Title:An Overview of Antiretroviral Agents for Treating HIV Infection in Paediatric Population
Volume: 27
Issue: 5
Author(s): Rita Melo*, Agostinho Lemos, António J. Preto, Beatriz Bueschbell, Pedro Matos-Filipe, Carlos Barreto, José G. Almeida, Rúben D.M. Silva, João D.G. Correia and Irina S. Moreira
Affiliation:
- Centro de Ciencias e Tecnologias Nucleares, Instituto Superior Tecnico, Universidade de Lisboa, CTN, Estrada Nacional 10 (km 139,7), Bobadela LRS 2695-066,Portugal
Keywords:
Paediatric HIV virus, Acquired ImmunoDeficiency Syndrome (AIDS), antiretroviral therapy, viral reservoirs,
drug design, Computer-Aided Drug Design (CADD).
Abstract: Paediatric Acquired ImmunoDeficiency Syndrome (AIDS) is a life-threatening and infectious
disease in which the Human Immunodeficiency Virus (HIV) is mainly transmitted through Mother-To-
Child Transmission (MTCT) during pregnancy, labour and delivery, or breastfeeding. This review provides
an overview of the distinct therapeutic alternatives to abolish the systemic viral replication in paediatric
HIV-1 infection. Numerous classes of antiretroviral agents have emerged as therapeutic tools for
downregulation of different steps in the HIV replication process. These classes encompass Non-
Nucleoside Analogue Reverse Transcriptase Inhibitors (NNRTIs), Nucleoside/Nucleotide Analogue Reverse
Transcriptase Inhibitors (NRTIs/NtRTIs), INtegrase Inhibitors (INIs), Protease Inhibitors (PIs),
and Entry Inhibitors (EIs). Co-administration of certain antiretroviral drugs with Pharmacokinetic Enhancers
(PEs) may boost the effectiveness of the primary therapeutic agent. The combination of multiple
antiretroviral drug regimens (Highly Active AntiRetroviral Therapy - HAART) is currently the standard
therapeutic approach for HIV infection. So far, the use of HAART offers the best opportunity for prolonged
and maximal viral suppression, and preservation of the immune system upon HIV infection. Still,
the frequent administration of high doses of multiple drugs, their inefficient ability to reach the viral reservoirs
in adequate doses, the development of drug resistance, and the lack of patient compliance compromise
the complete HIV elimination. The development of nanotechnology-based drug delivery systems
may enable targeted delivery of antiretroviral agents to inaccessible viral reservoir sites at therapeutic
concentrations. In addition, the application of Computer-Aided Drug Design (CADD) approaches
has provided valuable tools for the development of anti-HIV drug candidates with favourable pharmacodynamics
and pharmacokinetic properties.