Among this cohort of HIV-infected women, heavy alcohol consumption was independently associated with earlier death. Active illicit drug use was also associated with increased risk of mortality. In contrast to active drug use, however, heavy alcohol consumption was not associated with delayed time to cART initiation. Baseline factors associated with heavy alcohol use included tobacco use, hepatitis C, and illicit drug use. These findings underscore the importance of identifying alcohol use among HIV-infected women entering care and counseling on the hazards associated with alcohol consumption in general and when coinfected with hepatitis C.
Our finding of earlier death among heavy drinking HIV-infected women is consistent with the literature about women without HIV. Several large prospective cohort studies have evaluated the association between alcohol use and mortality among women. One study, examining data from the Nurses' Health Study, found a U-shaped relationship; light-to-moderate alcohol consumption (1.5–29.9
g of alcohol per day) was associated with decreased mortality, whereas heavy drinking (≥30
g of alcohol per day) was associated with increased mortality.20
An earlier study found that among heavy drinkers, women were at much greater relative risk than men for noncardiovascular death.21
Braithwaite et al.22
estimated the impact of alcohol use on survival among a cohort of HIV-infected individuals, the majority of whom were male. They examined 2702 HIV-positive people and found that hazardous alcohol consumption decreased overall survival by >3 years if frequency of alcohol use was once per week or greater and by 6.4 years with daily alcohol use. Decreased survival was also found among nonhazardous drinkers. Our finding that heavy alcohol consumption was associated with decreased survival among HIV-infected women, independent of such clinical factors as hepatitis C, cART, or CD4 count at baseline, suggests that the association between alcohol and mortality may be extended to HIV-infected women. Of interest, before adjustment for potential confounders, occasional alcohol use was associated with delayed death. Although this would be consistent with data from the Nurses' Health Study, this is an area that requires further investigation.
We found no differences in time to cART by level of alcohol consumption, which lends support to recent findings in the Swiss HIV Cohort Study, which examined treatment-naïve individuals with CD4 count <200
cells/μL across alcohol consumption levels and found no association between delayed cART initiation and alcohol consumption.23
However, our finding that active drug use was associated with delayed cART initiation in our cohort supports well-established evidence that physicians may be highly reluctant to prescribe cART to HIV-infected IDUs.24
Although we found no delay in cART initiation among heavy drinkers, alcohol use was associated with earlier death. One possible explanation is that although women with heavy alcohol consumption are receiving cART, their increased mortality may be secondary to lower adherence and, consequently, poorer response to cART. Hazardous alcohol consumption is a well-established risk factor for cART nonadherence.25–29
Given that our study population was exclusively HIV-infected women, it is important to note that gender-specific differences in alcohol use and antiretroviral adherence may exist. Evaluation of two longitudinal prospective cohort studies found a dose-response relationship between alcohol use and decreasing adherence among women only.30
Even small reductions in antiretroviral adherence may compromise its effectiveness and have important survival implications.31
It is also possible that increased mortality among women with heavy alcohol use may be irrespective of cART, which would be consistent with the literature from the Nurses' Health Study and the study by Klatsky et al.21
which have described a general association between heavy alcohol use and mortality. In addition, among HIV-infected individuals, alcohol abuse is one of the most important risk factors for bacterial community-acquired pneumonia.32
One study conducted among veterans with HIV infection found a strong linear association between bacterial pneumonia prevalence and level of alcohol use.33
The association between alcohol use and death among HIV-infected women is likely multifactorial.
We did not find a baseline diagnosis of depression to be associated with delayed CART or earlier death. This is in contrast to other cohorts of HIV-infected women, where depression and depressive symptoms have been associated with decreased medication adherence,34
In our cohort, if depression was recorded in the clinical record within 6 months of clinic enrollment, the participant was designated as having depression. This may have missed women who had undiagnosed or undocumented depression, which may explain why our findings differ from those of other cohort studies conducted among HIV-infected women that demonstrated that depression was associated with death.39
In addition, there is literature about HIV-infected individuals suggesting that those with mental health disorders engaged in mental healthcare have similar or even better outcomes than those without mental health disorders.40
In this study, factors associated with heavy alcohol consumption included hepatitis C and illicit drug use. Alcohol and illicit drug use frequently co-occur,41
and illicit drug users constitute the majority of new hepatitis C infections.42
Excess alcohol consumption is known to hasten the progression of liver disease related to hepatitis C and can reduce the effectiveness of treatment for hepatitis C infection.42,43
Women coinfected with HIV and hepatitis C must be screened for both alcohol and drug use and counseled on the hazards associated with alcohol use and progression of hepatitis C disease.
There are several limitations to our study. First, this is an observational cohort study; thus, there may have been residual confounding. In addition, our alcohol variable categorization was based on provider interview, resulting in a crude categorization of alcohol use. Although trained abstractors retrieved the data, provider documentation may have been variable, patients may have underreported alcohol use, and providers may not have adequately assessed alcohol use, resulting in some misclassification of alcohol use. Should the level of alcohol use have been underreported, however, it is likely that our estimates are conservative and actual associations are stronger. Notably, our sensitivity analysis revealed associations that were similar in direction and of slightly greater magnitude, although the confidence intervals were wide because of the small validation sample. Although the sensitivity analysis using ACASI data is reassuring, it is not in itself a gold standard. Thus, additional studies using validated alcohol assessments, such as the Alcohol Use Disorders Identification Test or the Time Line Follow Back, are needed to confirm our findings.44–47
In addition, both illicit drug use and depression were obtained from provider documentation, and, thus, it is possible that these variables may not have been adequately assessed or documented. Further, variables, including housing stability and baseline medication adherence, were not collected in our cohort and were unable to be assessed. Finally, our cohort was urban and predominantly African American, which may limit generalizability.
Despite these limitations, this study evaluating the association between baseline alcohol consumption and time to cART and death among HIV-infected women has important strengths. Our study is one of few to directly assess the impact of alcohol consumption on mortality among HIV-infected women. In addition our cohort consists of a large sample of women engaged in care, the majority of whom are urban African American women acquiring HIV via heterosexual contact, thus largely mirroring the epidemic of HIV among women in the United States.
In summary, alcohol use is common among HIV-infected women, and our results suggest that heavy alcohol consumption is associated with decreased survival. Future longitudinal studies should continue to examine alcohol use and HIV survival, as well as specific causes of death. In addition, given that alcohol is a modifiable risk factor for adverse HIV-related outcomes, providers should consistently screen for alcohol consumption and refer HIV-infected women with heavy alcohol use for treatment.