RESUMO
Background: Dolutegravir-based antiretroviral therapy (ART) is currently recommended as the preferred first-line ART in many resource-limited settings. However, little is known about the clinical experience of dolutegravir within a context of prevalent co-infections. Objectives: To assess virological outcomes, and iron, ferritin and C-reactive protein (CRP) levels among people living with HIV (PLWH) and co-infections after initiating or re-initiating dolutegravir-based ART. Method: This prospective study was conducted between August 2022 and August 2023. Study participants were recruited from an HIV opportunistic infection clinic. Screening for co-infections (syphilis, hepatitis B virus, cytomegalovirus and herpes simplex virus) was performed at baseline, prior to ART initiation. Plasma HIV viral load (VL), CRP, ferritin and iron levels were measured at baseline and at the 6-month follow-up period. Results: A total of 100 participants (51 women and 49 men) were enrolled in this study. The median age of the participants was 39 years. The prevalence of co-infections was 30%. Prior to ART initiation, participants with co-infections had higher VL, CRP and ferritin, and lower iron levels, compared to those without co-infections (P < 0.001). Following 6 months of ART, CRP and ferritin levels decreased while iron levels increased, regardless of co-infection status. However, CRP and ferritin remained significantly higher in those with co-infections despite similar and high rates of virologic suppression in both groups. Conclusion: The presence of co-infections in PLWH is associated with higher VL and with chronic inflammation. Ferritin and CRP decreased on dolutegravir-based ART but remained higher in people with co-infections despite similar rates of virologic suppression.
RESUMO
Increasing cases of multidrug-resistant pathogens have evolved into a global health crisis. ESKAPE group of bacteria are associated with antibiotic resistance, and infections caused by these pathogens result in high mortality and morbidity. However, de novo synthesis of antibiotics is expensive and time-consuming since the development of a new drug has to go through several clinical trials. Repurposing of old drugs for the treatment of antimicrobial resistant pathogens has been explored as an alternative strategy in the field of antimicrobial drug discovery. Ten non-antimicrobial compounds were screened for antibacterial activity on two ESKAPE organisms, Staphylococcus aureus and Pseudomonas aeruginosa. The drugs used in this study were amodiaquine an antimalarial drug, probenecid used to prevent gout, ibuprofen a painkiller, 2-amino-5-chlorobenzaxazole used as a tool for assessing hepatic cytochrome P450 activity in rodents, ellargic acid an antioxidant, quercetin an antioxidant and anti-inflammatory drug, N-N diacryloylpiperazine used to crosslink polyacrylamide gel in 2D-protein electrophoresis, epicatechin an antioxidant and antiviral drug, curcumin an anticancer drug, and quinine an antimalarial drug. Antibacterial susceptibility tests were carried out for the 10 compounds. Curcumin exhibited the most potent antimicrobial activity against both bacteria, with MICs of 50 µg/ml and 100 µg/ml for P. aeruginosa and S. aureus, respectively. Ellargic acid was found to have an MIC of 100 µg/ml against S. aureus. Curcumin caused protein and nucleic acid leakage from the bacterial cell membrane in both bacterial species. When curcumin was combined with ciprofloxacin, it was found to enhance the antibacterial effects of ciprofloxacin. The combination with ciprofloxacin reduced the MIC for ciprofloxacin from 0.5 µg/ml to 0.0625 µg/ml on P. aeruginosa and 0.25 µg/ml to 0.0625 µg/ml on S. aureus. The results obtained show that curcumin has antibacterial activity against S. aureus and P. aeruginosa and may enhance the antibacterial activity of ciprofloxacin.
