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

Department of Infectious Diseases, Aarhus University Hospital, 8200 Aarhus, Denmark
Department of Clinical Medicine, Aarhus University, 8000 Aarhus, Denmark
Author to whom correspondence should be addressed.
Viruses 2020, 12(4), 412;
Received: 3 March 2020 / Revised: 30 March 2020 / Accepted: 1 April 2020 / Published: 7 April 2020
(This article belongs to the Special Issue Antiretroviral Drug Development and HIV Cure Research)
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. View Full-Text
Keywords: HIV; drug delivery; antiretroviral therapy; HIV reservoir; nanotherapy HIV; drug delivery; antiretroviral therapy; HIV reservoir; nanotherapy
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Halling Folkmar Andersen, A.; Tolstrup, M. The Potential of Long-Acting, Tissue-Targeted Synthetic Nanotherapy for Delivery of Antiviral Therapy Against HIV Infection. Viruses 2020, 12, 412.

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