Abstract
HIV-1 drug therapies can prevent disease progression but cannot eliminate HIV-1 viruses from an infected individual. While there is hope that elimination of HIV-1 can be achieved, several approaches to reach a functional cure (control of HIV-1 replication in the absence of drug therapy) are also under investigation. One of these approaches is the transplant of HIV-1 resistant cells expressing anti-HIV-1 RNAs, proteins or peptides. Small RNAs that use RNA interference pathways to target HIV-1 replication have emerged as competitive candidates for cell transplant therapy and have been included in all gene combinations that have so far entered clinical trials. Here, we review RNA interference pathways in mammalian cells and the design of therapeutic small RNAs that use these pathways to target pathogenic RNA sequences. Studies that have been performed to identify anti-HIV-1 RNA interference therapeutics are also reviewed and perspectives on their use in combination gene therapy to functionally cure HIV-1 infection are provided.
Highlights
Several drugs are available for combination antiretroviral therapy, the current standard of care for HIV-1 infection
Additional data on the secondary structure of HIV-1 RNA in diverse HIV-1 strains could help in the identification of target sites that are conserved in both sequence and structure. short hairpin RNAs (shRNAs) can be evaluated for their potency against diverse viral strains to determine whether their target site is conserved in its accessibility, and potentially in its structure [97]
HIV-1 infection can be treated with combination drug therapy
Summary
Several drugs are available for combination antiretroviral therapy (cART), the current standard of care for HIV-1 infection. Sustained Control after Treatment Interruption) study [12,13,14] While these cases show that early treatment can result in at least a temporary functional cure, initiating early treatment cannot help those already infected with HIV-1 and most people who will become infected won’t be diagnosed soon enough for this approach to be successful. The treatment was prescribed to treat both relapsed acute myeloid leukemia and, potentially, HIV-1 infection [19] Since his transplant in 2007, Timothy Brown has been off cART and remains the only individual with an established infection who has been functionally cured of HIV-1.
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