Abstract
BACKGROUND: While cotrimoxazole has anti-inflammatory effects among people with Human Immunodeficiency Virus (PWH), its effect on lipid profiles is not well-characterized. We compared the lipid profiles of PWH on cotrimoxazole to those not on it and assessed its association with individual lipid parameters. METHODS: PWH on antiretroviral therapy (ART) were randomly selected from an urban HIV clinic at Kiruddu National Referral Hospital in Kampala, Uganda. Participants were administered an interviewer-administered study questionnaire, underwent anthropometric measurements, and had blood samples evaluated for total cholesterol, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and triglycerides. Non-HDL-c was the difference between total cholesterol and HDL-c and was considered elevated if > 4.0 mmol/l. Dyslipidemia was characterized as elevated total cholesterol (> 5.0 mmol/L), high LDL-c (> 4.14 mmol/L), high triglycerides (≥ 1.7 mmol/L), or low HDL-c (< 1.03 mmol/L for males and < 1.29 mmol/L for females. We used linear, logistic and modified Poisson regression analyses to determine if cotrimoxazole use was independently associated with the individual lipid parameters when controlling for age, smoking, dolutegravir, anthropometrics, alcohol use, HIV clinical stage and glycated hemoglobin. RESULTS: Among 395 PWH enrolled, 100 (25.3%) were on cotrimoxazole prophylaxis for a median (IQR) of 1.0 (0.6–2.5) year, and 364 (92.2%) were on dolutegravir-based ART with a median (IQR) ART duration of 4 (1.8–10.0) years. PWH on cotrimoxazole had significantly lower total cholesterol (4.2 vs. 4.6 mmol/l, p < 0.001), non-HDL-c (3.09 vs. 3.62 mmol/l, p < 0.001), and LDL-c (2.7 vs. 3.0 mmol/l, p = 0.002) compared to those not on the drug. Additionally, a higher proportion of those not on cotrimoxazole had low HDL-c (75.3% vs. 61.6%, p = 0.009) and elevated non-HDL-c (33.3% vs. 11.1%, p < 0.001). Compared to PWH not on cotrimoxazole, a significantly lower proportion of PWH on cotrimoxazole had dyslipidaemia (83.8% (n = 83) vs. 91.1% (n = 265), p = 0.045). After adjusting for confounders, cotrimoxazole use was independently associated with lower total cholesterol levels (adjusted beta coefficient (β) = -0.18, 95% confidence interval (CI) -0.35 to -0.01), p = 0.040), non-HDL-c (β = -0.34, 95% CI -0.58 to -0.11, p = 0.005) and lower odds for elevated non-HDL-c (adjusted prevalence ratio = 0.45, 95% CI 0.26–0.77, p = 0.003). CONCLUSION: Cotrimoxazole use was independently associated with lower total cholesterol and non-HDL-c levels. These findings suggest a potential lipid-lowering effect of cotrimoxazole, warranting further longitudinal investigation into its potential long-term cardioprotective benefits among PWH. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12944-025-02722-3.