Evaluation of Non-Contact Device to Measure Body Temperature in Sheep.

Non-contact devices have been used in the measurement of body temperature in livestock production as a tool for testing disease in different species. However, there are few studies about the variation and correlations in body temperature between rectal temperature (RT) and non-contact devices such as non-contact infrared thermometers (NCIT) and thermal imaging/infrared thermography (IRT). The objective of this work was to evaluate the accuracy of non-contact devices to measure the body temperature in sheep, considering six body regions and the possibility of implementing these systems in herd management. The experiment was carried out at the experimental farm of the Catholic University of Valencia, located in the municipality of Massanassa in July of 2021, with 72 dry manchega ewes, and we compared the rectal temperature with two types of non-contact infrared devices for the assessment of body temperature in healthy sheep. Except for the temperature taken by NCIT at the muzzle, the correlation between RT vs. NCIT or IRT showed a low significance or was difficult to use for practical flock management purposes. In addition, the variability between devices was high, which implies that measurements should be interpreted with caution in warm climates and open pens, such as most sheep farms in the Spanish Mediterranean area. The use of infrared cameras devices to assess body temperature may have a promising future, but in order to be widely applied as a routine management method on farms, the system needs to become cheaper, simpler in terms of measurements and quicker in terms of analyzing results.

Genotype by feeding regimen interactions for slaughter traits in rabbit and expected responses under restricted and full feeding.

The interaction between the genotype and feeding regimen (G×FR) for slaughter traits was estimated from data corresponding to 2557 animals under full (FF) and 2424 with restricted feeding (RF). Expected responses to selection under different scenario regarding feeding regimen were also calculated. Body weight at slaughter (SW), carcass weight (CW) and dressing out percentage (DoP) were analysed by using linear animal models in which records obtained under different feeding regimes were treated as different traits. Animals belonged to Caldes line, selected for average daily gain (G) under ad libitum feeding. The selection process information was included in the analyses. Marginal posterior mean of heritabilities were 0.102 for G, and 0.364, 0.257 and 0.167 for SW, CW and DoP under FF feeding. The corresponding values for animals fed on RF were 0.243, 0.203 and 0.379 for SW, CW and DoP, respectively. Genetic correlations between G and CW were positive and moderate, and those between G and DoP were low. The estimated genetic correlation between SW, CW and DoP under different feeding regimens were: 0.73, 0.69 and 0.87, respectively. These correlations cannot be said to be far enough from one to generate relevant G×FR interaction variance, which were estimated to be only 11.1%, 8.6% and 5.3% of the mean of the phenotypic variance for SW, CW and DoP, respectively. This lack of G×FR interaction variance, jointly with the higher heritability of DoP under RF, explains that the genetic improvement of DoP can be done more efficiently recording traits on animals under RF, even if the interest is on the performances under FF, i.e. by indirect selection.

Inhibitory Activity of Shrimp Waste Extracts on Fungal and Oomycete Plant Pathogens.

(1) Background: This study was aimed at determining the in vitro inhibitory effect of new natural substances obtained by minimal processing from shrimp wastes on fungi and oomycetes in the genera Alternaria, Colletotrichum, Fusarium, Penicillium, Plenodomus and Phytophthora; the effectiveness of the substance with the highest in vitro activity in preventing citrus and apple fruit rot incited by P. digitatum and P. expansum, respectively, was also evaluated. (2) Methods: The four tested substances, water-extract, EtOAc-extract, MetOH-extract and nitric-extract, were analyzed by HPLC-ESI-MS-TOF; in vitro preliminary tests were carried out to determine the minimal inhibitory/fungicidal concentrations (MIC and MFC, respectively) of the raw dry powder, EtOAc-extract, MetOH-extract and nitric-extract for each pathogen. (3) Results: in the agar-diffusion-assay, nitric-extract showed an inhibitory effect on all pathogens, at all concentrations tested (100, 75, 50 and 25%); the maximum activity was on Plenodomus tracheiphilus, C. gloeosporioides and Ph. nicotianae; the diameters of inhibition halos were directly proportional to the extract concentration; values of MIC and MFC of this extract for all pathogens ranged from 2 to 3.5%; the highest concentrations (50 to 100%) tested in vivo were effective in preventing citrus and apple fruit molds. (4) Conclusions: This study contributes to the search for natural and ecofriendly substances for the control of pre- and post-harvest plant pathogens.

Dairy Cows Activity under Heat Stress: A Case Study in Spain.

Heat stress plays a role in livestock production in warm climates. Heat stress conditions impair animal welfare and compromise the productive and reproductive performance of dairy cattle. Under heat stress conditions, dairy cattle modify their behavior. Thus, the assessment of behavior alterations can be an indicator of environmental or physiological anomalies. Moreover, precision livestock farming allows for the individual and constant monitoring of animal behavior, arising as a tool to assess animal welfare. The purpose of this study was to evaluate the effect of heat stress on the behavior of dairy cows using activity sensors. The study was carried out in Tinajeros (Albacete, Spain) during the summer of 2020. Activity sensors were installed in 40 cows registering 6 different behaviors. Environmental conditions (temperature and humidity) were also monitored. Hourly data was calculated for both animal behavior and environmental conditions. Temperature and Heat Index (THI) was calculated for each hour. The accumulated THI during the previous 24 h period was determined for each hour, and the hours were statistically classified in quartiles according to the accumulated THI. Two groups were defined as Q4 for no stress and Q1 for heat stress. The results showed that animal behavior was altered under heat stress conditions. Increasing THI produces an increase in general activity, changes in feeding patterns and a decrease in rumination and resting behaviors, which is detrimental to animal welfare. Daily behavioral patterns were also affected. Under heat stress conditions, a reduction in resting behavior during the warmest hours and in rumination during the night was observed. In conclusion, heat stress affected all behaviors recorded as well as the daily patterns of the cows. Precision livestock farming sensors and the modelling of daily patterns were useful tools for monitoring animal behavior and detecting changes due to heat stress.

Functional longevity in five rabbit lines founded on different criteria: Comparison at foundation and at fixed times after selection.

The enhancement of rabbit female functional longevity, that is the ability to avoid voluntary culling, is a paramount aspect for the sustainability of meat rabbit production; this trait represents a direct indicator of female robustness. The objective of our study was to compare the functional longevity of five rabbit lines at their foundation and at fixed times during their selection processes. Four of them are maternal lines (A, V, H and LP) selected for litter size at weaning. The fifth line is the paternal line R, founded and selected for post-weaning daily gain from 28 to 63 days. The comparison at foundation involved the complete data set (from March 1980 to March 2013; records of 15,670 does) and pedigree (19,405 animals). Latter comparisons were made when all lines shared the same environmental and management conditions, from March 1997 to September 1998 and from March 2011 to September 2012. In these second comparisons, the same model as that used in the comparison at foundation was used, but now the additive effect was excluded, only data from the corresponding periods were considered. At their foundation, lines V, H and LP showed larger functional longevity than lines A and R, being LP line that with the longest productive life. In the latter comparisons, lines A and R still showing the lowest functional longevities. However, as the selection process evolves, the differences between these two lines and the others were reduced. It could be concluded that the average longevity of a population greatly depends on the criteria followed for its foundation. In addition, along the selection for litter size, the differences of longevity between lines tend to decrease, this is due to an unintended selection for functional longevity, since only offspring from females reaching three parturitions are selected as breeding animals for the next generation.

Genetic analysis of functional longevity in a complete diallel crossing experiment involving four maternal rabbit lines.

In a diallel cross between four maternal lines of rabbits, the four maternal lines and the corresponding crossbred females (does) were evaluated concerning functional longevity, estimating their crossbreeding components. Sixteen genetic groups were produced by using four maternal lines of rabbit (A, V, H and LP (L)). The groups were distributed over 4 Spanish farms. In all farms, the V line was present as the reference group. A total of 7,211 does' longevity records were recorded. Using a Cox proportional hazard model of fixed effects, survival analysis was performed to study longevity analysing the hazard of death or culling. Does from lines A, H and V had similar risks of death or of being culled, and they were more susceptible compared with those from line L. The lowest hazard was associated with L line does. No significant differences were found between the average of all crosses and the V line except when comparing the V line to the cross between A and H lines, favouring the former (1.30 higher risk of replacement for AH animals). Significant differences between reciprocal crosses were observed between VH and HV, in favour of HV (0.72 of relative risk of replacement) and between LH and HL, in favour of HL (0.76 of relative risk). Line V had the highest risk due to the direct genetic effects, and these differences were significant with the lines H (1.40 of relative risk) and L (1.43 of relative risk). The differences in maternal genetic effects were small and not significant except between lines H and V in favour of V line (0.75 of relative risk). The estimated direct heterosis effects do not always follow the same trend but they showed the importance of the crossing between specialized lines to produce crossbred does for intensive meat rabbit production.

Impact of HIV on the survival of hepatocellular carcinoma in hepatitis C virus-infected patients.

BACKGROUND: Previous studies have suggested that hepatocellular carcinoma (HCC) has an aggressive presentation and a shorter survival in people with HIV (PWH). This could be due to later diagnosis or lower rates of HCC treatment, and not to HIV infection itself. AIM: :: To assess the impact of HIV on HCC survival in hepatitis C virus (HCV)-infected patients. METHODS: Multicenter cohort study (1999-2018) of 342 and 135 HCC cases diagnosed in HIV/HCV-infected and HCV-monoinfected patients. Survival after HCC diagnosis and its predictors were assessed. RESULTS: HCC was at Barcelona-Clinic Liver-Cancer (BCLC) stage 0/A in 114 (33%) HIV/HCV-coinfected and in 76 (56%) HCV-monoinfected individuals (P < 0.001). Of them, 97 (85%) and 50 (68%) underwent curative therapies (P = 0.001). After a median (Q1-Q3) follow-up of 11 (3-31) months, 334 (70%) patients died. Overall 1 and 3-year survival was 50 and 31% in PWH and 69 and 34% in those without HIV (P = 0.16). Among those diagnosed at BCLC stage 0/A, 1 and 3-year survival was 94 and 66% in PWH whereas it was 90 and 54% in HIV-negative patients (P = 0.006). Independent predictors of mortality were age, BCLC stage and α-fetoprotein levels. HIV infection was not independently associated with mortality [adjusted hazard ratio (AHR) 1.57; 95% confidence interval: 0.88-2.78; P = 0.12]. CONCLUSION: HIV coinfection has no impact on the survival after the diagnosis of HCC in HCV-infected patients. Although overall mortality is higher in HIV/HCV-coinfected patients, this seem to be related with lower rates of early diagnosis HCC in HIV-infected patients and not with HIV infection itself or a lower access to HCC therapy.

Low performance of ultrasound surveillance for the diagnosis of hepatocellular carcinoma in HIV-infected patients.

OBJECTIVE: To assess the performance of ultrasound surveillance for the diagnosis of hepatocellular carcinoma (HCC) in HIV-infected patients. METHODS: The GEHEP-002 cohort recruits HCC cases diagnosed in HIV-infected patients from 32 centers across Spain. The proportion of 'ultrasound lack of detection', defined as HCC diagnosed within the first 3 months after a normal surveillance ultrasound, and the proportion of 'surveillance failure', defined as cases in which surveillance failed to detect HCC at early stage, were assessed. To assess the impact of HIV, a control population of 104 HCC cases diagnosed in hepatitis C virus-monoinfected patients during the study period was used. RESULTS: A total of 186 (54%) out of 346 HCC cases in HIV-infected patients were diagnosed within an ultrasound surveillance program. Ultrasound lack of detection occurred in 16 (8.6%) of them. Ultrasound surveillance failure occurred in 107 (57%) out of 186 cases diagnosed by screening, whereas this occurred in 18 (29%) out of 62 diagnosed in the control group (P < 0.0001). HCC cases after ultrasound surveillance failure showed a lower frequency of undetectable HIV viral load at diagnosis. The probability of 1-year and 2-year survival after HCC diagnosis among those diagnosed by screening was 56 and 45% in HIV-infected patients, whereas it was 79 and 64% in HIV-negative patients (P = 0.038). CONCLUSION: The performance of ultrasound surveillance of HCC in HIV-infected patients is very poor and worse than that shown outside HIV infection. A HCC surveillance policy based on ultrasound examinations every 6 months might be insufficient in HIV-infected patients with cirrhosis.

Interferon-free therapy for treating hepatitis C virus in difficult-to-treat HIV-coinfected patients.

BACKGROUND/AIMS: Data regarding the use of all-oral direct-acting antivirals in HIV/hepatitis C virus (HCV)-coinfected patients with advanced liver fibrosis are required, because they are generally under-represented in clinical trials. This study sought to evaluate the use of these drugs in a cohort of coinfected patients, mostly with factors that have previously been recognized as predictors of treatment failure. METHODS: COINFECOVA-2 is an observational, multicenter study conducted in Eastern Spain. Data of all HIV/HCV-coinfected patients treated with direct-acting antiviral under real-life conditions were retrospectively collected, and factors associated with treatment success or safety were analysed. RESULTS: Among 515 included patients, 96% were on antiretroviral therapy and 89.5% had an HIV-RNA less than 50 copies/ml. HCV genotype (G) distribution was 47% G-1a, 20% G-4, 14.4% G-1b, and 12.8% G-3. Patients with cirrhosis were 54.2%, and 46% failed to prior HCV-therapies. Overall, 92.8% patients (95% confidence interval: 90.2-94.9) achieved sustained virologic response (SVR12). Cirrhosis was the only factor associated with treatment failure, and SVR12 rate was significantly lower in patients with liver stiffness at least 21 kPa. Adverse events were reported in 36.7%, but only two patients (0.4%) discontinued treatment because of adverse events. The bivariate analysis showed an association between ribavirin use and an increased risk of adverse events (odds ratio 2.84; 95% confidence interval: 1.95-4.1; P ≤ 0.0001). CONCLUSION: This heterogeneous cohort of coinfected patients showed a high rate of SVR12. Among cirrhotic patients, those with a liver stiffness at least 21 kPa had a higher probability of treatment failure. Ribavirin use seems to increase the appearance of adverse events.

Real-life experience with sorafenib for the treatment of hepatocellular carcinoma in HIV-infected patients.

OBJECTIVE: To report the real-life results of sorafenib use in a cohort of HIV-infected patients with hepatocellular carcinoma (HCC). METHODS: The GEHEP-002 cohort (ClinicalTrials.gov ID: NCT02785835) has recruited 302 HCC cases diagnosed in HIV-infected patients from 32 centers from Spain. RIS-HEP12 study included 44 (14%) cases that have received at least one dose of sorafenib. The overall survival after the start of treatment was the main efficacy outcome. Permanent discontinuation due to adverse events was the primary safety end point. RESULTS: Reasons for sorafenib use are HCC recurrence after previous curative therapy (n = 7), progression following transarterial chemoembolization (n = 6) and first treatment against HCC (n = 31). Nineteen (43%) patients harbored Child-Pugh B cirrhosis. Barcelona-Clinic Liver Cancer stage was A 3 (7%), B 6 (14%), C 30 (68%) and D 5 (11%). All patients were on antiretroviral therapy (ART). The median (Q1-Q3) duration of sorafenib treatment was 70 (31-158) days. Median survival was 7.2 months, whereas the median (Q1-Q3) duration of overall survival after the start of treatment was 4 (2-9.7) months. Twenty-six (59%) patients had any grade adverse events and 19 (43%) suffered a decompensation. Discontinuation due to adverse events occurred in 17 (38.6%) patients. There were no modifications or discontinuations of ART. CD4 cell counts and HIV viral load remained stable. CONCLUSION: The efficacy of sorafenib under real-life conditions in HIV-infected patients seems lower than that reported in the registration clinical trial. On the contrary, the tolerability of sorafenib appears to be similar to what is seen in patients without HIV infection. Sorafenib does not seem to modify the efficacy of ART.

Admissions for imported and non-imported parasitic diseases at a General Hospital in Spain: A retrospective analysis.

OBJECTIVE: To analyze imported and non-imported parasitic diseases as a cause of admission to a general hospital. METHODS: A retrospective analysis of hospital admissions for parasitic diseases between 2004 and 2013 performed by means of hospital information systems at a public hospital in the city of Castellón (Spain). RESULTS: During the period covered in this study, there were 204,349 admissions, 213 of which were for parasitic diseases (prevalence: 1.04/1000 admission). 129 were neglected parasitic tropical diseases and 61 were imported parasitic diseases. The main parasitic diseases were hydatidosis (24.9%), visceral leishmaniasis (22.5%) and malaria (12.2%). There was a decrease in admissions for visceral leishmaniasis in the 2004-2008 period from 27.7% to 15.9% in the 2009-2013 period (p < 0.001), and an increase in admissions for malaria from 5.0% to 21.3% (p < 0.001). 38 (20.3%) of the 187 patients with parasitic diseases were HIV infected. HIV infection was more common in patients with toxoplasmosis (94.1%; p < 0.001), cryptosporidiosis (66.7%; p < 0.02) and visceral leishmaniasis (46.4%; p = 0.003). There were 34 (18.2%) children with parasitic diseases. Twelve of the 28 patients with visceral leishmaniasis (42.9%; p < 0.001), and 11 of the 17 patients with soil-transmitted diseases were children (64.7%; p < 0.001). The cause of death in eight patients was parasitic disease related (mortality rate: 4.3%). The mortality rate for visceral leishmaniasis was significantly higher (14.3%; p = 0.01). CONCLUSION: The main cause is endemic parasitic diseases such as hydatidosis. Visceral leishmaniasis decreased during the period covered by the study, but malaria increased.

Telaprevir or boceprevir in HIV/HCV-1 co-infected patients in a real-life setting. Interim analysis (24 weeks). COINFECOVA-SEICV study.

INTRODUCTION: In general, HIV co-infected patients included in clinical trials evaluating the hepatitis C virus (HCV) therapy with telaprevir (TVR) or boceprevir (BOC) with advanced fibrosis, are scarce. We analyze data concerning the use of these drugs in a real-life clinical setting with patients affected by a more advanced degree of fibrosis in a Spanish cohort. METHODS: We evaluated safety and efficacy in an interim analysis encompassing the first 24 weeks of triple therapy with peginterferon (alfa-2a or alfa-2b), ribavirin and TVR or BOC in an observational, multicentre study. HIV/HCV genotype 1 co-infected patients beginning therapy from January 2012 to July 2013 were included. RESULTS: Enrolled patients were 155 (144 patients on TVR and 11 on BOC), average age was 47 years, 83% were male. With respect to HCV treatment, 44% were naïve, 13% relapsers, 17% partial responders, 21% null responders, and in seven patients, the previous response was unknown. All but three (98%) were under antiretroviral therapy (ART) (other than reverse transcriptase inhibitors, the backbone was raltegravir 43%, atazanavir 35%, and etravirine 28%). Median HCV-RNA at baseline was 6.1 log10, 54% were cirrhotic and 38% F3. At week 4, 93% of patients continued on therapy, 81% at w12, and 73% at w24. Virological failure was observed more frequently in: cirrhotic patients (19% [95% CI, 11-27]) vs F3 (12% [CI, 4-20]); patients with TT allele of the IL28B polymorphism (40% [CI, 18-61]) vs CT (21% [CI, 12-31]), or CC (2,2% [CI, -2-6]); previous null responders (37.5% [CI, 21-54]) vs partial responders (15.4% [CI, 1-29]), naïve (13% [CI, 5-21]) or relapsers (0% [CI, 0-0]); and in patients with a genotype subtype 1a (23.6% [CI, 57-76]) vs 1b (8.1% [CI, -1-17]). Overall, 17% had virological failure and in 8% treatment was discontinued due to adverse events. Severe adverse events occurred in 30 patients (19%). Haematologic disorders were the most common type including severe anaemia in 12 (7.7%) patients. Erythropoietin was employed in 41 patients (26.4%) and 11 (7.1%) received blood transfusions. Nineteen patients (12.2%) were treated with G-CSF, and 17 (11%) with thrombopoietin-receptor agonists. Five patients died (3.2%), three due to hepatic decompensation, one due to pneumonia and one due to pulmonary hypertension. CONCLUSIONS: In a real-life setting, therapy against HCV in co-infected patients with advanced liver fibrosis shows high virologic success at 24 weeks. However, frequent haematologic disorders are observed and a close monitoring and an intensive therapy are needed to optimize the results.

The effects of Maraviroc on liver fibrosis in HIV/HCV co-infected patients.

INTRODUCTION: The fibrogenesis analysis in quimeric CCR1 and CCR5 mice revealed that CCR5 mediates its pro-fibrogenic effects in hepatic cells and promoting stellate cells. The blockage of co-receptors could preserve the progression of hepatic fibrosis in HIV/HCV co-infected patients. OBJECTIVE: To evaluate the beneficial effects on hepatic fibrosis in HIV/HCV co-infected patients that are on antiretroviral therapy (ART) with CCR5 co-receptor antagonists. METHOD AND MATERIALS: A multicentre, retrospective pilot study of the evaluation of hepatic fibrosis at mid- and long-term by non-invasive methods in a HIV/HCV co-infected patients cohort in the Valencian Community (Spain) that received ART with a CCR5 co-receptor antagonist. The cut-off points of serum marker tests of hepatic fibrosis were: AST to Platelet Ratio Index (APRI)<0.5 (F0-F1); >1.5 F2; >2 Cirrhosis and Forns Index<4.2 excludes fibrosis; >6.9>F2 fibrosis. Inclusion criteria was established for HIV/HCV co-infected patients on ART with CCR5 co-receptor antagonists that had no previous history of interferon and ribavirin treatment or those who were null-responders and received CCR5 co-receptor antagonist treatment in the previous year. Patients with HBV infection were excluded. RESULTS: A total of 71 male patients (69%) were reported. A CD4 nadir <100 cells/uL was observed in 42% of patients and 62% (44/71) had a basal CD4 level >350 cells/uL. According to genotypes, 50% were G-1a, 14% G-1b, 11% G-3 and 25% G-4. The median duration of treatment with Maraviroc (MVC) was the following: 45% took it over a year, 41% over two years and 14% over three years. Before starting treatment with MVC, we observed an initial fibrosis of F0-F1 in 49% of patients, F2-F3 in 24% and F4 in 27%. The medium follow-up was of 18.45 months. Progression to a higher fibrosis level was observed in five patients, 11 patients improved at least one stage and the others were stable over time. There were 38 patients taking MVC over two years, 27 patients in this group (59.38%) did not modify their fibrosis, 3 patients (11%) progressed and 8 (29.62%) showed regression of liver fibrosis in one stage. CONCLUSIONS: The data above shows a benefit over fibrosis progression with MVC, expressed by fibrosis serum marker tests in HIV/HCV co-infected patients with CCR5 tropism. The prolong treatment with MVC (over two years) has a better effect on liver fibrosis.

Increasing incidence of hepatocellular carcinoma in HIV-infected patients in Spain.

BACKGROUND: To report the clinical and epidemiological characteristics of hepatocellular carcinoma (HCC) diagnosed in a cohort of human immunodeficiency virus (HIV)-infected patients in Spain. METHODS: All HIV-infected patients diagnosed of HCC in 18 hospitals in Spain before 31 December 2010 were included. The main characteristics of HCC cases are described and comparisons between cases according to the year of diagnosis are presented. RESULTS: Eighty-two cases of HCC in HIV-infected patients were included, all of them related to viral hepatitis coinfection: hepatitis C virus (HCV) in 66 (81%), hepatitis B virus (HBV) in 6 (7%), and HBV/HCV in 10 (12%). From 1999, when the first case of HCC was diagnosed, a progressive increment in the incidence of HCC in the cohort has occurred. In patients coinfected with HIV/HCV-coinfected patients, the incidence HCC increased from 0.2 to 2.8 cases per 1000 person-years between 2000 and 2009. Death occurred in 65 patients (79%), with a median survival of 91 days (interquartile range, 31-227 days). Three of 11 patients (28%) who received potentially curative therapy died, compared with 62 of 71 patients (87%) who did not receive curative therapy (P = .0001). Compared with cases of HCC diagnosed before 2005, cases diagnosed later did not show a higher survival rate. CONCLUSIONS: HCC is an emerging complication of cirrhosis in HIV-infected patients. A sharp increase in its incidence has occurred in those also infected by HCV in the recent years. Unfortunately, HCC is frequently diagnosed at an advanced stage, and mortality continues to be very high, with no significant changes in recent years. Earlier diagnosis, which may allow potentially curative therapy, is necessary.

Saquinavir exposure in HIV-infected patients with chronic viral hepatitis.

OBJECTIVES: The aim of this study was to assess the influence of hepatitis B virus or hepatitis C virus co-infection and the extent of liver fibrosis on saquinavir and ritonavir pharmacokinetics in HIV-infected subjects without liver function impairment. METHODS: A cross-sectional, comparative study enrolling HIV-infected adults receiving saquinavir/ritonavir 1000/100 mg twice daily or 1500/100 mg once daily was conducted. Patients with chronic viral hepatitis (HEP+) were grouped as having advanced liver fibrosis (HEP+/FIB+) or not (HEP+/FIB-) based on the FIB-4 index. Saquinavir and ritonavir trough concentrations (C(trough)) in plasma were determined by HPLC. The geometric mean ratio (GMR) was used to compare saquinavir and ritonavir C(trough) between HEP- and HEP+ patients, and the influence of the extent of liver fibrosis on saquinavir and ritonavir pharmacokinetics was explored using analysis of variance. RESULTS: One hundred and thirty-eight patients on twice-daily saquinavir/ritonavir (67 HEP-, 71 HEP+) and 36 patients on once-daily saquinavir/ritonavir (12 HEP-, 24 HEP+) were included. Saquinavir C(trough) was comparable between HEP- and HEP+ patients receiving either saquinavir/ritonavir 1000/100 mg twice daily [GMR 0.91, 95% confidence interval (CI) 0.60-1.37; P = 0.655] or 1500/100 mg once daily (GMR 0.88, 95% CI 0.39-1.97; P = 0.752). Similarly, ritonavir C(trough) was also comparable between HEP- and HEP+ patients. The extent of liver fibrosis was not significantly related to saquinavir or ritonavir C(trough) in patients receiving either of the two studied doses. CONCLUSIONS: Saquinavir C(trough) was not increased in HIV-infected patients with chronic viral hepatitis in the absence of liver function impairment. These results confirm that no specific dose modification of saquinavir/ritonavir should be recommended in this setting.