Personalising HIV therapy
HIV attacks and kills the immune cells, rendering the host susceptible to opportunistic infections. Over the years, extensive research has provided important information regarding HIV biology and mode of infection. This has culminated in the development of highly active antiretroviral therapy (HAART) — the only effective approach capable of halting virus replication. HAART combines drugs that block the activity of HIV enzymes, namely reverse transcriptase, protease and integrase.Unfortunately not all patients respond to HAART and the precise aetiology remains unknown. The EU-funded 'HIV coevolution and drug resistance' (HIV COEVOLUTION) project set out to investigate the mechanism behind this phenomenon in individuals who failed the antiretroviral therapy.Patients who failed to respond to the drug targeting integrase — the HIV enzyme responsible for inserting its genome into the host DNA — had their HIV repertoire sequenced. This identified the presence of particular integrase mutants that existed before commencement of therapy. This indicates the ability of HIV to escape from sub-optimal antiretroviral drug pressure through the selection of pre-existing drug-resistant mutants. These findings underscored the importance of using fully active antiretroviral regimens to treat all HIV-infected individuals.Genetic analysis of the HIV strains within infected individuals before and after HAART treatment was verified as a method for predicting future genotypic resistance to the inhibitor of the reverse transcriptase enzyme. HIV genome sequencing was also exploited by HIV COEVOLUTION scientists to assess virus tropism, in other words which cells are infected by the virus.Taken together, the molecular assays developed during HIV COEVOLUTION provide sensitive and accurate diagnostic tools for determining HIV resistance and tropism. Implementation of this deep-sequencing technology for clinical monitoring of HIV infection opens up new, cost-effective ways of deciding on the combination of antiretroviral drug therapies.
Keywords
HIV, highly active antiretroviral therapy, deep sequencing, HIV tropism
