Pharmacodynamics of efavirenz 400 mg in treatment-naïve Chinese HIV-infected patients in a prospective cohort study.

BACKGROUND: The plasma concentration of patients treated with efavirenz (EFV) 600 mg was found to exceed the upper limit of the proposed therapeutic window in most Chinese HIV-infected individuals; thus, dosage reduction of EFV to 400 mg daily warranted consideration. This study aimed to assess the pharmacodynamics of EFV 400 mg for HIV-1-infected patients in China. METHOD: Twenty cART-naïve individuals were enrolled in this study. EFV 400 mg combined with tenofovir (TDF) and lamivudine (3TC) as an initial antiretroviral regimen was administered for 48 weeks. EFV concentration and T cell subsets as well as HIV RNA load were evaluated at baseline and at 4, 12, 24, and 48 weeks. Moreover, neuropsychiatric adverse effects were also assessed by the Hamilton depression (HAMD) scale and Pittsburgh sleep quality index (PSQI). RESULTS: Eighteen males and two females whose median age was 26 (interquartile range [IQR]: 23-32) years completed 48 weeks of follow-up. The median EFV concentrations were 1.88 (IQR: 1.54-2.42), 1.74 (IQR: 1.36-1.93), 1.93 (IQR: 1.66-2.22), and 1.85 (IQR: 1.54-2.14) mg/L at weeks 4, 12, 24, and 48, respectively. The viral load was 4.59 (IQR: 4.10-5.19) log10 copies/mL at baseline, and it decreased by 4.6 (IQR: 3.98-5.18) log10 copies/mL from baseline to week 48. Three of 20 (15%), 10 of 20 (50.0%), 17 of 20 (85%), and 18 of 19 (95%) participants had a plasma viral load less than 50 copies/mL at weeks 4, 12, 24, and 48, respectively. The median CD4 cell count was 330 (IQR: 237-410) cells/µL at baseline, and it increased to 473 (IQR: 344-574) cells/µL at 48 weeks. The HAMD score was 5 (IQR: 3-9.8) and 3 (IQR: 2.25-4) at baseline and 48 weeks, respectively. The PSQI score was 4 (IQR: 2-5.8) and 3 (IQR: 2-4) at baseline and 48 weeks, respectively. Dizziness was the most common event, occurring in 70% of patients within the first 2 weeks of treatment. CONCLUSION: Patients prescribed with EFV 400 mg-containing agents demonstrated favourable virological and immunological responses. And the plasma EFV concentration was within the recommended therapeutic range, with fewer adverse reactions than with EFV 600 mg. EFV 400 mg was effective and safe in Chinese HIV-infected patients. TRIAL REGISTRATION: NCT04596488 ; Registered 21 October, 2020; Retrospectively registered.

Breast milk concentration of hydroxychloroquine in Chinese lactating women with connective tissue diseases.

PURPOSE: Considering the very limited while varying information about the excretion of hydroxychloroquine (HCQ) into human milk, we sought to determine the breast milk concentrations of HCQ in Chinese lactating patients with connective tissue diseases to assess the safety of HCQ in infants of this population. METHODS: Breastfeeding women who had been on HCQ for at least 1 year were recruited. Milk samples were collected at five time points over 12 h. Breast milk HCQ levels were measured by a validated high-performance liquid chromatography (HPLC) assay. According to the general daily milk consumption of 0.15 L/kg for an infant, the dose of HCQ received by the infants via breastfeeding was calculated. RESULTS: Thirty-three patients completed the study who received HCQ treatment with the following regimens: 0.1 g bid (n = 3), 0.2 g qd (n = 8), 0.2 g bid (n = 21), and 0.2 g qod (n = 1). The mean breast milk HCQ levels (µg/mL) over the 12-h sampling period for each dosage regimen group were 0.4, 0.7, 1.4, and 0.4, respectively. The dose of HCQ (mg) received by the infants via breastfeeding would be 0.4, 0.4, 0.9, and 0.2, which were 0.26%, 0.26%, 0.29%, and 0.26% of the daily maternal doses, respectively. The infant's weight-adjusted relative dose (mg/kg) was 0.1, 0.1, 0.2, and 0.1, respectively, equivalent to 1.9%, 3.0%, 3.0%, and 3.2% of the maternal dose per kilogram body weight, respectively. CONCLUSION: Our study found that HCQ has very low concentrations in breast milk. It is probably safe for the patients to give breastfeeding during HCQ therapy period.

A Review of Clinical Pharmacokinetic and Pharmacodynamic Profiles of Select Antiretrovirals: Focus on Differences among Chinese Patients.

OBJECTIVE: To identify the pharmacokinetic differences of antiretroviral drugs between HIV-infected Chinese patients and patients of other race/ethnicities. STUDY DESIGN: Results from prospective, open-label pharmacokinetic studies among Chinese and historical data from other race/ethnicities. PATIENTS: Pharmacokinetics of six commonly used antiretroviral drugs, including zidovudine, lamivudine, tenofovir disoproxil fumarate, nevirapine, efavirenz and lopinavir/ritonavir, was evaluated in HIV-infected Chinese patients and compared with historical data from other race/ethnicities. ANALYSIS: Pharmacokinetic analyses were performed at the steady state among HIV-infected Chinese patients. Safety data were collected during the follow-up. The pharmacokinetic parameters including maximal concentrations (Cmax), area-under-curve (AUC) and clearance (Cl/F) from the Chinese patients were compared to the historic data from other race/ethnicities. RESULTS: Current evidence, though limited, suggested that these antiretroviral agents were generally safe and effective among HIV-infected Chinese patients. However, compared with other racial groups, Chinese patients exhibited higher Cmax , AUC and lower Cl/F for most of the agents, and the incidences of adverse reactions, for example, liver toxicity, rash, and bone health, were more frequent. CONCLUSIONS: These pharmacokinetic differences suggest that lower dosages for commonly prescribed antiretroviral drugs in China might be appropriate to reduce drug-related adverse reactions, while maintain the antiviral efficacy.