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The main aim of this research is to identify the transmitted resistance (RT) of the Human Immunodeficiency Virus (HIV) in subjects from nine cities of Peru. For this, a descriptive and cross-sectional study was carried out in 135 adult subjects who agreed to participate through an informed consent. Blood samples were collected to perform the CD4 / CD8 cell count, viral load and HIV Genotyping. Socio-epidemiological information was collected from the participants through surveys. The results revealed a RT frequency of 9.8% (13/132). The information from this research might help improve the intervention and monitoring programs for antiretroviral resistance in the country.

Herpes simplex encephalitis (HSE) is the most common cause of sporadic focal encephalitis worldwide. Acyclovir is the treatment of choice of HSE since the 1980s. After the widespread use of acyclovir, HSE related mortality rate had reduced but resistant strains emerged. Acyclovir resistant HSV incidence was reported as about 0.5 % and 3.5 %-10 % in immunocompetent and immunocompromised patients, respectively. Herein, a 12-year-old immunocompetent patient with HSV-1 encephalitis who was successfully treated with combined acyclovir and foscarnet therapy is described. In the case of deteriorating clinical condition under acyclovir treatment even if the absence of demonstration of increased CSF HSV viral load, the possibility of acyclovir resistant HSE and the addition of foscarnet to the acyclovir treatment might be considered., (Sociedad Argentina de Pediatría.)

Darunavir is the gold standard protease inhibitor in antiretroviral treatment. It has undergone complete development through randomised clinical trials throughout the entire spectrum of HIV infection, with 2 different dosages and clear indications of when to use each one of them. It has been studied in mono, dual and triple therapy. It can also be administered boosted with either ritonavir or cobicistat. The data indicate that it is the antiretroviral with the greatest barrier against resistance development and that it is the drug with the longest residence time bound to its receptor (protease), thus having the longest dissociation time. Its limited impact on selected mutations in the protease by other inhibitors and its high barrier against resistance have resulted in its widespread commercial use being associated with a steady decrease in the mutations circulating in the protease having an impact on its activity. Supplement information: This article is part of a supplement entitled "Co-formulated cobicistat-boosted darunavir, emtricitabine, and tenofovir alafenamide for the treatment of HIV infection", which is sponsored by Janssen., (Copyright © 2018 Elsevier España, S.L.U. All rights reserved.)

Antiretroviral therapy (ART) is recommended for all patients infected by HIV-1. The objective of ART is to achieve an undetectable plasma viral load (PVL). Initial ART should be based on a combination of 3 drugs, including 2 nucleoside reverse transcriptase inhibitors (tenofovir in either of its two formulations plus emtricitabine or abacavir plus lamivudine) and another drug from a different family. Four of the recommended regimens, all of which have an integrase inhibitor as the third drug (dolutegravir, elvitegravir boosted with cobicistat or raltegravir), are considered preferential, whereas a further 3 regimens (based on elvitegravir/cobicistat, rilpivirine, or darunavir boosted with cobicistat or ritonavir) are considered alternatives. We present the reasons and criteria for switching ART in patients with an undetectable PVL and in those who present virological failure, in which case salvage ART should include 3 (or at least 2) drugs that are fully active against HIV. We also update the criteria for ART in specific situations (acute infection, HIV-2 infection, pregnancy) and comorbidities (tuberculosis or other opportunistic infections, kidney disease, liver disease and cancer)., (Copyright © 2017. Publicado por Elsevier España, S.L.U.)

Resistance-associated substitutions (RASs) to the new HCV NS5A inhibitor elbasvir may limit its efficacy and lead to virological failure in HCV-GT1a-infected patients. There are no data outside clinical trials evaluating their prevalence and impact in grazoprevir/elbasvir in GT1a-infected patients in Spain. A multicentre cross-sectional study of 632 initial patients was conducted. In 13 of these patients, the sample could not be amplified or a consensus sequence by Sanger sequencing could not be performed. Ultimately, 617 HCV-G1a-infected individuals treated at 84 Spanish hospitals from the 17 autonomous communities plus the 2 autonomous cities of Spain were analysed. HCV population sequencing was used to identify RAS to elbasvir and the mutational pattern and drug sensitivity were confirmed by geno2pheno[HCV]. Viruses bearing RASs to elbasvir were present in 6.2% of HCV-G1a infected patients. The most common RASs were the Y93C/H/N and Q30E/H/R (2.4% and 2.3%, respectively). Only 3.4% of the identified RASs to elbasvir conferred reduced susceptibility to elbasvir by geno2pheno[HCV], which exclusively identified the positions Q30H/R (n=7) and Y93C/H/N (n=8) as single mutations and Q30H+Y93H (n=4) and Q30R+Y93H (n=2) as double mutations as the major RASs to elbasvir. A lower prevalence of RASs to elbasvir was observed in our HCV-G1a Spanish cohort than reported previously in clinical trials evaluating patients from the USA. This information may be essential to guide the implementation of grazoprevir/elbasvir in Spain and to manage G1a-infected patients., (Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.)

Cytomegalovirus infection after a heart transplant is a recurrent medical condition. Its frequency increases when the donors are serum-positive, and the recipients are serum-negative to this virus. In the pediatric population, the infection only develops in a small percentage and the patients rarely present resistance to conventional treatment with ganciclovir and valganciclovir. We presented the first report of a pediatric case of the cytomegalovirus infection resistant to ganciclovir and valganciclovir after a heart transplant in a Peruvian public hospital with an unusual presentation. The resistance to these drugs was evident after 277 days of evolution of the disease considering the non-remission of the symptomatology and the persistence of an elevated viral load. The administration of foscarnet led to a clinical and laboratory improvement until remission of the disease.

Introduction: HIV viral load testing is a key factor to evaluate the accomplishment of the UNAIDS target of 90% of viral suppression among people receiving antiretroviral therapy. Pooled samples are a potentially accurate and economic approach in resource-constrained settings, but efficiency can be negatively affected by high prevalence rates of virological failure., Objective: Strategies were assessed to increase the relative efficiency of pooled HIV viral load testing in resource-constrained settings., Materials and Methods: We evaluated two strategies: a) plasma samples were not included in pools if patients had <12 months on antiretroviral therapy, patients had previous viral load >1,000 copies/ml, or were antiretroviral therapy naïve patients, and b) plasma pools were organized separately for first and second-line antiretroviral therapy regimens. Individual viral load tests were used to compare pooled results., Results: Negative predictive values were similar for patients on first (100.0%; 95% CI 99.5 to 100.0) and second-line antiretroviral therapy regimens (99.4%; 95% CI 96.9 to 99.9). However, the incidence of virological failure among individuals on first-line antiretroviral therapy was lower than second-line antiretroviral therapy patients (p <0.01), resulting in greater savings in laboratory tests in patients on first-line antiretroviral therapy (74.0%; 95% CI 71.0 to 76.7) compared with the group of patients on second-line antiretroviral therapy (50.9%; 95% CI 44.4 to 57.3) (p<0.01)., Conclusion: Selecting the samples to be included in the pools and selecting the pools according to ART regimens are criteria that could lead to decreased spending on laboratory tests for HIV viral load determination in resource-constrained settings.

Background and Objective: cytomegalovirus (CMV) infection is one of the most common complications in transplant patients, which can lead to multiple organ failure. The 80-90% of patients are cured with intravenous treatment standard (ganciclovir), or its oral prodrug (valganciclovir). In case there is no answer, we have alternatively another antiviral, foscarnet. A small number of patients do not respond to this, having a bad prognosis. The aim is to describe the case of a double lung transplant for cystic fibrosis, and recurrent CMV infection in which the use of leflunomide gets lower and even reach undetectable viral load., Description of Case: woman, 22 year old, double lung transplant for cystic fibrosis in March 2014. The CMV serology performed was positive in the donor and negative in the recipient. Controls viral load during prophylaxis with valganciclovir were negative in the receiver until the 6th month after transplantation, at which viral load was detected in controls (2 090 IU/ml). The patient was admitted to our hospital to receive intravenous treatment with ganciclovir, after one month with intravenous therapy viral load persisted positive (42 400 IU/ml). One study of resistance showed that was resistant to ganciclovir, so began treatment with intravenous foscarnet. This drug achieved negativizar viral load, so the treatment was discontinued, continuing with fortnightly controls viral load. After two months without treatment, viral load increased to 13 665 IU/ml, why was requested to Pharmacy Service the off-label use of leflunomide, with the intention that use oral therapy, instead of intravenous therapy. The patient was treated with valganciclovir until have the authorization of use of leflunomide, although unanswered, since in March 2015, at the start of leflunomide treatment the patient had a viral load of 17 344 IU/ml. The initial regimen was 100 mg of leflunomide daily for the first five days, followed by 20 mg every 12 hours. After fifteen days of treatment viral load had fallen to 531 IU/ml, becoming undetectable in one month. After four months of treatment the patient remains with undetectable viral load without having any adverse effect associated with it., Conclusion: our case is an example where the use of leflunomide in CMV infection resistant to other therapies is an effective and convenient alternative for patients because it keeps undetectable viral load with an oral therapy without having to enter the hospital for intravenous treatment., (Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.)

This document attempts to update the main tasks and roles of the Clinical Microbiology laboratory in HIV diagnosis and monitoring. The document is divided into three parts. The first deals with HIV diagnosis and how serological testing has changed in the last few years, aiming to improve diagnosis and to minimize missed opportunities for diagnosis. Technological improvements for HIV Viral Load are shown in the second part of the document, which also includes a detailed description of the clinical significance of low-level and very low-level viremia. Finally, the third part of the document deals with resistance to antiretroviral drugs, incorporating clinical indications for integrase and tropism testing, as well as the latest knowledge on minority variants., (Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.)

Objective: This consensus document is an update of combined antiretroviral therapy (cART) guidelines and recommendations for HIV-1 infected adult patients., Methods: To formulate these recommendations, a panel composed of members of the AIDS Study Group and the AIDS National Plan (GeSIDA/Plan Nacional sobre el Sida) reviewed the efficacy and safety advances in clinical trials, and cohort and pharmacokinetic studies published in medical journals (PubMed and Embase) or presented in medical scientific meetings. The strength of the recommendations, and the evidence that supports them, are based on modified criteria of the Infectious Diseases Society of America., Results: In this update, cART is recommended for all patients infected by type 1 human immunodeficiency virus (HIV-1). The strength and level of the recommendation depends on the CD4+T-lymphocyte count, the presence of opportunistic diseases or comorbid conditions, age, and prevention of transmission of HIV. The objective of cART is to achieve an undetectable plasma viral load. Initial cART should always comprise a combination of 3 drugs, including 2 nucleoside reverse transcriptase inhibitors, and a third drug from a different family. Three out of the ten recommended regimes are regarded as preferential (all of them with an integrase inhibitor as the third drug), and the other seven (based on a non-nucleoside reverse transcriptase inhibitor, a ritonavir-boosted protease inhibitor, or an integrase inhibitor) as alternatives. This update presents the causes and criteria for switching cART in patients with undetectable plasma viral load, and in cases of virological failure where rescue cART should comprise 3 (or at least 2) drugs that are fully active against the virus. An update is also provided for the specific criteria for cART in special situations (acute infection, HIV-2 infection, and pregnancy) and with comorbid conditions (tuberculosis or other opportunistic infections, kidney disease, liver disease, and cancer)., Conclusions: These new guidelines update previous recommendations related to cART (when to begin and what drugs should be used), how to monitor and what to do in case of viral failure or drug adverse reactions. cART specific criteria in comorbid patients and special situations are equally updated., (Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.)

Triple combination regimens consisting of lopinavir/ritonavir (LPV/r) plus 2 nucleoside/nucleotide analogs continue to be a valid option in initial antiretroviral therapy. Other protease inhibitors boosted with ritonavir (and in future with cobicistat) have been introduced, as well as other non-nucleoside analogs (rilpivirin) and 3 integrase inhibitors. None of the new regimens have shown superiority over LPV/r or comparisons are lacking. Therefore, regimens including LPV/r continue to be recommended as initial first-line or alternative strategies in most treatment guidelines. Dual combinations with LPV/r (plus raltegravir or lamivudine) are described in another article and can provide a similar response rate to triple combinations, better tolerance, and an improved cost-efficacy ratio, both for initial therapy and in simplification strategies. In contrast, LPV/r or darunavir/r monotherapy does not seem an acceptable option in treatment-naïve patients and is becoming increasingly less acceptable in simplification strategies., (Copyright © 2014 Elsevier España, S.L.U. All rights reserved.)

Introduction: Little has been published in Colombia on HIV drug resistance in patients taking antiretroviral treatment (ART). Currently, the Colombian guidelines do not recommend the use of genotypic antiretroviral resistance tests (GART) for treatment-naive patients or for those experiencing a first therapeutic failure., Objective: To determine the frequency of relevant resistance mutations and the degree of susceptibility/ resistance of HIV to antiretroviral drugs (ARVs) in ART-experienced patients., Materials and Methods: A non-random sample of 170 ART-experienced HIV patients with virologic failure and who underwent GART was recruited. A study of HIV drug resistance was carried out in two groups of patients: one group that underwent early GART and the other group that received late GART testing., Results: The most frequent type of resistance affected the non-nucleoside class (76%). The late-GART group had higher risk of nucleoside analog and protease inhibitor drug resistance, a higher number of resistance mutations and more complex mutational profiles than the early-GART group. A high cross resistance level (30%) was found in the nucleoside analog class. The least affected medications were tenofovir and darunavir., Conclusions: Our results suggest that performing GART late is associated with levels of ARV resistance that could restrict the use of an important number of essential ARV in subsequent regimens. There is a need to revise the current recommendations to include GART prior to start of treatment and after the first virologic failure.

The introduction of telaprevir in the therapeutic armamentarium for hepatitis C virus infection is a major advance, even in patients unresponsive to prior treatment with interferon and ribavirin. In this group of patients, sustained viral response is achieved in more than 80% of those with recurrence and who received triple therapy. In partial responders, more than half achieve cure with the triple combination of pegylated interferon, ribavirin and telaprevir. Unfortunately, the results are less good in null responders, especially given that many are of a certain age and have advanced fibrosis. Patients in this group should be carefully selected to identify those most likely to derive a benefit from triple therapy., (Copyright © 2013 Elsevier España, S.L. All rights reserved.)

Chronic hepatitis due to the hepatitis C virus (HCV) infection affects nearly 180 million people worldwide. This infection is curable. Until 1 year ago, the only treatment for genotype 1 HCV was the combination of pegylated interferon and ribavirin, which was only moderately effective (40-50%). The introduction of new antiviral agents, such as telaprevir, represents a change of paradigm and has revolutionized the treatment of this infection. This drug has increased the likelihood of viral response (to 80%) and has allowed treatment length to be shortened in more than 50% of patients. New stopping rules have been developed to avoid the development of resistances. Finally, special attention should be paid to potentially serious adverse effects, particularly anemia and cutaneous alterations., (Copyright © 2013 Elsevier España, S.L. All rights reserved.)

Introduction: In 2009 a deep change in ARV treatment took place in Spain with the introduction of new ARV drugs. The principal objective of the study was to determine the clinical situation of the patients in which DRV/r was introduced in the ARV therapy., Methods: Observational, cross sectional and multicentre study in which 91 reference hospitals participated. Patient's enrollment was carried out between 2008 and 2009. Data were collected retrospectively considering standard clinical practice., Results: 719 medical records were reviewed. Patients had a different clinical situation compared to nowadays with predominance of multiresistant virus which leaded to virologic failure. The principal reason for introducing DRV/r in the ARV regimen was the virologic failure (54.2%)., Conclusions: Considering this situation, DRV/r became a therapeutic option which represented a change in the ARV paradigm in that period.

Background: Cidofovir is an antiviral agent which inhibits the DNA polymerase of different viruses. Its use has been described for papillomavirus infections., Methods: Descriptive retrospective study, including patients with difficult to treat anogenital warts who were treated with cidofovir cream., Results: Nine immunocompetent patients were treated, where 6 of them had a complete response and 3 of them a partial response., Conclusion: Cidofovir cream could be a useful therapeutic alternative, although further studies are required to establish the best dosage and its cost-effectiveness., (Copyright © 2012 Elsevier España, S.L. All rights reserved.)

Since the discovery of the hepatitis C virus (HCV), a plethora of experimental models have evolved, allowing the virus's life cycle and the pathogenesis of associated liver diseases to be investigated. These models range from inoculation of cultured cells with serum from patients with hepatitis C to the use of surrogate models for the study of specific stages of the HCV life cycle: retroviral pseudoparticles for the study of HCV entry, replicons for the study of HCV replication, and the HCV cell culture model, which reproduces the entire life cycle (replication and production of infectious particles). The use of these tools has been and remains crucial to identify potential therapeutic targets in the different stages of the virus's life cycle and to screen new antiviral drugs. A clear example is the recent approval of two viral protease inhibitors (boceprevir and telaprevir) in combination with pegylated interferon and ribavirin for the treatment of chronic hepatitis C. This review analyzes the advances made in the molecular biology of HCV and highlights possible candidates as therapeutic targets for the treatment of HCV infection., (Copyright © 2012 Elsevier España, S.L. and AEEH y AEG. All rights reserved.)

The development of novel direct antiviral agents (DAAs) against hepatitis C virus (HCV) has represented a breakthrough in the treatment of chronic hepatitis C. Telaprevir and boceprevir are the first two protease inhibitor (PI) DAAs to be approved for combination therapy with pegylated interferon (PEG-IFN) and ribavirin (RBV). In genotype 1 monoinfected patients, triple PI therapy has increased sustained viral response (SVR) rates by approximately 30% compared with conventional combination therapy. The introduction of these drugs into clinical practice will modify the timing of monitoring parameters in diagnostic laboratories, especially with regard to stopping rules and to faster delivery of results. In the near future, new DAAs, directed against different targets of the HCV cycle (polymerase inhibitors, viral replication complex inhibitors and cyclophilin inhibitors), which are currently in various stages of clinical development, will be available. Some of these DAAs have already reached advanced phases of development, both in combination with PEG-IFN and RBV and in interferon-free therapy, with very high rates of SVR., (Copyright © 2013 Elsevier España, S.L. All rights reserved.)

As access to antiretroviral treatment increases in the developing countries, efforts towards making it easier and less costly to collect, store, and deliver the biological samples to reference laboratories, where the serological and genetic diagnosis techniques are performed, have become a high priority. Blood sampling on filter papers is an inexpensive and practical alternative to plasma for antiretroviral treatment monitoring in countries with limited resources and no access to cold chains or refrigeration. The main clinical applications and uses of blood-sampling onto filter papers (dried blood spots [DBS]) are reviewed, focusing on how these can be applied in monitoring HIV infection, particularly for use in National Health Programs in developing countries, or in resource-limited settings. A review is presented of studies that have used the DBS technique for quantifying viral load, analysis of antiretroviral drug-resistance mutations, early infant diagnosis, adult serological diagnosis, detection of viral p24 antigen, and molecular epidemiology of HIV-1, in different geographical locations. Those variables that could affect the use of DBS, particularly in the HIV field, as well as explaining how these procedures can be optimised to increase their sensitivity are also reviewed. The aim of this study was to review the advantages of implementing the DBS technique in the HIV field, especially in resource-constrained regions., (Copyright © 2011 Elsevier España, S.L. All rights reserved.)

Analysis of proviral DNA in HIV infection may have useful applications if techniques that are sufficiently sensitive to detect minor variants, such as single genome sequencing (SGS), are used. This technology, which is performed in DNA from whole blood, improves determination of co-receptor tropism and the detection of both circulating and archived resistance mutations (RM) that are undetectable in plasma. Many of these RM have clinical relevance and their identification could be useful in specific situations, such as the start of antiretroviral therapy to exclude the transmission of resistant strains, as information to be weighed in simplification strategies in patients with undetectable viral loads, and in antiretroviral-experienced patients with limited availability of clinical reports. Clonal analysis using SGS has yielded useful information on the pathogenesis and diagnosis of HIV-1 infection but, in its current design, is inappropriate for the clinical laboratory. The new generation of sequencing technology, which allows the simultaneous analysis of a large number of sequences, has begun to be applied in the analysis of the diversity of plasma HIV-1. The use of these highly sensitive, automated techniques in the analysis of HIV-1 cellular reservoirs will potentially allow all variants recorded during the history of the disease to become available. This information would be highly useful for the clinical management of HIV-1 infection at the individual and population level., (Copyright © 2013 Elsevier España, S.L. All rights reserved.)

Objective: The objective of this study was the analysis of the prevalence and type of primary resistance to antiretroviral drugs in patients diagnosed with HIV infection, and to determine the most appropriate empirical treatment to obtain a virological and immunological response., Patients and Methods: An observational analysis of patients with a de novo diagnosis of HIV infection during the period 2008-2010. Clinical, immunological and virological characteristics, including genotype analysis of resistance to antiretrovirals, were considered as independent variables. The dependent variable was an undetectable HIV viral load after six months of treatment. Data are provided as median (interquartile range) and absolute number (percentage)., Results: Seventy-three patients with a de novo diagnosis of HIV infection were included [53 males (73%); 36 (30-46) years-old; prior use of intravenous drugs: 5 patients (7%); hepatitis C virus co-infection: 13 individuals (18%)]. Ten patients (14%) showed symptoms attributable to acute HIV infection. A CD4+ T cell count lower than 350 mm(3) was detected in a 37% (n=27) of all patients. The initiation of antiretroviral therapy followed the GESIDA recommendations (no therapy: 20 patients; tenofovir+emtricitabine+efavirenz: 28 patients; abacavir+lamivudine+efavirenz: 1 patient; tenofovir+emtricitabine+protease inhibitors: 5 patients; abacavir+lamivudine+protease inhibitors: 1 patient; 18 patients were lost in the follow-up). After starting antiretroviral therapy, the resistance analyses detected the existence of primary resistance to antiretrovirals in 12.7% (confidence interval 95%: 3-22) of the patients, distributed as follows: isolated resistance to, nucleosides was detected in 2% (M184V), to nevirapine/efavirenz in 9% (K103N), and combined resistance to nucleosides and non-nucleosides in 2%; there were no cases of resistance to protease inhibitors. Consequently, antiretroviral therapy was changed in 5 (14%) out of 35 patients, attaining an undetectable HIV viral load at 6 months in all of them. The primary resistance to antiretrovirals was not related with epidemiological, virological (including infection by non B subtype) or immunological variables., Conclusions: In the present study, a change in the epidemiological pattern of de novo diagnosis of HIV infection in our area has been observed. The existence of resistance mutations in more than 5% of the new cases is noteworthy. This finding must be considered in order to establish the rules of empirical treatment in our area., (Copyright © 2011 Elsevier España, S.L. All rights reserved.)

A 45 year-old married man, with several sexual partners, initiated symptoms with nodosum erythema and in August 2008, is diagnosed of chronic hepatitis due to hepatitis B virus (HBV). Later he was diagnosed of Child A cirrhosis and hepatocarcinoma. He began HBV treatment with Entecavir 0.5 mg; then he underwent a V segment hepatectomy. In February 2009 he presented a relapse with a tumor of 14 mm on VI segment with AFP values of 68 ng/dl, so he underwent an ethanolization with good evolution. During the follow up, he has not presented evidence of relapse of hepatocarcinoma and continued with Entecavir 0.5 mg/d. In April 2010, after 72 weeks of therapy with good compliance, the patient presented a virological breakthrough (viral load 646 UI/dl) and Tenofovir was added to his therapy. Nowadays the patient is receiving double therapy for HBV and his last viral load, April 2012, was negative. This could be the first case in our country of a probable resistance to Entecavir; complementary tests are needed in order to rule out this suspicion.

Introduction: The GESIDA and National AIDS Plan panel of experts propose «preferred regimens» of antiretroviral treatment (ART) as initial therapy in HIV infected patients for 2012. The objective of this study is to evaluate the costs and the efficiency of initiating treatment with these «preferred regimens»., Methods: Economic assessment of costs and efficiency (cost/efficacy) using decision tree analysis model. Efficacy was defined as the probability of having a viral load <50 copies/ml at week 48, in an intention-to-treat analysis. Cost of initiating treatment with an ART regime was defined as the costs of ART and all its consequences (adverse effects, changes of ART regime, and drug resistance analyses) during the first 48 weeks. The perspective of the analysis is that of the National Health System, considering only differential direct costs: ART (official prices), management of adverse effects, studies of resistance and determination of HLA B 5701. The setting is Spain and the costs are those of 2012. A sensitivity deterministic analysis was conducted, building three scenarios for each regime: baseline, most favourable, and most unfavourable cases., Results: In the baseline case scenario, the cost of initiating treatment ranges from 6,895 euros for TDF/FTC+NVP to 12,067 euros for TDF/FTC+RAL. The efficacy ranges between 0.66 for ABC/3TC+LPV/r and 0.87 for TDF/FTC+RAL. Efficiency, in terms of cost/efficacy, varies between 9,387 and 13,823 euros per responder at 48 weeks, for TDF/FTC/EFV and TDF/FTC+RAL, respectively. In the most unfavourable scenario, the most efficient regime is TDF/FTC+NVP (9,742 per responder)., Conclusion: Considering the official prices of ART, the most efficient regimens are TDF/FTC/EFV (baseline case and most favourable scenarios), and TDF/FTC+NVP (most unfavourable scenario)., (Copyright © 2012 Elsevier España, S.L. All rights reserved.)

Objective: To analyze the epidemiological, clinical, and virological characteristics of patients newly diagnosed with active hepatitis B virus (HBV) infection based on the presence of positive hepatitis B surface antigen (HBsAg) in the digestive diseases department of a district hospital., Patients and Methods: We performed a 3-year prospective study in patients newly diagnosed with HBV infection. We analyzed epidemiological, clinical, and virological characteristics, complete HBV markers, quantification of HBV DNA, and infection by hepatitis delta virus. We performed genotyping and resistance testing in patients with a high viral load. Results were obtained for patientswho required liver biopsy., Results: We diagnosed 213 patients (18.8/10,000 inhabitants/year). Men accounted for 61%, and 59% were aged 20 to 40 years. Immigrants accounted for 53% of the population: 46% were from Rumania and 37% from Sub-Saharan African countries. At diagnosis, 2.3% had acute hepatitis (all with jaundice) and 3.3% had cirrhosis with portal hypertension. With the exception of cases of acute hepatitis, positive HBeAg was observed in 9%. Serum transaminase levels were normal in 62.2% of patients, HBV DNA was > 2,000 IU/mL in 33.8%, and delta virus was present in 3.3%. Genotyping and resistance testing were performed in 70 patients: the most common genotype was D, followed by A. Resistance was detected at baseline in only 2 cases: to adefovir in one case and to entecavir in another. Among the 36 biopsies performed, 32.4% showed inflammatory activity > or = 2, and 23.5% had fibrosis > or = 2 according to the METAVIR scoring system. According to clinical practice, specific treatment for HBV infection was necessary (any reason) in 17.4% of those diagnosed (3 patients per 100,000 inhabitants/year)., Conclusions: Despite prevention and vaccination, HBV infection is a health problem that most commonly affects the immigrant population and men. Serum transaminase levels are normal in 62.2% of patients. The most frequent genotype is D, followed by A, and baseline resistance is scarce.

The evaluation of new cases of HIV infection is relatively common in Spain, where several thousands of patients with new infections are diagnosed each year. Eighty per cent of them have a chronic HIV infection at the first clinical evaluation, which is symptomatic (late presenters) in up to 30% of patients. The initial evaluation of HIV infection is not only directed at determining the clinical, virological (plasma HIV RNA viral load, resistance test and viral tropism) and immunological (CD4+ T-cell cell count) situation of the patients, but must also address the study of their co-infections (hepatitis, tuberculosis) and comorbidities (cardiovascular, hepatic, renal and bone) and the risk of HIV transmission. This is needed in order to decide, whether or not to start antiretroviral treatment, and with which combined antiretroviral treatment to start with, the prophylaxis of opportunistic infections, and the treatment of coinfections and comorbidities. The past and current medical history, the physical examination and laboratory tests will help us decide if the patient is to receive therapeutic intervention. The level of CD4+ T-cell lymphocytes is the best marker to suggest when to start combined antiretroviral treatment, indicating whether or not to start prophylaxis against opportunistic infections (if patients have a CD4+ T-cell count below 200 cells/mm(3)), and in advanced patients should make us suspect the presence of active opportunistic diseases in symptomatic cases. The management of patients with HIV infection must also include appropriate health education on the modes of transmission and prevention of HIV infection, and also to explain its natural history and how it can be modified with proper antiretroviral treatment, as well as to promote a healthy life. No less important is the psychological support, as these patients must learn to live with a chronic infection, which managed properly can ensure a very good long-term prognosis and quality of life., (Copyright © 2011 Elsevier España, S.L. All rights reserved.)

Cytomegalovirus (CMV) resistance to antiviral drugs is an emerging problem and is due to selection of mutations in the viral genome. Although ganciclovir resistance is the most common and widely studied, there is resistance to all antiviral agents. Risk factors for the development of resistance are the absence of preexisting immunity to CMV, lung and pancreas transplantation, high viral loads, intense concomitant immunosuppressive therapy and prolonged exposure to ganciclovir or suboptimal levels of this drug. Antiviral resistance should be suspected when, despite adequate treatment exposure for 2 weeks, an increase in viral load, or persistence or clinical progression of CMV disease are detected. However, failure to respond cannot always be attributed to antiviral resistance nor does resistance always lead to poor clinical outcome. When resistance is suspected, phenotypic and genotypic confirmation is required. The most common mutations are those in the UL97 gene, which confers ganciclovir resistance. However, foscarnet and cidofovir can be used. The UL54 mutation is not uncommon, whether alone or in combination with UL97 mutations. The combination of UL54 and UL97 mutations is associated with high-grade and multiple resistance. Early detection of resistance is essential to prevent unfavorable outcome and the development of multi-drug resistance. In patients with a slow response to treatment and without mutations associated with resistance, plasma ganciclovir levels and specific CMV immunity should be investigated., (Copyright © 2011 Elsevier España S.L. All rights reserved.)

For years, intravenous ganciclovir has been the recommended treatment for cytomegalovirus (CMV) in transplant recipients. Recently, oral valganciclovir has been shown to induce a response to CMV similar to that produced by intravenous ganciclovir and could consequently be an alternative to ganciclovir in patients with non-severe disease. Sequential therapy with ganciclovir followed by valganciclovir, after the onset of clinical improvement, reduces costs and avoids prolonged hospital stays, thus benefitting patients. Optimal treatment duration is guided by clinical response and virological monitoring (polymerase chain reaction or antigenemia) and is maintained until the results are negative. Some groups use secondary prophylaxis in patients with risk factors for recurrence of CMV disease. Reducing the intensity of immunosuppression or complementing antiviral therapy with immunoglobulins can be considered in patients with severe disease or immunodepression. There are no conclusive data on the most effective treatment in ganciclovir-resistant CMV. Therapeutic decisions should be based on genotypic resistance studies, the patient's immune status and disease severity. Treatment consists of foscarnet alone or in combination with ganciclovir in the most severe forms and in high-resistance mutations, or in increasing the dose of ganciclovir in clinical forms or in mild resistance. There are no conclusive data on alternative antiviral drugs or complementary therapy with mTOR inhibitors. Several CMV vaccines are under development and the preclinical results are encouraging., (Copyright © 2011 Elsevier España S.L. All rights reserved.)

Hepatic complications currently represent one of the leading reasons for medical consultations, hospitalisation, and death in the HIV-infected population. This is due to a large extent to viral hepatitis, given its disproportionate frequency in this population. Chronic hepatitis B affects 5-10% of the HIV-infected population. Vaccination has reduced the incidence of liver disease related to hepatitis-B virus (HBV), and the availability of tenofovir has dramatically improved the prognosis of HIV/HBV carriers. Delta hepatitis affects around 15% of HIV-infected individuals in Europe harbouring positive HBsAg. It has the worst prognosis, given its accelerated course to cirrhosis and the absence of successful therapy. Lastly, chronic hepatitis C is the major cause of liver disease in the HIV population. Although classically linked to persons infected parenterally (i.e., intravenous drug users), outbreaks of acute hepatitis C among homosexual men have been reported over the last decade. Treatment with pegylated interferon plus ribavirin provides a cure in less than 40% of patients. However, the introduction of new direct acting antivirals against hepatitis- C virus (HCV) (telaprevir, boceprevir) has revolutionised the field, as HAART did in 1996 in the HIV field, improving the prognosis of co-infected patients. However, interactions between these drugs and antiretroviral agents and the risk of selective resistance pose huge threats in this population., (Copyright © 2011 Elsevier España, S.L. All rights reserved.)

Background and Objective: Adefovir dipivoxil monotherapy in lamivudine-resistant patients is associated with more frequent development of resistance than in naïve patients. The virological response during treatment predicts the risk of developing resistance. The aims of this study were to assess the efficacy of adefovir dipivoxil treatment in naïve and lamivudine-resistant patients and to determine whether virological response predicts the development of adefovir resistance., Patients and Method: This study included 82 patients with HBeAg-negative chronic hepatitis B (CHB) who received adefovir dipivoxil therapy. During active treatment, HBV-DNA values were determined by polymerase chain reaction; in addition, the presence of adefovir resistance-associated mutations was studied in cases of virological breakthrough., Results: Virological response at 12 and 24 months was 59% and 73% in naive patients compared with 40% and 67% in lamivudine-resistant patients, whereas virological breakthrough at 24 months was 9.5% in naïve patients compared with 20% in lamivudine-resistant patients. A small percentage (4%) of patients with virological response at 12 months showed virological breakthrough between 12 and 40 months versus 29.4% of patients without virological response (P=.03). In lamivudine-resistant patients, virological response at 12 months was not a predictive factor for the development of virological breakthrough., Conclusions: Adefovir dipivoxil monotherapy in lamivudine-resistant patients is associated with an increased tendency to develop virological breakthrough, which cannot be predicted by virological response at 12 months of treatment. In naive patients, an undetectable viral load at 12 months of treatment ensures the absence of virological breakthrough at 40 months of treatment., (Copyright © 2010 Elsevier España, S.L. All rights reserved.)

Objective: This consensus document is an update of antiretroviral therapy recommendations for adult patients with human immunodeficiency virus infection., Methods: To formulate these recommendations a panel made up of members of the Grupo de Estudio de Sida (Gesida, AIDS Study Group) and the Plan Nacional sobre el Sida (PNS, Spanish AIDS Plan) reviewed the advances in the current understanding of the pathophysiology of human immunodeficiency virus (HIV) infection, the efficacy and safety of clinical trials, and cohort and pharmacokinetic studies published in biomedical journals or presented at scientific meetings. Three levels of evidence were defined according to the data source: randomized studies (level A), cohort or case-control studies (level B), and expert opinion (level C). The decision to recommend, consider or not to recommend ART was established in each situation., Results: Currently, the treatment of choice for chronic HIV infection is the combination of three drugs of two different classes, including 2 nucleosides or nucleotide analogs (NRTI) plus 1 non-nucleoside (NNRTI) or 1 boosted protease inhibitor (PI/r), but other combinations are possible. Initiation of ART is recommended in patients with symptomatic HIV infection. In asymptomatic patients, initiation of ART is recommended on the basis of CD4 lymphocyte counts, plasma viral load and patient co-morbidities, as follows: 1) therapy should be started in patients with CD4 counts below 350 cells/microl; 2) When CD4 counts are between 350 and 500 cells/microl, therapy should be started in case of cirrhosis, chronic hepatitis C, high cardiovascular risk, HIV nephropathy, HIV viral load above 100,000 copies/ml, proportion of CD4 cells under 14%, and in people aged over 55; 3) Therapy should be deferred when CD4 are above 500 cells/microl, but could be considered if any of previous considerations concurs. Treatment should be initiated in case of hepatitis B requiring treatment and should be considered for reduce sexual transmission. The objective of ART is to achieve an undetectable viral load. Adherence to therapy plays an essential role in maintaining antiviral response. Therapeutic options are limited after ART failures but undetectable viral loads maybe possible with the new drugs even in highly drug experienced patients. Genotype studies are useful in these situations. Drug toxicity of ART therapy is losing importance as benefits exceed adverse effects. Criteria for antiretroviral treatment in acute infection, pregnancy and post-exposure prophylaxis are mentioned as well as the management of HIV co-infection with hepatitis B or C., Conclusions: CD4 cells counts, viral load and patient co-morbidities are the most important reference factors to consider when initiating ART in asymptomatic patients. The large number of available drugs, the increased sensitivity of tests to monitor viral load, and the ability to determine viral resistance is leading to a more individualized therapy approach in order to achieve undetectable viral load under any circumstances., (Copyright 2010 Elsevier España, S.L. All rights reserved.)

Although guidelines for the treatment of HIV-infected patients recommend triple drug antiretroviral therapy, because of the toxicity of these regimens, the complexity of treatment and its costs, other therapeutic options are desirable. Several clinical trials have shown that lopinavir/ritonavir (LPV/r) as a simplification strategy in antiretroviral therapy in HIV-infected patients who maintain suppression of viral replication while receiving conventional treatment regimens is safe and is associated with less toxicity than that due to prolonged exposure to protease inhibitors and nucleoside analogs. The present review summarizes the main results of the various retrospective studies on LPV/r as a simplification strategy of antiretroviral therapy in daily clinical practice.

Atazanavir (ATV) is a protease inhibitor (PI) in which its main qualities, compared to other PI are dosing convenience, good tolerability and excellent metabolic profile. These characteristics makes it more like a nonnucleoside than a PI, but with the increased genetic barrier common to PI. It is indicated in initial treatment, simplification treatment or a change due to toxicity and in first line rescue treatment. The administering of ATV boosted with ritonavir (300/100 mg/d) has been approved in Europe in all clinical situations. In naïve patients it has been combined with practically all the nucleoside analogue pairs and has shown to be as effective as lopinavir/ritonavir and even efavirenz. In the USA, this indication has been approved for almost 5 years and ATV has become the most prescribed PI, while the EMEA has approved it this year. ATV is an optimal drug to replace other antiretrovirals in simplification strategies or changes due to toxicity. In several studies it has been shown that, in patients with good virological control, it can LPV/r or another PI, the therapeutic efficacy being maintained, with excellent tolerance and an improved lipid profile, and decreasing the cardiovascular risk. This strategy is widely used in Spain. In this scenario some patients could benefit from non-boosted ATV treatment (400 mg/d). ATV is an effective and very attractive option in first line rescue treatments in which the virus shows little or no resistance to PI, as its simplicity and tolerability can improve problems with compliance, the main cause of therapeutic failure. In patients with moderate resistance to PI, ATV is as effective as LPV/r. The survival of patients with HIV infection is increasingly longer and factors such as tolerability, cardiovascular risk and the adaptability of the treatment to the lifestyle of the patient, become more important, therefore ATV must play an important role in the treatment of HIV-infection.