A balanced view of alcohol drinking and health should consider the amount of alcohol, beverage choice, drinking patterns and gender disparities. However, few studies with the general population (Grønbæk
et al.,
1995,
2000; Truelsen
et al.,
1998; Prescott
et al.,
1999) and none with HIV-infected populations have examined these aspects until now. One major finding in our data of HAART initiators was the highest risk associated with liquor use on each of the main outcome variables. Furthermore, previously published studies have demonstrated that an increase of at least 50 CD4
+ cell counts immediately after HAART initiation is associated with a markedly improved prognosis (Jacobson
et al.,
2002). Liquor users, however, were less likely to attain this response. From a clinical perspective, these findings have two important implications. First, by providing a biological explanation, our findings challenge previous alcohol studies attributing HAART differences mainly to poor adherence, which was carefully controlled in this study. Secondly, it indicates the need for health-care providers to be vigilant regarding alcohol use, particularly liquor use.
Because CD4 recovery may be associated with CD4 redistribution/peripheral expansion, increased thymus production (naïve cells) or both, it was important to undertake a detailed evaluation of each parameter (Gaulton
et al.,
1997; Heitger
et al.,
1997; Teixeira
et al.,
2001; Nobile
et al.,
2004). From a clinical and immunological perspective, the generation of naïve T cells is of greatest relevance because they are more effective in responding to neoantigens (Heitger
et al.,
1997; Douek
et al.,
2000; Teixeira
et al.,
2001). In this regard, findings from this cohort indicate that the thymus size increase and replenishment of cells were constrained by alcohol use, particularly by liquor consumption. Similarly, animal studies have demonstrated that alcohol decreases the cellularity of the thymus by inducing apoptotic changes, impairing mitochondrial function and decreasing the total glutathione concentration in the thymocytes (Monahan
et al.,
1997; Wang and Spitzer,
1997; Starkenburg
et al.,
2001; Pruett
et al.,
2003). However, alcohol impact was also evident over memory T cells indicating that additional mechanisms were impairing the immune system of drinkers.
While it is unclear why liquor is riskier than wine and beer, several potential mechanisms can be postulated. First, our results indicate that liquor users exhibited higher viral loads, and their viremia was less well controlled with treatment. This is consistent with the literature showing that virus replication in alcohol-dependent animals is significantly higher compared to controls and probably associated with the increased NF-κB activity (Dong
et al.,
2000; Wang
et al.,
2002). It could be hypothesized that animal findings, which utilize pure ethanol, are probably comparable to those of liquor.
Differences may also be attributed to their concentration of antioxidants, since antioxidants have been associated with increased proliferative responses, reduced lymphocyte apoptosis and viral replication (Roederer
et al.,
1990; Raju
et al.,
1994; Cayota
et al.,
1996; Kotler,
1998). Wine and beer possess high levels of vitamins and phytochemicals, and liquors are notably absent of them. Thus, the wine and beer containing antioxidants may lessen the deleterious effects of alcohol on total circulating CD4+ cells in patients on HAART (Cayota
et al.,
1996).
Besides, it is also possible that some trait(s) influencing a liquor preference may predispose an unhealthy lifestyle; however, we could not identify any additional risk factor. Tobacco smoking was similar between the groups. Thus, the mechanisms of the deleterious effects of liquor warrant further investigation.
A paucity of data exists regarding the impact of gender on the co-morbidity of HIV and alcohol. Moreover, the results concerning the gender effect on the immunovirological response to HAART have been mixed (Nicastri
et al.,
2007). However, most authors, after adjustment for potential confounders, do not report any difference in terms of these outcomes. We could have arrived at a similar conclusion if data had not been analyzed by alcohol types. Liquor and wine/beer had opposing effects, while women who consumed non-hazardous amounts of wine/beer had consistently better responses than their male drinking counterparts, and hazardous female drinkers of liquor performed poorer than hazardous and non-hazardous liquor-drinking males. Poorer responses parallel thymus volumes, suggesting an increased susceptibility to thymus damage caused by liquor consumption among women. However, the exact mechanism needs to be established in future studies.
We are aware that our observed significant effects may seem small. However, the context of change is important to be considered, namely, the early recuperation of lymphocyte counts and production of naïve cells are also small in order. Moreover, the changes we observed were mostly in opposite directions, adding further credence to the relevance of our findings for future research.
The current analysis of alcohol's impact on the health of HIV-infected individuals adds to the literature in several ways. First, to our knowledge, this is the first cohort study of HAART initiators that considers both the volume and pattern of consumption, as they relate to HAART response. Secondly, we included measurements of recent T-cell outputs and other clinically relevant outcome measurements (i.e. cognition and immune function). Third, contrary to most prior studies, our analysis of alcohol was in a longitudinal design with an ethnically diverse population and included a sizeable proportion of women. Fourth, the study design permitted us to examine the clinical trajectory of study subjects over time, and thus to delineate the role of adherence and other factors that might confound the biological effect of alcohol use on HAART effectiveness. Finally, we were able to avoid the confounding effects of individuals in therapy at diverse times, with all our participants initiating treatment. At present, alcohol studies that elucidate causal factors are needed to help inform public health authorities and health care providers.
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