Acquired Immunodeficiency Syndrome: Moreno S

Iribarren JA, Labarga P, Rubio R, Berenguer J, Miró JM, Antela A, González J, Moreno S, Arrizabalaga J, Chamorro L, Clotet B, Gatell JM, López-Aldeguer J, Martínez E, Polo R, Tuset M, Viciana P, Santamaría JM, Kindelán JM, Ribera E, Segura F, Anonymous00086, Anonymous00087. · Hospital Donostia, San Sebastián, Spain. · Enferm Infecc Microbiol Clin. · Pubmed #15596051 links to  free full text

Abstract: OBJECTIVE: This consensus document is an update of antiretroviral therapy (ART) recommendations for adult patients infected with the human immunodeficiency virus (HIV). METHODS: To formulate these recommendations, a panel composed 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 current understanding of the pathophysiology of HIV, the safety and efficacy findings from clinical trials, and the results from cohort and pharmacokinetic studies published in biomedical journals or presented at scientific meetings over the last years. Three levels of evidence were defined according to the source of the data: randomized studies (level A), cohort or case-control studies (level B), and expert opinion (level C). The decision to recommend, consider or not recommend ART was established in each of these situations. RESULTS: ART consisting of at least three drugs is currently the initial treatment of choice for chronic HIV infection. These regimens should include 2 NRTI + 1 NNRTI or 2 NRTI + 1 PI. 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 per L and plasma viral load, as follows: 1) Therapy should be started in patients with CD4+ counts of < 200 cells/microL; 2) Therapy should be started in most patients with CD4+ counts of 200-350 cells/microL, although it can be delayed when CD4+ count persists at around 350 cells/microL and viral load is low; and 3) Initiation of therapy can be delayed in patients with CD4+ counts of > 350 cells/microL. The initial objective of ART is to achieve an undetectable viral load. Adherence to therapy plays an essential role in maintaining the antiviral response. Because of the development of cross resistance, therapeutic options are limited when ART fails. Genotype studies are useful in these cases. Toxicity is a limiting factor in the use of ART, although the benefits outweigh the risks. In addition, the criteria for the use of ART are discussed in situations of acute infection, pregnancy, and post-exposure prophylaxis, and in the management of co-infection of HIV with HCV or HBV. CONCLUSIONS: CD4+ lymphocyte count is the most important reference factor for initiating ART in asymptomatic patients. The large number of available drugs, the increased sensitivity of tests to monitor viral load, and the possibility to determine viral resistance is leading to a more individualized approach to therapy.

Rubio R, Berenguer J, Miró JM, Antela A, Iribarren JA, González J, Guerra L, Moreno S, Arrizabalaga J, Clotet B, Gatell JM, Laguna F, Martínez E, Parras F, Santamaría JM, Tuset M, Viciana P. · Hospital 12 Octubre, Madrid, Spain. · Enferm Infecc Microbiol Clin. · Pubmed #12084354 links to  free full text

Abstract: OBJECTIVE: To provide an update of recommendation on antiretroviral treatment (ART) in HIV-infected adults.Methods. These recommendations have been agreed by consensus by a committee of the spanish AIDS Study Group (GESIDA) and the National AIDS Plan. To do so, advances in the physiopathology of AIDS and the results on efficacy and safety in clinical trials, cohort and pharmacokinetics studies published in biomedical journals or presented at congresses in the last few years have been reviewed. Three levels of evidence have been defined according to the data source: randomized studies (level A), case-control or cohort studies (level B) and expert opinion (level C). Whether to recommend, consider, or not to recommend ART has been established for each situation. RESULTS: Currently, ART with combinations of at least three drugs constitutes the treatment of choice in chronic HIV infection. In patients with symptomatic HIV infection, initiation of ART is recommended. In asymptomatic patients initiation of ART should be based on the CD41/mL lymphocyte count and on the plasma viral load (PVL): a) in patients with CD41 lymphocytes < 200 cells/mL, initiation of ART is recommended; b) in patients with CD41 lymphocytes between 200 and 300 cells/mL, initiation of ART should, in most cases, be recommended; however, it could be delayed when the CD41 lymphocyte count remains close to 350 cells/mL and the PVL is low, and c) in patients with CD41 lymphocytes > 350 cells/mL, initiation of ART can be delayed. The aim of ART is to achieve an undetectable PVL. Adherence to ART plays a role in the durability of the antiviral response. Because of the development of cross-resistance, the therapeutic options in treatment failure are limited. In these cases, genotypic analysis is useful. Toxicity limits ART. The criteria for ART in acute infection, pregnancy and postexposure prophylaxis and in the management of coinfection with HIV and hepatitis C and B virus are controversial. CONCLUSIONS: The current approach to initiating ART is more conservative than in previous recommendations. In asymptomatic patients, the CD41 lymphocyte count is the most important reference factor for initiating ART. Because of the considerable number of drugs available, more sensitive monitoring methods (PVL) and the possibility of determining resistance, therapeutic strategies have become much more individualized.

Miró JM, Antela A, Arrizabalaga J, Clotet B, Gatell JM, Guerra L, Antonio Iribarren J, Laguna F, Moreno S, Parras F, Rubio R, Santamaría JM, Viciana P, Anonymous00076. · Hospital Clínic Universitari, Barcelona. · Enferm Infecc Microbiol Clin. · Pubmed #11153204 links to  free full text

Abstract: OBJECTIVE: To update the recommendations for antiretroviral therapy (ART) in adult HIV-infected persons according to the new scientific advances and the existence of new antiretroviral drugs in the last two years. METHODS: The ART recommendations have been condensed by a panel of experts from the Spanish AIDS Study Group (Grupo de Estudio de Sida-GESIDA) of the Spanish Infectious Diseases and Clinical Microbiology Society (SEIMC) and from the Clinical Advisory Panel (CAP) of the Secretariat of the Spanish National Plan on AIDS (SPNS) of the Ministry of Health. Three levels of evidence have been established depending if the data came from randomized and controlled studies, from cohort or case-control studies or from descriptive studies and expert opinions, for that purpose we have reviewed the advanced in HIV pathophysiology and results of efficacy (clinical, virologic and immunologic) and security (toxicity) from clinical trials involving ART lasting at least 12 months, from cohort studies and pharmacokinetic and security data of antoiretrovírico drugs, presented in international conferences or published in biomedical journals in the last two years. In each situation we have established either to recommend or to consider or not recommend ART. RESULTS: Nowadays, ART consistent of at least three drugs constitutes the election therapy for chronic HIV infection, since it delays clinical progression, increases significantly the survival and diminishes hospital admissions and associated costs. The decision to start ART must be based upon three elements: presence or absence of symptoms, plasma vírica load and CD4+ cells counts. Thus, in asymptomatic cases with a high CD4+ cells count (> 500/microliter) and low vírica load (< 10,000 copies/ml by branched DNA bDNA or < 20,000 copies/ml by reverse-transcription polymerase chain reaction [RT-PCR] or nucleic acid sequence based amplification [NASBA]) we recommend to delay ART. In symptomatic patients we recommend to start it, and in asymptomatic patients, we could recommend or consider ART initiation depending on the risk of progression, established by the vírica load and the CD4+ cells count. In any case, if therapy is started, the objective must be to reach an indetectable vírica load (< 50 copies/ml). The adherence to ART plays a key role for its initial moment and for the duration of the antiviral response. ART can achieve a restoration of cellular immunity inb the advanced patients. There are few therapeutic options in failing patients due to cross-resistance. Resistance studies can be useful in this setting. The toxicity (lypodistrophy) is a new and limiting factor of ART which requires to look for new therapeutic options. ART criteria for acute infection, pregnancy, post-exposure prophylaxis and when to use resistance testing are discussed. CONCLUSIONS: In this moment, there is a more conservative attitude towards starting ART than in previous recommendations in which a virus eradication was considered. On the other hand, the high number of disposable drugs, the more sensitive monitorization methods (plasma vírica load) and the possibility of performing resistance studies make therapeutic strategies more dynamic and individualized for each patient and situation. In any case, it is mandatory to ensure a perfect adherence to ART from the patients.

Miró JM, Antela A, Arrizabalaga J, Clotet B, Gatell JM, Guerra L, Iribarren JA, Laguna F, Moreno S, Parras F, Rubio R, Santamaría JM, Viciana P. · Hospital Clínic Universitari, Barcelona. · Enferm Infecc Microbiol Clin. · Pubmed #11109725 links to  free full text

Abstract: OBJECTIVE: To update the recommendations for antiretroviral therapy in adult HIV-infected persons according to the new scientific advances and the existence of new antiretroviral drugs in the last two years. METHODS: The antiretroviral therapy recommendations have been condensed by a panel of experts from the Spanish AIDS Study Group (Grupo de Estudio de sida-GESIDA) of the Spanish Infectious Diseases and Clinical Microbiology Society (SEIMC) and from the Clinical Advisory Panel of the Secretariat of the Spanish National Plan on AIDS (SPNS) of the Ministry of Health. Three levels of evidence have been established depending if the data came from randomised and controlled studies, from cohort or case-control studies or from descriptive studies and expert opinions. For that purpose we have reviewed the advances in HIV pathophysiology and results of efficacy (clinical, virologic and immunologic) and security (toxicity) from clinical trials involving antiretroviral therapy lasting at least 12 months, from cohort studies and pharmacokinetic and security data of antiretroviral drugs, presented in international conferences or published in biomedical journals in the last two years. In each situation we have established either to recommend or to consider or not recommend antiretroviral therapy. RESULTS: Nowadays, antiretroviral therapy consisting of at least three drugs constitutes the election therapy for chronic HIV infection, since it delays clinical progression, increases significantly the survival and diminishes hospital admissions and associated costs. The decision to start antiretroviral therapy must be based upon three elements: presence or absence of symptoms, plasma viral load and CD4+ cells counts. Thus, in asymptomatic cases with a high CD4+ cells count (> 500/microL) and low viral load (< 10,000 copies/ml by branched DNA [bDNA] or < 20,000 copies/ml by reverse-transcription polymerase chain reaction [RT-PCR] or nucleic acid sequence based amplification [NASBA]) we recommend to delay antiretroviral therapy. In symptomatic patients we recommend to start it, and in asymptomatic patients, we could recommend or consider antiretroviral therapy initiation depending on the risk of progression, established by the viral load and the CD4+ cells count. In any case, if therapy is started, the objective must be to reach an undetectable viral load (< 50 copies/ml). The adherence to antiretroviral therapy plays a key role for its initial moment and for the duration of the antiviral response, antiretroviral therapy can achieve a restoration of cellular immunity in the advanced patients. There are few therapeutic options in failing patients due to cross-resistance. Resistance studies can be useful in this setting. The toxicity is a new and limiting factor of antiretroviral therapy which requires to look for new therapeutic options. Antiretroviral therapy criteria for acute infection, pregnancy, post-exposure prophylaxis and when to use resistance testing are discussed. CONCLUSIONS: In this moment, there is a more conservative attitude towards starting antiretroviral therapy than in previous recommendations in which a virus eradication was considered. On the other hand, the high number of disposable drugs, the more sensitive monitorization methods (plasma viral load) and the possibility of performing resistance studies make therapeutic strategies more dynamic and individualised for each patient and situation. In any case, it is mandatory to ensure a perfect adherence to antiretroviral therapy from the patients.

Hernández B, Dronda F, Moreno S. · Hospital Ramón y Cajal, Department of Infectious Diseases, Servicio de Enfermedades Infecciosas, Carretera de Colmenar, Km 9,100, 28034 Madrid, Spain. · Expert Opin Pharmacother. · Pubmed #19191678 No free full text.

Abstract: Progressive multifocal leukoencephalopathy (PML) is a demyelinating viral disease produced by the John Cunningham (JC) virus, which is ubiquitously distributed. Up to 80% of adults seroconvert to JC virus. Classically, PML is a life-threatening AIDS-defining disease of the CNS, usually occurring in severely immunocompromised individuals. Until now, and despite several therapeutic attempts, there is no specific treatment for PML. Soon after the widespread use of combination antiretroviral therapy (CART), several studies showed prolonged survival for patients with AIDS-associated PML who were treated with CART. The outcome of PML in patients receiving CART is unpredictable at disease onset. Prognostic markers are needed. The JC virus DNA detection in cerebrospinal fluid by nucleic acid amplification techniques and the CD4+ cell count are the most promising parameters. Higher levels of CD4+ cell counts were independently associated with an improved survival in different clinical observations. A summary of the main current knowledge about AIDS-related PML is presented. The most effective strategy is to optimize CART to completely suppress HIV-1 viral load and allow the best CD4+ T-cell immune recovery. Nowadays, AIDS-related PML is no longer an ultimately fatal disease. A substantial number of HIV-1-infected patients with this condition can improve with CART.

Moreno S, Hernández B, Dronda F. · Hospital Ramón y Cajal, Universidad de Alcalá, Madrid, Spain. · AIDS Rev. · Pubmed #17078482 No free full text.

Abstract: Tuberculosis associated with HIV infection continues to be an important problem throughout the world. Since the advent of HAART, the medication of HIV-infected patients who have to receive concomitant treatment for tuberculosis has become a difficult task. The two main problems faced by clinicians include the significant pharmacokinetic interactions between rifamycins, a cornerstone in antituberculosis therapy, and protease inhibitors and nonnucleoside reverse transcriptase inhibitors, which are essential components of antiretroviral combination regimens, as well as the best moment to initiate antiretroviral therapy in patients with tuberculosis. The therapy of choice for patients with no previous antiretroviral experience includes an antituberculous regimen with rifampin and an efavirenz-based antiretroviral regimen. No dose adjustments of these drugs seem to be necessary. Nevirapine can be an alternative to efavirenz in this situation. For patients who cannot take efavirenz, either due to resistance or intolerance, rifabutin and a boosted protease inhibitor can be coadministered, with the necessary dose adjustments. No definite recommendations can be given regarding the optimal timing of antiretroviral therapy, but a delay of two months after initiation of antituberculosis therapy would be advisable and seems to be safe in most patients.

Dronda F, Moreno S. · Servicio de Enfermedades Infecciosas, Hospital Ramón y Cajal, Madrid, Spain. · Rev Clin Esp. · Pubmed #15142497 No free full text.

This publication has no abstract.

Pérez-Elías MJ, Moreno S, Gutiérrez C, López D, Abraira V, Moreno A, Dronda F, Casado JL, Antela A, Rodríguez MA. · Infectious Diseases Unit, Hospital Ramón y Cajal, Madrid, Spain. · AIDS. · Pubmed #15821395 No free full text.

Abstract: BACKGROUND: Regimens with two nucleoside analogue reverse transcriptase inhibitors (NRTI) plus tenofovir DF have been associated with a high failure rate when administered as first line therapy. Little is known about patients with undetectable viral loads who are switched to these regimens. METHODS: A post-hoc review of the virological outcomes at 24 weeks of patients who switched from a successful (< 50 copies/ml) highly active antiretroviral therapy regimen to a tenofovir plus two NRTI combination. RESULTS: Fifty-five patients started a two NRTI plus tenofovir regimen mostly because of previous toxicity/intolerance of the original drugs (74%). After 24 weeks, only 17 patients (31%) remained virologically suppressed. Patients with a regimen including a didanosine plus tenofovir-based regimen had significantly poorer outcomes than those on other combinations (success rate 5 versus 47.1%, P = 0.001). In contrast, patients on a regimen including zidovudine plus tenofovir showed a trend towards a better outcome (75 versus 27%, P = 0.083). Multivariate analysis confirmed the combination of didanosine plus tenofovir as the only variable associated with a higher rate of failure (odds ratio 17.7; 95% confidence interval 2.1-147; P = 0.007). Patients with previous reverse transcriptase mutations presented virological failure in all cases. At failure a new pattern, including the K65R mutation with M184V or thymidine analogue mutations, was observed. CONCLUSIONS: Even in patients with suppressed viraemia, a two NRTI plus tenofovir regimen is associated with a high virological failure rate, but significant variations are found depending on the nucleosides included.

Aranzabal L, Casado JL, Moya J, Quereda C, Diz S, Moreno A, Moreno L, Antela A, Perez-Elias MJ, Dronda F, Marín A, Hernandez-Ranz F, Moreno A, Moreno S. · Department of Infectious Diseases, Hospital Ramón y Cajal, Madrid, Spain. · Clin Infect Dis. · Pubmed #15712082 No free full text.

Abstract: BACKGROUND: Coinfection with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) is a known risk factor for hepatotoxicity in patients receiving highly active antiretroviral therapy (HAART). The aim of this study was to evaluate the role of HCV-related liver fibrosis in HAART-associated hepatotoxicity. METHODS: In a prospective study involving 107 patients who underwent liver biopsy, fibrosis was graded according 5 stages, from F0 (no fibrosis) to F4 (cirrhosis). Hepatotoxicity was defined as an increase in levels of aspartate aminotransferase and alanine aminotransferase to >5 times the upper limit of normal, or a >3.5-fold increase if baseline levels were abnormal. The incidence of hepatotoxicity was compared with liver fibrosis stage and with time and composition of HAART. RESULTS: Overall, 27 patients (25%) had hepatotoxic events (5.1 events/100 person-years of therapy). The incidence was greater for patients with stage F3 or F4 fibrosis (38%) than for those with stage F1 or F2 fibrosis (15%; 7.6 vs. 3 events/100 person-years; relative risk, 2.75; 95% confidence interval, 1.08-6.97; P=.013). Duration of HCV infection, duration of HAART, diagnosis of acquired immunodeficiency syndrome, HCV load, HCV genotype, and nadir CD4(+) cell count did not affect the risk of hepatotoxicity. Of the 86 patients who received nonnucleoside reverse-transcriptase inhibitors (NNRTIs), 11 (13%) developed liver toxicity. In these patients, fibrosis stages F1 and F2 were associated with similar rates of toxicity (3 events/100 person-years for patients who received nevirapine, 3.3 events/100 person-years for those who received efavirenz, and 3.4 events/100 person-years for those who received non-NNRTIs). There was a greater incidence among patients with F3 or F4 fibrosis who received NNRTIs (11.7 events/100 person-years for patients who received nevirapine, and 8.6 events/100 person-years for those who received efavirenz), compared with those who received non-NNRTIs (4 events/100 person-years). CONCLUSIONS: HAART-associated hepatotoxicity correlates with liver histological stage in patients coinfected with HIV and HCV. There was no difference in hepatotoxicity risk for different antiretroviral therapies in patients with mild-to-moderate fibrosis.

Corral I, Quereda C, Antela A, Pintado V, Casado JL, Martín-Dávila P, Navas E, Moreno S. · Servicio de Neurología, Hospital Ramón y Cajal, Madrid, Spain. · J Neurovirol. · Pubmed #12587077 No free full text.

Abstract: Neurological complications caused by varicella-zoster virus (VZV) were diagnosed in 13 human immunodeficiency virus (HIV)-infected patients in our hospital. There was a favorable influence of highly active antiretroviral therapy (HAART) in the prevalence of these disorders among acquired immunodeficiency syndrome (AIDS) patients: Since 1996, only 1 of 961 AIDS patients had VZV neurological disease, compared to 9 of 1088 patients before that year (P =.02). Polymerase chain reaction (PCR) detected VZV DNA in cerebrospinal from 4 of 5 patients with VZV neurological disease, and from 2 of 130 HIV-infected patients with other neurological diseases (sensitivity 0.8, specificity 0.98 [95% confidence intervals 0.45-1 and 0.96-1, respectively], positive predictive value 0.94).

Navas E, Martín-Dávila P, Moreno L, Pintado V, Casado JL, Fortún J, Pérez-Elías MJ, Gomez-Mampaso E, Moreno S. · No affiliation provided · Arch Intern Med. · Pubmed #11784229 No free full text.

This publication has no abstract.

Pintado V, Martín-Rabadán P, Rivera ML, Moreno S, Bouza E. · Clinical Microbiology-Infectious Diseases Department, Hospital General Universitario Gregorio Marañón, Universidad Complutense, Madrid, Spain. · Medicine (Baltimore). · Pubmed #11204503 No free full text.

Abstract: Visceral leishmaniasis is an endemic infection in Mediterranean countries, where it has become a frequent complication of acquired immunodeficiency syndrome (AIDS). The incidence of visceral leishmaniasis is increasing in Spain due to human immunodeficiency virus (HIV)-related cases, but some aspects of its epidemiology, clinical features, and management remain unknown. In addition, no comparative clinical studies about the disease in HIV-infected and non-HIV-infected patients have been reported. During a 24-year period, 120 cases of visceral leishmaniasis were diagnosed at our institution and 80 (66%) were associated with HIV infection. The mean age at diagnosis was higher in HIV-infected that in non-HIV-infected patients (33.2 versus 23.2 yr; p = 0.002), but the male/female ratio was similar in both groups. The main risk factor for HIV infection was intravenous drug abuse (78.7%). The clinical presentation of leishmaniasis was similar in both groups, but HIV-infected patients had a lower frequency of splenomegaly than HIV-negative individuals (80.8% versus 97.4%; p = 0.02). HIV-infected patients had a greater frequency and degree of leukopenia, lymphocytopenia, and thrombocytopenia. Most of them were profoundly immunosuppressed (mean CD4+ lymphocyte count, 90 cells/mm3) at the time of diagnosis of leishmaniasis, and 53.7% had AIDS. The sensitivity of serologic studies for Leishmania was significantly lower in HIV-infected than in non-HIV-infected patients (50% versus 80%; p < 0.001), but the diagnostic yield of bone marrow aspirate (67.1% versus 79.4%) and bone marrow culture (62.9% versus 66.6%) was similar in both groups. After initial treatment, the response rate was significantly lower in HIV-infected than in non-HIV-infected individuals (54.8% versus 89.7%; p = 0.001). The relapse rate was 46.2% and 7.5%, respectively (p < 0.001). Secondary prophylaxis with antimonial compounds or amphotericin B seems to be useful in preventing relapses in HIV-infected patients. The mortality rate was higher (53.7% versus 7.5%; p < 0.001) and the median survival time shorter (25 versus > 160 mo; p < 0.001) in AIDS patients than in HIV-negative individuals. Although leishmaniasis could contribute to death in a significant number of HIV-infected patients, it was the main cause of death in only a few of them. The CD4+ lymphocyte count and the use of highly active antiretroviral therapy and secondary prophylaxis for leishmaniasis were the most significant prognostic factors for survival in AIDS patients. Visceral leishmaniasis behaves as an opportunistic infection in HIV-infected individuals and should be considered as an AIDS-defining disease.

Corral I, Quereda C, Pérez-Elías MJ, Moreno S. · No affiliation provided · J Neurovirol. · Pubmed #12587078 No free full text.

This publication has no abstract.