Effects of Lifetime History of Use of Problematic Alcohol on HIV Medication Adherence

Abstract

Background:

The effects of previous alcohol abuse on antiretroviral therapy (ART) adherence have been less studied.

Materials and Methodology:

Participants were randomized to a 3-month group intervention or an individual-enhanced standard-of-care condition and assessed over 6 months. Individual assessment at baseline, 3, and 6 months was done; interviews included lifetime history of problematic alcohol use.

Results:

A total of 80 HIV-positive individuals on ART were recruited. In all, 35% of participants reported a history of problematic alcohol use, 37% had a detectable viral load, 55% were nonadherent, and 24% reporting skipping medication in the previous 3 months. There was no association between a history of problematic use and an adherence at any time point, that is, at baseline (t = −.7, P = .47), midpoint (t = −.39, P = .69), and 6-month follow-up (t = −1.2, P = .23).

Conclusion:

Results suggest that a history of problematic alcohol use may not impact ART adherence.

Introduction

Antiretroviral therapy (ART) has resulted in significant reductions in morbidity and mortality of HIV-infected individuals. However, the complex antiretroviral (ARV) drug combination can be difficult to take as the drugs may need to be taken at work, in strict relationship with meals, or may interfere with normal sleep times. ^1,2 Highly active antiretroviral therapy (HAART) can profoundly inhibit viral replication and delay disease progression. To achieve this in clinical practice, strict adherence to complex drug combination is required; missing even a few doses can result in the development of resistance strains of HIV. ³ The development and transmission of resistant or mutant viral strains are of public health importance.

A variety of factors predict medication adherence among HIV-infected adults ⁴ ; however, there is scarcity of the information available on the relationship between previous problematic alcohol use and medication adherence. ⁵ It is important to know the impact of alcohol on HIV medication adherence, as available data suggest that significant proportion of HIV clinic populations exhibits moderate to problem drinking behaviors. ⁶ Here problem drinking is defined as alcohol consumption sufficient to lead to health problems and decrements in social functioning, which do not necessarily meet the diagnostic criteria for alcohol abuse or dependence. ⁷ Problem drinking includes hazardous, heavy, and binge drinking. Previous studies have demonstrated that individuals who use alcohol may be less willing to begin ARV treatment and have greater difficulty in adhering to treatment regimens as compared with individuals who do not engage in substance use. Nonadherence to ARV treatment may be an important factor in the relationship between alcohol abuse and HIV disease progression, including the development of psychiatric symptoms and mental impairment. The burden of alcohol-related disease transmission is especially high in South Africa, ⁸ yet little is known about the patterns of alcohol use, which interfere with ARV medication adherence. This study was carried out to estimate the association of a lifetime history of problem drinking and medication nonadherence. Second, this study sought to explore the association between a lifetime history of problematic drinking and an HIV viral load (VL).

Methods

This randomized controlled trial was conducted in the Department of Internal Medicine of a tertiary care hospital and research institute, the Post Graduate Institute of Medical Education & Research in Chandigarh, Northern India. HIV-infected individuals were recruited from the Immunodeficiency Clinic by study staff not associated with patient care. The enrollment period extended over 2 years, from 2009 to 2011. Participants were randomly assigned to condition, that is, group (medication adherence intervention [MAI]) or individual (enhanced standard of care) and followed for 6 months. Participants completed psychosocial, behavioral, and biological assessments at baseline, 3, and 6 months.

Study Cohort

HIV-infected men and women enrolled to participate were new to ARV treatment (ie, within 3-12 months of ARV treatment initiation), at least 18 years of age and capable of providing informed consent. Those individuals who were currently pregnant or breast-feeding, previously exposed to nevirapine (NVP) at the time of labor, currently hospitalized, mentally ill, actively using illegal drugs, or hospitalized were excluded from the study participation. In addition, those reporting problematic alcohol use at the time of enrollment were excluded and referred for on-site care at the alcohol and substance use treatment unit. Participants were randomized to study condition using a table of random numbers following baseline assessment. Individuals reporting a lifetime history of problematic alcohol use were counseled to refrain from alcohol or substance use. The study group assigned to MAI condition was led by trained health practitioners and nonmedical psychologists in which participants received 1-month, 1-hour sessions of medication information combined with problem-solving skills in an experimental/interactive group format. The control group was assigned to an enhanced standard-of-care condition in which participants were shown nutritional videos and videos related to general health, without specific information on ART adherence. Adherence was assessed monthly by pill count, pharmacy refill, and self-reported skipped medication doses within the previous 3 months. Current self-reported adherence was assessed using a visual analog scale in combination with a pill count assessment conducted by a pharmacist at each study visit. Lifetime problematic alcohol use and current alcohol use were assessed by participant self-report. Biological assessment of disease status and treatment outcome was assessed using CD4 count and VL.

Statistical Analyses

Adherence was determined by the maximum amount of pills to be taken in once daily dose (2 or 4 pills for all participants), accounting for the time of day the participants were assessed, assuming that at the time of assessment they may not have yet taken all their pills for the day. The amount taken (and the correct amount to be taken) was assessed by pill count and corroborated using pharmacy refill records. Changes in adherence over time were dichotomized as either improved adherence or decreased/same level of adherence. Viral loads and CD4 counts were log transformed. Data analyses were conducted using chi-square (χ ² ) tests of independence, mixed between-within analysis of variance to assess group differences, and logistic regression using a 2-tailed significance level of .05 to assess the ability of associated psychosocial measures to predict the improvement in adherence. Missing data were excluded via pairwise deletion. All tests were performed using IBM SPSS version 19.0. We hypothesized that a lifetime history of problematic alcohol abuse is associated with low levels of medication adherence. The effects of structured adherence intervention and counseling on problem drinking were compared with an enhanced standard of care for adherence to ARV medication.

Ethical Clearance

Prior to study onset, institutional review board (IRB) approval was obtained from the University of Miami IRB, and ethical review committee approval was obtained from the Post Graduate Institution for Medical Education & Research (PGIMER), the Indian Council of Medical Research (ICMR), and the National AIDS Control Organization (NACO).

Results

A total of 80 participants (70 males and 10 females) were recruited over a 1-year period. The mean age was 38.1 ± 8.6 years. In all, 62% reported living in a rural area, 78% were married, and nearly half (49%) of spouses were HIV positive. Half of the sample had a primary school level of education, and most had a monthly income of ≤3000 INR (Indian rupees). The mean time since HIV diagnosis was 18.2 ± 24.6 months, and the mean time on ARVs was 6.9 ± 3.0 months. Pill count adherence was not associated with time on ARV medications (r = .16, P = .17), distance from clinic (r = −.07, P = .54), income (r = .06, P = .73), and having an HIV-positive spouse (χ ² = .45, P = .51). Outliers (±2 standard deviations from the mean, n = 2) were removed from the analysis of baseline adherence scores; however, there was no difference in outcomes obtained when including or excluding outliers identified at baseline. All participants were included in the follow-up analyses. At baseline, 56% of group condition and 54% of individual condition participants were nonadherent by pill count and 23% of group and 26% of individual condition participants self-reported skipping their medication at least once over the last 3 months; pill count and self-report were not associated (r = −.16, P = .15).

Problematic Alcohol Use, Adherence, and Health Outcomes

At baseline, of the total sample, 28 (35%) participants endorsed a history of problematic alcohol use and 30 (37%) participants had a detectable VL. A comparison between problem users and nonproblem users did not identify differences in continuous (t = .50, P = .62) and dichotomous VL outcomes (χ ² =.53, P = .47), indicating there was no difference in mean VL between those with a history of problematic alcohol use and those without. At baseline, 55% were nonadherent by pill count and 24% reporting skipping medication in the previous 3 months.

Long-Term Adherence Outcomes

There was no association between a history of problematic alcohol use and adherence by pill count at each of the 3 time points, baseline (t = −.7, P = .47), midpoint (t = −.39, P = .69), and 6-month follow-up (t = −1.2, P = .23). In order to evaluate the impact of the history of problematic alcohol use on adherence, change in adherence scores were calculated by subtracting the baseline from the midpoint adherence scores and the midpoint from the long-term follow-up scores. Scores were dichotomized as either improved adherence (post- to preintervention < 0) or unchanged/decreased adherence (post- to preintervention ≥ 0). Postintervention adherence in both the conditions improved (Fisher exact test, P < .001), and there was no difference in pill count adherence between the conditions (χ ² = .07, P = .79). Similar to the improvements in adherence at midpoint demonstrated previously in the entire sample (eg, Jones et al, 2012), improvements were obtained among the subsample of participants with a history of problematic alcohol use (P ≤ .001), and no differences were identified between the improvements within conditions among those with a history of alcohol problems. ⁹

Discussion

Alcohol use is a growing public health problem within the context of HIV infection and treatment adherence, highlighting a need to examine previous alcohol problems and its impact on adherence among HIV-infected individuals. Problem drinking associated with decreased medication adherence demonstrates the importance of performing pretreatment assessments of alcoholism prior to the initiation of HIV medications, including in-depth assessments of frequency of use and family/living situation and subsequent counseling on the negative effects of alcohol on ART. Patients should especially be educated on the potential for harmful and sometimes fatal drug–drug interactions. Cook and colleagues found that problem drinking affected at least 1 in 5 persons in Pennsylvania clinics. ¹⁰ The National Survey of Drug Use in India recorded alcohol use in the past year among 21% of adult males assessed; current use of alcohol ranged from 7% to 75%. ¹¹ In a study of problem drinking in a medical population, Sri and colleagues reported problem drinking among almost a quarter (23.3%) of medical and surgical inpatients in a general hospital using the CAGE questionnaire. ¹² Patients presenting with a history of alcohol or substance abuse may also be experiencing cognitive and memory difficulties, which may also account for nonadherence among HIV-positive individuals no longer using alcohol.

Our study results support those found in a previous study by Hinkin et al, ⁴ in which current drug use or drug dependence but not current alcohol abuse or alcohol dependence was associated with suboptimal medication adherence. ⁴ Longitudinal assessments of the effects of drug and alcohol abuse on HIV outcomes have showed that substance abuse continues to be a major risk factor in contracting HIV and that substance abuse is associated with further deleterious outcomes on adherence. ¹³ In this study, of the total sample, one-third of participants had a history of problematic alcohol use and slightly more than one-third had a detectable VL. Earlier in vitro studies have reported increased viral replication in cells exposed to alcohol, suggesting that alcohol has a direct effect on disease progression. ¹⁴ However, a comparison between problem users and nonproblem users did not identify differences in continuous or dichotomous VL outcomes, indicating that there was no difference in the mean VL between those with a history of problematic alcohol use and those without. This suggests that a history of heavy alcohol use may not have the negative effects on this population that are associated with current use.

There was no association between the history of problematic alcohol use and adherence by pill count over the 6-month course of study participation. Consistent with earlier studies by Hinkin et al ⁴ and Halkitis et al, ⁵ no association was found between alcohol consumption and nonadherence ^4,5 and HAART administration. ¹⁵ In contrast, several key studies have shown considerable and consistent association between alcohol consumption and nonadherence to HIV medication, such as Hicks and colleagues in 2007. ¹⁶ For example, in a study by Cook et al, HIV-infected individuals with problem drinking were more likely to report taking medicine off schedule as compared with the HIV-infected people without problem drinking. ¹⁰ Among problem drinkers, those without hazardous drinking were more likely to miss a dose followed by those with binge drinking and heavy drinking. ¹⁷ In fact, all levels of drinking were associated with higher odds of not using HAART compared to alcohol abstinence, such that dose-dependent worsening of adherence was found to exist with increasing alcohol consumption. ¹⁷ The highest degree of nonadherence was found in those in whom alcohol use was classified as problem drinking (defined as meeting criteria for an alcohol use disorder). ¹⁸ There may be various factors contributing to the association between alcohol consumption and nonadherence. HIV medication users are advised to refrain from alcohol consumption, due to both the potential for harmful interactions and the harmful side effects of drinking (eg, the role of forgetfulness), ¹⁹ which might interfere with medication adherence ²⁰ and treatment. Sankar et al reported that people who consume less alcohol missed medication more often. ¹⁹ In addition, a history of alcohol use has been correlated with lifetime tendency toward high-risk sexual behavior, ²¹ increasing the likelihood of sexual transmission of the virus.

Although participants in this study with a lifetime history of alcohol abuse were not found be less medication adherent, preventing alcohol use, abuse, or dependence in patients with history of problematic drinking, before the initiation of ARVs, may have significantly improved ART adherence and HIV-treatment outcomes. Antiretroviral therapy counseling and preparedness of an individual prior the initiation of ARV medications have prime importance in improving the adherence outcomes and in reducing the risk of transmission of resistant HIV virus. Counseling for medication adherence and engagement in care have taken a central role in HIV-treatment recommendations, and clinicians should continue to work with patients to devise tailored strategies to deal with more effective alcohol treatment in HIV-infected individuals, with the goal of enhancing medication adherence and preventing drug toxicities and resistance.

Conclusion

Concurrent alcohol intake along with ARV medications has been known to decrease adherence. This study highlighted that the lifetime history of problematic alcohol use may not impact ART adherence. Adherence to ART and VL suppression may be achievable at levels similar to patients without lifetime history of problematic alcohol use if abuse or dependence ceases at the initiation of medication. Future studies should examine the interventions to reduce alcohol abuse or dependence in this population.