Abstract
Alcohol abuse and AIDS remain two of the leading public health problems, not only in the United States but throughout the world. Approximately amongst 5% of the total US population, abuses alcohol and this statistic has been fairly consistent during recent years. However, the prevalence of alcohol abuse among HIV-positive individuals has been estimated to be between 29 and 60% in the US [1]. Alcohol use has also been implicated as an important risk factor in HIV transmission. In addition, the incidence of HIV infection has been found to be associated with the overall level of alcohol consumption. In a meta-analysis study, drinkers were found to be at a 77% higher risk of HIV-infection than non-drinkers [2]. In another meta-analysis of studies conducted in Africa, the HIV incidence among alcohol-users was found to be 70% higher than non-users [3]. Over the last decade, several elegant studies have shown that alcohol consumption enhances virus replication and accelerates the onset of SIV-induced AIDS in macaques [4-6]. A general consensus is emerging that alcohol consumption may promote virus replication and accelerate the onset of clinical disease. This accelerated onset of disease can be attributed to the fact that alcohol is known to adversely affect the immune system. Alcohol adversely affects the central nervous system and HIVassociated neurological disorders are known to play an important role in overall HIV pathogenesis. In several studies, alcohol has been shown to exacerbate the CNS effects of HIV-1 on ventricular volumes in the brains of infected individuals. The effect on white matter is associated with pathologies like myelin pallor, gliosis and multinucleated giant cells which were found to be much more pronounced in HIV+ individuals who consumed alcohol [7]. In view of these data, it is reasonable to believe that alcohol abuse is likely to influence the health status of patients infected with HIV. This issue of Current HIV Research presents a collection of 8 original research and review articles that focus on the effects of alcohol abuse on HIV pathogenesis in clinical situations as well as in various model systems. In a very interesting article, Agudelo, Nair and colleagues report the presence of a DRD2 polymorphism in 165 HIV-infected alcohol abusers. In another study conducted by Miguez- Burbano and colleagues, levels of brain derived neurotophic factor were found to be inversely correlated with alcohol consumption among HIV+ individuals, suggesting compromised neuroplasticity in these patients. The study by Thayer and colleagues establishes a correlation between risky sexual behavior, frequency of alcohol use and dorsal default mode network connectivity strength which is one of the four connectivity networks in the brain. In yet another elegant study conducted in the African- American population, Sales and colleagues also showed a positive correlation between alcohol use and risky sexual behavior. In the area of basic research, Mastrogiannis and colleagues report the very interesting finding that alcohol enhances HIV-1 replication in macrophages; this provides definitive evidence for increased virus replication due to alcohol consumption. Their study provides novel information that alcohol suppresses several miRNAs (28, 125b, 150, 198, 223, 382) APOBEC3G, APOBEC3H, IFN regulatory factor 7 and retinoic acid-inducible gene I, all of which are known to be involved in HIV replication. There are 3 reviews which provide current information in the area of HIV and alcohol research. The reviews by Molina et al. and Amedee et al. provide a comprehensive overview of advances in the field with particular emphasis on non-human primate modes. These reviews will be immensely helpful to the readers in terms of our current understanding of alcohol abuse and HIV pathogenesis. The last review deals with alcohol and its impact on both HIV and HCV infection. Approximately 25% of HIV-infected patients are co-infected with hepatitis C virus (HCV), therefore the information covered in this review will be useful for researchers involved in studying co-infection. Since the detailed characterization of HCV infection of the CNS is relatively new, this is an area of research that should see extensive growth in the coming years.
Keywords: AIDS, hepatitis C virus, HIV-1, HIV-associated neurocognitive disorders (HAND), CNS, neurodegenerative diseases, oxidative stress, SIV.