ABSTRACT
BACKGROUND: Research suggests that integrase strand transferase inhibitor use can lead to weight gain, and data from sub-Saharan countries are limited. This study investigated changes in weight in Namibians switched from tenofovir DF/emtricitabine/efavirenz (TEE) to tenofovir DF/lamivudine/dolutegravir (TLD). METHODS: Longitudinal, retrospective, and quantitative study from outpatient records of Namibians living with HIV/AIDS switched from efavirenz-to dolutegravir-based regimen at four clinics. A linear mixed effects model predicting weight 6 months prior to the switch, time of the switch, and at 6, 12-, and 18-months post-switch was run. A second analysis comparing change in weights between males and females was also run. RESULTS: 242 patients switched from TEE to TLD. Compared to patient weight at the time of the switch, weights were significantly higher at 6 (+0.9 kg, p = 0.004), 12 (+1.7 kg, p < 0.001), and 18 months (+1.4 kg, p < 0.001) post-switch. There was no significant weight change for males, but females had a significant weight gain at 12 (+1.58 kg, p = 0.012) and 18 months (+1.49 kg, p = 0.024) post switch. CONCLUSIONS: Females living with HIV in Namibia gain weight when switched from TEE to TLD. Clinical implications on the development of cardiometabolic complications is unclear and mechanisms by which the weight gain occurs are unknown.
Subject(s)
Anti-HIV Agents , HIV Infections , HIV Integrase Inhibitors , Male , Female , Humans , HIV Infections/drug therapy , Retrospective Studies , Benzoxazines/adverse effects , Tenofovir/therapeutic use , Lamivudine/therapeutic use , Emtricitabine/therapeutic use , Weight Gain , HIV Integrase Inhibitors/adverse effects , Anti-HIV Agents/therapeutic useABSTRACT
BACKGROUND: Gentamicin and amikacin are aminoglycoside antibiotics which are renally excreted and known to be nephrotoxic. Estimate of glomerular filtration rate (eGFR) per body surface area is lower in neonates than in adults and exposure to these drugs could lead to more suppression in kidney function. The aim of this study was to determine maximum and minimum plasma concentrations (Cmax and Cmin), time to reach Cmin levels of gentamicin and amikacin, and to assess eGFR in preterm and term neonates. METHODS: Two groups of patients were recruited, 44 neonates receiving gentamicin (5 mg/kg/24 h) and 35 neonates receiving amikacin (15 mg/kg/24 h) by slow intravenous injection. Patients on amikacin had been on gentamicin before being switched to amikacin. Two blood samples were drawn for the determination of the maximum and minimum plasma concentration. Primary outcomes were determination of Cmax, Cmin, and the time it took to clear the aminoglycoside to a plasma concentration below the toxicity threshold (gentamicin: < 1 mcg/mL; amikacin: < 5 mcg/mL. RESULTS: Therapeutic range for Cmax of gentamicin (15-25 mcg/mL) or amikacin (30-40 mcg/mL) was achieved in only 27.3 and 2.9% of neonates, respectively. Percentage of neonates reaching plasma concentrations below the toxicity threshold within the 24-hour dosing interval was 72.7% for gentamicin and 97.1% for amikacin. Positive correlation between gentamicin clearance and postnatal age borderline statistical significance (p = 0.007), while the correlation between amikacin clearance and postnatal age was poor and not statistically significant (r2 = - 0.30, p = 0.971). CONCLUSION: Although eGFR decreased significantly as a function of postnatal age in neonates receiving amikacin, the majority (91.4%) of these neonates were able to clear the drug to < 5 mcg/mL within a 24-hour dosing interval.
