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Objective To assess the changes on the HIV protease gene in plasma and peripheral blood mononuclear cell ( PBMC) compartments during viral replication episodes in patients on boosted-darunavir monotherapy ( mtDRV/rtv). Methods A prospective study was carried out in which adult HIV-1-infected patients who started mtDRV/rtv after viral suppression for ≥6 months with no major darunavir-related resistance mutations were enrolled. Patients with two consecutive plasma HIV RNA measurements > 200 HIV-1 RNA copies/mL were considered as having virological failure ( VF), while patients with two consecutive plasma HIV RNA measurements > 50 copies/mL without meeting the VF criteria were considered to have virological rebound ( VR). HIV protease genotypic profiles from plasma and PBMCs were performed at baseline and at VF and VR episodes. Results One hundred and fifty patients were included in the study, with overall VF and VR rates of 14% ( n = 21) and 14.7% ( n = 22), respectively. No major darunavir resistance mutations were observed in the plasma or PBMC samples. Circulating and cell-associated viruses showed a wild-type protease gene sequence in 54% and 23% of patients, respectively while the remainder patients only harboured minor protease inhibitor-associated mutations. Full concordance between plasma RNA and PBMC DNA protease genotypes was found in 23% of the sequences. Conclusions No darunavir-related mutations were found in patients with VF or VR, either in plasma or in PBMCs; thus, simplification to mtDRV/rtv does not comprise future antiretroviral treatment options. [ABSTRACT FROM AUTHOR]

Objective: To describe in detail the epidemiology, diagnosis, clinical management, treatment options, impact on quality of life and unmet needs of patients with advanced liver fibrosis (F3-F4) associated with non-alcoholic steatohepatitis (NASH) in Spain., Methodology: Delphi study of two rounds of consultation rounds with 41 expert hepatologists from 16 autonomous communities to collect their experience in clinical practice., Results: The estimated prevalence of adult patients diagnosed with F3-F4 fibrosis associated with NASH in Spain is 0.019% (95% confidence interval [CI]: 0.019-0.020%). Approximately 7,588 adults with this condition are currently diagnosed and managed in the Digestive System Services of Spanish hospitals, and around 1,881 new patients are diagnosed each year. Management is multidisciplinary and includes the specialties of Digestive System, Endocrinology and Internal Medicine, considering the frequently associated metabolic comorbidities (obesity, type 2 diabetes mellitus or dysmetabolic iron overload). Despite a clear impact on quality of life, this it is not routinely evaluated in clinical practice. The most widely used non-invasive diagnostic techniques are transitional elastography and liver fibrosis index 4 (FIB-4). The absence of effective and safe treatments appears as the main unmet need for the management of these patients., Conclusions: This study provides a representation of the current situation of patients diagnosed with F3-F4 fibrosis associated with NASH in Spain, increasing the evidence available and contributing to informed decision-making by professionals and the health system., (Copyright © 2023 The Authors. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: There are contradictory data about the influence that hepatitis C virus (HCV) has on immune activation and inflammation in patients coinfected with human immunodeficiency virus (HIV) and HCV., Methods: HIV/HCV-coinfected patients receiving antiretroviral treatment who achieved a sustained virological response with interferon-free regimens were consecutively enrolled in a prospective study. The following factors were assessed before, immediately after the end of, and 1 month after the end of therapy: expression of HLA-DR/CD38, PD-1, and CD57 on CD4+ and CD8+ T-cells; measurement of the total HIV DNA load in peripheral blood mononuclear cells; and determination of plasma levels of soluble CD14 (sCD14), lipopolysaccharide (LPS), 16S ribosomal DNA (rDNA), interleukin 6 (IL-6), D-dimers, and high-sensitivity C-reactive protein (hsCRP)., Results: Ninety-seven patients were consecutively included. At the end of therapy and 1 month later, there were significant reductions in the expression of HLA-DR and CD38 in CD4+ and CD8+ T cells, as well as levels of proviral HIV DNA, sCD14, LPS, 16S rDNA, and D-dimer (P < .001). By contrast, the expression of PD-1 and CD57 in CD4+ and CD8+ T cells and levels of IL-6 and hsCRP did not change. The improvement in levels of immune activation markers, proviral HIV DNA, and microbial translocation markers did not translate into an increased CD4+ T-cell count or increased ratio of the CD4+ T-cell count to the CD8+ T-cell count., Conclusions: HCV eradication in HIV/HCV-coinfected patients results in significant decreases in levels of immune activation markers, proviral HIV DNA load, microbial translocation markers, and D-dimers. These findings support the use of HCV treatment for all HIV/HCV-coinfected patients, even those with low-grade fibrosis.

Background: There are several regimens for starting antiretroviral treatment, but it remains unknown whether either of them is more advantageous regarding the time course and magnitude of human immunodeficiency virus (HIV) RNA decay in semen., Objective: To evaluate the differential effect of different antiretroviral drug families on viral kinetics in seminal plasma (SP) of treatment-naive HIV-infected patients., Methods: Phase II, randomized, open-label study in which participants were randomized 1:1:1 to receive tenofovir-disoproxil fumarate (DF) plus emtricitabine, and either cobicistat-boosted elvitegravir (EVGcobi), rilpivirine (RPV), or ritonavir-boosted darunavir (DRVrtv). The primary endpoint was the proportion of participants with undetectable HIV-RNA in SP at week 12. HIV type 1 (HIV-1) RNA was measured in paired SP and blood plasma (BP) at baseline and after 1, 2, 4, 6, 8, 12, 18, and 24 weeks. Elvitegravir (EVG), RPV, and darunavir (DRV) concentrations were quantified by the liquid chromatography-tandem mass spectrometry method., Results: In SP, the HIV-RNA decay rate with RPV was as fast as with EVGcobi; by week 12, all participants in the RPV and the EVGcobi groups reached an undetectable viral load but only 58.3% in the DRVrtv arm (P = .003). The highest SP/BP drug concentration ratio was for EVG (0.43), followed-up by RPV (0.19), and DRV (0.10). For both EVG and RPV, the SP concentrations exceeded >2-fold the protein binding-adjusted EC90 for wild-type HIV-1; for DRV, only 33.7% of the SP showed concentrations above the protein binding-adjusted EC90., Conclusions: In SP, both RPV and EVGcobi, associated to tenofovir-DF and emtricitabine, behave similarly and achieve an undetectable viral load much faster than DRVrtv., Registration: European Medical Agency (No. EudraCT: 2014-001348-39)., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com)

Objectives: To evaluate if there are significant drug-drug interactions between cobicistat-boosted elvitegravir and 800 mg darunavir once daily taken simultaneously, as has been suggested previously., Methods: The study population consisted of three groups of unselected volunteers taking a regimen of elvitegravir, cobicistat, emtricitabine and tenofovir disoproxil fumarate (150, 150, 200 and 300 mg, respectively) co-formulated in a single tablet plus 800 mg darunavir (group A); only co-formulated elvitegravir, cobicistat, emtricitabine and tenofovir disoproxil fumarate (group B); and cobicistat-boosted darunavir (800 mg darunavir + 150 mg cobicistat) plus two nucleos(t)ide analogues (group C). Elvitegravir, cobicistat and darunavir concentrations at the end of the dosing interval ( C 24 ) were quantified using a validated LC with tandem MS method., Results: A total of 170 samples were obtained from 24, 32 and 32 patients in groups A, B and C, respectively. In group A, the elvitegravir C 24 were similar to those in group B (233.67 versus 250.39 ng/mL) ( P  =   0.406) and the darunavir C 24 were similar to those in group C (1293.54 versus 1319.34 ng/mL) ( P  =   0.908). The cobicistat C 24 were comparable in groups A and B (20.2 versus 20.9 ng/mL) and slightly higher in group C (27.7 ng/mL) ( P  =   0.059)., Conclusions: The results provide evidence of similar elvitegravir and darunavir C 24 concentrations when these drugs are co-administered as co-formulated elvitegravir, cobicistat, emtricitabine and tenofovir disoproxil fumarate plus 800 mg darunavir or dosed separately., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Plasma HIV p24 is considered a significant predictor of CD4 + T cell decline and progression to AIDS in HIV-infected patients. We evaluated the p24 levels in patients on triple therapy and after switching to ritonavir-boosted protease inhibitor monotherapy (mtPI/rtv), as well as the relationships with virological and immunological evolution., Materials and Methods: Plasma samples from patients participating in two studies of simplification to mtPI/rtv were analysed for presence of p24, using a boosted enzyme-linked immunosorbent assay specific for mature p24. Only patients with available samples at baseline (on triple therapy) and during a follow-up of at least 12 months after switching to mtPI/rtv were included., Results: A total of 233 samples from 51 patients were analysed. After switching to mtPI/rtv and a median follow-up of 24 months, 14 patients maintained continuous undetectable viraemia, and 37 patients experienced a total of 49 transient viraemic episodes. Unexpectedly, the evolutionary p24 patterns were uniform for most patients, both before and after switching to mtPI/rtv, independently of the virological behaviour, fitting into one of three categories: persistent undetectable p24 levels, positive p24, matching only with the viraemic episodes, and persistent detectable p24 levels. The last group showed lower CD4 + T cell counts and percentages, as well as lower CD4 + /CD8 + T cell ratios after 12 and 24 months of follow up., Conclusion: Treatment simplification to mtPI/rtv does not influence the behaviour of p24 in plasma. Patients with continuous positive p24, despite undetectable viraemia, showed worse immunological evolution., (Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.)

The aim of this study was to assess whether hepatitis C virus (HCV) coinfection would affect the clinical and immunological outcome of HIV-infected patients following a simplification strategy. A prospective cohort of HIV-infected patients starting a ritonavir boosted darunavir monotherapy (mtDRV/rtv) was followed for 24 months. HCV infection was evaluated by HCV viremia and hepatic fibrosis. Immune activation was studied as HLA-DR CD38 coexpression on CD4(+) and CD8(+) T cells and also the quantification of plasma sCD14 levels. Microbial translocation was studied by the plasma levels of 16S rDNA and lipopolysaccharide (LPS). A total of 150 HIV-infected patients were enrolled in this study, including 46 individuals also infected with HCV (30.6%). HIV/HCV coinfection did not decrease mtDRV/rtv efficacy, since similar rates of HIV-1 intermittent viremia (HCV: 26.6% vs. no-HCV: 34.7%) and episodes of virological failure (HCV: 22.2% vs. no-HCV: 11.2%, p-value = 0.381) were found. No major differences were found between both groups at baseline, although higher HLA-DR(+)CD38(+)CD4(+) T cell counts were found in the coinfected group (HCV: 6.65% vs. no-HCV: 4.55%, p-value = 0.032); this difference was maintained in the 24 months of follow-up. After the 24-month follow-up, both groups, HIV-monoinfected patients and HIV/HCV-coinfected patients, presented similar immune activation and microbial translocation profiles. In conclusion, the use of a simplified mtDRV/rtv strategy compromises neither HIV nor HCV viremic control in coinfected patients, although a higher immune activation of CD4(+) T cells was found.

Cross-sectional study comparing seminal human immunodeficiency virus type 1 (HIV-1) shedding in patients receiving boosted protease inhibitor monotherapy (mtPI/rtv) (n = 66) versus triple therapy (TT) (n = 61). Seminal HIV-1 shedding rates in patients with undetectable plasma HIV-RNA were 16.0% on mtPI/rtv compared with 28.6% on TT (p 0.173). Aviraemic status and time on viral suppression were independently associated with lack of seminal HIV-1 shedding. During TT, non PI/rtv-based regimens were associated with a better control of HIV infection in semen despite similar time on viral suppression. The use of mtPI/rtv in well-controlled patients is not associated with increased seminal HIV excretion compared with TT., (Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

The purpose of this article is to evaluate the evolution of microbial translocation (MT) and its role in CD4 and CD8 T cells immune activation (IA) in HIV-1-infected patients on ritonavir-boosted darunavir monotherapy (mtDRV/rtv).Prospective study of consecutive HIV-1-infected patients switched to mtDRV/rtv as a simplification regimen. Subjects were classified according to the virological behavior during a 24-month follow-up as continuous undetectable viral load, blips, intermittent viremia, and virological failure (VF). MT was evaluated by plasma LPS and 16S genomic rDNA (16S rDNA) levels, whereas IA was assessed by the coexpression of HLA-DR and CD38 in CD4 and CD8 T cells, and plasma sCD14 levels.Seventy-one patients were included in this substudy of the MonDar cohort (ClinicalTrials.gov: NCT01505722). At baseline, CD4 (ρ = -0.352, P = 0.01) and CD8 T-cell activation (ρ = -0.468, P < 0.001) were correlated with time with viral suppression, but not with MT markers. A significant decrease in plasma LPS levels was found only in patients without VF (baseline, 77.8 vs month 24, 60.4 pg/mL; P < 0.001]. Both plasma 16S rDNA and sCD14 levels were unchanged irrespective of the viral behavior. The only variable independently associated with a decrease in CD4 and CD8 T cells activation was an undetectable HIV-1 viremia (β = 4.78, P < 0.001 and β = 2.93, P = 0.005, respectively).MT does not have a pivotal role in T-cell activation, at least in patients with long-term viral suppression. The viremic episodes and VF are the main factors related to CD4 and CD8 T-cells IA, even during mtDRV/rtv.

Invasion of the malaria vector Anopheles gambiae midgut by Plasmodium parasites triggers transcriptional changes of immune genes that mediate the antiparasitic defense. This response is largely regulated by the Toll and Immune deficiency (IMD) pathways. To determine whether A. gambiae microRNAs (miRNAs) are involved in regulating the anti-Plasmodium defense, we showed that suppression of miRNA biogenesis results in increased resistance to Plasmodium falciparum infection. In silico analysis of A. gambiae immune effector genes identified multiple transcripts with miRNA binding sites. A comparative miRNA microarray abundance analysis of P. falciparum infected and naïve mosquito midgut tissues showed elevated abundance of miRNAs aga-miR-989 and aga-miR-305 in infected midguts. Antagomir inhibition of aga-miR-305 increased resistance to P. falciparum infection and suppressed the midgut microbiota. Conversely, treatment of mosquitoes with an artificial aga-miR-305 mimic increased susceptibility to P. falciparum infection and resulted in expansion of midgut microbiota, suggesting that aga-miR-305 acts as a P. falciparum and gut microbiota agonist by negatively regulating the mosquito immune response. In silico prediction of aga-miR-305 target genes identified several anti-Plasmodium effectors. Our study shows that A. gambiae aga-miR-305 regulates the anti-Plasmodium response and midgut microbiota, likely through post-transcriptional modification of immune effector genes., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Our aim was to assess the evolution and the impact that blips, intermittent low-level viraemia and virological failure (VF) episodes have on patients' immune activation (IA) profiles during ritonavir-boosted darunavir monotherapy (mtDRV/rtv). A prospective cohort of human immunodeficiency virus-1-infected patients who switched to mtDRV/rtv was followed for 2 years. Cellular IA was assessed according to HLA-DR and CD38 expression in CD4(+) and CD8(+) T-cells and their naïve, effector memory and central memory subpopulations, and systemic IA was evaluated according to sCD14 and D-dimer levels. Seventy-five patients from the MonDAR cohort were selected for this substudy, and classified according to viral outcome as having continuous undetectable viraemia (n = 19), blips (n = 19), intermittent viraemia (n = 21), and VF (n = 16). The IA profile was closely linked to viral behaviour. Patients on viral suppression for 24 months showed a significant decrease in CD4(+) and CD8(+) T-cell activation and sCD14 and D-dimer levels. Patients with transient low-level viraemia episodes (blips and intermittent viraemia) showed cellular and systemic IA similar to baseline values. In contrast, significant increases in T-cell activation and sCD14 and D-dimer levels were observed in patients with VF. Baseline levels of HLA-DR(+)CD38(+)CD8(+) T-cells of >6.4% were independently associated with the emergence of VF. Therefore, mtDRV/rtv might be considered as a safe simplification strategy, on the basis of the IA results, whenever viral replication is under medium-term and long-term control. Transient low-level viraemia episodes do not affect patients' IA status. Moreover, HLA-DR(+)CD38(+)CD8(+) T-cell baseline levels should be considered when patients are switched to mtDRV/rtv., (© 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.)

The aim of this study was to characterize timing, kinetic, and magnitude of CMV-specific immune response after hematopoietic stem cell transplantation (HSCT) and its ability to predict CMV replication and clinical outcomes. Using cell surface and intracellular cytokine staining by flow cytometry, CMV-specific T-cell response was measured in blood, while CMV viral load and chimerism were determined by real-time PCR. Patients that reconstituted CMV-specific T-cell response within 6 weeks after Allo-SCT showed a more robust immune response (CD8(+) : 0.7 cells/μl vs. 0.3/μl; P-value = 0.01), less incidence of CMV replication (33% vs. 89.5%; P-value = 0.007), reduced viral loads (1.81 log copies/ml vs. 0 copies/ml; P-value = 0.04), and better overall survival (72%; CI: 0.53-0.96 vs. 42% CI: 0.24-0.71; P-value = 0.07) than patients with a delayed immune reconstitution. Viremic patients had significantly higher transplant-related mortality than nonviremic patients after 1 year (33% CI: 0.15-0.52 vs. 0% CI: 0.05-0.34; P-value = 0.01). Risk factors independently associated with viral replication were receptor pretransplant CMV-positive serostatus (P-value = 0.02) and acquiring CMV-specific T-cell response after 6 weeks post-transplantation (P-value = 0.009). In conclusion, timing of acquiring a positive CMV-specific T-cell immune response after transplantation may identify patients with different risk for viral replication and different clinical outcomes, including survival., (© 2014 Steunstichting ESOT.)

Despite advances in prevention, cytomegalovirus (CMV) recurrence is an important challenge in high-risk organ recipients. The present study prospectively evaluates the impact of CMV-specific T-cell immune response and secondary prophylaxis on the risk of recurrence in a cohort of CMV high-risk organ recipients and whether it is possible to determine a safe standardized viral load value below which CMV disease is unlikely. Thirty-nine recipients were included. Thirty-six had primary infections, and 88.9% recurred. Rate and duration of recurrent CMV infection was similar in patients with and without secondary prophylaxis: 57.9% vs. 53.6%, P = 0.770 and 16 vs. 15 days, P = 0.786, respectively. The only factor independently associated with no episodes of CMV recurrence was the acquisition of CMV-specific T-cell immune response (OR: 0.151, 95% CI: 0.028-0.815; P = 0.028). Cytomegalovirus diseases (N = 5) occurred in patients with CMV viral load above 1500 IU/ml who did not follow the planned monitorization schedule. Our observations suggest that episodes of recurrent CMV infection are common after preemptive therapy despite secondary prophylaxis and that CMV-specific T-cell immune response is associated with a decreased risk of recurrent infections. Preemptive therapy may be safe in patients at high risk for CMV infection with strict close monitoring of the CMV viral load., (© 2014 Steunstichting ESOT.)

Malaria parasite transmission requires the successful development of Plasmodium gametocytes into flagellated microgametes upon mosquito blood ingestion, and the subsequent fertilization of microgametes and macrogametes for the development of motile zygotes, called ookinetes, which invade and transverse the Anopheles vector mosquito midgut at around 18-36 h after blood ingestion. Within the mosquito midgut, the malaria parasite has to withstand the mosquito's innate immune response and the detrimental effect of its commensal bacterial flora. We have assessed the midgut colonization capacity of five gut bacterial isolates from field-derived, and two from laboratory colony, mosquitoes and their effect on Plasmodium development in vivo and in vitro, along with their impact on mosquito survival. Some bacterial isolates activated the mosquito's immune system, affected the mosquito's lifespan, and were capable of blocking Plasmodium development. We have also shown that the ability of these bacteria to inhibit the parasites is likely to involve different mechanisms and factors. A Serratia marcescens isolate was particularly efficient in colonizing the mosquitoes' gut, compromising mosquito survival and inhibiting both Plasmodium sexual- and asexual-stage through secreted factors, thereby rendering it a potential candidate for the development of a malaria transmission intervention strategy., (© 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.)

A cross-sectional study of 77 chronic HIV-infected children revealed higher levels of biomarkers of inflammation (ultrasensitive C-reactive protein, D-dimer and β-2-microglobulin), immune activation (HLA-DR+ CD38+ CD4+ and CD8+ T cells) and microbial translocation [lipopolysaccaride (LPS), microbial 16S rDNA and sCD14] than 32 healthy controls. Immune activation was higher in viremic children, but microbial translocation occurred independently of viraemia and T cell activation. Our results do not support a relevant role of microbial translocation in T cell activation in chronic HIV-infected children, proposing a need to develop strategies to minimize microbial translocation in the future.

Objective: To assess the impact of blips and persistent viremia episodes on cell-associated HIV-DNA reservoir in extensively pretreated patients receiving ritonavir-boosted darunavir monotherapy (MtDRV/rtv) for 24 months., Design and Methods: Patients from the MonDAR prospective study (NCT01606722) who received at least 6 months of MtDRV/rtv and had at least two available peripheral blood mononuclear cells (PBMCs) samples were selected and classified according to the viral outcome as continuous undetectable viremia (cUV; n = 40), blips (n = 31), intermittent viremia (IV; n = 23), and virological failure (VF, two consecutive viral loads >200 copies/ml; n = 20). Proviral HIV-DNA was quantified by real-time PCR in PBMCs samples at baseline, and months 6, 12, 18 and 24. Additionally, HIV-DNA levels were exhaustively analyzed at virological failure and blip episodes., Results: The HIV-DNA levels remained constant during the 24 months in every group. Neither blips nor intermittent viremia influenced the HIV-DNA levels at short-term or at middle term. By contrast, virological failure episodes gave rise to a significant increase in proviral DNA (2.15 vs. 2.32 log10 HIV-DNA copies/10 PBMCs; P = 0.042). Basal proviral DNA levels more than 2 log10 copies/10 PBMCs predicted the time to viral rebound at any given cut-off point (>20, >50, and >200 copies/ml. HR: 3.02, 2.61, and 3.02, respectively; P ≤ 0.03. Besides, an adherence less than 95% was also strongly associated with virological failure (HR, 3.17; P = 0.021)., Conclusion: Blip episodes and intermittent viremia did not affect the cellular HIV reservoir dynamic during MtDRV/rtv. Higher adherence and an HIV-DNA levels less than 2 log10 copies/10 PBMCs at baseline were associated with a lower risk of virological failure.

Background: This study aimed to evaluate whether low darunavir (DRV) minimum plasma concentration (Cmin) values contribute to virological outcomes during DRV/ritonavir monotherapy (mtDRV/rtv)., Methods: This was a prospective observational single-arm 96-week efficacy study in virologically suppressed subjects on triple therapy switched to mtDRV/rtv (800/100 mg every 24 h). Previous virological failures (VF) on protease-inhibitor-based regimens were allowed if the historical resistance tests showed no major resistance mutation to DRV/rtv. VF was defined as two consecutive HIV RNA measurements of >200 copies/ml. Efficacy was analysed by per-protocol and by intention-to-treat analyses. Plasma DRV Cmin values were measured by LC-MS/MS., Results: A total of 150 subjects were included. At week 96, the efficacy rate on treatment was 83.6% (95% CI 77.2%, 90.0%) by per-protocol analysis and 67.6% (95% CI 60.0%, 75.2%) by intention-to-treat. In the whole cohort the median (IQR) DRV Cmin was significantly higher during the periods of undetectable than of detectable viraemia (1.82 µg/ml [1.47-2.46] versus 1.56 µg/ml [0.93-2.32]; P=0.006) as well as in the subjects with blips and VF. However, a cutoff point sufficiently sensitive and specific could not be found., Conclusions: The DRV Cmin values are related to viral control during mtDRV/rtv, but therapeutic drug monitoring cannot be recommended routinely as a precise cutoff point is unknown. Adherence is a key success factor on this regimen.

There is significant intra- and intersubject variability in lopinavir (LPV) plasma concentrations after standard dosing; thus, this prospective study was conducted to determine whether low plasma LPV concentrations could be associated with virological outcome throughout lopinavir-ritonavir maintenance monotherapy (mtLPVr) in the clinical practice setting. If this hypothesis would be confirmed, LPV drug monitoring could improve the efficacy of mtLPVr regimens. Patients with previous virological failure (VF) on protease inhibitor-based regimens were also included if the genotypic resistance tests showed no major resistance mutation associated with reduced susceptibility to lopinavir-ritonavir. VF was defined as 2 consecutive determinations of HIV RNA levels of >200 copies/ml. Efficacy was analyzed by per-protocol analysis. Plasma LPV trough concentrations were measured by high-performance liquid chromatography using a UV detector. A total of 127 patients were included (22% with previous failure on protease inhibitors). After 96 weeks, the efficacy rate was 82.3% (95% confidence interval [CI(95)], 75.3 to 89.3%). Virological efficacy was independent of LPV plasma concentrations even when LPVr was given once daily. An adherence of <90% (HR, 4.4 [CI(95), 1.78 to 10.8; P = 0.001]) and the presence of blips in the preceding 12 months (HR, 3.06 [CI(95), 1.17 to 8.01; P = 0.022]) were the only variables independently associated with time to VF. These findings suggest that the LPV concentrations achieved with the standard doses of LPVr are sufficient to maintain virological control during monotherapy and that measurement of LPV concentrations is not useful for predicting virological outcome. Tight control of viral replication in the previous months and strict adherence throughout the mtLPVr regimen could improve the virological efficacy of this maintenance regimen.

CMV DNA loads measured by the new Abbott RealTime CMV PCR were significantly higher than those quantitated by the Abbott CMV PCR kit (approximately 1 log(10)), and provided a better estimate of the actual CMV load present in plasma specimens as inferred by the use of the WHO standard., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Little is known about cytomegalovirus (CMV) infection after face transplantation, since only two of the 11 cases of face transplantation reported worldwide have documented a CMV infection after transplantation. Herein, we present the first report of a composite-tissue face allotransplant recipient at high risk for CMV infection (D(+)/R(-) [CMV serpositive donor positive/CMV seronegative receptor]) undergoing preemptive treatment. Preemptive treatment was safe and effective for controlling CMV infection and thus promoting early acquisition of a CMV-specific immune response that protected the patient from late-onset CMV disease.

Background: It has been suggested that preemptive therapy against cytomegalovirus (CMV) infection after transplantation promotes a CMV-specific immune response. Our objective was to determine whether solid-organ transplant patients at high risk for CMV infection treated preemptively acquire a CMV-specific immune response and whether the acquired immune response confers immunity by controlling subsequent CMV replication episodes and by protecting from late-onset CMV disease., Methods: Patients were followed up for 18 months after transplantation. CMV viral load was determined using real-time polymerase chain reaction assays, and the T-cell immune response was characterized by intracellular cytokine staining., Results: The 21 patients studied developed CMV replication episodes at a median of 4 weeks (range 2-8 weeks) after transplantation and a CMV-specific T-cell response within a median of 12 weeks (range 10-20 weeks). The decline in the incidence of CMV replication episodes is inversely correlated with the acquisition of the CMV-specific T-cell response (linear regression r=0.781, Pearson correlation=-0.883; P=0.001). There were no CMV replication episodes after week 47 of transplantation. In addition, after acquisition of the immune response, 42 replication episodes were cleared without treatment. The time taken for immune clearance of replication correlated with the peak viral load (P=0.01). No incidence of CMV early or late-onset disease was detected., Conclusions: Our results demonstrate that preemptive therapy is a safe and an effective strategy for the control of CMV infection in solid-organ transplant recipients at high risk for CMV infection. This is the first study that reports a therapeutic effect of the acquisition of CMV-specific immune response during preemptive treatment., (© 2011 by Lippincott Williams & Wilkins)

Background: The use of pre-emptive or prophylactic treatment to control cytomegalovirus (CMV) replication after solid organ transplant (SOT) remains controversial. The aim of this study was to evaluate whether administration of pre-emptive treatment to control viral replication guided by a highly sensitive diagnostic tool is an effective approach for preventing CMV disease, even in high-risk transplant recipients., Methods: Plasma samples from eight SOT patients were tested using antigenaemia and real-time PCR (RT-PCR) assays. Pre-emptive treatment was administered guided by RT-PCR when viral load values were >1,000 copies/ml., Results: All patients developed episodes of CMV infection, but none of them developed CMV disease or indirect effects. No patient in this study died or experienced graft rejection. Treatment was needed in 10 replication episodes. At the end of treatment, four had undetectable levels and the other six were cleared 3 weeks later. In 42.6% of tested samples RT-PCR was more sensitive for detecting viral infection., Conclusions: Pre-emptive monitoring of SOT patients at high risk for CMV infection protected patients from developing CMV disease during the first 6 months after transplant. The use of this sensitive method for guiding pre-emptive treatment diminished viral load early enough that it did not have consequences for patient health.