Acquired Immunodeficiency Syndrome: Martínez E

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.

Martínez E, Gatell JM. · No affiliation provided · Rev Clin Esp. · Pubmed #10522426 No free full text.

This publication has no abstract.

Martínez E, Arnaiz JA, Podzamczer D, Dalmau D, Ribera E, Domingo P, Knobel H, Riera M, Pedrol E, Force L, Llibre JM, Segura F, Richart C, Cortés C, Javaloyas M, Aranda M, Cruceta A, de Lazzari E, Gatell JM, Anonymous00159. · Infectious Diseases Unit, Hospital Clinic, Institut d'Investigacions Biomediques August Pi i Sunyer, University of Barcelona, Villarroel 170, 08036 Barcelona, Spain. · N Engl J Med. · Pubmed #12968087 links to  free full text

Abstract: BACKGROUND: We assessed the strategy of substituting nevirapine, efavirenz, or abacavir for a protease inhibitor in patients infected with human immunodeficiency virus type 1 (HIV-1) in whom virologic suppression had been achieved. METHODS: We randomly assigned 460 adults who were taking two nucleoside reverse-transcriptase inhibitors and at least one protease inhibitor and whose plasma HIV-1 RNA levels had been less than 200 copies per milliliter for at least the previous six months to switch from the protease inhibitor to nevirapine (155 patients), efavirenz (156), or abacavir (149). The primary end point was death, progression to the acquired immunodeficiency syndrome, or an increase in HIV-1 RNA levels to 200 copies or more per milliliter. RESULTS: At 12 months, the Kaplan-Meier estimates of the likelihood of reaching the end point were 10 percent in the nevirapine group, 6 percent in the efavirenz group, and 13 percent in the abacavir group (P=0.10 according to an intention-to-treat analysis). HIV-1 RNA could be amplified in 21 of the 29 patients in whom virologic failure developed during treatment with study medication (72 percent), and resistance mutations to the study medication and to at least one of the nucleoside reverse-transcriptase inhibitors in the regimen that failed were detected in all but 1 of the 21 patients. Twenty-three of the 29 patients with virologic failure during treatment with study medication had received prior suboptimal therapy with nucleoside reverse-transcriptase inhibitors. Fewer patients in the abacavir group (6 percent) than in the nevirapine group (17 percent) or the efavirenz group (17 percent) discontinued the study medication because of adverse events (P=0.01). The proportion of patients with fasting lipid levels warranting therapeutic intervention decreased significantly in the abacavir group, but the prevalence of clinical lipodystrophy did not change significantly in the three groups. CONCLUSIONS: When therapy was switched from a protease inhibitor to nevirapine, efavirenz, or abacavir in patients with virologic suppression, there was a trend toward a higher rate of virologic failure among those given abacavir.

Blanch J, Rousaud A, Martínez E, De Lazzari E, Peri JM, Milinkovic A, Perez-Cuevas JB, Blanco JL, Gatell JM. · Clinical Institute of Psychiatry and Psychology, Hospital Clínic Universitari de Barcelona, Barcelona, Spain. · J Acquir Immune Defic Syndr. · Pubmed #12447011 No free full text.

Abstract: INTRODUCTION: Lipodystrophy (LD) represents an important problem for HIV-1-infected patients receiving highly active antiretroviral therapy (HAART), although its impact on quality of life (QoL) has not been properly studied. DESIGN: Cross-sectional, nonrandomized, observational study performed on consecutive, clinically stable outpatients taking HAART for more than 1 year. METHODS: Data on patients' characteristics, HIV-1 infection, treatment adherence and adverse effects, overall QoL measured by the Profil der Lebensqualität Chronischkranker (PLC), and the presence of LD defined by clinical criteria were assessed. RESULTS: Eighty-four (56%) of 150 interviewed patients fulfilled criteria for LD. Patients with LD were older, had been taking antiretroviral treatment longer, and reported a poorer physical status than patients without LD. Surprisingly, LD itself was not found to influence overall QoL. However, homosexual patients, unemployed patients, and those patients undergoing current psychiatric treatment showed greater impairment on some of the QoL subscales related to psychological well-being if they suffered from LD. CONCLUSION: The impact of HIV-related LD on QoL depends on certain patient characteristics, rather than on the presence of LD itself.

García F, de Lazzari E, Plana M, Castro P, Mestre G, Nomdedeu M, Fumero E, Martínez E, Mallolas J, Blanco JL, Miró JM, Pumarola T, Gallart T, Gatell JM. · Clinic Institute of Infectious Diseases and Immunology, IDIBAPS, Hospital Clínic, Faculty of Medicine, University of Barcelona, Spain. · J Acquir Immune Defic Syndr. · Pubmed #15167289 No free full text.

Abstract: Current treatment guidelines for HIV infection recommend a relatively late initiation of highly active antiretroviral therapy (HAART). Nevertheless, there is still a concern that immune recovery may not be as complete once CD4+ T cells have decreased below a certain threshold. This study addressed the long-term response of CD4+ T-cell counts in patients on HAART and analyzed the influence of baseline CD4+ T-cell counts, baseline viral load, and age. An observational analysis of evolution of CD4+ T cells in 861 antiretroviral therapy-naive chronic HIV-1-infected patients who started treatment consisting of at least 3 drugs in or after 1996 was performed. Patients were classified in 4 groups according to baseline CD4+ T cells: <200 cells/mm3, 200-349 cells/mm3, 350-499 cells/mm3, and >or=500 cells/mm3. The main outcome measures were proportion of patients with CD4+ T cells <200/mm3 and >500/mm3 at last determination and rate of CD4+ T-cell recovery. Patients were followed-up for a median of 173 weeks (interquartile range [IQR], 100-234). There were no differences in follow-up between the 4 groups. CD4+ T cells increased in the whole cohort from a median of 214 cells/mm3 (IQR, 90-355) to 499 cells/mm3 (IQR, 312-733) (P<0.001). Compared with the group with a baseline CD4+ T-cell count of >or=500/mm3, the relative risk of having a last determination of CD4+ T-cell counts >200 cells/mm3 was 0.79 (95% CI, 0.75-0.83), 0.92 (95% CI, 0.89-0.96) and 1 for baseline CD4+ T cells <200 cells/mm3, 200-349 cells/mm3, and 350-499 cells/mm3, respectively. The relative risk of having a last determination of CD4+ T-cell counts >500 cells/mm3 was 0.32 (95% CI, 0.27-0.39, P<0.001), 0.69 (95% CI, 0.60-0.79, P<0.001), and 0.94 (95% CI, 0.83-1.06, P=0.38) for baseline CD4+ T-cell counts <200 cells/mm3, 200-349 cells/mm3, and 350-0499 cells/mm3, respectively, compared with a baseline CD4+ T-cell count of >or=500 cells/mm3. The increase in CD4+ T cells from baseline was statistically significant and was maintained for up to 4 years of follow-up. This increase seemed to slow down after approximately 3 years and reached a plateau after 4-5 years of follow-up even in patients who achieved and maintained viral suppression in plasma. Long-term immune recovery is possible regardless of baseline CD4+ T-cell count. However, patients who start therapy with a CD4+ T-cell count <200 cells/mm3 have poorer immunologic outcome as measured by the proportion of patients with CD4+ T cells <200/mm3 or >500/mm3 at last determination. It seems that the immune recovery slows down after approximately 3 years of HAART and reaches a plateau after 4-5 years of HAART.

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.

Navarrete P, Morente V, García F, Alós L, Arnedo M, Plana M, Gil C, Caballero M, Miró JM, Martínez E, Fumero E, Castro P, Blanco JL, Mallolas J, Blanch JL, Cruceta A, Mestre G, Pumarola T, Gallart T, Gatell JM. · Infectious Diseases Unit, Clinic Institute of Infectious Diseases and Immunology, Faculty of Medicine, University of Barcelona, Barcelona, Spain. · Antivir Ther. · Pubmed #14760898 No free full text.

Abstract: In 81 antiretroviral-navie HIV-1 chronic-infected patients, we found a correlation among tonsillar tissue viral load, and virological and immunological measures in blood at baseline. No correlation was observed after 1 year of antiretroviral therapy. A protease inhibitor-containing regimen was the best predictor of good tonsillar tissue virological response.

Marcos MA, Jiménez de Anta MT, de la Bellacasa JP, González J, Martínez E, García E, Mensa J, de Roux A, Torres A. · Dept of Microbiology, Institute of Infections and Immunology, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Universitat de Barcelona, Barcelona, Spain. · Eur Respir J. · Pubmed #12608431 links to  free full text

Abstract: Streptococcus pneumoniae is suspected to cause an important proportion of community-acquired pneumonia (CAP) whose aetiology cannot be detected with conventional tests. In this study, the authors evaluated the diagnostic yield of a new immunochromatographic membrane test (ICT) for the detection of the S. pneumoniae antigen in the urine of patients admitted with diagnosed CAP. ICT was performed in unconcentrated and concentrated urine from all the patients. ICT was repeated 1 month after discharge in a group initially testing positive. The authors also studied the ICT in clinically stable human immunodeficiency virus type 1 (HIV1)-infected patients. S. pneumoniae antigen was detected in all of the 68 (100%) patients tested with definitive pneumococcal pneumonia. In five of these cases ICT was only positive when it had been performed on the patients. The S. pneumoniae antigen was also detected in 36 (69.2%) of 52 patients with probable pneumococcal pneumonia and in 50 of 277 (18%) patients without pneumococcal pneumonia. ICT remained positive in 16 (69.5%) of 23 patients, 1 month after hospital discharge. Nasopharyngeal colonisation with S. pneumoniae was detected in 8 (12%) of 68 clinically stable HIV1 infected patients, but none tested ICT positive. The Binax NOW it immunochromatographic membrane test is a rapid, sensitive and specific test for detecting pneumococcal community-acquired pneumonia in adults. The test may remain positive for several weeks after pneumococcal pneumonia.

Collazos J, Blanco MS, Guerra E, Mayo J, Martínez E. · Section of Infectious Diseases, Hospital de Galdakao, Vizcaya, Spain. · Clin Chem Lab Med. · Pubmed #11205696 No free full text.

Abstract: To evaluate the serum urate levels in AIDS patients with infections of the central nervous system (CNS), 46 patients who had at least two measurements of urate were included. A maximum of four measurements per patient were considered: prior to the CNS involvement (U-PRIOR), at the time of CNS involvement (U-CNS), after treatment for the CNS infection (U-AFTER), and the last measurement before death (U-LAST). Serum U-CNS levels were significantly lower than U-PRIOR values (p=0.038). U-AFTER levels were higher than U-CNS in the patients who improved (p=0.25), and lower in the patients who did not improve (p=0.026). There were no significant differences among the four diagnostic groups in U-CNS measurement (p=0.29) but they were found in U-AFTER determinations (p=0.018), probably as a result of the different response to treatment. Hypouricemia seemed to be associated with lower survival periods. We conclude that hypouricemia is common in AIDS patients with CNS infections, probably as a result of increased renal losses of urate, and that it may have prognostic significance. CNS infections are associated with significant decreases in serum urate levels in comparison with previous values. The urate concentrations seem to increase after successful treatment of the CNS infections, whereas they decrease further in patients who do not improve.