By: Ranier Simons, ADAP Blog Guest Contributor
It is indisputable that the advent of antiretroviral treatment (ART) has saved many lives and improved the health outcomes of people with HIV. Treatment has advanced over the past few decades from toxic regimens like AZT to more tolerable cocktail regimens like Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide). Side effects vary between drugs and even between people who take the same drug. As such, people who stay on ART for extended periods sometimes switch medication regimens due to undesirable side effects that develop from long-term use or acute responses to cocktail components. Infectious disease doctors weigh the pros and cons of medications for patients in an effort to enable the highest benefit with the least harm. This is why medical science constantly studies and evaluates drugs to reach a consensus of therapeutic value versus harm.
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A recent study addresses the concern of weight gain for some patients of black African ancestry due to ART. The March 2023 issue of eClinical Medicine contains a study examining the effect of switching from efavirenz to dolutegravir in adults living with HIV in Johannesburg, South Africa. The study published in March was a prospective cohort study of adults (16 years or older) of black African ancestry who started ART between January 2010 and December 2020.[1] The study subjects were ART naïve patients who started fixed-dose regimens of tenofovir disoproxil fumarate (tenofovir), efavirenz, and lamivudine or emtricitabine which were established first-line regimens during the study period. The World Health Organization recommended dolutegravir, an integrase strand transfer inhibitor (INSTI), as an alternative to efavirenz in first-line ART in 2016, updating it as the preferred drug in 2018.[2] The change came because dolutegravir was proven more effective at long-term viral suppression, had less resistance, and increased tolerance over efavirenz.[1]
Dolutegravir became available to the clinic of the patients in the study cohort in 2019. There were 794 patients who were switched to dolutegravir and 794 who remained on efavirenz. All of the patients continued with the fixed doses of tenofovir disoproxil fumarate with lamivudine or emtricitabine and were observed for 12 months. The only change was swapping dolutegravir for efavirenz in one group compared to no swap in the other group. Results showed that those switching to dolutegravir had a mean weight change of 2.8kg (SD: 6.7kg), contrasting with 1.5kg (SD: 5.2kg) of those remaining on efavirenz.
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Weight gain is of concern because it could lead to other health issues, such as an increased risk for hypertension and diabetes. Typically some HIV patients experience wasting in some stages of disease progression, and ART results in weight gain as the body’s immune system strengthens.[1] This is desirable, especially since treatment initiation of patients in low and middle-income countries is frequently delayed until advanced disease states. However, weight gain is not good in HIV patients who are already overweight or may become overweight due to the dolutegravir.[1]
The prospective cohort study was done in response to two large clinical trials done in sub-Saharan Africa in 2020. The New Antiretroviral and Monitoring Strategies in HIV-infected Adults in Low-income countries (NAMSAL) trial and The ADVANCE trial displayed notable weight gain in people treated with dolutegravir compared to efavirenz.[3] The prevalence of obesity and ART utilization are both increasing in sub-Saharan Africa.[1]
It is crucial to continue clinical trials to verify if weight gain is caused by dolutegravir in efavirenz’s absence or if efavirenz somehow holds back weight gain in the absence of dolutegravir. It is also essential to determine if dolutegravir-related weight gain is sustained over time and if it increases other disease risks. Dolutegravir is cost-effective, has high efficacy, and is tolerated better, thus reducing the need to switch patients to more expensive second-line regimens. Since it is presently here to stay, examining how to mitigate its potential for adverse risk increases of other conditions is imperative.
[1] Brennan, A., Nattey, C., Kileel, E., Rosen, S., Maskew, M., Stokes, A., Fox, M., Venter, W. (2023). Change in body weight and risk of hypertension after switching from efavirenz to dolutegravir in adults living with HIV: evidence from routine care in Johannesburg, South Africa. eClinicalMedicine, Vol 57. https://doi.org/10.1016/j.eclinm.2023.101836
[2] Update of recommendations on first- and second-line antiretroviral regimens, World Health Organization, Geneva, Switzerland (2019). Retrieved from https://apps.who.int/iris/bitstream/handle/10665/325892/WHO-CDS-HIV-19.15-eng.pdf
[3] Volny-Anne, A. (2020, July 17). 96 weeks results from two African studies confirm dolutegravir non-inferiority but highlight continued weight gain. Retrieved from https://www.aidsmap.com/news/jul-2020/96-weeks-results-two-african-studies-confirm-dolutegravir-non-inferiority-highlight
Disclaimer: Guest blogs do not necessarily reflect the views of the ADAP Advocacy Association, but rather they provide a neutral platform whereby the author serves to promote open, honest discussion about public health-related issues and updates.
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