HIV reservoirs in vivo and new strategies for possible eradication of HIV from the reservoir sites

Abstract

Even though the treatment of human immunodeficiency virus (HIV)-infected individuals with highly active antiretroviral therapy (HAART) provides a complete control of plasma viremia to below detectable levels (<40 copies/mL plasma), there is an unequal distribution of all antiretroviral drugs across diverse cellular and anatomic compartments in vivo. The main consequence of this is the acquisition of resistance by HIV to all known classes of currently prescribed antiretroviral drugs and the establishment of HIV reservoirs in vivo. HIV has a distinct advantage of surviving in the host via both pre-and postintegration latency. The postintegration latency is caused by inert and metabolically inactive provirus, which cannot be accessed either by the immune system or the therapeutics. This integrated provirus provides HIV with a safe haven in the host where it is incessantly challenged by its immune selection pressure and also by HAART. Thus, the provirus is one of the strategies for viral concealment in the host and the provirus can be rekindled, through unknown stimuli, to create progeny for productive infection of the host. Thus, the reservoir establishment remains the biggest impediment to HIV eradication from the host. This review provides an overview of HIV reservoir sites and discusses both the virtues and problems associated with therapies/strategies targeting these reservoir sites in vivo.

Magnetic resonance imaging of folic acid-coated magnetite nanoparticles reflects tissue biodistribution of long-acting antiretroviral therapy

“…3,4 The virus is, notably, present for long periods of time in gut-associated lymphoid tissue, lymph nodes, and brain reservoirs, thus constituting obstacles for viral eradication. 5 One way to improve viral reduction is by viral reservoir-targeted long-acting antiretroviral nanoparticles that engage monocyte-macrophages as drug carriers. 6 With this in mind, a number of particle decorations that target circulating monocytes and tissue macrophages are in development.…”

Stochastic Model for Langerhans Cells and HIV Dynamics In Vivo

“…Langerhans cells (LCs), which are members of the dendritic cells family and are professional antigen-presenting cells, reside in epithelial surfaces such as the skin and act as one of the primary, initial targets for HIV infection [8]. They specialize in antigen presentation and belong to the skin immune system (SIS) and play a major role in HIV pathogenesis.…”

“…They specialize in antigen presentation and belong to the skin immune system (SIS) and play a major role in HIV pathogenesis. As part of the normal immune response, LCs capture virions at the site of transmission in the mucosa (peripheral tissues) and migrate to the lymphoid tissue where they present to naive T cells and hence are responsible for large-scale infection of CD + 4 T lymphocytes [8]. These cells play an important role in the transmission of HIV to CD + 4 cells [9]; thus, LC-CD + 4 cell interactions in lymphoid tissue, which are critical in the generation of immune responses, are also a major catalyst for HIV replication and expansion.…”

First-Pass Metabolism Changes After Long-Term Garlic Supplementation

“…The suboptimal penetration of highly active antiretroviral therapy (HAART) drugs into the virus reservoirs and sanctuary sites ensures that the replication-competent HIV viruses or integrated HIV virions remain sheltered from HAARTs pharmacological activity (Saksena et al, 2010). Persistent virus replication thus sustains continuous colonization of different tissues and cellular targets, which contributes to the disease relapse and to the emergence of virus resistance to HAART therapy (Saksena et al, 2010;Hoggs et al, 2006).…”

“…Persistent virus replication thus sustains continuous colonization of different tissues and cellular targets, which contributes to the disease relapse and to the emergence of virus resistance to HAART therapy (Saksena et al, 2010;Hoggs et al, 2006). Drug resistance is usually triggered by increased gene expression of the efflux transporters in the infected cells, resulting in even lower amounts of antiretrovirals residing in the HIV reservoirs (Löscher&Potschka, 2005;Kis et al, 2009).…”