Dolutegravir reported Adverse Drug Reactions: a systematic review protocol
Creators: name: Wadesango, Lesley
name: Mensah, Kofi
Publisher: name: Open Science Framework
Year: 2022
Subjects: subject: Medicine and Health Sciences
subject: dolutegravir adverse reactions

description: Until recently the first line regimen for treatment of HIV was Tenofovir (TDF)-Emtricitabine (FTC) and Efavirenz (EFV) (National Department of Health, 2019).This regimen has been shown to have a low resistance barrier, and there are high incidences of toxic effects among some patients (Venter et al., 2019). With prolonged use of the efavirenz, its low genetic barrier can result in the build-up of drug-resistant mutations (“Dolutegravir-Based or Low-Dose Efavirenz–Based Regimen for the Treatment of HIV-1,” 2019). This contributes to increased mortality, the spread of HIV with drug-resistance mutations, and an increased prevalence of primary drug resistance (“Dolutegravir-Based or Low-Dose Efavirenz–Based Regimen for the Treatment of HIV-1,” 2019). Additionally, EFV causes adverse neurosensory effects (“Dolutegravir-Based or Low-Dose Efavirenz–Based Regimen for the Treatment of HIV-1,” 2019).The above mentioned reasons are why EFV was downgraded in the latest international recommendations (“Dolutegravir-Based or Low-Dose Efavirenz–Based Regimen for the Treatment of HIV-1,” 2019) According to the latest antiretroviral therapy (ART) clinical guidelines, the first-line regimen is now tenofovir disoproxil fumarate (TDF)-lamivudine (3TC)-dolutegravir (DTG) (National Department of Health, 2019). The fixed-dose combination (FDC) (TDF 300 mg + 3TC 300 mg + DTG 50 mg) is also referred to as TLD (National Department of Health, 2019 ).Dolutegravir is an integrase strand inhibitor (INSTI) and has a high genetic barrier to resistance and as a result was introduced as the preferred first-line treatment for HIV by the World Health Organization (WHO) in 2018 (“Dolutegravir-Based or Low-Dose Efavirenz–Based Regimen for the Treatment of HIV-1,” 2019). In 2019, a review of the above mentioned guidelines mentioned that a first-line regimen of DTG combined with two nucleoside reverse-transcriptase inhibitors (NRTIs) such as TDF and 3TC also leads to higher viral suppression and lower risk of discontinuing treatment compared with efavirenz (EFV) based regimens (World Health Organization, 2019). However the recommendation came with warnings that exposure to dolutegravir at conception may be related to neural-tube defects in infants (WHO, 2019). Risks of insomnia and a significant increase in body weight have also been associated with dolutegravir use (WHO, 2019).This calls for close monitoring of patients as the drug is being introduced. Reports from previous studies of a higher risk of IRIS, weight gain, insomnia and neural tube defects among people receiving DTG have raised concerns about its safety (Batista et al., 2019). It is important to do this systematic review because there is limited data on the safety of dolutegravir. A review of existing studies is imperative to establish the safety profile of this drug. It will aid in filling any knowledge gaps in the health care system on the drug’s safety. Although the drug appears to be safe, reports of insomnia, weight gain and neural tube defects are alarming. This study will assist in creating awareness of known adverse reactions to DTG, unknown rarer and or severe adverse reactions, adverse reactions associated with dolutegravir and use of other drugs and the effects of demographic factors on adverse reactions