Dolutegravir is a critically important antiretroviral medicine that is set to become the backbone of South Africa and many other countries’ HIV programmes. While the drug has recently made headlines because of a potential safety risk, most of what we know about the medicine indicates that it represents an important improvement over existing medicines. (You can read more about the safety risk here.)
Dolutegravir is featured prominently in South Africa’s recently advertised antiretroviral tender – the award of which is expected early in December. The medicine is set to become part of the standard combination of first line medicines given to most people in South Africa living with HIV in 2019. Six generic combinations containing dolutegravir have been registered in South Africa according to a report in Business Day. At the time of writing the lowest private sector price for dolutegravir listed on the Medicine Price Registry is R705 (US$50) per month. (For more details on other countries in Southern and Eastern Africa see this briefing document.)
Dolutegravir was first approved by the United States Food and Drug Administration in 2013. It is part of a class of antiretroviral medicine called integrase inhibitors. When HIV infects a cell, it combines its viral genetic code into the human cell’s own code – this is called integration, using the integrase enzyme. Dolutegravir blocks this integration enzyme, so HIV can’t make any more copies of itself, hence ‘’integrase inhibitor’’. Dolutegravir is the first integrase inhibitor that would be widely used by people living with HIV in the developing world.
Why people are excited about dolutegravir:
- It is highly effective: Dolutegravir is very effective at suppressing someone’s viral load quickly (the amount of copies of HIV in the blood). This is important for the long-term health of the person taking it. An undetectable viral load also means a person will no longer be able to transmit HIV to anyone else.
- It is well tolerated: In clinical trials there have been far fewer side effects reported from people using dolutegravir as compared to people using the drug that dolutegravir will replace, efavirenz (EFV). This includes fewer central nervous system side effects such as depression and anxiety. The improved tolerability of dolutegravir should make it easier for people to adhere to treatment in the long term. While not totally free from side effects, it is a big step forward.
- It is easy to take: People only require a small dosage of dolutegravir. The small dose makes it ideal to combine in a single tablet with other antiretrovirals. It also means the pills can be much smaller.
- It has few interactions with other medicines: dolutegravir has fewer drug interactions compared to EFV. One interaction we know about is with the tuberculosis medicine rifampicin. This is important given high rates of TB and HIV co-infection. While more evidence is needed, right now people with HIV and TB are being given an increased dose of dolutegravir to account for the drug interaction. Another interaction is with a diabetes drug called metformin (where we drop the dose of metformin a little if used with dolutegravir). It also should not be taken at the same time as with antacids or food supplements, if possible (you can take these at a different time of the day).
- It has a high barrier to resistance: dolutegravir has a higher genetic barrier to developing drug resistance compared to efavirenz. This will reduce the need for people to switch treatment lines since it is anticipated that extremely few people will develop resistance to dolutegravir. This is also important for people who are already resistant to another type of antiretroviral medicine – called a non-nucleoside reverse transcriptase inhibitor (NNRTI).
- It can be more affordable: The smaller dose means less active pharmaceutical ingredient (API) is needed (the bit of the drug that actually works in the body). The low dosage means dolutegravir could be produced by itself profitably by generic manufacturers for around ZAR 300 / US$ 21 per person each year. A deal was announced in September 2017 capping the public sector price in 92 low- and middle-income countries at US$ 75 per person a year for a combination tablet of tenofovir, lamivudine and dolutegravir (TLD). This price cap was for countries covered in the Medicines Patent Pool (MPP) license, thus excluded 39 countries including Thailand and Malaysia despite the fact that the drug is not protected by any patents there. After one year of active advocacy with the MPP, the Clinton Health Access Initiative (CHAI), the originator pharmaceutical company and the generic supplier; treatment advocates succeeded to ensure that the pricing deal will be honoured in those 39 countries too given the MPP licence allows supply to countries where there are no patents. As per today all African countries could benefit from this deal except Algeria. This country and others excluded should take other steps to ensure price reductions, such as issuing compulsory licenses.
This is an edited extract from a new dolutegravir briefing developed by Health GAP. To download the colourful and informative briefing click here.
Lotti Rutter and Maureen Milanga are Associate Directors of International Policy & Advocacy at Health GAP based in South Africa and Kenya respectively.