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1.
Clin Exp Immunol ; 203(3): 424-432, 2021 03.
Article in English | MEDLINE | ID: mdl-33187018

ABSTRACT

The role of lymphocytes and their main subsets as prognostic factors of death in SARS-CoV-2-infected patients remains unclear, with no information obtained from patients outside China. We aimed to assess whether measuring lymphocyte subpopulations added clinical value to the total lymphocyte counting regarding mortality when they were simultaneously tested at hospital admission. Peripheral blood was analysed in 701 polymerase chain reaction (PCR)-confirmed consecutive patients by lysed-no washed flow cytometry. Demographic and clinical features were registered in electronic medical records. Statistical analysis was performed after a 3-month follow-up. The 112 patients who died were older and had significantly higher frequencies of known co-morbidities than survivor COVID-19 patients. A significant reduction in total lymphocytes, CD3+ , CD4+ , CD8+ and CD19+ counts and CD3+ percentage was found in the group of deceased patients (P < 0·001), while the percentage of CD56+ /CD16+ natural killer (NK) cells was significantly higher (P < 0·001). Multivariate logistic regression analysis showed a significantly increased risk of in-hospital death associated to age [odds ratio (OR) = 2·36, 95% confidence interval (CI) = 1·9-3·0 P < 0·001]; CD4+  T counts ≤ 500 cells/µl, (OR = 2·79, 95% CI = 1·1-6·7, P = 0·021); CD8+  T counts ≤ 100 cells/µl, (OR = 1·98, 95% CI = 1·2-3·3) P = 0·009) and CD56+ /CD16+ NK ≥ 30%, (OR = 1·97, 95% CI = 1·1-3·1, P = 0·002) at admission, independent of total lymphocyte numbers and co-morbidities, with area under the curve 0·85 (95% CI = 0·81-0·88). Reduced counts of CD4+ and CD8+ T cells with proportional expansion of NK lymphocytes at admission were prognostic factors of death in this Spanish series. In COVID-19 patients with normal levels of lymphocytes or mild lymphopenia, imbalanced lymphocyte subpopulations were early markers of in-hospital mortality.


Subject(s)
Antigens, CD/blood , CD4-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/metabolism , COVID-19 , Hospital Mortality , SARS-CoV-2/metabolism , T-Lymphocyte Subsets/metabolism , Age Factors , Aged , Aged, 80 and over , CD4 Lymphocyte Count , COVID-19/blood , COVID-19/mortality , Female , Follow-Up Studies , Humans , Male , Middle Aged , Predictive Value of Tests , Spain
2.
J Antimicrob Chemother ; 69(9): 2536-40, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24833755

ABSTRACT

OBJECTIVES: To present clinical experience with a regimen including abacavir/lamivudine + darunavir/ritonavir in a cohort of HIV-1-infected patients. METHODS: A retrospective, multicentre cohort study, including all consecutive adult HIV-1-infected patients who started abacavir/lamivudine + darunavir/ritonavir from April 2008 to December 2010 and had at least one follow-up visit. The primary endpoint was HIV-1 viral load (VL) <40 copies/mL at week 48. RESULTS: One hundred and eighty-three patients (42 naive and 141 experienced) from 19 hospitals in Spain were studied. The median follow-up was 26.7 (0.5-58.6) months, 79.8% were men, the median age was 47.1 (21.4-80.5) years, 26.2% had AIDS and 38.8% were positive for hepatitis C virus. At baseline, the median CD4 count was 246 cells/mm(3) in naive patients and 393 cells/mm(3) in experienced patients and the median VL was 4.80 and <1.59 log copies/mL, respectively. At week 48, 81.8% of naive patients and 84.2% of experienced patients receiving the regimen reached a VL <40 copies/mL, whereas at 96 weeks this occurred in 90.5% and 92.8%, respectively. CD4 cell count increases at 48 and 96 weeks were +176.5 and +283.5 cells/mm(3) in naive patients and +74.9 and +93 cells/mm(3) in experienced patients, respectively. Overall, 86 (47%) patients discontinued the study regimen, in many cases possibly related to non-medical reasons, such as drug switches to reduce cost or changes in address due to economic constraints. Three patients died of causes unrelated to therapy and 19 (10.4%) discontinued the regimen due to adverse events. CONCLUSIONS: In our cohort, abacavir/lamivudine + darunavir/ritonavir was safe, well tolerated and achieved high rates of virological suppression. In a proportion of patients, discontinuation of this effective regimen was possibly due to non-medical reasons.


Subject(s)
Anti-HIV Agents/therapeutic use , Antiretroviral Therapy, Highly Active/methods , Dideoxynucleosides/therapeutic use , HIV Infections/drug therapy , Lamivudine/therapeutic use , Ritonavir/therapeutic use , Sulfonamides/therapeutic use , Adult , Aged , Aged, 80 and over , Anti-HIV Agents/adverse effects , Antiretroviral Therapy, Highly Active/adverse effects , Cohort Studies , Darunavir , Dideoxynucleosides/adverse effects , Drug Combinations , Female , HIV-1/isolation & purification , Humans , Lamivudine/adverse effects , Male , Middle Aged , Retrospective Studies , Ritonavir/adverse effects , Spain , Sulfonamides/adverse effects , Treatment Outcome , Viral Load , Young Adult
3.
Curr HIV Res ; 10(6): 513-20, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22716109

ABSTRACT

OBJECTIVE: To evaluate long-term outcomes in patients maintaining a nevirapine (NVP)-based regimen. METHODS: Retrospective, multicenter, cohort study including patients currently receiving an NVP regimen that had been started at least 5 years previously. Demographic, clinical, and analytical variables were recorded. RESULTS: Median follow-up was 8.9 (5.7-11.3) years. Baseline characteristics: 74% men, 47 years old, 36% drug users, 40% AIDS, 40% HCV+, 51.4% detectable HIV-1 viral load, CD4 count 395 (4-1,421)/µL, 19% CD4 < 200/µL, 27% ALT grade 1-2, 36% AST grade 1-2. Thirty percent ART-naive, 83%received NVP associated with 2 nucleoside analogues during the study period, and 17% a protease inhibitor. A significant improvement was observed in general health status markers, including hemoglobin, platelets, and albumin, regardless of HCV coinfection. CD4 cell gain was +218 and +322/µL after 6 and 9 years, respectively (+321 and +391 in naive patients). Triglycerides significantly decreased in pretreated patients, whereas the percentage of patients with HDLc < 1.03 mmol/L and LDL-c > 3.37 mmol/L significantly decreased in a subsample with available values. A significant decrease in transaminases, alkaline phosphatase, and Fib4 score was observed, mainly in HCV+ and ARV-naive patients. CONCLUSIONS: In patients who tolerate NVP therapy, (even those with HCV coinfection), long term benefits may be significant in terms of a progressive improvement in general health status markers and CD4 response, a favorable lipid profile, and good liver tolerability.


Subject(s)
Acquired Immunodeficiency Syndrome/drug therapy , Anti-HIV Agents/administration & dosage , Hepatitis C/drug therapy , Liver/drug effects , Nevirapine/administration & dosage , Substance-Related Disorders/epidemiology , Acquired Immunodeficiency Syndrome/blood , Acquired Immunodeficiency Syndrome/epidemiology , CD4 Lymphocyte Count , Cholesterol/blood , Cohort Studies , Coinfection , Drug Therapy, Combination , Female , Follow-Up Studies , Hepatitis C/blood , Hepatitis C/epidemiology , Humans , Male , Middle Aged , Retrospective Studies , Spain/epidemiology , Time Factors , Treatment Outcome , Triglycerides/blood , Viral Load
4.
N Engl J Med ; 344(3): 159-67, 2001 Jan 18.
Article in English | MEDLINE | ID: mdl-11172138

ABSTRACT

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.


Subject(s)
AIDS-Related Opportunistic Infections/prevention & control , Anti-Infective Agents/therapeutic use , Antiretroviral Therapy, Highly Active , HIV Infections/drug therapy , HIV-1 , Pneumonia, Pneumocystis/prevention & control , Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use , AIDS-Related Opportunistic Infections/drug therapy , Adult , CD4 Lymphocyte Count , Female , HIV Infections/immunology , HIV Infections/virology , HIV-1/genetics , Humans , Male , Multivariate Analysis , Pneumonia, Pneumocystis/drug therapy , RNA, Viral/blood , Statistics, Nonparametric
5.
J Infect Dis ; 177(3): 579-85, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9498435

ABSTRACT

The immunodeficiency caused by human immunodeficiency virus (HIV) infection may be related to loss of diversity in the T cell receptor (TCR) repertoire. A cross-sectional study of the CD4 TCR repertoire was done for patients at various stages of HIV infection. Semiquantitative polymerase chain reaction was used to study the relative usage of the variable chain beta (BV) subfamilies and the size distributions of transcripts (CDR3 size analysis) within these subfamilies. The relative usage of the TCRBV subfamilies of patients and controls was not significantly different. The proportion of subfamilies with abnormal CDR3 size patterns was higher in the HIV-infected patients (25%, 95% confidence interval [CI], 17%-33%) than in the controls (7.2%, 95% CI, 2.3%-12.1%; P < .001), with a significant negative correlation between the number of CD4 cells and the percentage of abnormal TCRBV subfamilies. These results indicate that progressive loss of CD4 T cells is accompanied by increasing disruptions within the T cell receptor repertoire.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , HIV Infections/immunology , Receptor-CD3 Complex, Antigen, T-Cell/genetics , Receptors, Antigen, T-Cell, alpha-beta/genetics , CD4 Lymphocyte Count , Cross-Sectional Studies , Humans , Polymerase Chain Reaction , RNA, Messenger/genetics , Sequence Analysis, DNA
6.
AIDS ; 12(18): 2467-72, 1998 Dec 24.
Article in English | MEDLINE | ID: mdl-9875585

ABSTRACT

OBJECTIVES: To evaluate the efficacy of highly active antiretroviral therapy (HAART) in 12 patients with AIDS-associated progressive multifocal leukoencephalopathy (PML). PATIENTS AND METHODS: The diagnosis of PML was established by brain biopsy in six patients and by neuroimaging findings and PCR detection of JC virus in cerebrospinal fluid (CSF) in six patients. We also studied 13 consecutive AIDS patients with biopsy-proven PML cared for in the same institution before HAART was available. Eleven patients of the HAART group and eight patients of the control group received intravenous arabinoside cytosine cycles. RESULTS: With HAART, the median decrease in the HIV viral load was 3.58 log10 copies/ml and the median increase in the CD4 cell count was 74x10(6)/l. The median survival time after PML diagnosis was 545 days in the HAART group and 60 days in the control group (P<0.001, log-rank test). In the HAART group, the neurological deficits improved substantially in six patients and stabilized in six patients. Eleven patients underwent follow-up cranial computed tomography or magnetic resonance scan that showed improvement of PML lesions in 10 patients and stabilization in one patient. Follow-up CSF analysis showed clearance of JC virus in six out of seven patients who had an initial positive result. CONCLUSIONS: This study shows that HAART may increase the survival, clinical status and radiological features of AIDS patients with PML. Clearance of JC virus from CSF has been found, suggesting that immune reconstitution can interrupt the JC virus lytic cycle.


Subject(s)
AIDS-Related Opportunistic Infections/drug therapy , Anti-HIV Agents/therapeutic use , Leukoencephalopathy, Progressive Multifocal/drug therapy , AIDS-Related Opportunistic Infections/diagnosis , AIDS-Related Opportunistic Infections/mortality , Adult , Drug Therapy, Combination , Female , Humans , Leukoencephalopathy, Progressive Multifocal/diagnosis , Leukoencephalopathy, Progressive Multifocal/mortality , Magnetic Resonance Imaging , Male , Middle Aged , Radiography , Skull/diagnostic imaging , Treatment Outcome
8.
Enferm Infecc Microbiol Clin ; 8(9): 560-4, 1990 Nov.
Article in Spanish | MEDLINE | ID: mdl-2099857

ABSTRACT

We have evaluated the efficacy of fluconazole, 50 mg/day for 2 weeks, to treat oropharyngeal candidiasis in immunologically compromised patients. There were overall 27 patients, 25 of which were HIV+ and 2 had neutropenia. The rate of clinical response at the end of therapy, and one week and one month afterwards were 96%, 76% and 64%, respectively. The microbiological eradication was achieved in 36% of patients. The tolerance of the drug was satisfactory, although in 3 cases features of hepatic toxicity were detected. The convenience, good tolerance and clinical efficacy of fluconazole make it the therapy of choice for oropharyngeal candidiasis in immunologically compromised patients.


Subject(s)
Candidiasis, Oral/drug therapy , Fluconazole/therapeutic use , Immunologic Deficiency Syndromes/complications , Adult , Candidiasis, Oral/complications , Female , Fluconazole/adverse effects , HIV Infections/complications , Humans , Male , Middle Aged , Neutropenia/complications , Prospective Studies
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