Safety and Effectiveness of Dolutegravir-based Regimens in Hiv Patients at Queen Elizabeth Central Hospital, Malawi

Abstract

Introduction: Dolutegravir (DTG) is a second-generation integrase strand transfer inhibitor (INSTI) recommended by WHO for the treatment of HIV in low-and middle-income countries. DTG is safe, potent, and tolerable with a wide barrier to resistance, unremarkable drug-drug interactions, and good pharmacokinetic profile. Apart from safety and effectiveness data from clinical trials conducted in developed countries, DTG safety and effectiveness data from resource-limited settings is scarce. There is particularly no data in Malawi since the guideline change to DTG-based ART regimen in. This study 2019 seeks to assess the safety and effectiveness of DTG-based regimens in a Malawian population. Objective: The main objective of the study is to assess the safety and effectiveness of Dolutegravir-based regimens in HIV patients at Queen Elizabeth Central Hospital, in Malawi. Methods: This was a descriptive retrospective cohort study which included analytical retrospective cohort methods during exploratory data analysis. It was conducted at Umodzi Family Clinic at Queen Elizabeth Central Hospital in Malawi. Sample size was calculated using the Cochran formula and a consecutive sampling technique was used. Data was extracted from participants’ records and additional safety data was obtained using a structured data collection tool. Means and standard deviations were used to summarize normally distributed continuous variables while median and interquartile range for variables that were not normally distributed. Frequencies and percentages were used for the categorical variables. For continuous variables, two sample t-tests or sign rank tests were used for inferential analyses depending on data distribution. For categorical variables, proportions were compared amongst those who developed the adverse effects xiii Final version_07 September 2022 and those who did not, and Pearson’s Chi-test or Fishers exact test was used for inferential data analysis. To identify the influence of other variables on the outcome of interest, logistic regression was used. Multivariable regression analysis was done to adjust for potential confounders. The level of significance was set at 0.05 for all the analyses. Results: A total of 262 participants were included in the study. Of these 163(62%) participants were females. The mean age was 42.3 years and 65% of the participants were aged between 35-65 years. Participants reported side effects such as: neuropsychiatric symptoms 18(6.87), hypersensitivity reactions 34(12.9), diarrhoea 5(1.91), back pain 21(8.02), abdominal pain11(4.20), dizziness, muscle aches 5(1.91), nausea 15(5.73), vomiting 6(2.29), weakness15(5.75), and dysuria 7(2.08). DTG based- regimens were associated with diarrhoea, nausea, vomiting and dysuria. All covariates of interest could not explain the occurrence of mild hypersensitivity reaction in participants experiencing the symptom. The median viral load significantly dropped from 40 (IQR:40-839) to 30 (IQR:30-40) in about six months of follow up in participants on DTG-based ART regimen (p= 0.000). The concurrent use of herbal medication was associated with (dizziness, back pain, abdominal pain, weakness, and dysuria) and use of concurrent medication was associated with (neuropsychiatric symptoms and back pain) Discussion and Conclusion: DTG-based regimen was associated with mild hypersensitivity reactions, nausea, vomiting dysuria, and diarrhoea. However, no association was observed between presence of neuropsychiatric symptoms and DTG-based regimen. Therefore, DTG-based regimen was safe and were not associated with serious adverse events. DTG-based regimen was also effective in suppressing and maintaining viral load to undetectable level.