October 26, 2015
Although resistance didn't develop to dolutegravir in studies of people starting treatment -- and a poster at EACS is helpful for summarising these data12 -- the resilience to resistance was still thought to be due to the other drugs in the combination.
Also, although dolutegravir can sometime overcome drug resistance to other integrase inhibitors if used early enough -- notably to raltegravir and elvitegravir -- this is not always the case, even using a higher dose of 50 mg twice daily.
Whether the mono and dual therapy results are sustained will depend on why dolutegravir is special and the mechanism for this protection. Resistance might be developing, but just at a very slow rate. Or dolutegravir might be causing a type of resistance that changes the structure of HIV in a way that makes it difficult to replicate -- and this is why viral load stay so low.
If dolutegravir causes HIV to mutate in a way that makes other current drugs less effective this could actually be a serious complication. Careful research is essential to look at this possibility as HIV has a history of escaping from effective treatment and mutating so that it ultimately becomes more difficult to treat.
Another concern is that many people in the dolutegravir mono and dual therapy studies were on stable treatment. Unpredictable viral load rebound in a few cases -- whether in the first weeks or in several years time -- might come with a risk of seroconversion symptoms and of becoming infectious to partners. This risk is at a time when treatment as prevention is only just getting established as a real and reliable strategy to prevent HIV transmission.
We need to understand the few cases where people had viral rebound, together with the relationship this has to previous use of integrase inhibitor treatment.
For all the potential benefits, the following bullet list show why further research is needed before this can be tried outside a study setting.
Given these cautions, for people wanting to join a research study, the early data is encouraging, especially if there are clinical reasons for needing to use fewer drugs. If this is the case, then the most cautious approach would be to include 3TC as dual therapy, and have very close monitoring.
|Remarkable Results With Dolutegravir Monotherapy|
|Researchers Discuss Questions Surrounding HIV Treatment, Prevention|
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