Characterization of susceptibility and resistance to novel categories of anti-HIV compounds

Antiretroviral therapy (ART), although still effective, is associated with long-term complications such as cardiovascular and metabolic diseases and increasing rates of drug resistance.

We want to explore the roles of two categories of novel anti-HIV compounds: integrase strand transfer inhibitors (INSTI) and specific dipeptides (DP), as alternatives to drugs, nucleoside analgoues, which can cause irreversible mitochondrial dysfunction. For INSTI, we want to understand the mechanisms of drug resistance across diverse HIV subtypes.

This is very important as this drug-class is today positioned as drugs-of-choice globally.

More specifically we hypothesize that natural polymorphisms, pre-existing and off-target drug resistance mutations affect outcomes of INSTI-regimens via novel mechanisms depending on viral subtype.

For the DP, the strategy is to further understand the mechanisms of action, if resistance can be developed, its activity against diverse HIV subtypes alone and together with INSTIs. Our hypothesis will be tested by bioinformatics, biochemical and virological tools. Our study will fill several knowledge gaps with regard to INSTI resistance and differences between HIV subtypes.

It will also reveal more information about the potential future role of the novel class of naturally occurring anti-HIV drugs, DP. If successful these compounds will with time substitute the more toxic anti-HIV drugs used today.