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Antimicrobials during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
Dolutegravir is an anti-HIV drug. In 116 women who used the drug during pregnancy, there was no significant increase in the frequency of congenital anomalies (Antiretroviral Registry, 2018). Among 426 women in Botswana who took dolutegravir during the first trimester, there were four neural tube defects (Crawford et al., 2020). In another 396 women who used the drug with efavirenz (another anti-HIV agent), there were no neural tubes defects, and no increased frequency of congenital anomalies.
Dolutegravir
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Keith A. Pappa, Mark A. Wainberg, Andrew R. Zolopa
Dolutegravir is a human immunodeficiency virus (HIV) integrase strand–transfer inhibitor (INSTI), consisting of a chiral nonracemic tricyclic carbamoyl pyridone–containing heterocycle core and a benzyl carboxamide moiety. Dolutegravir was discovered using a pharmacophore-based design approach to construct a bioisostere of the integrase phosphodiester substrate. As such, dolutegravir was designed to bind two divalent magnesium ions within the integrase catalytic active site, which effectively prevents the productive integration of viral and host deoxyribonucleic acid (DNA) substrates through inhibition of the second biochemical step catalyzed by HIV integrase known as strand transfer. Dolutegravir has no appreciable inhibition of the first biochemical step catalyzed by integrase known as 3’ processing, which is consistent with the two-metal binding mechanism of action (Johns et al., 2013). Dolutegravir is a specific inhibitor of HIV-1 and HIV-2 and has some antiviral activity against select non-HIV viruses, as described in section 2a, Routine susceptibility.
Chapter 10: Treatment of active tuberculosis in special populations
Published in Canadian Journal of Respiratory, Critical Care, and Sleep Medicine, 2022
Ryan Cooper, Stan Houston, Christine Hughes, James C. Johnston
Dolutegravir and raltegravir may be used with rifampin, provided doses are increased to account for the enhanced metabolism (see Table 1).41–44 It should be noted, however, that twice-daily dosing of some components of an ART regimen adds significant complexity and pill-burden and that this can challenge consistent adherence to ART. In a recent randomized controlled trial involving people with HIV and TB receiving rifampin-based treatment, twice-daily raltegravir was less effective at controlling HIV than an efavirenz-based, once-daily regimen.41 The difference was largely attributed to reduced adherence to the more complicated ART regimen in the raltegravir arm.41 Although a single, small phase-one study suggests that dolutegravir can be given once daily with rifabutin, there is less published clinical experience with this regimen.45 Other members of the integrase-inhibitor class — bictegravir and elvitegravir — cannot be used with the rifamycins.23
Trajectories of fertility intentions among women living with HIV in South Africa
Published in AIDS Care, 2021
Katherine B. Rucinski, Kimberly A. Powers, Audrey E. Pettifor, Vivian Black, Brian W. Pence, Benjamin H. Chi, Helen Rees, Sheree R. Schwartz
Data from Botswana further underscore the importance of comprehensively assessing and addressing women’s reproductive health needs within HIV treatment programmes. Preliminary findings from the Tsepamo Study indicated that women who conceive while taking dolutegravir may experience an increased risk for neural-tube defects in their newborns (Zash, Makhema, & Shapiro, 2018). The World Health Organization (WHO), the United States Food and Drug Administration, and the European Medicines Agency's Pharmacovigilance Risk Assessment Committee responded with a renewed focus on limiting dolutegravir use for women intending to become pregnant (European Medicines Agency, 2018; United States Food and Drug Administration, 2018; WHO, 2018). While recent date are more reassuring, prompting WHO to now recommend the use of dolutegravir for pregnant women and those of childbearing potential (WHO, 2019), the prevalence of neural-tube defects remains greater in association with dolutegravir exposure than with other types of antiretrovirals (Zash, Holmes, et al., 2019).
Safety implications of combined antiretroviral and anti-tuberculosis drugs
Published in Expert Opinion on Drug Safety, 2020
Maddalena Cerrone, Margherita Bracchi, Sean Wasserman, Anton Pozniak, Graeme Meintjes, Karen Cohen, Robert J Wilkinson
Due to its high potency and genetic barrier to resistance, dolutegravir is the drug of choice for the treatment of HIV recommended by the WHO. Nevertheless, its administration with RIF is currently recommended at the double dose of 50 mg twice daily. Adding an extra dose can represent a challenge to its implementation in low and middle-income countries, due to potential for decreased patient adherence and increased cost. Preliminary data on using the standard dolutegravir 50 mg daily dose together with RIF in healthy volunteers are promising [43], hence assessing the safety and efficacy of the standard dose of dolutegravir of 50 mg once daily in PLWH infected with TB as a next step is a research priority to accelerate dolutegravir global implementation. More data informing on the most appropriate dose of raltegravir to adopt in patients with HIV-associated TB are also needed in order to expand its use in this population. Tenofovir alafenamide is gradually replacing tenofovir disoproxil fumarate in many of the newly approved ART combinations and also as pre-exposure prophylaxis option for HIV [219] in light of its safer profile in terms of nephrotoxicity and bone health. Drug interaction and efficacy studies in patients with HIV-associated TB are necessary to expand the access to patients on TB treatment, especially when concomitant renal impairment is present.