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D Podzamczer

Publications and source records attributed to D Podzamczer.

At least 19 recordsLinked to original sources
PubMed2005

Once-daily antiretroviral therapy: Spanish Consensus Statement.

BACKGROUND: Administration of antiretroviral therapy (ART) once daily is creating extraordinary interest among the members of the scientific community and also among those who receive the therapy. However, in clinical practice, some doubts remain about its use. OBJECTIVES: This document examines the characteristics and possibilities of treatment administered once daily. METHODS: Consensus of 248 Spanish experts in the field. RESULTS: Once-daily dosing is considered an added value which could favour adherence and, therefore, efficacy, as well as the quality of life of certain patients, however, the objective of adequate adherence in the long term is often difficult to achieve regardless of the treatment used. In theory, any patient can receive once-daily therapy, although some patients could particularly benefit from it, e.g. those with unfavourable social or personal circumstances, including drug users, patients whose treatment must be supervised, patients receiving multiple medications, or those who need rescue therapy after multiple treatment failures. At present, it is possible to design once-daily ART using some of the combinations of drugs considered as first-choice in national and international recommendations for antiretroviral therapy, but the options are still limited. The marketing of new drugs with this characteristic could allow us to increase the number and types of patient who can benefit from once-daily regimens, including those patients who need rescue therapy. CONCLUSIONS: Once-daily ART is a good alternative to regimens administered several times each day when a potent combination of active drugs is available.

Anti-HIV Agents↗
PubMed2004

Therapeutic immunization with an inactivated HIV-1 Immunogen plus antiretrovirals versus antiretroviral therapy alone in asymptomatic HIV-infected subjects.

To determine whether the addition of an inactivated-gp120-depleted HIV-1 Immunogen to antiretrovirals (ARTs) conferred a beneficial effect on delaying time to virologic failure relative to that obtained by ARTs alone, a phase II clinical trial was performed in 243 asymptomatic, ART naïve, HIV-1 seropositive adults. The Cox model showed that HIV-1 Immunogen treatment was associated with a 34% decrease in the risk of virologic failure (P = 0.056). When the analysis incorporated baseline HIV-RNA stratification the risk of virologic failure in the HIV-1 Immunogen Arm was significantly reduced a 37% compared to the IFA placebo Arm (P = 0.034). The data suggest that therapeutic immunization plus ARTs could influence virologic control.

AIDS Vaccines↗
PubMed2004

Incidence and molecular typing of Mycobacterium kansasii in a defined geographical area in Catalonia, Spain.

A retrospective population-based study was conducted between January 1990 and December 1998 to investigate the incidence of Mycobacterium kansasji disease and the heterogeneity of the isolates in a well-defined geographical area in Catalonia, Spain. A total of 136 patients were identified. Overall incidence and incidence in AIDS patients was 1.5 (95% CI 1.2-1.8) and 1089.6 (95% CI 689-1330) cases/100,000 persons per year respectively, which is comparable to that reported from most of other geographical areas. Surprisingly, although 7 subtypes of M. kansasii have been consistently reported, in the present study 91 of the 93 isolates (97.8%) tested for genotype were subtype I, regardless of HIV status of the patients. In conclusion, the high rate of infection observed in the AIDS population contributes significantly to the burden of the M. kansasii disease in our area. M. kansasii disease in our geographical area was almost exclusively caused by subtype I regardless of HIV status.

Acquired Immunodeficiency Syndrome↗
PubMed2003

New patterns of HIV-1 resistance during HAART.

HIV-1 resistance and subsequent virologic failure occur in a substantial proportion of HIV-infected patients receiving HAART regimens. In the present article, we summarize new data on resistance to current and forthcoming antiretroviral drugs which will help in the interpretation of the results of resistance tests and the individualization of therapy. Nucleoside analog mutations (NAMs) (M41L, D67N, K70R, L210W, T215Y/F and K219Q/E) are associated with reduced susceptibility to most nucleoside analogs and the nucleotide tenofovir. This recently approved drug has shown a reduced virologic response in the presence of three or more NAMs, including M41L or L210W, as well as in the presence of T69 insertions. Hypersusceptibility (IC50 < 0.5) to non-nucleoside reverse transcriptase inhibitors (NNRTIs) has recently been described in association with increased resistance to nucleoside analogs, and it seems to enhance the immunologic and virologic reponses in patients receiving efavirenz-containing regimens. New protease inhibitors (PIs) have a lower cross-resistance profile, although more clinical data are needed to establish appropriate PI sequencing to promote sustained virologic success. Cross-resistance between amprenavir (APV) and lopinavir (LPV/r) in the presence of only four APV-related mutations has been described, suggesting that phenotypic tests should be applied before prescribing LPV/r to APV-experienced patients. Resistance to the new entry inhibitor class compound T-20 (enfuvirtide) has also been detected.

Antiretroviral Therapy, Highly Active↗
PubMed2001

A randomized trial of the discontinuation of primary and secondary prophylaxis against Pneumocystis carinii pneumonia after highly active antiretroviral therapy in patients with HIV infection. Grupo de Estudio del SIDA 04/98.

BACKGROUND: Prophylaxis against Pneumocystis carinii pneumonia is indicated in patients with human immunodeficiency virus (HIV) infection who have less than 200 CD4 cells per cubic millimeter and in those with a history of P. carinii pneumonia. However, it is not clear whether prophylaxis can be safely discontinued after CD4 cell counts increase in response to highly active antiretroviral therapy. METHODS: We conducted a randomized trial of the discontinuation of primary or secondary prophylaxis against P. carinii pneumonia in HIV-infected patients with a sustained response to antiviral therapy, defined by a CD4 cell count of 200 or more per cubic millimeter and plasma HIV type 1 (HIV-1) RNA level of less than 5000 copies per milliliter for at least three months. Prophylactic treatment was restarted if the CD4 cell count declined to less than 200 per cubic millimeter. RESULTS: The 474 patients receiving primary prophylaxis had a median CD4 cell count at entry of 342 per cubic millimeter, and 38 percent had detectable HIV-1 RNA. After a median follow-up period of 20 months (758 person-years), there had been no episodes of P. carinii pneumonia in the 240 patients who discontinued prophylaxis (95 percent confidence interval, 0 to 0.85 episode per 100 person-years). For the 113 patients receiving secondary prophylaxis, the median CD4 cell count at entry was 355 per cubic millimeter, and 24 percent had detectable HIV-1 RNA. After a median follow-up period of 12 months (123 person-years), there had been no episodes of P. carinii pneumonia in the 60 patients who discontinued prophylaxis (95 percent confidence interval, 0 to 4.5 episodes per 100 person-years). CONCLUSIONS: In HIV-infected patients receiving highly active antiretroviral therapy, primary and secondary prophylaxis against P. carinii pneumonia can be safely discontinued after the CD4 cell count has increased to 200 or more per cubic millimeter for more than three months.

AIDS-Related Opportunistic Infections↗
PubMed2001

The role of nevirapine in the treatment of HIV-1 disease.

Nevirapine (Viramune, Boehringer Ingelheim) is a non-nucleoside reverse transcriptase (RT) inhibitor (NNRTI) effective in the treatment of HIV-1 infected antiretroviral-naive and -experienced patients. Some recent studies have suggested that nevirapine-based regimens may have an efficacy similar to protease inhibitor (PI)-based regimens, at least in naive patients with CD4+ > 200 microl, while it lacks the drawbacks inherent in PI-containing regimens, such as lipodystrophy and metabolic alterations. Switching from a PI-containing regimen to a nevirapine-containing regimen seems to retain the virological response to therapy and it may also limit or reverse the development of some metabolic disorders induced by PIs. Nevirapine is also effective in preventing mother-to-child transmission of HIV-1 disease and in the treatment of HIV-1 infected children. Nevirapine is well-tolerated, rash being the most common severe adverse effect observed. Hepatotoxicity may also appear with nevirapine, mainly in patients with chronic hepatitis C and/or altered liver function tests. This side effect may occasionally be life-threatening but it can be safely managed in most patients.

Anti-HIV Agents↗
PubMed2000

Evaluating changes in health status in HIV-infected patients: Medical Outcomes Study-HIV and Multidimensional Quality of Life-HIV quality of life questionnaires. Spanish MOS-HIV and MQOL-HIV Validation Group.

OBJECTIVE: To compare the sensitivity to change of two HIV-health-related quality of life (HRQoL) questionnaires--the Medical Outcomes Study (MOS-HIV) and Multidimensional Quality of Life (MQOL-HIV) for use in clinical research. METHODS: A sample of 296 HIV-infected patients starting or switching antiretroviral treatment were randomly assigned either the MOS-HIV or MQOL-HIV questionnaires at baseline and after 3 months of treatment. Ceiling and floor effects were evaluated. Sensitivity to change was assessed by comparing the percentage of dimensions with statistically significant pre-post-treatment changes and the effect sizes in those groups of patients who reported improvement and no change in self-report questions (overall, physical, mental and social health status) and clinical characteristics (number of opportunistic infections, number of symptoms, viral load level and CD4+ count). RESULTS: Ceiling effects were found in HRQoL scores at baseline and after 3 months of treatment in Pain (42.3-41.6%), Role Function (73.1-77.6%) and Social Function (60.9-63%) on MOS-HIV subscales, and in Social Support (38.2-37.6%) and Partner Intimacy (38.2-33.7%) on MQOL-HIV. For patients who improved in self-reported and objective clinical indicators of health status, mean percentage of dimensions with statistically significant pre-post-treatment changes was 86.4% on MOS-HIV and 50% on MQOL-HIV, where mean standardized effect size was 0.45 on MOS-HIV and 0.33 on MQOL-HIV for the total of dimensions. CONCLUSIONS: Based on sensitivity to change the results suggest that for 3 months both questionnaires can be used, but the MOS-HIV is more sensitive than the MQOL-HIV for use in clinical research.

Adolescent↗
PubMed2000

Clearance of human herpesvirus type 8 viraemia in HIV-1-positive patients with Kaposi's sarcoma treated with liposomal doxorubicin. Caelyx/KS Spanish Study Group.

OBJECTIVE: To assess the impact of liposomal doxorubicin on human herpesvirus type 8 (HHV-8) cell viraemia in HIV-infected patients with Kaposi's sarcoma. DESIGN: Prospective, non-controlled, multicenter study. METHODS: The presence of HHV-8 DNA was investigated by polymerase chain reaction in peripheral blood mononuclear cells from 46 HIV-positive patients with Kaposi's sarcoma. Samples were tested at baseline and every 3 months during treatment with liposomal doxorubicin. CD4 cell counts, plasma HIV RNA, and clinical outcome were recorded at baseline and at follow-up visits. RESULTS: HHV-8 sequences were detected in 32 (70%) patients at baseline. No significant differences were found between subjects with HHV-8 positive and negative results. The proportion of patients with positive HHV-8 viraemia decreased to 38% (10 of 26) after 3 months of treatment with liposomal doxorubicin (P < 0.01). Overall, 12 of 22 (57%) subjects with positive HHV-8 cell viraemia at baseline became negative during the treatment period. However, in one of them HHV-8 reappeared 8 months later despite being on therapy. On the other hand, six of eight subjects with negative HHV-8 at baseline remained negative thereafter. There were no significant changes in plasma HIV RNA, total lymphocyte, or CD4 cell counts during the treatment period. Clinical response of Kaposi's sarcoma to liposomal doxorubicin and clearance of HHV-8 viraemia did not correlate well. CONCLUSIONS: HHV-8 cell viraemia significantly decreased during treatment with liposomal doxorubicin in HIV-infected patients with Kaposi's sarcoma, although the clinical response and HHV-8 clearance did not correlate well.

AIDS-Related Opportunistic Infections↗
PubMed2000

Thrice-weekly sulfadiazine-pyrimethamine for maintenance therapy of toxoplasmic encephalitis in HIV-infected patients. Spanish Toxoplasmosis Study Group.

An open, randomised, multicentre trial was conducted to evaluate the efficacy of thrice-weekly versus daily therapy with sulfadiazine-pyrimethamine in the prevention of relapses of toxoplasmic encephalitis in HIV-infected patients. Between February 1994 and July 1997, 124 patients with HIV infection were enrolled after resolution of the first acute episode of toxoplasmic encephalitis treated with sulfadiazine-pyrimethamine. Patients were randomly assigned to receive either a daily regimen consisting of sulfadiazine (1 g) twice a day plus 25 mg pyrimethamine and 15 mg folinic acid daily (n = 58), or a thrice-weekly regimen consisting of the same doses of sulfadiazine and folinic acid plus 50 mg pyrimethamine (n = 66). After a median follow-up period of 11 months (range 1-39 months), no differences were found in the incidence of toxoplasmic encephalitis relapses between the groups, there being 14.9 episodes per 100 patient-years (95% CI: 2.8-20.2) in the daily-regimen group versus 14.1 episodes (95% CI: 2.3-17.2) in the intermittent-regimen group. The estimated cumulative percentages of relapse at 12 months were 17% and 19%, respectively (P = 0.91). In a Cox multivariate analysis, not taking antiretroviral therapy was the only variable independently associated with relapse (adjusted risk ratio: 4.08; 95%CI: 1.32-12.66). Baseline CD4+ cell counts, prior AIDS, mental status, sequelae and allocated maintenance therapy regimen were not independent predictors of relapse. No differences were observed in the survival rate (P = 0.42), or in the incidence of severe adverse effects (P = 0.79). The efficacy of the thrice-weekly regimen was similar to that of the daily regimen in the prevention of relapses of toxoplasmic encephalitis. Administration of antiretroviral therapy was the only factor associated with a lower incidence of relapse.

AIDS-Related Opportunistic Infections↗
PubMed1999

A randomized study comparing triple versus double antiretroviral therapy or no treatment in HIV-1-infected patients in very early stage disease: the Spanish Earth-1 study.

BACKGROUND: Most current guidelines state that antiretroviral therapy should be considered for HIV-infected patients with plasma HIV RNA > 5000-10000 copies/ml and CD4 cells > 500 x 10(6) cells/l. However, there is increasing concern about whether this is the optimal point to begin treatment or whether it is better to delay the initiation to more advanced stages. OBJECTIVE: To study the immunological and virological benefits of starting antiretroviral therapy at these early stages. METHODS: A total of 161 HIV-infected asymptomatic patients with CD4 cell count > 500 x 10(6) cells/l and viral load > 10000 copies/ml were randomly assigned to one of five treatment groups: no treatment, twice daily zidovudine and thrice daily zalcitabine (ZDV-ddC), twice daily zidovudine and didanosine (ZDV-ddI), twice daily stavudine and didanosine (D4T-ddI), or a twice daily three-drug regimen with stavudine and lamivudine and ritonavir. The endpoints were progression to < 350 x 10(6) cells/l CD4 cells, to < 500 x 10(6) cells/l with either two Centers for Disease Control class B symptoms or an increase of viral load > 0.5 log10 copies/ml above baseline, or to AIDS or death. In various substudies, the lymphoid tissue and cerebrospinal fluid viral load, development of genotypic resistance, proliferative responses to mitogens and cytomegalovirus, and HIV-1 specific antigens and other immunophenotypic markers were also analysed. RESULTS: Progression rates to study endpoints within 1 year were greater in the control group (31%) than in all groups receiving antiretroviral therapy pooled together (5%; estimated hazard ratio 7.41; 95% confidence interval 5.72-74.55; P < 0.001). The peak mean viral load decrease was greater in the three-drug group when compared with any of the three groups with a two-drug regimen (2.32, 1.65, 1.72 and 1.84, respectively; P < or = 0.001). At 1 year, viral load remained below 20 copies/ml in 30 out of 33 patients in the three-drug group (91%) and in only eight out of 94 patients (9%) in two-drug groups (P = 0.001). The peak mean increase in CD4 cells was also greater in the three-drug group than in the double treatment arms (259 versus 85, 144 and 145 x 10(6) cells/l, respectively; P = 0.001). By comparison, 36% of patients in the three-drug group regimen had to change the therapy as a result of adverse events. Substudies were performed in 60 patients recruited at two sites. Tonsillar tissue HIV RNA was measured in seven patients (two in the two-drug groups and five in the three-drug group) in whom plasma HIV RNA was < 20 copies/ml at 1 year. It was 15151 and 133333 copies/mg tissue in the two patients from the two-drug group, < 40 copies/mg tissue in four patients in the three-drug group, and 485 copies/mg in one patient in the three-drug group. At 1 year there was a mean increase of 4.21+/-2.94% in CD8+CD38+ cells in the control group and a decrease of 9.48+/-3.36% in the two-drug groups (P = 0.01), and 19.87+/-3.64 in the three-drug group (P = 0.001 and P = 0.05, for comparisons with control group and two-drug groups, respectively). Although proliferative responses to cytomegalovirus antigens were significantly greater in those receiving antiretroviral therapy, response to HIV-1 p24 antigen was not detected in any patient in either treatment group. CONCLUSIONS: This study supports the recommendation to start antiretroviral therapy with a three-drug combination during very early stages of HIV-1 disease, at least if viral load is above a cut-off point (10000 copies/ml in our study). The risk of progression was sevenfold higher in non-treated patients at 8 months of follow-up. Some immune system parameters improved toward normal values after 1 year of antiretroviral therapy, but the proliferative response of CD4 T lymphocytes against the p24 HIV-1 antigen was not recovered. Therapeutic approaches with more potent, better-tolerated and more convenient regimens will increasingly favour early intervention with antiretroviral t

Adult↗
PubMed1999

A randomized study comparing instruments for measuring health-related quality of life in HIV-infected patients. Spanish MOS-HIV and MQOL-HIV Validation Group. Medical Outcomes Study HIV Health Survey.

OBJECTIVE: To compare the feasibility, reliability, validity and sensitivity to change of the MOS-HIV and MQOL-HIV in order to determine their suitability for use in clinical research. METHODS: Five hundred and fifty-eight HIV-infected patients and 80 healthy blood donors were randomly assigned to receive the MOS-HIV or MQOL-HIV. Test-retest reliability was assessed in 98 clinically stable patients, and responsiveness in 296 patients initiating or switching anti-retroviral treatment. Feasibility was assessed using mean time of administration and percentage of missing responses. Reliability was assessed using Cronbach's alpha and the intraclass correlation coefficient (ICC). Construct validity was assessed by correlating questionnaire scores with EuroQol-5D scores, number of symptoms, CD4 cell count and viral load. The area under the curve (AUC) was used for discrimination between patients and healthy donors, and HRQoL scores were compared across disease stage. Responsiveness was assessed by calculating the standardized effect size (SES). RESULTS: Mean administration time was 16 minutes for both questionnaires. On the MOS-HIV 18.9% patients had missing responses compared with 33.6% on the MQOL-HIV. Cronbach's alpha values were higher for MOS-HIV sub-scales (0.78-0.89) than MQOL-HIV sub-scales (0.44-0.82), and neither instrument showed good test-retest reliability (ICC values of 0.24-0.85 for MOS-HIV versus 0.48-0.82 for MQOL-HIV). AUC values for the MOS-HIV were 0.6-0.86, compared with 0.5-0.79 for the MQOL-HIV, and the MOS-HIV had higher correlations with symptoms (r = -0.28 to 0.79) and EuroQol scores (r = 0.4-0.66) than the MQOL-HIV (r = -0.15 to 0.42 and r = -0.11 to 0.59, respectively). Neither instrument discriminated well between disease stages. Eight of 11 MOS-HIV sub-scales and the Mental Health Summary Score were responsive to change (SES, 0.18-0.36), compared with six of 10 MQOL-HIV sub-scales and MQOL Index (SES, 0.16-0.27). CONCLUSIONS: Neither instrument demonstrated completely satisfactory psychometric properties for use in clinical research, although the MOS-HIV performed slightly better on feasibility and validity and the MQOL-HIV on test-retest reliability.

Adolescent↗
PubMed1999

Analysis of the discontinuation of protease inhibitor therapy in routine clinical practice.

We evaluated the frequency of and reasons for discontinuation of protease inhibitor therapy in a cohort of HIV-infected patients in a prospective observational study. We included 230 HIV-infected patients who had started protease inhibitor therapy between November 1996 and July 1997. Mean baseline CD4 count was 138 cells/microl and HIV-RNA 4.5 log10. Forty-five percent of patients had prior AIDS and 77% had been treated with nucleoside analogues. Saquinavir-treated patients were at a less advanced stage of HIV disease. Overall, 41.3% of patients discontinued therapy, and their last HIV-RNA measured higher than that of patients who continued therapy: 4.07 vs. 2.70 log10 (p < 0.0001). Reasons for discontinuation of therapy were poor adherence (including abandonment) (18.6%), drug intolerance (12.1%), virological failure (7%) and physician decision (3.5%). In a multivariate model, factors associated with drug discontinuation were not taking indinavir (OR 0.26, 95% CI 0.12-0.59) and being pretreated with nucleoside analogues (OR 3.42, 95% CI 1.58-7.42). We concluded that in routine clinical practice a high proportion of patients discontinued protease inhibitors during the first 6 months of therapy, the main reason being the patient's own decision (abandonment or poor adherence). Psychological support and counselling are warranted in patients when initiating protease inhibitor therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1999

[Evidence-based medicine and the validation of quality-of-life questionnaires: the Spanish version of the MOS-HIV questionnaire for the evaluation of the quality of life in patients infected by HIV].

BACKGROUND: To validate the Spanish version of the MOS-HIV questionnaire for measuring quality of life in HIV-infected patients. METHODS: 275 HIV-infected patients distributed in three diagnostic categories (asymptomatic, symptomatic and AIDS) and 40 blood donors as healthy controls were recruited from 23 Spanish hospitals and answered the MOS-HIV. Feasibility was assessed by analysing the mean time of administration and the percentage of patients with missing response. Internal consistency was assessed using Cronbach's alpha. A subsample of 48 stable patients completed the questionnaire on two occasions to assess test-retest reliability using the Intraclass Correlation Coefficient. Validity was assessed by calculating the area under the Receiver's Operating Characteristics (ROC) curve between patients and controls, and by correlating MOS-HIV scores with the VAS of Euroqol, the number of symptoms, the CD4+ count and viral load. RESULTS: The mean time of administration was 16 minutes and 18.9% of patients did answer the MOS-HIV with some missing response. All the scales showed high internal consistency (Cronbach's alpha = 0.78-0.89). Test-retest reliability of Physical Health (PHS) and Mental Health (MHS) Summary Scores was 0.58 y 0.85, respectively. The MOS-HIV discriminated between patients and controls (ROC = 0.77, CI = 0.69-0.85 and ROC = 0.80, CI = 0.72-0.88, for the PHS and MHS, respectively). The correlation of the scales of the MOS-HIV with the CD4+ count and viral load was low (r = -0.26 to 0.3), and with the number of symptoms and the VAS of Euroqol were moderate (r = -0.28 to -0.49 and r = 0.4 to 0.66, respectively). CONCLUSIONS: Considering evidence-based medicine principles, the Spanish version of the MOS-HIV has shown adequate feasibility, reliability and validity for its use in clinical research, but their use in clinical practice is limited because of their time of administration, the low reproducibility of some scales and the features of their scoring system.

Adolescent↗