Acquired Immunodeficiency Syndrome: Arrizabalaga J

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.

Negredo E, Paredes R, Bonjoch A, Tuldrà A, Fumaz CR, Gel S, Garcés B, Johnston S, Arnó A, Balagué M, Jou A, Tural C, Sirera G, Romeu J, Cruz L, Francia E, Domingo P, Arrizabalaga J, Ruiz I, Arribas JR, Ruiz L, Clotet B. · Fundació Lluita contra la SIDA, Hospital Universitari Germans Trias i Pujol, Badalona, Spain. · Antivir Ther. · Pubmed #16021868 No free full text.

Abstract: This multicentre, randomized, open-label, prospective trial is evaluating the effects of switching treatment from a protease inhibitor (PI)-containing regimen to one containing the non-nucleoside reverse transcriptase (RT) inhibitor nevirapine in human immunodeficiency virus (HIV)-infected patients with durable viral suppression but suffering from lipodystrophy. Objectives of this ongoing study are to evaluate the effects of this switch on changes in body shape and metabolic abnormalities associated with acquired HIV-related lipodystrophy syndrome (AHL), as well as on maintenance of viral suppression and immunological and psychological effects. Preliminary data involving 57 patients with 3 months of follow-up show an initial improvement of AHL in two regions, the face and arms. There is also a tendency toward improved cholesterol and triglyceride levels and improved quality of life among patients receiving the nevirapine-containing regimen. Maintenance of viral suppression was equivalent in both treatment groups. Additional data with longer follow-up are needed to confirm these results.

Zulaika D, Agirrebengoa K, Andía A, Arrizabalaga J, Bustillo JM, Cámara MM, Corral J, Orive MC, Goikoetxea J, Iribarren JA, López de Munain J, Lorenzo JM, Martín Gudino MJ, Martínez E, Mayo J, Portu J, Rodríguez FJ, Silvariño R, Zubero Z. · Plan del Sida en el País Vasco, Osakidetza-Servicio vasco de salud, San Sebastian, Gipuzkoa, Spain. · Gac Sanit. · Pubmed #15104976 links to  free full text

Abstract: OBJECTIVE: To describe the epidemiological characteristics of new cases of HIV infection diagnosed from 1997-2001 and compare them with AIDS cases (1991-2001). METHODS: Data were retrospectively collected on new cases of HIV infection detected in the Basque Country (1997-2001) and were compared with AIDS cases (1991-2001). RESULTS: A total of 912 new cases of HIV infection were diagnosed. In 299 of the new cases (32.8%), HIV and AIDS were diagnosed simultaneously. The most common mechanism of transmission was heterosexual transmission, followed by intravenous and homo/bisexual transmission. Significant epidemiological differences (p < 0.001) were found with regard to AIDS cases. CONCLUSIONS: Sexual transmission has replaced intravenous drug use as the most common mechanism of HIV transmission. A large percentage of patients were simultaneously diagnosed with HIV and AIDS, indicating the need for new prevention strategies.

Berenguer J, Miralles P, Arrizabalaga J, Ribera E, Dronda F, Baraia-Etxaburu J, Domingo P, Márquez M, Rodriguez-Arrondo FJ, Laguna F, Rubio R, Lacruz Rodrigo J, Mallolas J, de Miguel V, Anonymous00321. · Infectious Diseases Service of Hospital Gregorio Marañón, 28007, Madrid, Spain. · Clin Infect Dis. · Pubmed #12684918 No free full text.

Abstract: We analyzed survival rates, neurologic function, and prognostic factors for 118 consecutive patients with acquired immunodeficiency syndrome-associated progressive multifocal leukoencephalopathy (PML) treated with highly active antiretroviral therapy (HAART) in 11 hospitals throughout Spain. Seventy-five patients (63.6%) remained alive for a median of 114 weeks (2.2 years) after diagnosis of PML. Neurologic function of the survivors was categorized as cure or improvement in 33, stabilization or worsening in 40, and unknown in 2. The baseline CD4+ cell count was the only variable found with prognostic significance. The odds ratio of death was 2.71 (95% confidence interval, 1.19-6.15) for patients with CD4+ cell counts of <100 cells/microL, compared with patients who had CD4+ cell counts of > or =100 cells/microL. One-third of patients with PML died despite receipt of HAART; neurologic function improved in approximately one-half of the survivors. A CD4+ cell count of <100 cells/microL was associated with higher mortality.

von Wichmann MA, Camino X, Txoperena G, Arrizabalaga J, Rodríguez-Arrondo F, Iribarren JA. · Unidad de Enfermedades Infecciosas, Hospital Nuestra Señora de Aránzazu, San Sebastian. · Enferm Infecc Microbiol Clin. · Pubmed #11256242 links to  free full text

Abstract: BACKGROUND: Persistent neutropenia is frequent in HIV infected patients with severe immunodeficiency. G-CSF induces proliferation and differentiation of granulocyte precursors. Our objective has been to assess the response to G-CSF therapy on patients with advanced HIV disease and prolonged neutropenia. METHODS: A retrospective analysis of databases containing demographic information, analytic controls and hospitalizations related to neutropenia for patients attending our Infectious Diseases Unit from December 1, 1992 to January 30, 98. The episodes with absolute neutrophil counts lower than 1,000 x 10(6)/l at least during 7 days which descend below 500 x 10(6)/l at any moment were included. RESULTS: 36 episodes were included. 9 episodes started on treatment with G-CSF. The median duration was 9 (3-76) weeks. Hospitalization with fever related to neutropenia was significantly less frequent in episodes which received G-CSF (22.2%) than episodes without (66.7%). CONCLUSION: In this study, a significantly lower risk of hospitalization due to fever and neutropenia was associated with administration of G-CSF in patients with absolute neutrophil counts lower than 500 x 10(6)/l.