Influence of alcohol consumption on adherence to and toxicity of antiretroviral therapy and survival

Abstract

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.

Figure 1

Percentage of medication nonadherence on a given calendar day among HIV-positive and HIV-negative patients with different levels of alcohol consumption. The effects of alcohol consumption on the same or a proximal day on medication adherence are shown. “No” denotes a day with no active or recent alcohol consumption, “post” denotes a day with no active alcohol consumption but with alcohol consumption on the previous day, and “yes” denotes a day of active alcohol consumption. HIV-positive patients have a lower threshold at which alcohol impacts nonadherence. SOURCE: Adapted from Braithwaite et al. 2005a.

Figure 2

Percentage of days with medication nonadherence among people who reported consuming alcohol on the same calendar day, stratified by alcohol consumption levels. Panel A shows the data without any adjustment, whereas panel B shows the data with adjustment for each participant’s mean alcohol consumption.* Both panels provide the data for all study participants as well as for HIV-positive and HIV-negative participants separately. Adjusting results for mean daily consumption improves identification of the consumption threshold (approximately two drinks) at which clinically significant nonadherence occurs and reduces apparent differences between HIV-positive and HIV-negative participants. Thus, whereas in unadjusted analyses the threshold at which alcohol impacts adherence appears to be lower for HIV-positive patients than for HIV-negative patients, the curves for the two groups are more similar once consumption has been adjusted for mean daily alcohol consumption. SOURCE: Adapted from Braithwaite et al. 2008. *For the adjustment, the person’s mean daily quantity of alcohol consumed was subtracted from the quantity of alcohol he reportedly consumed on a particular day.

Figure 3

Percentage of days with medication nonadherence among study participants who had consumed alcohol on the same calendar day, with alcohol consumption classified in terms of the participants’ self-rated threshold for cognitive impairment (“none” versus “buzzed” versus “drunk”). Clinically significant nonadherence occurred at drinking levels that resulted in participants reporting feeling “buzzed.” SOURCE: Braithwaite et al. 2008.

Figure 4

Example of an algorithm for integrating alcohol screening and treatment into clinical care of HIV patients. Several possible algorithms are supported by current data. As health informatics and clinical decision supports become more commonplace in clinical care, algorithms such as this one have increasing potential to influence how care is delivered.