Dolutegravir was approved by the United States Food and Drug Administration in 2013. Dolutegravir is also known as DTG.
DTG, a once-daily integrase strand transfer inhibitor, has a high barrier to resistance, suppresses HIV viral load quickly, and is usually well-tolerated. DTG has been recommended in the World Health Organization’s (WHO) HIV treatment guidelines as an alternative first-line treatment since 2015, and it was added to the WHO list of essential medicines since June 2017.
May 2018: A potential safety issue has emerged from observational trials in Botswana, which affects women living with HIV who are using DTG at the time of conception. There is no evidence to date that DTG is unsafe during pregnancy, neural tube disorders, a birth defect occurred among 4/426 infants born to women who were using DTG at conception. We support the WHO recommendation for alternative regimens proven to be safe and effective during pregnancy for women of child-bearing age, or, in the absence of other options, that women of child-bearing years using DTG have access to continuous use of contraception. We will be following new information, its analysis and changes in recommendations closely as more data become available. Hopefully, DTG will be proven to be safe and effective for women in child-bearing years. We believe the DTG continues to be an important drug for people outside of this risk category.
Following the license between the Medicines Patent Pool (MPP) and ViiV Healthcare, generic competition for DTG is likely to occur in countries that are included in this voluntary licence, and in countries where DTG is not patented.
Initially 92 countries were in the voluntary licence for DTG, leaving 39 middle-income countries excluded. After CHAI’s announcement of a $75 regimen of DTG with tenofovir and lamivudine (TLD), we highlighted this discrepancy to CHAI. We have received confirmation that the $75 price has now been extended to the 39 excluded middle-income countries, although we are still waiting for publication of an official announcement, including a list of eligible countries.
The compound patent for dolutegravir is expected to expire in 2026. The patent has been granted in Algeria, China, Colombia, EAPO member countries, Indonesia, Mexico, Morocco, Philippines, South Africa, Turkey and Ukraine, and is pending in Brazil, Egypt, India, Malaysia, Nigeria and Vietnam.
An assessment by our partner, I-MAK reported that ViiV’s claim to a patent is not as strong as initially thought; it characterizes the patent on DTG as ‘questionable’. Patent offices in both Egypt and Brazil have rejected preliminary patents on DTG. See the DTG Roadmap for more information on finding the best route to access.
In April 2014, dolutegravir was licensed to the Medicines Patent Pool (through separate licenses for adult and pediatric formulations). The pediatric license includes 121 countries. The adult license includes all countries in sub-Saharan Africa, least-developed countries, low-income countries, Egypt, India, Indonesia, Philippines, Turkmenistan and Viet Nam. In addition, the licenses allow for the sale of generic versions of dolutegravir outside the licensed countries where there are no patents in force. The license granted to Medicines Patent Pool has been sub-licensed to nine companies.
A fixed-dose combination containing DTG plus abacavir/lamivudine (ABC/3TC) , has received regulatory approval. In addition to patents on DTG and ABC, patents on the combination of ABC/3TC and the combination of ABC/3TC/DTG may have an impact on the use of a regimen consisting of ABC/3TC and DTG.
The combination patent on ABC/3TC/DTG, which is expected to expire in 2031, has been granted in Colombia, Mexico, Mongolia and South Africa, and is pending in Albania, Algeria, ARIPO member countries, EAPO member countries, China, Costa Rica, Dominican Republic, Ecuador, Egypt, India, Indonesia, Malaysia, Morocco, Nigeria, Peru, Philippines, Thailand, Tunisia, Ukraine and Vietnam.
The MPP DTG license also covers combinations containing abacavirABC and DTG within the same geographical scope.