Academic journal article Alcohol Research

Influence of Alcohol Consumption on Adherence to and Toxicity of Antiretroviral Therapy and Survival

Academic journal article Alcohol Research

Influence of Alcohol Consumption on Adherence to and Toxicity of Antiretroviral Therapy and Survival

Article excerpt

Antiretroviral therapy (ART) has substantially altered the fate of HIV-infected people, transforming the infection from an invariably fatal disease to a chronic condition manageable by pharmacotherapy. However, in order for ART to be effective, patients must adhere strictly to an often-demanding treatment regimen. Alcohol consumption may impact survival of HIV-infected patients through a variety of pathways. Some of these are not related to the effectiveness of ART (e.g., alcohol-induced immunosuppression that exacerbates the HIV-related immunosuppression, increased hepatotoxicity, and increased mortality from non-HIV-related causes). However, some pathways mediating alcohol's negative effect on survival are related to ART effectiveness. In particular, alcohol consumption may reduce adherence to ART, leading to decreased ART effectiveness and, ultimately, increased HIV-related mortality. Both clinical data and computer simulations have yielded information about the impact of alcohol consumption on medication adherence in both HIV-infected and noninfected patients. The findings suggest that alcohol-related nonadherence may account for a substantial amount of preventable mortality among HIV-infected patients. These findings may have clinical implications with respect to optimal treatment for HIV-infected patients who also consume alcohol. KEY WORDS: Alcohol consumption; human immunodeficiency virus (HIV); HIV treatment; antiretroviral therapy; medication adherence; immunosuppression

Combination antiretroviral therapy (ART)-highly potent therapy "cocktails" of three or more antiretroviral drugs (ARVs)-has transformed HIV care. Prior to the advent of ART in the late 1990s, infection with the human immune deficiency virus (HIV) was viewed as a "death sentence." Thus, in 1995, the standardized annual mortality rate was approximately 500 per 1,000 personyears (Hooshyar et al. 2007), and acquired immune deficiency syndrome (AIDS) was the most prevalent cause of death among individuals aged 25-44 in the United States (Centers for Disease Control and Prevention 1994). Following the introduction and dissemination of combination ART, deaths from HIV infection plummeted to onefifth of their prior level (i.e., 100 per 1,000 personyears in 2002) (Hooshyar et al. 2007). This sharp reduction in HIV mortality suggests that approximately 80 percent of deaths in HIV-infected individuals are being prevented or postponed through the availability of ART. As a result, HIV infection has metamorphosed into a chronic disease manageable with pharmacotherapy.

Although HIV-related deaths have declined dramatically from their peak in the preART era, preventable HIV-related deaths still are common among the many patients who do not adhere strictly to their ARV medications. ART typically involves a complex regimen of several pills that must be taken at different times during the day, and to ensure its longterm effectiveness, at least 95 percent of drug doses need to be taken exactly as directed (Paterson et al. 2000). However, studies found that only 39 percent to 91 percent of ART doses are taken as directed (Braithwaite et al. 2007; Chesney et al. 2000), resulting in reduced treatment effectiveness. Alcohol consumption is a strong and consistent risk factor for poor ART adherence across a wide spectrum of patient cohorts and care settings (Cook et al. 2001; Lucas et al. 2002; Samet et al. 2004; Tucker et al. 2003). This article explores the pathways through which alcohol consumption may impact survival among HIV-infected people, particularly those related to reduced ART adherence.

IMPACT OF ALCOHOL CONSUMPTION ON HIV MORTALITY

Alcohol consumption may increase mortality among HIV-infected patients through many pathways. Some of these are mediated by alcoholinduced changes in ART effectiveness, whereas others are independent of ART effectiveness. This article emphasizes pathways mediated through changes in ART adherence, because the high proportion of HIV- deaths preventable by ART suggests that ART adherence has a substantial effect on preventable mortality and morbidity. …

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