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Background Guidelines for kidney function monitoring and antiretroviral drug dosing are available and respectively refer to glomerular filtration rate and creatinine clearance (CrCl). Objective The aim of the study was to compare kidney function estimates vs. measured 24-h CrCl in HIV-infected subjects. Methods A cross-sectional design was used, with comparison of Cockcroft–Gault (CG), original and simplified modification of diet in renal disease (MDRD) equations vs. measured 24-h CrCl. Subjects were HIV-infected, 18–70 years old, without pre-existing kidney disease. Results Results are presented as mean (±standard deviation), unless otherwise stated. The study population consisted of 90 patients, of whom 71% were male, with a mean age of 45 years (±6.5 years). At the time of evaluation, the mean body mass index was 23 (±3.3); mean serum creatinine was 0.91 mg/dL (±0.2 mg/dL); and mean blood urea nitrogen (BUN) was 34.7 mg/dL (±10.6 mg/dL). Differences between paired methods were all significant ( P<0.00001), except between CG and simplified MDRD ( P=0.21; Pearson r=0.81). In univariate analysis, male gender, CD4 nadir, hepatitis B virus coinfection, BUN and current CD4 cell count showed a significant positive correlation ( P<0.2) with the difference between measured 24-h CrCl and either CG or simplified MDRD estimates. In multivariate analysis, only BUN showed a significant positive correlation ( P<0.05). Conclusions Estimates were lower than the measurements of 24-h CrCl. Original MDRD estimates were lower than those with other equations. CG and simplified MDRD estimates showed a satisfactory correlation. [ABSTRACT FROM AUTHOR]

7-11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK [ABSTRACT FROM AUTHOR]

PREVALEAT II (PREmature VAscular LEsions and Antiretroviral Therapy II) is an ongoing multicenter, longitudinal cohort study aimed to the evaluation of cardiovascular risk in advanced naïve HIV-infected patients starting their first HAART. It includes all consecutive naïve pts with <200 CD4 cells/ml who start any PI/r-based or NNRTI-based+2 NRTIs regimen. Pts are subjected to epi-aortic vessels ultrasonography, brachial artery flow mediated dilation (FMD), endothelial cytokine inflammatory markers value at time 0 and after 3, 6 and 12 months. Data about independent risk factors for CV disease are taken at time 0. Viral load, CD4+ counts, serum lipid values, glucose, body mass index (BMI) are recorded at every control. We enrolled 47 pts: 76,6% males, 87,2% caucasians, 40,4% cigarette smokers, 10,6% HCV co-infected, 6,4% had lipodystrophy. 29,8% homosexuals, 12,8% drug addicts, 51,1% heterosexuals. At baseline, 23,4% of pts had pathologic BMI, 31,91% had a epi-aortic vessels lesion (IMT and/or plaque), 27,65% had pathologic FMD; ICAM1 was pathologic in 46,80%, VCAM1 in 53,19%, IL-6 in 51,06%, D-dimers in 29,79%, hsCRP in 23,40%. 27 pts completed stage T1 of the study (after 3 months); percentages and significance level of variations are the following: 44,44% had a lesion of the epi-aortic vessels (p=0,28), 48,14% had a pathologic FMD (p=0,08), ICAM1 was pathologic in 59,26% (p=0,30), VCAM1 in 70,37% (p=0,15), IL-6 in 74,07% (p=0,05), D-dimers in 14,81% (p=0,12), hsCRP in 25,92% (p=0,80). 27 pts completed stage T2 of the study (6 months). Percentages and significance level of variations in regard of baseline are the following: 51,85% had a epi-aortic vessels lesion (p=0,462); 25,92% had pathologic FMD (p=0,37). 10 pts completed stage T3 of the study (12 months): 60% had a epi-aortic vessels lesion (p=0,07); 40% had pathologic FMD (p=0,49). No significant change has been showed in the trend of variation of inflammatory cytokines at T2 and T3. Our data, at baseline, evidence that advanced naïve pts show a relevant deterioration of CV conditions in terms of US data, FMD and cytokine markers. At T1, US and FMD seem to further worsen; cytokines, except D-dimers, show a worsening trend, too. At T1 and T2, prevalence of vessel lesion and pathologic FMD is yet higher, with a p value closer to significance level. Further data deriving from the follow-up of missing pts are warranted to better understand the evolution of the CV risk profile in this setting of pts. [ABSTRACT FROM AUTHOR]

Background & Aims: Ultrasound is the imaging modality most widely utilized in the general population for diagnostic purposes. Controlled attenuation parameter is a novel noninvasive method for assessing steatosis. Our aim was to investigate whether the clinical value of controlled attenuation parameter in patients referred for abdominal ultrasound examinations is affected by liver fibrosis., Methods: Consecutive patients referred for abdominal ultrasound examinations were enrolled. Controlled attenuation parameter and liver stiffness were assessed with the FibroScan (Echosens, France). Liver fibrosis was staged according to published cutoffs of liver stiffness measurements. Pearson's or Spearman's rank correlation coefficient was used to test the association between two study variables. Optimal cutoff of controlled attenuation parameter for diagnosing liver steatosis (S≥2) was 256 dB/m. The diagnostic performance and accuracy of dichotomized controlled attenuation parameter, ultrasound and body mass index were analysed using the imperfect gold standard methodology., Results: A total of 726 subjects (464 males and 262 females) were studied. Five hundred and eight-nine (81.1%) patients were affected by chronic viral hepatitis. Correlation of controlled attenuation parameter with ultrasound score was 0.48 and 0.57 in patients with and without chronic viral hepatitis respectively. In patients with chronic viral hepatitis, ultrasound, dichotomized controlled attenuation parameter and body mass index showed performance of 58.2%, 82.3% and 46.7%, respectively, whereas in patients without chronic viral hepatitis, the performance was 86.4%, 68.6% and 48.6% respectively., Conclusions: In patients with chronic viral hepatitis and advanced liver fibrosis, controlled attenuation parameter performs better than ultrasound for assessing liver steatosis, whereas in patients without viral hepatitis and with nonsignificant liver disease ultrasound shows the best performance., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To assess HIV-related nucleic acids in cervico-vaginal secretions and the factors associated with them., Design: Observational study., Setting: Department of Obstetrics and Gynaecology, University of Pavia, Italy., Population: HIV-positive patients attending a cytology service., Methods: Paired blood and cervico-vaginal lavage samples were obtained from 122 known HIV-seropositive patients during periodic visits for cytologic screening for lower genital tract neoplasia. Vaginal specimens for the diagnosis of bacterial vaginosis, trichomonas vaginalis and candida infection were also obtained. HIV-1-RNA in plasma, proviral HIV-1-DNA, cell associated and cell-free HIV-1 RNA in cervico-vaginal secretions were quantitatively evaluated by competitive polymerase chain reaction (c-PCR) and reverse transcriptase PCR (cRT-PCR)., Main Outcome Measure: Prevalences of HIV related nucleic acids in cervico-vaginal secretions and their univariate and multivariate associations with clinical variables., Results: Proviral HIV-1 DNA, cell-associated and cell-free HIV-1 RNA were detected in 50% (61/122), 37.7% (46/122) and 32.8% (40/122) of the patients, respectively. In logistic regression analysis, the presence of HIV-1 RNA in blood was the factor which correlated best with the detection of HIV-1 DNA (OR = 5.48, 95% CI = 2.28-13.20), cell-associated (OR = 4.85; 95% CI = 1.89-12.45) and cell-free HIV-1 RNA (OR = 4.63, 95% CI = 1.74-12.33) in cervico-vaginal samples. However, between 20% and to 35% of patients who tested negative for blood HIV-1 RNA were positive for either HIV-1 DNA or HIV-1 RNA detection in cervico-vaginal lavages. Bacterial vaginosis was associated with an increased prevalence of cell-associated (OR = 3.58, 95% CI = 1.22-10.54) and cell-free HIV-1 RNA (OR = 2.94, 95% CI = 1.0-8.7) detection in cervico-vaginal secretions. Additional factors associated with increased prevalence of HIV-1 RNA detection were advanced stage of HIV disease and vulvovaginal candidiasis., Conclusions: Although the presence of HIV-1 RNA in blood is the factor which correlates best with the detection of HIV-related nucleic acids in cervico-vaginal secretions, the shedding of HIV in the genital tract can occur in 20-30% of non-viremic subjects. Bacterial vaginosis and candida infection could have a facilitating role in local HIV viral replication and shedding.

Aims: To define the pharmacokinetic profile of efavirenz (EFV) in HIV-1 infected patients, when administered alone or with nelfinavir (NFV)., Methods: Eleven HIV-positive patients, in steady-state treatment with EFV and 11 patients in steady-state treatment with EFV+NFV, were evaluated. Blood samples for pharmacokinetic analysis were obtained during a dosage interval. Plasma concentrations of EFV were determined by h.p.l.c., Results: No significant difference was found between the principal pharmacokinetic parameters of EFV when administered alone or in combination with NFV (mean AUC: 57.1-7727.3 vs 60.9+/-12.3 microg ml-1 h; mean CL/F: 0.18+/-0.072 vs 0.16+/-0.04 l h-1 kg-1; mean Cmax: 4.0+/-1.7 vs 4.3+/-1.2 microg ml-1, and mean tmax: 4.1+/-1.7 vs 3.5+/-0.5 h) Mean trough plasma concentrations (C0) of EFV were 1.64+/-0.93 microg ml-1, with and without NFV. A good correlation was found between C0 and AUC(0,24h) (r=0.96; P<0. 01)., Conclusions: Despite the common metabolic pathway, there was no significant influence of NFV on the pharmacokinetics of EFV. EFV exhibits a relatively low interindividual variability and a dosing regimen of 600 mg day-1 assures plasma concentrations that are adequate for inhibition of viral replication.

Aims: To investigate the pharmacokinetic profile of the protease inhibitor saquinavir (SQV) after multiple doses in HIV-positive patients and to evaluate the possibility of predicting total body exposure of SQV from concentrations determined at single time points., Methods: Twenty HIV-positive patients on steady-state treatment with SQV (Hard-Gel-Capsule, Invirase(R)) were enrolled in this study. Serial blood samples were obtained during a dosing interval. SQV plasma concentrations were determined by high performance liquid chromatography (h.p.l.c.) and pharmacokinetic parameters were determined by noncompartmental techniques., Results: There was a marked interindividual variability in SQV pharmacokinetic parameters with a 11-fold variability in total systemic exposure to SQV, as expressed by AUC(0,8h) values (range: 268-3009 ng ml-1 h, CV: 69%). The oral clearance shows an interindividual CV of 75%. A strong correlation (r=0.94) was found between SQV plasma concentration at 3 h (C3 h ) and AUC(0,8h)., Conclusions: This study shows that C3 h is a good predictor for total body exposure of SQV and might be useful to predict SQV disposition in HIV-positive patients on steady-state treatment.