Dyslipidemia among adult people living with HIV on dolutegravir - based antiretroviral therapy at a private tertiary hospital in Kampala, Uganda: burden and determinants.

BACKGROUND: Understanding the burden of dyslipidemia and its associated factors among adult people living with HIV on dolutegravir (DTG) based anti-retroviral therapy (ART) is critical to provide clinical guidance and risk reduction strategies in our setting. METHODS: We conducted a cross-sectional study on adult people living with HIV on DTG based ART between July and August 2022 at Mengo Hospital, a private not for profit missionary hospital owned by the Church of Uganda. Dyslipidemia was defined as: Total cholesterol (TC) ≥ 5.2 mmol/l, or high-density lipoprotein (HDL) < 1 mmol/l for men and < 1.3 mmol/l for women, or triglycerides (TG) ≥ 1.7 mmol/l, and low-density lipoprotein (LDL) ≥ 3.4 mmol/l. A participant was considered to have dyslipidemia if they had any of the lipid profile parameters in the above ranges. Socio-demographic information, clinical data and behavioral characteristics were collected. Fasting lipid profile and fasting blood glucose levels were also measured. Bivariate and multivariate analyses were done using a generalized linear model regression of the Poisson family with a log link (modified Poisson) using robust standard errors since the prevalence of dyslipidemia was more than 10%. Adjusted prevalence ratios (PR) were reported with their 95% confidence intervals (CI). A p-value of less than 0.05 was considered statistically significant. RESULTS: A total of 341 participants were included. The prevalence of dyslipidemia was 78.0%, (95%CI:73.3-82.1). The highest prevalence was for low HDL (72.1%, 95%CI 67.1-76.7) followed by high TG (20.2%, 95%CI: 16.3-24.9), high TC (12.0%, 95%CI: 9.0-15.9) and high LDL (6.5%, 95%CI: 4.3-9.6). Female sex (aPR:1.55, 95%CI: 1.32-1.84, p < 0.001) and previous use of protease inhibitor (PI) based ART regimen (aPR:1.26, 95%CI: 1.04-1.53, p = 0.018) were significantly associated with dyslipidemia. CONCLUSION: We demonstrate that the prevalence of dyslipidemia is very high as it was present in more than three quarters of the study participants. Female sex and previous use of PI based ART regimen were significantly associated with dyslipidemia. Management of dyslipidemia should be integrated in the HIV treatment package and we recommend further inquiry into the temporal relationship between dyslipidemia and DTG among ART patients, if any.

Blood glucose outcomes of anti-retroviral therapy naïve Ugandan people with HIV with pre-diabetes mellitus initiated on dolutegravir for 48 weeks.

BACKGROUND: The Uganda ministry of Health recommends frequent blood glucose monitoring for the first six months on dolutegravir, in people with HIV (PWH) having pre-diabetes mellitus (pre-DM). We sought to determine if indeed PWH with pre-diabetes started on dolutegravir had worse blood glucose outcomes at 48 weeks compared to those with normal blood glucose. METHODS: In this matched cohort study, we compared 44 PWH with pre-DM and 88 PWH with normal blood glucose at baseline. The primary outcome was change in mean fasting blood glucose (FBG) from baseline to week 48 and 2-hour blood glucose (2hBG) from baseline to week 36 compared between the two groups. RESULTS: There was significant increase in FBG in PWH with normal blood glucose (mean change in FBG(FBG): 3.9 mg/dl, 95% confidence interval (95% CI): (2.2, 5.7), p value (p) = < 0.0001) and decrease in those with pre-DM (FBG: -6.1 mg/dl, 95%CI (-9.1, -3.2), p = < 0.0001) at 48 weeks. 2hBG was significantly lower than at baseline in both groups with the magnitude of reduction larger in those with pre-DM at 12 weeks (adjusted differences in mean drop in 2hBG (a2hBG): -19.69 mg/dl, 95%CI (-30.19, -9.19), p = < 0.0001) and 36 weeks (a2hBG: -19.97 mg/dl, 95%CI (-30.56, -9.39), p = < 0.0001). CONCLUSION: We demonstrated that Ugandan ART naïve PWH with pre-diabetes at enrollment have consistent improvement in both fasting blood glucose and glucose tolerance over 48 weeks on dolutegravir. Intensified blood glucose monitoring of these patients in the first six months of dolutegravir may be unnecessary.

Self-reported gastrointestinal adverse effects of non-steroidal anti-inflammatory drugs in female students with dysmenorrhoea at Makerere University: prevalence, discontinuation and associated factors. a cross sectional study.

BACKGROUND: Primary dysmenorrhoea occurs in up to 50% of menstruating females. Non-steroidal anti-inflammatory drugs (NSAIDs) are the most commonly used therapeutic remedies for dysmenorrhoea in Uganda. However, NSAIDs are associated with a 3-5 fold increase in the risk of gastrointestinal (GI) adverse drug effects. OBJECTIVES: We aimed to determine the prevalence and associated factors of self-reported NSAID-related GI adverse effects in female students who use NSAIDs in managing dysmenorrhoea-associated pain at Makerere University. DESIGN: A cross-sectional study. SETTING: Makerere University's main campus, situated North of Kampala, Uganda. PARTICIPANTS: 314 female students pursuing an undergraduate programme at Makerere University and residing in different halls of residence and hostels. OUTCOMES: Social demographic data, menstrual history and treatment data. RESULTS: Overall, 314 valid responses were received from female students with a median age of 22 years (IQR: 18-29 years). The median age at menarche was 13 years (IQR: 9-18 years). 41% (n=129/314) of the respondents had used medication for dysmenorrhoea and 32% (n=41/129) of whom reported NSAID-associated GI adverse effects with nausea being the most frequently reported (44%, n=18/41)Factors independently associated with GI adverse effects were: age at menarche (p=0.026), duration of menstruation (p=0.030) and use of ibuprofen (p=0.005). Females taking ibuprofen for dysmenorrhoea were about four times as likely to have NSAID-associated GI adverse effects (adjusted OR 3.87, 95% CI 1.51 to 9.91) than those who did not receive ibuprofen. Logistic regression was used to determine factors associated with self-reported adverse effects of NSAIDs among the female students. A p<0.05 was considered statistically significant. CONCLUSION: We found a considerably high prevalence of NSAID-related GI adverse effects driven by factors such as age at menarche and ibuprofen use.

Navigating duplication in pharmacovigilance databases: a scoping review.

OBJECTIVES: Pharmacovigilance databases play a critical role in monitoring drug safety. The duplication of reports in pharmacovigilance databases, however, undermines their data integrity. This scoping review sought to provide a comprehensive understanding of duplication in pharmacovigilance databases worldwide. DESIGN: A scoping review. DATA SOURCES: Reviewers comprehensively searched the literature in PubMed, Web of Science, Wiley Online Library, EBSCOhost, Google Scholar and other relevant websites. ELIGIBILITY CRITERIA: Peer-reviewed publications and grey literature, without language restriction, describing duplication and/or methods relevant to duplication in pharmacovigilance databases from inception to 1 September 2023. DATA EXTRACTION AND SYNTHESIS: We used the Joanna Briggs Institute guidelines for scoping reviews and conformed with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews. Two reviewers independently screened titles, abstracts and full texts. One reviewer extracted the data and performed descriptive analysis, which the second reviewer assessed. Disagreements were resolved by discussion and consensus or in consultation with a third reviewer. RESULTS: We screened 22 745 unique titles and 156 were eligible for full-text review. Of the 156 titles, 58 (47 peer-reviewed; 11 grey literature) fulfilled the inclusion criteria for the scoping review. Included titles addressed the extent (5 papers), prevention strategies (15 papers), causes (32 papers), detection methods (25 papers), management strategies (24 papers) and implications (14 papers) of duplication in pharmacovigilance databases. The papers overlapped, discussing more than one field. Advances in artificial intelligence, particularly natural language processing, hold promise in enhancing the efficiency and precision of deduplication of large and complex pharmacovigilance databases. CONCLUSION: Duplication in pharmacovigilance databases compromises risk assessment and decision-making, potentially threatening patient safety. Therefore, efficient duplicate prevention, detection and management are essential for more reliable pharmacovigilance data. To minimise duplication, consistent use of worldwide unique identifiers as the key case identifiers is recommended alongside recent advances in artificial intelligence.