Letter to the editors | Volume 37, Article 243, 17 Nov 2020 | 10.11604/pamj.2020.37.243.25512

Rollout of dolutegravir-based antiretroviral therapy in sub-Saharan Africa and its public health implications

Herieth Ismael Wilson, Herry Mapesi

Corresponding author: Herry Mapesi, Ifakara Health Institute, Ifakara branch, Ifakara, United Republic of Tanzania

Received: 12 Aug 2020 - Accepted: 27 Oct 2020 - Published: 17 Nov 2020

Domain: Infectious disease

Keywords: HIV/AIDS, dolutegravir, pharmacovigilance

©Herieth Ismael Wilson et al. Pan African Medical Journal (ISSN: 1937-8688). This is an Open Access article distributed under the terms of the Creative Commons Attribution International 4.0 License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Cite this article: Herieth Ismael Wilson et al. Rollout of dolutegravir-based antiretroviral therapy in sub-Saharan Africa and its public health implications. Pan African Medical Journal. 2020;37:243. [doi: 10.11604/pamj.2020.37.243.25512]

Available online at: https://www.panafrican-med-journal.com/content/article/37/243/full

Home | Volume 37 | Article number 243

Letter to the editors

Rollout of dolutegravir-based antiretroviral therapy in sub-Saharan Africa and its public health implications

Rollout of dolutegravir-based antiretroviral therapy in sub-Saharan Africa and its public health implications

Herieth Ismael Wilson1, Herry Mapesi1,2,3,&

 

1Ifakara Health Institute, Ifakara branch, Ifakara, United Republic of Tanzania, 2Swiss Tropical and Public Health Institute, Basel, Switzerland, 3University of Basel, Basel, Switzerland

 

 

&Corresponding author
Herry Mapesi, Ifakara Health Institute, Ifakara branch, Ifakara, United Republic of Tanzania

 

 

To the editors of the Pan African Medical Journal    Down

Globally, approximately 33 million people are living with Human Immunodeficiency Virus (HIV) and more than 60% of them live in sub-Saharan Africa. Widespread availability of antiretroviral treatment (ART) has reduced morbidity and mortality among people living with HIV (PLHIV). The increase in life expectancy in PLHIV has been associated with an increased burden of non-communicable diseases (NCDs), mainly being metabolic disorders [1]. PLHIV have an increased risk of developing NCDs since traditional risk factors for NCDs such as obesity, genetic predisposition and sedentary life intersect with HIV-specific risk factors such as long-term exposure to ART and chronic inflammation [2]. Integrase-strand-transfer inhibitors (INSTI)-based regimens have recently been rolled out as the new first-line treatment in most low and middle-income countries due to their excellent safety profile, lower price, and sustained treatment success compared to the currently used ART regimens [3]. In sub-Saharan Africa, most of the current guidelines recommends the use of dolutegravir-based regimens as the first line ART among PLHIV [3]. However, there is a lack of studies to evaluate long-term side effects of dolutegravir-based regimens among PLHIV living in low and middle-income countries.

 

Dolutegravir-based regimens and excess weight gain: recent studies have demonstrated excessive weight gain among PLHIV switched from other ART regimens such Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI)-based regimens to dolutegravir-based regimens [4]. The same effect has been observed among ART-naïve patients starting treatment with dolutegravir-based regimen compared to patients starting treatment with NNRTI-based regimens [5]. Although short-term weight gain is a positive prognostic factor for PLHIV, who are underweight due to advanced HIV disease, the development into obesity increases the risk of developing cardiovascular diseases [6]. As a consequence, the current World Health Organization guidelines cautioned clinicians about the potential implications of possible weight gain associated with dolutegravir-based regimens [7].

 

Dolutegravir-based regimens and neural tube defects: in 2018, there was a safety signal alert from Botswana Tsepamo birth-outcome surveillance study, which results indicated an increased absolute risk of neural-tube defects in infants born to women who used dolutegravir-based regimen at conception compared to those who used other non-dolutegravir-based regimen [8]. The public release of this report by drug monitoring authorities led to uncertainty about the use of dolutegravir-based regimen among women of reproductive potential. In The New England Journal of Medicine, Rebecca Zash and colleagues reported the follow-up results from the same surveillance demonstrating a potential association between dolutegravir exposure at conception and the development of neural-tube defects among women of childbearing potential [9].

 

What lessons do we take from the previous studies evaluating potential side effects of using dolutegravir-based regimens in PLHIV? First, it is currently unknown whether the increased risk of developing excess weight gain among ART-naïve patients starting a dolutegravir-based regimen will be observed also sub-Saharan African settings, specifically in rural environments, where the living conditions and comorbidities might be quite different. The risk factors for developing excessive weight gain include black ethnicity, being a woman, low CD4 count and high HIV viral load [4,5]. This is of particular concern since in sub-Saharan Africa, majority of PLHIV are women, and still patients present to the health care facilities with advanced HIV disease with low CD4 count, and high HIV viral load. Second, PLHIV with viral suppression from older ART regimen such as NNRTI have an increased risk of developing excess weight gain once switched to dolutegravir-based regimen [4]. Third, there is a potential risk of developing neural-tube defects among women who were using dolutegravir-based regimen during conception.

 

Despite the urgent need to introduce new ART in sub-Saharan Africa, establishment of proper pharmacovigilance systems is essential for monitoring the safety of these new medications. In order to detect rare events such as short-term weight gain and development of neural-tube defects, a large number of exposures is needed, which is possible only if after introduction of new drugs in the community and systematic reporting is done. Implementing improved pharmacovigilance systems will not only help to monitor the safety of new antiretroviral drugs, but also to monitor medications from other chronic diseases requiring lifelong treatment such as hypertension, diabetes mellitus, cancers and epilepsy, all of which are on the rise in low-income and middle-income countries. Furthermore, it will provide data on pharmacokinetics and safety in pregnancy since this information is usually available on average six years after registration of the new drug [10].

 

 

Conclusion    Down

It is vital that low-income and middle-income countries improve their pharmacovigilance systems to produce robust and high-quality evidence to monitor the safety of new drugs. Additionally, there is an urgent need for longitudinal post-licensing studies to evaluate potential mechanisms of newly detected adverse events such as the dolutegravir signal for a possible neural-tube defect, which might be easier to capture in settings with a high number of HIV-positive women in childbearing age.

 

 

Competing interests Up    Down

The authors declare no competing interests.

 

 

Authors´ contributions Up    Down

HIW and HM conceptualized the work, gathered the evidence and wrote the paper. Both authors read and approved the final paper.

 

 

Acknowledgements Up    Down

HM received a scholarship from the Swiss Government Excellence Scholarships for Foreign Scholars (ESKAS-Nr: 2018.0004). In addition, we would like to acknowledge the contribution made by Prof. Maja Weisser from the University Hospital Basel for reviewing the manuscript.

 

 

References Up    Down

  1. Wong C, Gange SJ, Moore RD, Justice AC, Buchacz K, Abraham AG et al. Multimorbidity Among Persons Living with Human Immunodeficiency Virus in the United States. Clinical Infectious Diseases. 2018 Apr 3;66(8):1230-1238. PubMed | Google Scholar

  2. Lake JE, Currier JS. Metabolic disease in HIV infection. The Lancet Infectious Diseases. 2013 Nov;13(11):964-75. PubMed | Google Scholar

  3. Unitaid. New high-quality antiretroviral therapy to be launched in South Africa, Kenya and over 90 low- and middle-income countries at reduced price. Accessed July 22, 2020.

  4. Lake JE, Wu K, Bares SH, Debroy P, Godfrey C, Koethe JR et al. Risk Factors for Weight Gain Following Switch to Integrase Inhibitor-Based Antiretroviral Therapy. Clinical Infectious Diseases. 2020 Feb 26;ciaa177. PubMed | Google Scholar

  5. Sax PE, Erlandson KM, Lake JE, McComsey GA, Orkin C, Esser S et al. Weight Gain Following Initiation of Antiretroviral Therapy: Risk Factors in Randomized Comparative Clinical Trials. Clin Infect Dis. 2020 Sep 12;71(6):1379-1389. PubMed | Google Scholar

  6. Barceló C, Guidi M, Thorball CW, Hammer C, Chaouch A, Scherrer AU et al. Impact of Genetic and Nongenetic Factors on Body Mass Index and Waist-Hip Ratio Change in HIV-Infected Individuals Initiating Antiretroviral Therapy. Open Forum Infect Dis. 2020 Jan 22;7(1):ofz464. PubMed | Google Scholar

  7. World Health Organization. Update of recommendations on first- and second-line antiretroviral regimens. Accessed July 23, 2020.

  8. Zash R, Makhema J, Shapiro RL. Neural-Tube Defects with Dolutegravir Treatment from the Time of Conception. New England Journal of Medicine. 2018 Sep 6;379(10):979-981. PubMed | Google Scholar

  9. Zash R, Holmes L, Diseko M, Jacobson DL, Brummel S, Mayondi G et al. Neural-Tube Defects and Antiretroviral Treatment Regimens in Botswana. New England Journal of Medicine. 2019 Aug 29;381(9):827-840. PubMed | Google Scholar

  10. Colbers A, Mirochnick M, Schalkwijk S, Penazzato M, Townsend C, Burger D. Importance of Prospective Studies in Pregnant and Breastfeeding Women Living With Human Immunodeficiency Virus. Clin Infect Dis. 2019 Sep 13;69(7):1254-1258. PubMed | Google Scholar

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Letter to the editors

Rollout of dolutegravir-based antiretroviral therapy in sub-Saharan Africa and its public health implications

Letter to the editors

Rollout of dolutegravir-based antiretroviral therapy in sub-Saharan Africa and its public health implications

Letter to the editors

Rollout of dolutegravir-based antiretroviral therapy in sub-Saharan Africa and its public health implications

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Rollout of dolutegravir-based antiretroviral therapy in sub-Saharan Africa and its public health implications