Moderate alcohol consumption may be more harmful to people with HIV

Safe drinking limits for people living with HIV may be lower than the recommendations for the rest of the population, a large US cohort study suggests, especially in people not taking antiretroviral therapy. The findings are published by the journal Drug and Alcohol Dependence.

The study findings indicate that only one country – the United Kingdom – is currently recommending a level of alcohol consumption for the general population that would also minimise the harm of alcohol consumption for people living with HIV. All other national drinking limits for safer consumption would still place people with HIV at increased risk of alcohol-related harm compared with counterparts without HIV, the study shows. The study found that drinking more than 14 units a week – about one drink a day in US terms – increased the risk of death for men with HIV. The increased risk of death only became evident for men without HIV at higher levels of alcohol consumption.

Safe drinking advice now varies widely from country to country. Recently issued United Kingdom guidance recommends no more than 14 units a week for men and women, compared to the equivalent of 24 units a week for men in the United States (14 drinks per week) and 35 units a week in Spain. US guidance recommends women to restrict alcohol intake to 12 units a week, whereas Spanish guidance recommends no more than 21 units a week for women.

High alcohol consumption raises the risk of developing a wide range of cancers, particularly breast cancer in women, and bowel cancer, oesophageal cancer and cancers of the mouth and throat in both sexes.

The risk of cancers in the mouth, throat and oesophagus (gullet) is further raised by smoking in people who drink alcohol. Alcohol also increases the absolute risk of liver cancer.

High alcohol consumption also increases the risk of stroke and cardiovascular disease, in particular by raising blood pressure. There is considerable debate as to whether drinking a small amount of alcohol protects against heart disease.

United Kingdom drinking advice has been calculated so that for a person who drinks 14 units or less each week, the risk of dying of an alcohol-related condition is one in a hundred. In a briefing for journalists issued by the Science Media Centre last month, Professor Matt Field of Liverpool University’s UK Centre for Tobacco and Alcohol Studies set out the absolute risk of some cancers at higher levels of alcohol consumption: “Among men, approximately 8 in 1000 non-drinkers or drinkers who stick to the weekly limit (no more than 14 units per week) are at risk of developing liver cancer, but this rate rises to 11 in 1000 for men who drink between 14 and 35 units per week. But for cancer of the oesophagus, the rates are increased for men who drink even within the weekly guideline (13 in 1000) compared to those who abstain completely (6 in 1000), and further increased for those who exceed the guideline (25 per 1000 in men who drink between 14 and 35 units per week).”

The Veterans Aging Cohort Study

The US study was designed to test whether alcohol consumption is associated with a greater degree of harm in the HIV-positive population compared to an uninfected population with similar characteristics. The study population consisted of military veterans receiving care through Veterans Health Administration health care facilities in the United States who had been enrolled into the Veterans Aging Cohort Study (VACS). The study comprised 18,145 people with HIV and 42,228 uninfected individuals who had reported any alcohol consumption when asked a series of questions about alcohol use as part of routine medical follow-up. The study excluded women, who make up only 3% of the VACS population, therefore making it difficult to draw any reliable conclusions from findings in women.

The researchers then looked at mortality and “physiologic injury” – laboratory markers which predict physical illness. The latter was calculated using the VACS Index, a well-validated scoring system which predicts hospitalisation and morbidity including fractures. The VACS Index score has been shown to change in response to alterations in alcohol consumption and drug use, and to changes in treatment adherence. The score is calculated using the following measurements: haemoglobin, kidney function, hepatitis C infection, viral load, CD4 count and FIB-4 score calculated with reference to ALT/AST and platelet count.

The median age of study participants was 52.5 years for men living with HIV and 54 years for uninfected men. Thirty-one per cent of those with HIV and 16% of those without HIV had hepatitis C infection. Approximately three-quarters of men with HIV (76%) had an undetectable viral load.

Although the majority of those with HIV who reported alcohol use were light or moderate drinkers, consuming less than 14 US drinks per week (81%), the researchers classified 24% of men with HIV as having an “unhealthy” level of alcohol consumption based on responses to the AUDIT-C questionnaire, which asks about the number of days on which drinking takes place, the quantity drunk and the frequency of heavy drinking (six or more drinks in one day). A male drinker would fall into this category if they reported drinking no more than two to three times a week and drank at least three standard drinks on each occasion, or reported ever consuming six or more drinks on one occasion. Thresholds for unhealthy drinking in the AUDIT-C questionnaire are lower for women and for people aged over 65.

During a median follow-up period of 4.8 years the mortality rate was 2.7 deaths per 100 person-years among men with HIV and 1.8 per 100 person-years among men without HIV. When mortality rates were plotted by alcohol consumption, those men living with HIV with the highest range of consumption, whether measured by total number of drinks (70+ drinks per month), by AUDIT-C score (8-12) or by heavy episodic drinking (daily), had mortality rates almost twice as high as those with the lowest consumption (around 5 deaths per 100 person-years of follow-up). The difference in mortality was far less pronounced for men without HIV infection (approximate 25% increase in mortality).

Mortality at all levels of alcohol consumption was higher for men with HIV than those without, but the difference in mortality rates became greater as alcohol consumption rose.

A similar pattern was evident when the mean VACS Index scores were compared for different levels of alcohol consumption. Use of the VACS Index – which correlates with physiological injury – showed that there was no level of alcohol consumption that was protective in men with HIV whereas drinking between 3 and 29 US standard drinks per month was protective for people without HIV.

Multivariate analysis which adjusted for the effects of race, smoking and hepatitis C showed that men with HIV who drank between 30 and 69 drinks per month had a 30% higher risk of death during the follow-up period than men who drank only 1 or 2 drinks per month (HR 1.30, 95% confidence interval 1.14-1.50). Men with HIV who drank more than 70 drinks per month had a 50% increased risk of death (HR 1.50, 95% CI 1.28-1.76). In comparison, those without HIV had an increased risk of mortality only when they consumed more than 70 drinks per month (HR 1.13, 95% CI 1.00-1.28).

Why might alcohol be more harmful for people with HIV?

The investigators say that people with HIV are probably more vulnerable to the harmful effects of alcohol because they have higher blood alcohol levels for every unit of exposure, an explanation supported by a separate VACS cohort study which showed that people with HIV reported intoxication at lower levels of alcohol consumption, with the effect most pronounced in people with detectable viral load. (McGinnis) The authors of that study suggested that alcohol absorption may be higher in people with untreated HIV infection due to “intestinal barrier dysfunction”, and that body mass index is lower on average in people with HIV. Another study found that blood alcohol levels are higher in untreated HIV infection.

The investigators concluded that “HIV-positive individuals consuming more than 30 drinks per month are at increased risk of all-cause mortality and physiologic frailty. This would translate to a recommended drinking limit … of no more than 1 drink containing alcohol per day.”

Implications for alcohol advice

Thirty drinks a month may not sound like a lot, but different countries have different ways of calculating alcohol consumption. In the United States one “standard drink” contains 14g of alcohol. In Australia a “standard drink” contain 10g of alcohol. In the United Kingdom one “unit” of alcohol contains 8g of alcohol. In UK units, 70 drinks a month is the equivalent of 30 units a week, while 30 drinks a month – the level at which harm became evident in the US Veterans cohort – is the equivalent of 13 units a week – almost the same as the new limit for safer drinking recommended for the general population by the UK’s Department for Health last month (14 units).

In practical terms, the UK recommends drinking no more than 6 glasses of wine, or six pints of beer, or 14 small measures of spirits, each week, with drinking spread over several days.

How people choose to interpret these findings will depend on their attitude to risk. For some, total abstinence may be the only comfortable way to deal with alcohol-related risk, but others may conclude that the increase in the absolute risk of alcohol-related harm for people with HIV detected in this study is small enough to make little difference to their views on alcohol consumption.

The major limitation of this study is that it looked at alcohol consumption only in men. Further research is needed in a large cohort of women with HIV where reliable information about alcohol consumption has been recorded. Nevertheless, the greater harm caused by a unit of alcohol in women is well established, suggesting that findings for men are highly likely to apply to women, but at lower levels of alcohol consumption.