of the science procedures, they may still be subject to biases. Socially sensitive behaviors such as alcohol use assessed by self-report may be underreported, suggesting that rates of drinking in this study should be considered lower-bound estimates. A strength of this study was our use of a biological screening test to determine current drug use. However, because the screening test only detected drug use in the past 72 to 96 hours we may have omitted active drug users from the study.
 
Another limitation of our study was our definition of non-adherence applied equally to all medication regimens, which differ in their demand for optimal adherence. (1, 23, 24) With these limitations in mind, we believe that the current study results have important implications for improving HIV treatment adherence among people who are receiving ART and actively use drugs.
 
Adherence interventions that specifically target people living with HIV who continue drug use have shown inconsistent evidence of effectiveness. (25) While there are multiple challenges to improving ART adherence posed by intoxication and other drug-related factors, our data show that intentional non-adherence presents additional barriers to treatment. Unlike unintentional non-adherence, intentionally missing medications stems from beliefs about medication efficacy, necessity, and concerns. (26) As noted in previous research, interactive toxicity beliefs may result in a sense of having to choose between continued drug use and HIV treatment. (12) Health care providers should assess patient understanding of ART and specifically assess beliefs regarding their medications in relation to substance use. Health care providers are uniquely positioned to counter interactive substance use toxicity beliefs and their associated concerns that impede adherence. Future research should test efficient and effective educational messages to correct interactive toxicity beliefs that contribute to intentional ART non-adherence and treatment failure.

 
 
 
 
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