Acquired Immunodeficiency Syndrome: Ribera 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.

Crespo M, Caragol I, Falcó V, Ribera E, Urban S, Pahissa A. · Infectious Diseases Department, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain. · Enferm Infecc Microbiol Clin. · Pubmed #18208763 links to  free full text

Abstract: OBJECTIVE: The efficacy of recombinant interleukin-2 (rIL-2) was assessed in HIV-infected patients with advanced immune suppression and a discordant immune response to highly active antiretroviral therapy (HAART). The primary endpoint was median change in CD4+ T-cell counts at the end of treatment as compared to baseline. Secondary endpoints were safety and changes in the various T-cell subpopulations. MATERIAL AND METHODS: In a prospective cohort study, 19 patients with HIV-RNA < 50 copies/mL and < 200 CD4+ T cells/mm3 without a significant increase in the previous 12 months were scheduled to receive 6 cycles of 4.5 x 10(6) IU subcutaneous rIL-2 daily for 5 consecutive days, every 4 weeks. RESULTS: Median age was 43 years, and 64% had a previous AIDS-defining event. Median nadir and baseline CD4+ cell counts were 36 and 99 cells/mm3, respectively. Three patients discontinued treatment and one experienced grade 4 side effects. CD4+ T-cell counts increased to 147 cells/mm3 (range, 24-285) at 1 month following completion of treatment (P = 0.002), and 180 cells/mm3 (range, 38-280) at 18 months (P < 0.001). This improvement was associated with a significant decrease in expression rates of the activation markers, HLA-DR and CD38. CONCLUSION: Our results suggest that in patients with advanced HIV-infection showing a blunted immune response to HAART, rIL-2 might increase the pool of CD4+ T-cells by down-regulating the status of immune activation.

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.

Jordano Q, Falcó V, Almirante B, Planes AM, del Valle O, Ribera E, Len O, Pigrau C, Pahissa A. · Infectious Disease Division, Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain. · Clin Infect Dis. · Pubmed #15156452 No free full text.

Abstract: We studied all human immunodeficiency virus (HIV)-infected patients with invasive pneumococcal disease who received their diagnosis during 1996-2002 to investigate the incidence of this disease in the highly active antiretroviral therapy era and to study the influence of CD4 lymphocyte count on the clinical presentation and outcome of disease. The overall incidence of invasive pneumococcal disease was 11.3 cases per 100,000 person-years in adult patients without known HIV infection and 677 cases per 100,000 person-years in HIV-infected patients. This incidence remained stable over the study period. Clinical presentation, severity of illness, and number of recurrent episodes were similar in patients with CD4+ cell counts of >200 or < or =200 cells/ microL. Patients receiving trimethoprim-sulfamethoxazole (TMP-SMZ) were more likely to present with TMP-SMZ-resistant pneumococci than were those who were not receiving this agent (76.7% vs. 43.6%; P=.007). The mortality rate was high (21%).

Hidalgo A, Falcó V, Mauleón S, Andreu J, Crespo M, Ribera E, Pahissa A, Cáceres J. · Department of Radiology, Hospital General Universitari Vall d'Hebron, Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Paseo Vall d'Hebron 119-129, 08035 Barcelona, Spain. · Eur Radiol. · Pubmed #12695843 No free full text.

Abstract: The aim of this study was to assess the value of high-resolution CT in distinguishing between Pneumocystis carinii and non- Pneumocystis carinii pneumonia (PCP) in patients HIV-positive and high risk to have PCP. We performed a prospective study in 30 patients with <200 CD4 lymphocytes, clinical symptoms of pulmonary disease and chest X-ray non-conclusive for pulmonary infection. Evaluated CT findings included ground-glass opacities, reticulation, tree-in-bud appearance, consolidation, cystic lesions, bronchiectasis and lymphadenopathies. The diagnosis of "examination suggestive of PCP" was applied to cases showing a diffuse or predominant ground-glass pattern in the upper fields, associated or not with reticulations and small cystic lesions. The sensitivity, specificity, positive predictive value and negative predictive value of high-resolution computed tomography (HRCT) for the diagnosis of PCP was 100, 83.3, 90.5 and 100%, respectively. Pneumocystis carinii pneumonia was not demonstrated in any of the cases classified as "examination not suggestive of PCP". Significant small airway disease was not observed in any of the PCP cases. We conclude that HRCT is a reliable method for differentiating PCP from other infectious processes in HIV-positive patients and a good method to rule our PCP. Its inclusion in the diagnostic algorithm of lung infections is justified in these patients.

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.

Vallejo Camazón N, Rodríguez Pardo D, Sánchez Hidalgo A, Tornos Mas MP, Ribera E, Soler Soler J. · Servicios de Cardiología, Hospital General Vall d'Hebron, Barcelona, Spain. · Rev Esp Cardiol. · Pubmed #12199987 links to  free full text

Abstract: Prolongation of the QT interval is associated with a high risk of serious ventricular tachyarrhythmias, usually torsade de pointes (TdP) polymorphic ventricular tachycardia, although monomorphic ventricular tachycardia may also develop. Both congenital and acquired forms have been reported, acquired forms being much more prevalent. An association between human immunodeficiency virus (HIV) infection and a higher rate of dilated cardiomyopathy has also been recognized. The severity of immunodeficiency seems to influence both the incidence and severity of cardiomyopathy. A higher prevalence of QT prolongation has been reported among hospitalized HIV-positive patients with HIV infection, possibly related to drugs prescribed for such patients or to an acquired form of long QT syndrome arising from HIV infection. We report a case of QT prolongation and development of ventricular arrhythmia in one HIV patient that started with intravenous clarithromycin and cotrimoxazole therapy.