Ultrastructural Findings and Possible Therapeutic Targets, at Micro and Nanoscales in Rectal Mucosa of Patients with HIV/AIDS

Background: Several studies have shown that human immunodeficiency virus (HIV) maintains residual replication in the lymph nodes of patients with undetectable viral load in peripheral blood despite highly active antiretroviral therapy (HAART). In other words, while the virus is eliminated in the peripheral blood by antiretroviral drugs, it continues to infect and replicate in new cells in the lymphoid tissue. This shows that the treatments used today against HIV do not achieve the total elimination of the virus in the body.

Other studies demonstrated that the concentrations of antiretrovirals at the lymph node level were lower compared to the concentrations in peripheral blood, not reaching optimal levels to stop viral replication. Additional investigations in intestinal mucosa showed that HIV RNA can be detected in the intestine of patients with successful HAART, suggesting that the intestinal mucosa is a cellular reservoir where HAART inhibits viral replication but does not eradicate the virus, therefore that it is necessary to carry out more in-depth studies in order to improve the understanding of the pathogenesis of HIV at the level of the intestinal mucosa. The above-captioned issues motivated the present investigation in search of micro- and nanoscale findings with a possible therapeutic approach.

Objective: The present study aimed to determine the ultrastructural findings on Rectal Mucosa (RM) of patients with HIV/AIDS and anorectal pathologies (ARP), at micrometric and nanometric scales.

Materials and Methods: 5 patients were evaluated, 18 - 55 years old, with ARP (HIV co-infection with HPV, n = 4, and HIV-negative patient with HPV infection) (control n = 1), who were referred to the Coloproctology Unit of the HUC, and subjected to rectoscopy and biopsy. RM samples were identified, placed in a sterile plastic bottle with 1 mL of 2% glutaraldehyde, and immediately transported for routine processing of fine cut (60 - 90 nm) to be evaluated via Transmission Electron Microscopy (TEM). They were fixed with Karnovsky solution with Millonig phosphate buffer (pH 7.4 and 320 mOsm) and post-fixed with OsO4 under the same conditions of pH and osmolarity.

Results: Ultrastructural findings, at 10-6 scale: 1) Intestinal mucosa: vacuoles of mucus of different sizes that seem to be fused. 2) Smooth muscle cells: loss of definition of contractile myofilaments mass. 3) Unmyelinated axons and terminals of Schwann cells (SC): Edema and loss of their plasma membranes in some areas of association with axon terminals as well as abundant collagen fibers associated with SC. Ultrastructural findings, at 10-9 scale: 1) Smooth muscle cells: folded wrapper cores and edema of mitochondria and rough endoplasmic reticulum cisterns (RER). 2) Myelinated axon terminals: Loss of synaptic vesicles. 3) Fibroblasts: One observes mitochondria and cisterns of RER with alterations. All these alterations can generate intestinal and anorectal dysfunction in these patients. The use of nanotechnology can be very useful for the therapeutic approach to HIV, offering unique advantages, such as improving the bioavailability, water solubility, stability, and targeting capacity of antiretroviral drugs, especially in those difficult sites for an effective therapeutic approach.

Conclusions: HIV causes changes in rectal and muscular mucosa despite HAART treatment with undetectable viral load. Nano-drugs could play an important role in drug delivery in sites where conventional ART has limited access, so as to achieve sufficient concentrations to execute optimal therapeutic responses and virus eradication in anatomical and intracellular sites.