Viral diversity plays an important role in the pathogenesis of HIV disease. However, within an individual, HIV can vary substantially from one tissue or cell type to another, thereby creating viral compartments. HIV compartmentalization has been well documented in the brain, cerebrospinal fluid, and genital tract, although there are also data for viral compartmentalization within the gut, lung, liver, kidney, and breast milk. The precise mechanisms that lead to the development of HIV compartmentalization have not been adequately examined but likely include differential immune selection pressures, cell type-specific differences in replication or gene expression, local concentrations of antiviral drugs and/or drug resistance, and co-infections that alter the cellular microenvironment. Identifying and characterizing distinct viral sub-populations enhances our overall understanding of HIV pathogenesis and could ultimately result in the development of novel strategies to impair the ability of these viruses to adapt to and/or infect a given cell/tissue type.

Commonly misused substances such as alcohol, cocaine, heroin, methamphetamine, and opioids suppress immune responses and may impact viral pathogenesis. In recent years, illicit use of opioids has fueled outbreaks of several viral pathogens, including the human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV). This review focuses on the myriad of mechanisms by which drugs of abuse impact viral replication and disease progression. Virus–drug interactions can accelerate viral disease progression and lead to increased risk of virus transmission.

Background: There are only limited data on whether HIV infection occurs within the liver; therefore, we explored early and late stages of the HIV life cycle in two hepatocyte cell lines – Huh7.5 and Huh7.5_JFH1 – as well as in primary human hepatocytes. Results: Integrated HIV DNA was detected in Huh7.5 and Huh7.5_JFH1 cells, as well as in primary hepatocytes, and was inhibited by the integrase inhibitor raltegravir in a dose-dependent manner. HIV p24 protein was also detected in cell culture supernatants at days 1, 3, 5, and 7 post-infection and was inhibited by AZT, although levels were modest compared to those in a lymphocyte cell line. Culture supernatants from HIV-infected hepatocytes were capable of infecting a non-hepatic HIV indicator cell line. Conclusions: These results indicating low-level HIV replication in hepatoctyes in vitro complement evidence suggesting that HIV has deleterious effects on the liver in vivo.