The Potential of Long-Acting, Tissue-Targeted Synthetic Nanotherapy for Delivery of Antiviral Therapy Against HIV Infection

• Published in: Viruses Vol. 12; no. 4; p. 412
• Main Authors: Halling Folkmar Andersen, Anna, Tolstrup, Martin
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 07-04-2020; MDPI
• Subjects: Analysis; Anti-HIV agents; Anti-HIV Agents - administration & dosage; Anti-HIV Agents - pharmacokinetics; Antiretroviral agents; Antiretroviral drugs; antiretroviral therapy; Antiviral agents; Bioavailability; Biological Availability; Brain - drug effects; Clinical Trials as Topic; Dosage and administration; drug delivery; Drug delivery devices; Drug Delivery Systems; Drug development; Drug dosages; Drug resistance; Drug targeting; Drug therapy; Drug Therapy, Combination - methods; Enzymes; HIV; HIV infections; HIV Infections - drug therapy; HIV reservoir; HIV-1 - drug effects; Human immunodeficiency virus; Humans; Infections; Liver; Lymph nodes; Lymph Nodes - drug effects; Lymphatic system; Metabolism; Methods; Nanomedicine; Nanoparticles; nanotherapy; Nervous system; Oral administration; Pharmaceuticals; Pharmacokinetics; Review; Viruses; Denmark; drug delivery; HIV; HIV reservoir; antiretroviral therapy; nanotherapy
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v12040412

Oral administration of a combination of two or three antiretroviral drugs (cART) has transformed HIV from a life-threatening disease to a manageable infection. However, as the discontinuation of therapy leads to virus rebound in plasma within weeks, it is evident that, despite daily pill intake, the treatment is unable to clear the infection from the body. Furthermore, as cART drugs exhibit a much lower concentration in key HIV residual tissues, such as the brain and lymph nodes, there is a rationale for the development of drugs with enhanced tissue penetration. In addition, the treatment, with combinations of multiple different antiviral drugs that display different pharmacokinetic profiles, requires a strict dosing regimen to avoid the emergence of drug-resistant viral strains. An intriguing opportunity lies within the development of long-acting, synthetic scaffolds for delivering cART. These scaffolds can be designed with the goal to reduce the frequency of dosing and furthermore, hold the possibility of potential targeting to key HIV residual sites. Moreover, the synthesis of combinations of therapy as one molecule could unify the pharmacokinetic profiles of different antiviral drugs, thereby eliminating the consequences of sub-therapeutic concentrations. This review discusses the recent progress in the development of long-acting and tissue-targeted therapies against HIV for the delivery of direct antivirals, and examines how such developments fit in the context of exploring HIV cure strategies.