Julia Poeta

Plasma concentrations of efavirenz are associated with body weight in HIV-positive individuals

BACKGROUNDnEfavirenz is among the most widely used antiretroviral drugs. Increased efavirenz exposure has been associated with CNS side effects and also with the chance of emergence of resistance upon treatment interruptions. The objective of this study was to evaluate factors associated with efavirenz plasma concentrations in a cohort of HIV-infected individuals.nnnMETHODSnFrom July 2009 to March 2010, HIV-infected patients with efavirenz as part of antiretroviral therapy (600 mg at night), undetectable viral load for at least 1 year and CD4 cell count >200 cells/mm(3) were consecutively enrolled at the HIV/AIDS ambulatory care unit in southern Brazil. Plasma samples were taken 18-23 h after efavirenz last dose and analysed by validated ultra-performance liquid chromatography.nnnRESULTSnForty-one subjects were included (21 females). Mean age and weight were 45.4 years and 70.9 kg, respectively. Mean efavirenz plasma concentration was 2.20u200a±u200a2.17 mg/L. Most plasma concentrations (73%) were within the therapeutic window (1-4 mg/L); 17% were below and 10% above the limits. There were no significant associations between efavirenz concentration and age, CD4 cell count, time on antiretroviral treatment and gender. There was significant and inverse correlation between efavirenz concentrations and body weight (Pu200a=u200a0.013) and body mass index (Pu200a=u200a0.001).nnnCONCLUSIONSnIn this cohort of well-controlled HIV-positive individuals, patients with lower weight or body mass index had a higher chance of presenting elevated plasma concentrations of efavirenz. Therapeutic drug monitoring to adjust dose might be a helpful tool to decrease efavirenz dose in order to minimize costs and adverse effects.

Ultra-performance liquid chromatographic method for simultaneous quantification of HIV non-nucleoside reverse transcriptase inhibitors and protease inhibitors in human plasma

Um metodo rapido para a determinacao de seis inibidores de protease (indinavir, amprenavir, saquinavir, atazanavir, lopinavir e ritonavir) e de dois inibidores nao-nucleosidicos da transcriptase reversa (efavirenz e nevirapine), empregando cromatografia liquida de ultra-eficiencia com detector de arranjo de diodos foi desenvolvido e validado. Apos extracao liquido-liquido de 0,5 mL de plasma com metil-tert-butil eter, os analitos foram separados em uma coluna ACQUITY UPLC BEH® C18 (2,1 × 150 mm, d.p.xa01,7 μm), eluida com um gradiente de tampao fosfato trietilamonio pH 3.0 e acetonitrila. O tempo total de analise cromatografica foi de 9,5 min. As curvas de calibracao foram lineares entre 0,1 a 10,0 μg mL-1. O limite inferior de quantificacao foi 0,1 μg mL-1 para todos os farmacos. A exatidao esteve entre 94,9 e 103,5%. Os coeficientes de variacao intra e inter-dias foram inferiores a 7,7% para todos os analitos. Os rendimentos de extracao foram superiores a 88,2%.

Prevalência de câncer colorretal associado ao papilomavírus humano: uma revisão sistemática com metanálise

Introduction: Colorectal cancer is one of the most prevalent types of tumors worldwide. Deaths caused by these malignant tumors remain high and have stayed practically at the same level for the last few decades. Among the established risk factors for the development of cancer are infections due to pathogens or viruses. Among the viruses, the human papillomavirus (HPV) is the most prevalent, with over 180 strains, 40 of which are directly related to anogenital infections. Objective: Systematically assess the main studies which link HPV to colorectal cancer with meta-analysis. Methods: The search strategy adopted was the logic based on specific descriptors (English language), in combination with the Boolean operators (AND/OR). The search was conducted in the following databases: PubMed, ScienceDirect, and Scientific Electronic Library Online (SciELO), between April and May 2015. Results: 1,549 samples were assessed, with 956 (61.7%) being males. Six hundred thirty out of 1,358 cases of colorectal cancer due to HPV were diagnosed (51.9%). From these, 408 of 767 (51.9%) were male and 404 of 598 (67.5%) were linked to HPV 16 and 18, with tumor prevalence in the area of the cervix (253 of 411; 61.3%). From the total of 598 samples for the prevalence estimate of HPV 16 and 18, the number of cases with similar numbers was 204 (31.7%) and 200 (35.8%), respectively. Relatively significant numbers were found in the area of the cervix, 253 (61.3%), and the area of the rectum, 158 (38.7%). Conclusion: After conducting the present study, the link between HPV and colorectal cancer was made evident, without a distinction between the sexes, with similar values between HPV 16 and HPV 18.Introduction:nColorectal cancer is one of the most prevalent types of tumors worldwide. Deaths caused by these malignant tumors remain high and have stayed practically at the same level for the last few decades. Among the established risk factors for the development of cancer are infections due to pathogens or viruses. Among the viruses, the human papillomavirus (HPV) is the most prevalent, with over 180 strains, 40 of which are directly related to anogenital infections.nnnObjective:nSystematically assess the main studies which link HPV to colorectal cancer with meta-analysis.nnnMethods:nThe search strategy adopted was the logic based on specific descriptors (English language), in combination with the Boolean operators (AND/OR). The search was conducted in the following databases: PubMed, ScienceDirect, and Scientific Electronic Library Online (SciELO), between April and May 2015.nnnResults:n1,549 samples were assessed, with 956 (61.7%) being males. Six hundred thirty out of 1,358 cases of colorectal cancer due to HPV were diagnosed (51.9%). From these, 408 of 767 (51.9%) were male and 404 of 598 (67.5%) were linked to HPV 16 and 18, with tumor prevalence in the area of the cervix (253 of 411; 61.3%). From the total of 598 samples for the prevalence estimate of HPV 16 and 18, the number of cases with similar numbers was 204 (31.7%) and 200 (35.8%), respectively. Relatively significant numbers were found in the area of the cervix, 253 (61.3%), and the area of the rectum, 158 (38.7%).nnnConclusion:nAfter conducting the present study, the link between HPV and colorectal cancer was made evident, without a distinction between the sexes, with similar values between HPV 16 and HPV 18.

Related factors to atazanavir plasma levels in a cohort of HIV positive individuals with undetectable viral load

OBJECTIVEnTo evaluate the factors associated with plasma concentrations of atazanavir (ATV) in a cohort of well-controlled HIV infected subjects (undetectable viremia).nnnDESIGNnCross-sectional study where 69 subjects were consecutively enrolled between April and November, 2011.nnnMETHODSnPatients had to be on atazanavir for at least six months, undetectable viral load for a period equal to or longer than 12 months, T CD4+ lymphocyte count higher than 200 cells/mm(3), and aged between 18 years and 70 years old. Exclusion criteria were pregnancy, any neurologic disease, active opportunistic disease, hepatitis or cancer. Atazanavir plasma levels were measured by ultra-performance liquid chromatography.nnnRESULTS AND DISCUSSIONnOverall, 54 patients (mean age of 47 years and 50% women) were included in the analysis. Those without ritonavir (unboosted atazanavir) had statistically lower plasma concentrations than those with ritonavir boosted atazanavir (p=0.001) and total and indirect bilirubin were statistically associated with plasma concentration of atazanavir (r=0.32 and r=0.33 respectively; p<0.05 in both cases). No statistical association was found among gender, ethnicity, age, weight, body mass index (BMI), lipid profile, and the plasma concentration of atazanavir.nnnCONCLUSIONnIn summary, as expected, concomitant ritonavir use was the only factor associated with atazanavir plasma levels. Prospective studies with a larger sample size might help to observe an association of atazanavir concentrations to other characteristics such as body weight, since the p-value showed to be close to significance (p=0.068).