The Relationship Between Efv Plasma Concentrations And Clinical Efficacy And Toxicity

Object To develop a quick and high-through LC-MS/MS method for the simultaneous quantitation of lamivudine (3TC), stavudine(d4T), zidovudine(AZT), efavirenz(EFV), nevirapine(NVP), and lopinavir/ritonavir (LPV/RTV) in human plasma. Method A combination of protein precipitation and liquid-liquid extraction was used to extract all compounds. The mobile phase consisted of A (0.1% formic acid in water):B (methanol) (20:80, v/v). The chromatographic system consisted of Eclipse XDB-C18 (150 mm×4.6 mm, 5μm) analytical column bought from Agilent Company (USA). The flow rate of the mobile phase was kept at 0.5 mL/min. Quantification was performed using multiple reaction monitoring (MRM) mode to study parent→product ion (m/z) transitions for 3TC(230.2→112.2), d4T (225.0→126.8), NVP(267.0→226.0), AZT (268.0→127.0), EFV(316.0→243.9), LPV(629.3→155.42), RTV(721.6→268.3) and IS (514.8→275.9), respectively. Results The method showed a good linearity in a concentration range of 20-3200ng·mL-1 for 3TC, d4T, AZT, and 40-6400ng·mL-1 for EFV, NVP and 62.5-100000ng·mL-1 for LPV,12.5-2000ng ·mL-1 for RTV. Mean intra- and inter-day precision were less than 15% and the accuracy were between 85% and 115% for all seven analytes. The whole run is 12 minutes. Conclusion This method was successfully applied to analyze some clinical plasma samples. And this LC-MS/MS method could simultaneously quantify 3TC, d4T, AZT, EFV, NVP, LPV and RTV plasma concentration and can be used for investigating the relationship between blood drug concentrations and clinical efficacy and toxicity. Object to assess the relationship between mean EFV plasma concentration and clinical effects and central nervous system toxicity(CNS Toxicity) rate during the first 48-weeks follow up; Method according to the inclusion and exclusion criteria, eligible subjects were recruited and demographic information, baseline HIV load, CD4 cell count of patients were recorded. Blood sample for EFV plasma level detection and CNS toxicity record, CD4 cell count were collected every 12 weeks for 48 weeks. HIV-RNA detection was made in the 48th week after antiretroviral therapy(ART). Analysis about the association between mean concentration of EFV and patients clinical effects and CNS toxicity were made; Results 42 subjects completed the whole follow up and patients'gender, age, body weight and body mass index(BMI) did not influence the EFV plasma level statistically. According to the average concentration of EFV during first year, there were 8(19%) subjects below 2mg/L,22(52%) patients between 2-4mg/L and 12(29%) patients above 4mg/L. The CD4 cell counts of patients with EFV above 4mg/L increased more quickly than those EFV concentration 2-4mg/L and below 2mg/L(211±176 versus 151±145 versus 172±105, Mean±SD), however, there were no statistical differences between them(P>0.05). Patients with EFV above 2mg/L had a higher rate of HIV replication suppression than those below 2mg/L after one year's ART(76% versus 25%), and the difference was statistically significant (P=0.005). The CNS toxicities rates were not statistically different among these three groups. Conclusions During the first 48-weeks ART, frequent EFV measurement and giving necessary change of treatment maybe beneficial to achieve complete HIV suppression. If the concentration was above 2mg/L, there is unnecessary to make EFV dose changed, while the level below 2mg/L, regular clinic visits should be made to keep up adherence and pay attention to the treatment failure.