As we celebrate World AMR Awareness Week (WAAW), enabling access to new treatments can contribute to overcoming resistance to older treatments. For example, in 2013 MPP’s licences on second-line treatments such as atazanavir contributed to facilitating access to second line treatments that enabled people with resistance to first-line treatment to transition to a WHO recommended second-line regimen at that time.

But perhaps one of the best examples of how access to treatments can contribute to combatting antimicrobial resistance is MPP’s licence on dolutegravir. Dolutegravir (DTG) has emerged as a key medication in the fight against resistance for people living with HIV. DTG in the form of the fixed-dose combination TLD (tenofovir, lamivudine, dolutegravir), is the standard regimen being used across low- and middle-income countries (LMICs), with at least 19 million people taking TLD every single day.

Since 2019, WHO has recommended use of dolutegravir as part of the preferred first-and second-line treatment regimen for all population groups. It is more effective, easier to take, and has fewer side effects than other drugs currently in use. DTG also has a high genetic barrier to developing drug resistance, thus supporting its long-term durability and effectiveness, providing people with a better treatment option and strengthening the fight against drug resistance.[1]

Dr Zesca Meyer, HIV Outpatient Department of Eerste River Hospital, South Africa says:

“We serve a cohort of 1700 people living with HIV attending our Outpatient Department. We started switching our patients in 2020 to the DTG-containing regimen and the one-pill-a-day TLD, taken in the morning, has been a game-changer. Our patients are happy to take it. With the previous combination medication, a lot of people were experiencing headaches and dizziness. One of our adolescent boys had said that he was used to feeling so dizzy at night, and the switch to DTG meant that he could go out with his friends. Before the switch to DTG, he didn’t want to go out because he would feel so bad, which would also lead him to skip his medication.  With DTG-based regimens adherence has been very good, because it’s well tolerated with very little side effects and that is so important to preserve against the development of drug resistance.”

Evidence suggests that DTG-based antiretroviral therapy has been associated with high levels of HIV viral load suppression. Moreover, DTG as a drug has a high barrier to resistance which means that cases of resistance are rare. Research by WHO indicates that up to 10 percent of adults starting HIV treatment can have drug resistance to the non-nucleoside reverse transcriptase inhibitors (NNRTI) drug class[2]. In the case of efavirenz, resistance has been shown to be particularly high among children with WHO now recommending non-efavirenz based therapy[3].

The availability of DTG regimens in LMICs is in no small part due to the work of the Medicines Patent Pool (MPP) in partnership with ViiV Healthcare, manufacturers of generic versions and a wide range of other partners and stakeholders. MPP’s unique licensing model has meant that generic pharmaceutical manufacturers have been able to produce DTG and DTG-based combinations at a much lower cost, with many more millions of people able to access this life-saving treatment.

 

[1] HIV drug resistance report 2021. Geneva: World Health Organization; 2021. Licence: CC BY-NC-SA 3.0 IGO (last accessed Nov. 16, 2023 at https://www.who.int/publications/i/item/9789240038608)

Loosli T, Hossmann S, Ingle SM, Okhai H, Kusejko K, Mouton J, Bellecave P, van Sighem A, Stecher M, d’Arminio Monforte A, Gill MJ, Sabin CA, Maartens G, Günthard HF, Sterne JAC, Lessells R, Egger M, Kouyos R. sHIV-1 drug resistance in people on dolutegravir-based ART: Collaborative analysis of cohort studies. medRxiv [Preprint]. 2023 Apr 5:2023.04.05.23288183. doi: 10.1101/2023.04.05.23288183. Update in: Lancet HIV. 2023 Oct 10;: PMID: 37066200; PMCID: PMC10104228. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10104228/

[2] WHO 2022 fact sheet: https://www.who.int/news-room/fact-sheets/detail/hiv-drug-resistance#:~:text=Up%20to%2010%25%20of%20adults,previous%20exposure%20to%20antiretroviral%20drugs.

[3] WHO 2022 fact sheet: https://www.who.int/news-room/fact-sheets/detail/hiv-drug-resistance#:~:text=Up%20to%2010%25%20of%20adults,previous%20exposure%20to%20antiretroviral%20drugs.