How does dolutegravir work?
All antiretroviral drugs work by interfering with HIV's ability to replicate. HIV's replication process has several different steps. Different classes of antiretroviral drugs block HIV from being able to complete different steps in this process. Your treatment will contain a combination of these antiretroviral drugs that together are able to keep your viral load low and prevent new HIV from being made.
Dolutegravir belongs to a class of drugs known as integrase inhibitors - these stop HIV from inserting its DNA into the CD4 cell. Without being able to do this, HIV cannot take control of your CD4 cells.
Why does dolutegravir have a high barrier to resistance?
When you say that a drug has a high barrier to resistance, you're normally describing the number of changes that a virus has to make in order for the drug to become ineffective. It can also describe how likely those changes are to occur. There are a number of features about the structure of dolutegravir (DTG) and the way it works that makes it harder for HIV to adapt and get past DTG.
One of the things that scientists look at is how long the drug stays in your body after taking it. To measure this they use what's known as a drug's 'half-life'. A drug's half-life describes how long it takes for the body to break down the drug. In the case of DTG, the drug stays in your body for longer periods of time. This means that you can take your treatment less frequently (once a day instead of several times). It also means that you have a higher level of protection if you miss a dose, which makes building up drug resistance less likely.
DTG is a relatively strong anti-HIV drug. It's able to stop the replication of HIV at lower concentrations. Other drugs require you to take higher doses in order to be effective.
What are neural tube defects and should I be worried about them?
Neural tube defects are a type of health problem that can develop in babies during the early stages of pregnancy. In 2018, there was a scare that women of childbearing age should not be given dolutegravir after a small study in Botswana showed that taking dolutegravir in the early stages of pregnancy could be linked to an increased risk of neural tube defects in infants.
More evidence has become available to show that the risk is much smaller than first thought. For most women, the benefits of taking dolutegravir will outweigh these risks. For women on reliable contraception, not planning on becoming pregnant, these possible side effects are not a concern. But for women who want to have babies soon, or who are in the early stages of pregnancy, this may be something they want to discuss with a healthcare worker.
Ultimately the advice around dolutegravir is that women should understand what the benefits and risks are for them, and be able to make their own decisions about their treatment. They should have access to both reliable contraception and a range of good treatment options, so they can make informed and healthy choices that are right for them.