The present paper describes the possible connection between alcohol consumption and adherence to medicine used to treat human deficiency viral (HIV) infection. Highly active antiretroviral therapy (HAART) has a positive influence on longevity in patients with HIV, substantially reducing morbidity and mortality, including resource-poor settings such as South Africa. However, in a systematic comparison of HAART outcomes between low-income and high-income countries in the treatment of HIV-patients, mortality was higher in resource-poor settings. Specifically, in South Africa, patients often suffer from concomitant tuberculosis and other infections that may contribute to these results. Alcohol influences the use of medicine for opportunistic infections (e.g., pneumonia, tuberculosis), or coinfections HIV-hepatitis viruses-B (HBV) and C (HCV), cytomegalovirus, or herpes simplex virus. Furthermore, alcohol use may negatively impact on medication adherence contributing to HIV progression. The materials used provide a data-supported approach. They are based on analysis of published (2006–2011) world literature and the experience of the authors in the specified topic. Intended for use by health care professionals, these recommendations suggest approaches to the therapeutic and preventive aspects of care. Our intention was to fully characterize the quality of evidence supporting recommendations, which are reflecting benefit versus risk, and assessing strength or certainty.
Failure to recognize alcohol behaviour remains a significant problem that impairs efforts directed towards the prevention and management of patients with alcoholic liver damage. Although there are limitations in the available data, the World Health Organization’s Global Alcohol database, which has been in existence since 1996, has been used to estimate worldwide patterns of alcohol consumption, and it allows comparisons of alcohol-related morbidity and mortality. The burden of alcohol-related disease is highest in the developing world, including South Africa. Pithey and Parry [
We performed a systematic review of published PubMed literature, searching for articles that contained information about “alcohol”, “HIV” and “antiretroviral therapy” published between January 2006 and June 2011. We did not limit our search to literature published in English. We found over 365 results using the key words “alcohol,” “adherence,” “ART” and “HIV,” from which we selected 230 articles that we analyzed.
From these initial results, we selected 25 articles to be included in the “disease progression” sections and 38 articles to be included in the “adherence” section. Particular attention was placed on those papers that provided an indication of the type and the amount of alcohol consumed. In order to obtain more focused results so that we could, where necessary, refer to South Africa, we also included the words “South Africa” in the search. However, we did not have “South Africa” as an exclusion criterion. Main reasons for excluding articles include poor characterization of alcohol consumption patterns, incomplete or poor characterization of adherence to medication or/and disease progression,
Although not specific for the main topics discussed, some relevant papers published prior to 2006 contained important information that was used to reinforce our arguments and were therefore discussed as well.
Figure
Methods used for literature search.
Rehm and Parry [
Interactions between Alcohol and HIV Disease Progression.
Ref. | Study settings | Population characteristics | Alcohol use patterns | Main findings |
---|---|---|---|---|
[ | USA | 696 HIV positive patients | 10.4% reported hazardous drinking (>14 drinks/week or >4 drinks/occasion for men and >7 drinks/week or >3 drinks/occasion for women) | Hazardous drinking associated with liver disease, defined as aspartate aminotransferase to platelet ratio index >1.5 (RR 3.72, 95% CI 1.40–9.87) |
[ | Italy | 190 patients (71 HIV monoinfected, 53 HCV monoinfected and 66 HIV/HCV coinfected) | The extent of advanced liver fibrosis, defined as liver stiffness ≥9.5 kPa, correlate with alcohol intake (nonsignificant in HIV monoinfected patients, | |
[ | France | 20940 HIV positive patients | Alcohol consumption of any kind in 25 (92.6%) of 27 patients who died from end-stage liver disease | Proportion of excessive alcohol consumption higher in 2003 compared to 1995 ( |
[ | France | 24000 HIV positive patients | Excessive alcohol consumption (>30 g/day) reported in 23 (47.9%) of 48 patients who died from end-stage lived disease | The combination of alcohol and HCV coinfection led 12 (25.0%) deaths |
[ | France | 210 HIV positive patients with a history of injectable drug use or HCV (60 HIV positive and 150 HIV-negative). | 76 patients suffered from excessive drinking, with similar rate between HIV positive individuals and HIV-negative individuals | HIV positivity (OR 2.2, CI 1.1–4.5) and excessive drinking (OR 1.9, CI 1.0–3.9) independently associated with cirrhosis |
[ | Spain | 2168 HIV positive patients, including 181 (8.3%) cases of cirrhosis | 95 (52.5%) cirrhotic patients admitted current or past alcohol abuse | Alcohol consumption associated with cirrhosis (OR 3.5, 95% CI 2.5–4.8, |
[ | Spain | 91 HIV positive patients 30 (33.0%) patients suffered from liver toxicity | High alcohol consumption risk factor for liver toxicity (OR 3.35, 95% CI 2.43–4.62, | |
[ | USA | 164 HIV positive patients | Patients consumed alcohol 88 (53.6%) were hazardous drinkers | Hazardous drinking associated with worsening of dyslipidemia (OR 3.18, 95% CI 0.99–12.05, |
[ | USA | 300 HIV positive patients, | 60% of sample reported prior or current alcohol abuse | Alcohol use independent predictor for pneumonia in HIV positive smokers ( |
[ | Spain | 122 HIV-infected adults | Alcohol abuse independent predictor for bacteremic pneumococcal disease (OR 5.28) | |
[ | Spain | 25 HIV-1-postive patients with cerebrovascular ischemia | Cerebrovascular ischemia associated with history of high alcohol intake (OR 7.13, 95% CI 1.69–30.11, | |
[ | USA | 72 HIV-negative light/nondrinkers, 70 HIV positive light/nondrinkers, 70 HIV positive heavy drinkers and 56 HIV-negative heavy drinkers | 142 (53.0%) light/nondrinkers | Synergistic interaction between alcohol abuse and HIV infection with respect to motor and visuomotor speed |
[ | USA | 31 male HIV positive patients, 27 patients with alcoholism, 43 patients with HIV infection and alcoholism comorbidity, and 22 normal healthy controls | 70 (56.9%) patients with alcoholism | HIV and alcoholism comorbidity impair upper motor limb to a greater degree that HIV alone ( |
[ | USA | 40 HIV positive patients, 38 alcoholic patients, 47 alcoholic HIV positive patients, and 39 controls | 85 (51.8%) patients with alcoholism | Immediate episodic memory impaired in HIV positive patients with alcoholism comorbidity |
[ | USA | 1539 HIV positive patients | 845 (54.9%) had a history of alcohol abuse or dependence | History of alcohol abuse or dependence not associated with neuropathic pain caused by HIV-associated sensory neuropathy |
[ | Italy | 76 HIV positive patients with bacterial community-acquired pneumonia 32 (42.1%) were receiving ART | 25 (32.9%) alcohol abusers | Alcohol abuse not associated with a longer time before clinical stability was achieved |
[ | USA | 299 HIV positive patients. | Amount of alcohol consumed per week or alcohol overuse not predictors of liver test abnormalities | |
[ | France | 1175 HIV-infected patients | Alcohol consumption not associated with HCV-related serious adverse reactions |
Neuman et al. [
Neuman et al. [
The following section will review several studies that analyzed the relationship between alcohol misuse and HIV disease progression. Two important laboratory determinants of the rate of disease progression are the CD4+ cell counts and the plasma viral load.
Hazardous drinking is often associated with liver disease [
From 287 deaths that occurred in 2005 among 24000 HIV positive patients followed at multiple centers in France, 48 (16.7%) can be attributed to end-stage liver disease [
While both HIV positivity and excessive drinking were independently associated with cirrhosis, the proportion of patients with cirrhosis was higher in HIV positive individuals (18/60, 30.0%), compared to HIV-negative individuals (23/150, 15.3%) (
Among 181 cases of liver cirrhosis in a large sample of 2168 HIV positive patients, 149 (82.3%) were caused by HCV, 3 (1.6%) were caused by HBV, 5 (2.8%) were caused by dual HBV/HCV coinfection, and 12 (6.6%) were caused by triple HBV/HCV/hepatitis D virus coinfection [
Many processes related to the consumption or breakdown of alcohol that contribute to alcohol-induced liver disease are mediated by small proteins known as cytokines, which are produced and secreted by liver cells and many other cells throughout the body [
Dyslipidemia, consisting of hypertriglyceridemia, low high-density lipoprotein (HDL) cholesterol, and elevated low-density lipoprotein (LDL) cholesterol, is being observed with increasing frequency among persons living with HIV. Hazardous alcohol consumption, particularly among Hispanic individuals and in individuals consuming the highest amounts of alcohol, worsens dyslipidemia [
Alcohol use and not being on HAART (
Cerebrovascular ischemia was associated with a history of high alcohol intake, and fewer months on HAART (OR 0.97, 95% CI 0.96–0.99;
A history of alcohol abuse or dependence was not associated with neuropathic pain caused by HIV-associated sensory neuropathy [
Significant differences were found between HIV positive heavy drinkers and HIV-negative light drinkers with respect to motor and visuomotor speed, pointing to a synergistic interaction between alcohol abuse and HIV infection [
Impaired upper limb function was observed between clinical groups (HIV positive patients, patients with alcoholism, and patients with HIV infection and alcoholism comorbidity) and controls in terms of upper motor composite score (
Immediate episodic memory was found to be impaired in HIV positive patients suffering from alcoholism, compared to either HIV positive patients without a drinking problem, HIV-negative patients suffering from alcoholism or normal controls [
Alcohol abuse was not associated with a longer time before clinical stability was achieved among patients who developed bacterial community-acquired pneumonia [
While alcohol abuse is generally associated with HIV disease progression, several studies did not find such an association. For example, Crum-Cianflone et al. [
Compared to healthy noninjecting drug users (IDU), HIV patients who were not alcohol abusers (control population), HIV IDU only, HIV alcohol abusers, and IDU alone were each significantly associated with a lower level of CD4+ lymphocyte recovery (
Table
The Role of Alcohol on the Immune System and the HIV Viral Load.
Ref. | Study settings | Population characteristics | Alcohol use patterns | Main findings |
---|---|---|---|---|
[ | USA | 220 HIV-1-infected IDUs receiving HAART | Heavy alcohol consumption (daily or 3-4 times per/week) reported in 139 (63.2%) patients. | Heavy alcohol consumption associated with 4 times lower chance of achieving undetectable viral load and 2 times higher chance of having a CD4+ cell count of <500 cells/ |
[ | USA | 595 HIV positive patients | 245 (41.2%) subjects consumed alcohol | Heavy alcohol consumption associated with lower CD4+ cell counts only among subjects not on ART ( |
[ | USA | 231 HIV positive drug users | 126 (54.5%) participants consumed alcohol There were 53 (22.9%) frequent alcohol users (≥2 alcoholic drinks daily). | Frequent alcohol use (≥2 drinks/day) associated with CD4+ cell counts ≤200 cells/ |
[ | USA | 391 HIV positive patients | 154 (39.4%) report past week alcohol consumption with mean number of 4 drinks | Consuming >5 drinks/week predictor for unsuppressed viral load (≥400 copies/mL) (OR 4.2, 95% CI 1.1–18.5, |
[ | USA | 2056 HIV-infected women and 569 HIV-uninfected women | 33.6% of HIV positive women consumed ≥8 drinks/week 51.8% of HIV positive women consumed 1–7 drinks/week | Consuming ≥8 drinks/week related to higher risk of death (OR 3.39, 95% CI 1.54–7.44, |
[ | USA | 2702 HIV positive patients | Individuals were categorized as nondrinkers (no alcohol consumption), hazardous drinkers (consume ≥5 standard drinks on drinking days), and nonhazardous drinkers (consume <5 standard drinks on drinking days) | Nonhazardous alcohol consumption decreased survival by >1 year if frequency of consumption was ≥1/week, and by 3.3 years with daily consumption (from 21.7 years to 18.4 years). |
Alcohol abuse after contacting HIV seems to accelerate disease progression through a direct effect on CD4+ cells. Of note is the detrimental role played by alcohol consumption on CD4+ cell counts, particularly among individuals not on ART [
In patients not on ART, heavy alcohol consumption was associated with lower CD4+ cell counts compared to patients with a history of abstinence. At-risk drinkers (4 drinks/week for women and 5 drinks/week for men) were less likely to have a current HAART prescription (
The type of alcohol being consumed is important with regards to outcome in HIV positive patients currently taking HAART [
Moderate alcohol use (<1 drink per day for the past 6 months) did not significantly increase the rate in CD4+ cell count decline to ≤200 cells/
Consuming ≥8 alcoholic drinks/week was related to a higher risk of death [
Drug and/or alcohol abuse and suboptimal ART adherence are predictors of virological failure [
Alcohol Consumption and Nonadherence to ART.
Ref. | Study settings | Population characteristics | Alcohol use patterns | Main findings |
---|---|---|---|---|
[ | USA | 391 HIV positive patients | 154 (39.4%) report past week alcohol consumption, for a mean number of 4 drinks | At-risk drinkers (4 drinks/week for women and 5 drinks/week for men) are less likely to have current HAART prescription ( |
[ | USA | 1074 HIV positive patients | 315 (29.4%) patients presented with current or past history of drugs and/or alcohol abuse | Current or past history of drugs and/or alcohol abuse (OR 2.10, 95% CI 1.32–3.35, |
[ | USA | 43 HIV positive children | Alcohol abused by caregiver | Substance use by the caregiver associated with having higher viral loads in children patients ( |
[ | USA | 197 HIV-infected individuals with history of alcohol problems who were receiving HAART | 79 (40.1%) use alcohol | HIV positive drinkers less adherent to HAART than HIV positive alcohol abstainers ( |
[ | USA | 1944 HIV positive patients | 55% of 640 men and 28% of 1304 women consumed low levels of alcohol | Binge drinking (OR 1.75, 95% CI 1.17–2.64, |
[ | USA | 82 HIV positive African-American patients | Alcohol can affect ART adherence through conscious decisions to skip medication while drinking and not through drunken forgetfulness | |
[ | USA | 5887 HIV positive patients | 3573 (60.7%) respondents report alcohol use in past 12 months | Alcohol use in past 12 months associated with nonadherence (OR 1.3, 95% CI 1.1–1.5, |
[ | USA | 105 HIV positive patients without alcohol dependence | Mean monthly alcohol consumption was | Monthly alcohol consumption associated with missed medication in the past 2 weeks (OR 1.08, CI 1.02–1.15, |
[ | USA | 275 HIV positive patients with alcohol use disorders | An average of 84.9 standard drinks over the thirty days prior to the baseline interview | Alcohol consumption ( |
[ | USA | 1671 HIV positive women | 60% of sample were abstainers and 26% were light drinkers (<3 drinks/week) | Light drinking (<3 drinks/week) (OR 1.51, CI 1.30–1.76, |
[ | USA | 67 HIV positive patients | Alcohol dependence is a specific and significant predictor of ART nonadherence in women only ( | |
[ | USA | 643 HIV positive IDUs | Fewer at-risk drinkers that nondrinkers reported receiving ART (OR 1.19, 95% CI 0.59–2.42) | |
[ | USA | 145 HIV positive patients | 60 (41.4%) participants were current drinkers | 1 in 4 drinkers report stopping medication while consuming alcohol |
[ | USA | 335 HIV positive IDUs | Heavy alcohol use associated with first nonstructured treatment interruption (OR 1.58, 95% CI 0.92–2.70), early (within the first year) versus late treatment interruption (OR 1.55, 95% CI 0.51–4.73), and interruption of longer duration (≥6 months) (OR 3.21, 95% CI 0.83–12.5) | |
[ | USA | 1354 HIV positive women for whom HAART was indicated | Light drinking (OR 1.39, 95% CI 1.03–1.89, | |
[ | USA | 224 HIV positive patients | Baseline prevalence of past year hazardous drinking was 27% (AUDIT score ≥8) | Hazardous drinking associated with nonadherence |
[ | France | 445 HIV positive patients | 329 (73.9%) patients consumed ≤1 unit of alcohol/day at baseline | Baseline alcohol consumption associated with nonsignificant nonadherence after 4 months ( |
[ | France | 276 HIV positive IDUs receiving HAART | Approximately 84% of patients report alcohol consumption during the past 6 months | Monthly alcohol consumption during past 6 months associated with ART nonadherence (OR 1.15, CI 1.08–1.23, |
[ | France | 1010 HIV positive patients | 59 (5.8%) patients report daily alcohol consumption | Nonadherence more common among subjects who consume alcohol daily (OR 0.39, CI 0.20–0.58, |
[ | France | 2340 HIV positive patients receiving HAART. | 12% of patients had symptoms of potential alcohol abuse/dependence during the previous 12 months (CAGE questionnaire score of ≥2) | Harmful alcohol consumption associated with nonadherence to HAART ( |
[ | Switzerland | 6709 HIV positive patients | Increasing alcohol intake associated with deteriorating adherence to ART (OR 1.25, 95% CI 1.10–1.43) | |
[ | Sweden | 946 HIV positive patients | 15.5% of patients report alcohol and drug problems | Adherent patients more likely not to have problems with alcohol (OR 1.8, 95% CI 9 1.18–3.01, |
[ | Australia | 1106 HIV-infected patients | Alcohol use associated with self-reported nonadherence (OR 1.47, 95% CI 1.03–2.09, | |
[ | South Africa | 12 HIV positive patients receiving HAART | Alcohol abuse identified as barrier to adherence | |
[ | South Africa | 8 male HIV positive patients | Patients delay HIV treatment while coping with alcohol dependence | |
[ | South Africa | 56 HIV positive children | Alcohol use by caregiver associated with poorer ART adherence in children patients ( | |
[ | Cameroon | 533 HIV positive patients | 60 (11.3%) patients reported binge drinking | Binge drinking associated with interruption of ART |
[ | Ethiopia | 422 HIV positive patients | 31 (7.3%) subjects report alcohol consumption, 6 of which did so on a regular basis | Alcohol drinking associated with nonadherence (OR 0.210, CI 0.071–0.617, |
[ | Botswana | 300 adult HIV positive patients | Alcohol use predicted poor ART adherence ( | |
[ | Benin, Côte d’Ivoire, and Mali | 2920 HIV positive patients | Current drinking (OR 1.4, 95% CI 1.1–2.0), especially hazardous drinking (OR 4.7, 95% CI 2.6–8.6), associated with nonadherence | |
[ | Brazil | 306 HIV positive patients | 37.6% of sample consumed alcohol in month prior to baseline interview | ART nonadherence associated with alcohol use in month before baseline interview (OR 1.61, 95% CI 1.08–2.39, |
[ | Brazil | 295 HIV positive patients | 109 (37.3%) subjects consumed alcohol in month prior to baseline interview | Nonadherence to ART associated with alcohol use ( |
[ | Thailand | 205 HIV positive patients | 13 (6.3%) subjects report current alcohol use | Current alcohol use sole predictor of nonadherence to HAART (OR 1.67, CI 1.05–2.48, |
[ | India | 198 HIV-infected patients receiving HAART | Alcohol use associated with nonadherence (OR 5.68, 95% CI 2.10–15.32, | |
[ | USA | 1030 HIV-infected women | No delay in ART initiation between heavy drinkers and nondrinkers | |
[ | USA | 300 HIV positive men who have sex with men | 43% of sample report alcohol consumption in first 2 weeks post-baseline | No association found between alcohol use and nonadherence |
[ | UK | 394 HIV positive patients | Excessive alcohol consumption borderline significantly lower in patients receiving HAART ( | |
[ | Uganda | 2311 HIV positive patients | 123 (5.3%) used moderate levels of alcohol and 360 (15.5%) used high levels of alcohol | Alcohol consumption in past year (assessed using AUDIT-C) negatively associated with late presentation for treatment (OR 0.65, 95% CI 0.44–0.96, |
Following the introduction of HAART in 1996, individuals living with HIV taking this form of medication have benefited from improvements in immunological and virological parameters, as well as an improved quality of live and longevity [
Numerous studies from around the world document the detrimental effect of alcohol on HAART adherence, from the United States [
In addition to nonadherence, at-risk drinkers were less likely to have a current HAART prescription. As a result, at-risk drinking was a predictor of not being on HAART [
Concurrent crack cocaine use is associated with even lower adherence (OR 3.61, 95% CI 1.56–8.35,
Nonadherence is often associated with unsuppressed viremia. For example, Shacham et al. [
The reasons behind the association between alcohol consumption and nonadherence are varied. For example, due to the belief that alcohol should not be mixed with their medication, people living with HIV/AIDS may interrupt their medication when they are drinking [
Drinking patterns were found to differ across gender and ethnic groups. For example, hazardous drinking was more predominant among African-American (
Several other factors are also related to nonadherence. Each additional year of life was associated with further decrease in adherence (OR 0.96, 95% CI 0.92–1.00,
Significance of alcohol consumption diminishes once stress is factored in, suggesting that life stress may be one of the main causes for alcohol and drug consumption in HIV positive individuals, and alcohol consumption may in turn lead to nonadherence [
An interesting observation reported in a South African study is that many participants refused to disclose their HIV status to their family out of fear that their family would consume alcohol as result of such news, highlighting the wide-spread alcohol consumption in some communities [
Based on findings from these studies, it is recommended that HIV treatment programs address at-risk drinking as well [
There have also been reports of no association between alcohol consumption and delayed HAART initiation [
The association between ART adherence and the development of class-specific ART resistance represents a clinical problem. During multidrug therapy, differential drug exposure increases the likelihood of developing resistance. In addition, ART with higher potency and higher genetic barriers to resistance decrease the incidence of resistance for companion ART at all adherence levels. Drug resistance mutations proliferate under conditions of nonsuppressive ART, which is usually the result of inadequate drug exposure [
The primary goal of ART is to increase disease-free survival through suppression of viral replication and improvement in immunological function. The optimal time to initiate treatment is influenced by these known benefits and the risk of drug toxicity, potential emergence of viral drug resistance, and the need for lifetime therapy. The complexities of adherence-resistance relationships are related to characteristics of the virus, the medication, misuse of alcohol, and their interactions. Nevertheless, the effectiveness of ART can be limited by lack of access to therapy. Additionally, a set of acquired behaviour, such as alcohol misuse and poor adherence and/or intolerance, can lead to ART resistance. Therefore, especially in low-income populations, the education of individuals who live with HIV and alcohol abuse is relevant.
Knowledge of class-specific adherence-resistance relationships may help clinicians and patients tailor therapy to match individual patterns of adherence in order to minimize the development of resistance and treatment failure. In addition, in low-income settings, this information may guide the selection of optimal drug combinations and regimen sequences to improve the durability of ART. Moreover, alcohol use and alcohol dependence are widespread in the general population. Many people suffering from alcohol use disorders also suffer from other psychiatric disorders including drug abuse disorders. Importantly, persons living with HIV should be assessed not only for their immunologic and virologic statuses, but also for comorbidities.
This is particularly important but rarely assessed or/and reported in the literature. Modeling or condition simulation may introduce these interactions in the context of the corresponding topic leading to possible interventions.
An important objective of our study is to bring awareness of these complex interactions in the medical and education fields. Awareness should lead to cooperation between patients living with HIV, their caregivers, and researchers looking into the mechanism of relationship between the virus, disease progression, alcohol, and its comorbidities. Multiple substances of misuse, such as combined alcohol and cocaine, might be associated with behaviour and metabolic consequences not measured or not considered in these analyses. These drug-induced biological phenomena may promote disease progression and CD4+ cell loss, as well as poor adherence with prescribed medication and/or inadequate micronutrient and macronutrient intake. Because the patterns of substance abuse observed in these HIV positive cohorts might not be common or typical of other HIV populations, these findings can be generalized only to other infected populations with similar patterns of substance abuse. Further studies targeting HIV heavy alcohol users, that control for other confounding behavioural and metabolic variables, need to be conducted to confirm and extend the knowledge in this area. Moreover, a network of direct discussion is needed between people living with HIV/AIDS, medical personnel treating HIV and/or addictions, epidemiology researchers, as well as policy makers and treatment planners.
The authors acknowledge the US President’s Emergency Fund for AIDS Relief (PEPFAR) through the US Centers of Disease Control and Prevention (CDC) (PO S-SF750-06-M-0781), and the South African Medical Research Council for funding some of the activities that informed this paper. Its contents, however, are solely the responsibility of the authors and do not necessarily represent the official views of the CDC, PEPFAR, or other organizations referred to above.