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Biomedical subjects

A Sánchez-Quijano

Publications and source records attributed to A Sánchez-Quijano.

At least 19 recordsLinked to original sources
PubMed2004

Analysis of quasispecies in the viral 5' untranslated region of hepatitis C virus to evaluate ribavirin mutagenic effect in patients receiving ribavirin and interferon-alfa.

In the study presented here the ribavirin mutagenic effect was investigated by analyzing quasispecies in the viral 5' untranslated region of hepatitis C virus in six patients with chronic infection who started interpheron-alpha and ribavirin therapy. A remarkable mutation rate during treatment was found in only one individual. This patient had a sustained response and harbored a type 3a virus strain. The different mutated clones in this patient demonstrated no apparent close relationship that could suggest lack of selection pressure by ribavirin. The mutations were located within the loops of subdomains IIIb and IIId of the internal ribosomal entry site. This is an interesting initial finding that needs to be substantiated in a larger trial.

5' Untranslated Regions↗
PubMed2002

Changes in thymus volume in adult HIV-infected patients under HAART: correlation with the T-cell repopulation.

An important thymus role has been suggested in T-cell repopulation after HAART in adult HIV-1 infected patients. Thymus volume increase after treatment has been described in HIV-1 infected children but not in adult patients. The objective of this work was to evaluate the effect of HAART on the thymic volume of adult HIV-1 infected patients and its relation with the T-cell repopulation. Twenty-one adult patients following 24 weeks under HAART were included in the study. All patients underwent a thoracic computed tomography (CT) evaluation for the measurement of thymic volumes at weeks 0, 12 and 24. Baseline thymus volume showed a significant correlation with the patient's age. Thymic volume significantly increased after 24 weeks of HAART. Besides, a significant correlation between changes in the thymus volume and changes in both total and naïve CD4+ cell counts was found. Only patients with increases > or =100 CD4+ cell counts after treatment significantly increased the thymic volume. These data show the first evidence of an early change in thymic volume of adult HIV-1 infected patients under HAART. This increase was related to the rise of both total and naïve CD4+ cell counts suggesting a functional role of thymic volume increase.

Adult↗
PubMed2001

Influence of highly active antiretroviral therapy on the outcome of subclinical visceral leishmaniasis in human immunodeficiency virus-infected patients.

Seventeen human immunodeficiency virus-infected patients who were harboring untreated subclinical visceral leishmaniasis (VL) were prospectively followed up. None of the 11 patients who received highly active antiretroviral therapy (HAART) presented with symptomatic VL during follow-up, whereas 2 out of 6 patients who received therapy other than HAART had an episode of overt kala-azar. These findings suggest that HAART does not induce the evolution of latent VL into symptomatic disease.

AIDS-Related Opportunistic Infections↗
PubMed2001

HIV-1 plasma viremia not increased in patients receiving highly active antiretroviral therapy after influenza vaccination.

The effect of vaccinating patients with sustained undetectable HIV-1 viremia (VL) achieved with highly active antiretroviral therapy was prospectively investigated. During the 1998 influenza immunization period, 39 HIV-1-infected patients who showed a VL<20 copies/ml for at least 6 months before the study entry date were vaccinated for influenza. Twenty-two vaccinees were immunized at entry. Seventeen controls were followed for 4 weeks after entry, crossing over then to the vaccination group. The proportion of patients with undetectable VL was not significantly different between the vaccination and control groups 2 and 4 weeks after entry. Therefore, influenza immunization of patients with undetectable viremia achieved with highly active antiretroviral therapy does not seem to affect VL.

Adult↗
PubMed2001

Minimal liver injury in chronic hepatitis C virus infection is associated with low levels of soluble TNF-alpha/Fas receptors and acquisition in childhood.

BACKGROUND/AIMS: The rate of progression to cirrhosis of chronic hepatitis C might be related to an upregulation of TNF-alpha/Fas pathways. METHODS: The serum levels of soluble TNF-alpha type II receptor (sTNFr-II) and soluble Fas antigen (sFas) were analyzed in patients with different histological outcomes of chronic parenterally acquired HCV infection of similar duration. RESULTS: One hundred and forty-five HCV-infected patients had a known duration of infection. Twelve (8.3%) patients had minimal changes and were assigned to the case group. The control group was selected from the 24 (17%) patients with cirrhosis and the 54 (37%) with chronic active hepatitis (CAH). Two controls, one with CAH and one with cirrhosis, were paired with the cases following these criteria: duration of infection, transmission route and sex. The proportions of genotype 1b and HCV RNA serum levels were similar among the groups. The median serum levels of sTNFr-II and sFas were significantly lower in the case group than in the control groups. The cases were significantly younger when they became infected than the control groups. Indeed, most cases were infected within the first 10 years of life. sTNFr-II and age at infection were independently associated with the minimal injury case group. When sTNFr-II was excluded from the logistic regression model, sFas and age at infection were independently associated with the case group. CONCLUSION: The rate of progression of parenterally acquired chronic hepatitis C to end-stage liver disease might be related to an upregulation of the TNF-alpha/Fas pathways and an age-dependent host response.

Adolescent↗
PubMed2001

Low levels of HIV-1 plasma viral load in patients infected with HIV-1 subtype b and advanced immunosuppression.

OBJECTIVES: Some HIV-1 infected patients show low levels of viraemia despite having advanced immunosuppression. Cases with falsely undetectable viraemia by conventional PCR have been reported when patients were infected with non-B subtypes. The aim of this study was to investigate whether this immunovirological discordance can be due to the presence of HIV-1 non-B subtypes, and whether a modified PCR procedure can yield different HIV viraemia values in these cases. METHODS: Fifteen HIV-infected patients either naive for antiretroviral drugs or under treatment, with HIV plasma viraemia below 1000 copies/mm(3)and CD4+ cell counts lesser than 500 or 300 cells/mm(3), respectively, were included. Serotyping, genotyping and HIV plasmatic viraemia determinations were performed in all individuals. RESULTS: In five out of six treatment-naive patients the virus was categorized as non-B subtype by serotyping, although only one case was confirmed by genotyping as HIV-2. Eight out of nine patients under antiretroviral therapy were subtype B carriers by serotyping and confirmed by genotyping. The remaining patient was determined as a subtype A carrier by both procedures. A modified PCR procedure (Amplicor HIV Monitor Test version 1.5) did not yield higher viral load levels than the former version. CONCLUSIONS: The presence of HIV-1 subtypes non-B can explain a minority of cases of this immunovirological discordance, but in most of them the reason is still unknown. Likewise, a PCR procedure adapted for detecting HIV-1 non-B subtypes fails to find higher plasma viraemia in patients with such a discordance.

Adult↗
PubMed1999

Reduction of immune system activation in HIV-1-infected patients undergoing highly active antiretroviral therapy.

The aim of this work was to analyze the effects of highly active antiretroviral therapy on the chronically activated immune system of 26 antiretroviral-naive HIV-1-infected patients. Samples from baseline to week 24 or 36 of treatment were tested for serum levels of beta2-microglobulin, tumor necrosis factor alpha and soluble tumor necrosis factor alpha receptor type II, as well as for human leukocyte antigen-DR expression on T cells. After starting therapy, the mean HIV-1 RNA serum levels decreased and the mean CD4 + cell counts increased from baseline to week 36 (P< 0.001). Mean levels of tumor necrosis factor alpha receptor type II, tumor necrosis factor alpha and beta2-microglobulin as well as expression of human leukocyte antigen-DR were significantly reduced at the end of follow-up (P<0.01). Deactivation kinetics of these parameters was similar in patients with CD4+ counts>200 cells/microl at baseline versus those with CD4 + counts < 200 cells/microl at baseline, despite higher activation at baseline in the group with <200 cells/microl. In summary, this study shows that highly active antiretroviral therapy is able to induce a strong deactivation of the immune system of HIV-1-infected patients.

Acquired Immunodeficiency Syndrome↗
PubMed1999

High frequency of serious side effects from meglumine antimoniate given without an upper limit dose for the treatment of visceral leishmaniasis in human immunodeficiency virus type-1-infected patients.

Organic pentavalent antimonials are one of the mainstays of treatment for visceral leishmaniasis (VL). Few data are available on the toxicity and efficacy of these drugs at the dosing schedule recommended by the Centers for Disease Control and Prevention (CDC) (Atlanta, GA). We analyzed 25 VL episodes in human immunodeficiency virus (HIV)-infected patients who were treated with meglumine antimoniate (MA) at the CDC-recommended dose in southern Spain. Adverse effects were observed in 14 (56%) VL episodes. In 7 (28%), treatment with MA was permanently discontinued due to serious adverse effects that included acute pancreatitis, acute renal failure, and leukopenia. Three (12%) patients died during therapy due to severe acute pancreatitis attributable to MA. The dosing regimen of MA currently recommended for treating VL is associated with a high rate of serious side effects in HIV-1-infected patients.

Adult↗
PubMed1998

[Impact of medical approach on the presentation form of AIDS defined by clinical episodes].

BACKGROUND: In recent years there has been a change in the opportunistic diseases incidence in HIV-infected patients. The change could be related to the use antiviral therapy and chemoprophylaxis strategies. The aim of the present study was to evaluate if medical intervention is able to modificate the clinical presentation of AIDS and the CD4+ lymphocyte counts at time of AIDS diagnosis. PATIENTS AND METHODS: The first AIDS-defining condition and the CD4+ count at time of AIDS diagnosis were analyzed in 95 HIV-infected patients who developed an AIDS-defining disease since April 1989 until March 1996, retrospectively reviewed. Patients who had been previously followed at an AIDS Unit were compared with those who had not. RESULTS: The frequency of Pneumocystis carinii pneumonia as the first AIDS-defining condition was lower in medically followed patients. Among this group, AIDS cases who received chemoprophylaxis with isoniazide showed a decrease in the rate of tuberculosis. No differences were found in CD4+ lymphocyte counts between both groups. CONCLUSIONS: As a result of medical intervention significant changes have occurred in the spectrum of initial AIDS-defining conditions in relation to medical intervention; a decrease in the frequency of Pneumocystis carinii pneumonia and tuberculosis have been found; however, the CD4+ lymphocyte counts at time of AIDS diagnosis are not modificated by medical intervention.

AIDS-Related Opportunistic Infections↗
PubMed1998

Influence of hepatitis C virus infection on the mortality of antiretroviral-treated patients with HIV disease.

The aims of this study were to analyze the mortality directly attributable to chronic viral hepatitis in HIV-1 infected patients and to investigate the influence of hepatitis virus infections on the survival of this population. A cohort of 328 HIV-1 infected, antiretroviral-treated patients, followed up from 1989 to 1996, was investigated in the study. The median follow-up period of the cohort was 120 weeks. The median baseline CD4 + cell count of the cohort was 303 cells/mm3. Hepatitis C virus, hepatitis B virus and hepatitis D virus infections were present in 214 (65%), 16 (4.9%) and 9 (2.7%) patients, respectively. Sixty-seven (20.4%) subjects died but there was no information on the vital status of 36 patients (11%). The causes of mortality were AIDS in 49 (73%), liver failure in 3 (4.5%) and other causes in 15 (22.4%). The cohort was divided into two groups for survival analysis, the groups consisting of persons infected by a hepatitis virus and persons without hepatitis virus infection. There was no difference in survival between the two groups (p = 0.31, log-rank). It is concluded that mortality among HIV-1/hepatitis virus coinfected patients with moderate to severe immunosuppression is mostly due to AIDS, and that the survival of these subjects is not influenced by the presence of hepatitis virus infections, particularly hepatitis C virus.

Adult↗
PubMed1998

Dynamics of serum cytokines in patients with visceral leishmaniasis and HIV-1 co-infection.

Serum cytokine levels and peripheral T cell subpopulations of HIV-1-infected patients before, during and after active visceral leishmaniasis (VL) were analysed and compared with appropriate controls. At VL diagnosis, co-infected patients showed higher serum levels of interferon-gamma (IFN-gamma) than matched HIV-1 controls without VL, and lower serum concentrations of IL-10 than non-immunocompromised VL controls. High levels of tumour necrosis factor-alpha (TNF-alpha) and IFN-gamma were present in the sera of HIV-1-infected patients with active VL. TNF-alpha remained elevated after VL recovery. A steady decline in the CD4+ cell count, an increase of serum HIV viraemia and a progressive seroconversion for the HIV-1 p24 antigen was observed during the course of VL disease. Thus, an aberrant activation of the TNF system with possible negative immunological and virological consequences is present in HIV-1-infected patients with VL. A more extensive prospective validation of these findings in a bigger cohort of patients will nevertheless be necessary. The results support the hypothesis that different opportunistic infection agents may trigger the production of proinflammatory cytokines during immunodeficiency, and in this way accelerate the course of HIV-1 disease.

AIDS-Related Opportunistic Infections↗
PubMed1998

Evidence for a role of T-helper type 2 cytokines in the acquisition of human immunodeficiency virus syncytium-inducing phenotype.

BACKGROUND: The objective of the present study was to investigate the relationship between the serum cytokine pattern of T-helper (Th) response and the acquisition of syncytium-inducing (SI) human immunodeficiency virus type 1 (HIV-1) variants in HIV-1-seropositive patients treated with antiretroviral drugs. METHODS: Serum cytokines of Th1/Th2 responses were analysed in a case-control study of 20 individuals selected from a cohort of HIV-1-infected patients without SI variants at entry, who developed or did not develop SI virus during a prospective follow-up. A group of 10 patients with SI variants at study entry was also evaluated. Serum concentration of interferon (IFN) gamma, interleukin (IL) 2, IL-4 and IL-10 was evaluated by mean of a commercial enzyme immunoassay. RESULTS: Despite close matching for immunological (CD4+ cell count) and virological (p24 antigen, serum HIV viraemia) parameters, SI-converting patients showed at baseline significantly lower serum levels of IL-2 and higher concentrations of IL-4 than those who remained persistently negative for SI variants. Shortly after the phenotype conversion, SI-converting patients were characterized by significantly high serum concentration of IL-4 and by low levels of IFN-gamma (Th2-like pattern). Patients with SI phenotype at study entry featured lower mean levels of both IL-4 and IL-10, but mean IFN-gamma and IL-2 values were higher, although the clinical and immunological baseline was also poorer and no statistical analysis could be applied. CONCLUSION: Serum cytokine pattern of Th1/Th2 response differs between patients with NSI and SI phenotype. Our data strongly suggest that the Th2 cytokine pattern could be associated with the acquisition of the SI HIV-1 phenotype.

Case-Control Studies↗
PubMed1998

Prevalence of and factors associated with visceral leishmaniasis in human immunodeficiency virus type 1-infected patients in southern Spain.

The actual prevalence of visceral leishmaniasis among human immunodeficiency type 1 (HIV-1)-infected patients in the Mediterranean basin remains unknown. There is also controversy about the risk factors for Leishmania infantum and HIV-1 coinfection. To appraise the prevalence of visceral leishmaniasis in patients infected with HIV-1 in southern Spain and to identify factors associated with this disease, 291 HIV-1 carriers underwent a bone marrow aspiration, regardless of their symptoms. Giemsa-stained samples were searched for Leishmania amastigotes. Thirty-two (11%) patients showed visceral leishmaniasis. Thirteen (41%) patients had subclinical cases of infection. Centers for Disease Control and Prevention (CDC) clinical category C was the factor most strongly associated with this disease (adjusted odds ratio [OR], 1.88 [95% confidence interval, 1.22 to 2.88]), but patients with subclinical cases of infection were found in all CDC categories. Female sex was negatively associated with visceral leishmaniasis (adjusted OR, 0.42 [95% confidence interval, 0.18 to 0.97]). Intravenous drug users showed a higher prevalence than the remaining patients (13.3 versus 4.9%; P = 0.04), but such an association was not independent. These results show that visceral leishmaniasis is a very prevalent disease among HIV-1-infected patients in southern Spain, with a high proportion of cases being subclinical. Like other opportunistic infections, subclinical visceral leishmaniasis can be found at any stage of HIV-1 infection, but symptomatic cases of infection appear mainly when a deep immunosuppression is present. There is also an association of this disease with male sex and intravenous drug use.

AIDS-Related Opportunistic Infections↗
PubMed1997

Human immunodeficiency virus infection modifies the natural history of chronic parenterally-acquired hepatitis C with an unusually rapid progression to cirrhosis.

BACKGROUND/AIMS: To investigate the possible role of HIV infection in the natural history of chronic parenterally-acquired hepatitis C. METHODS: A multicenter cross-sectional study was performed in 547 patients with chronic parenterally-acquired hepatitis C with or without HIV infection (116 HIV-positive and 431 HIV-negative). Approximate duration of HCV infection was estimated in all patients included, and histologic diagnoses made at different time intervals following HCV infection were analyzed in both groups. Factors related to serum HCV-RNA levels were also investigated. RESULTS: Histologic findings were similar in liver biopsies from both HIV-infected and noninfected patients. However, in the first 10 years, 13 out of 87 (14.9%) HIV-positive subjects developed cirrhosis, in comparison with 7 out of 272 (2.6%) in the HIV-negative group (p < 0.01). Similar results were found in the first 5 and 15 years, respectively, and most of the HIV-negative patients with cirrhosis (42 out of 56) developed cirrhosis in a time interval longer than 15 years. Consequently, mean interval from estimated time of HCV infection to cirrhosis was significantly longer in HIV-negative than HIV-positive patients (23.2 vs. 6.9 years; p < 0.001). Chronic active hepatitis (with and without cirrhosis) and long duration of HCV infection were significantly associated with higher HCV load (p < 0.05). Finally, HIV-positive patients with CD4+ cell counts > 500 cells/ml showed a lower HCV load than those with < 500 cells/ml (p < 0.05). CONCLUSIONS: HIV infection modifies the natural history of chronic parenterally-acquired hepatitis C with an unusually rapid progression to cirrhosis. HIV-related immunodeficiency may be a determinant of higher hepatitis C viremia levels and more severe liver damage.

Adult↗
PubMed1997

Unexpected high prevalence of hepatitis C virus genotype 4 in Southern Spain.

BACKGROUND/AIMS: A unusually high rate of HCV-infected individuals in whom the HCV genotype cannot be ascertained by means of single PCR and LIPA procedures has recently been reported in our area. The aim of the present study was to investigate the epidemiological, clinical and molecular characteristics of these patients. METHODS: Cross-sectional study. Eighty anti-HCV-positive patients with chronic liver disease, 45 (56.25%) of them intravenous drug users, were included. HCV genotyping was carried out in all patients using commercial single PCR and LIPA procedures. Samples where no HCV RNA amplification and/or indeterminate HCV genotype were found were also tested by means of a nested PCR. HCV viral load was measured in all patients. RESULTS: HCV genotyping was not achieved in 23 (28.75%) individuals. No amplification of HCV RNA was found in 19 of them, and in four other cases the LIPA procedure did not allow identification of a distinct HCV genotype. After the use of nested PCR+LIPA, it was found that the HCV genotype 4 was found in 11 of those 23 individuals (47.82%). Ten of these 11 HCV genotype 4-harboring individuals were intravenous drug users. The HCV viral load was lower in HCV genotype 4-harboring individuals than in those whom the genotypes 1, 2 or 3 were found (p<0.001). CONCLUSIONS: A high rate of HCV genotype 4-harboring cases has been found among HCV-infected individuals in Southern Spain. Had only single PCR been used, these individuals could have been wrongly regarded as non-viremic.

Chronic Disease↗
PubMed1997

Viraemia and p24 antigenaemia are independent risk factors for the emergency of a zidovudine-resistant genotype in nucleoside analogue-treated HIV-1 infection.

We aimed to determine, in an observational retrospective study, whether baseline HTV-1 RNA is an independent predictive factor for the emergence of a genotype associated with zidovudine resistance and whether previously identified predictive factors remain independent when viraemia is taken into account. Fifty nucleoside-naive HIV-1-infected individuals initiating zidovudine therapy (in 11 cases associated with didanosine) were submitted to clinical, immunological and virological monitoring at entry and every 12 weeks thereafter. The critical endpoint of the study was the influence of key baseline characteristics (CD4 cell counts, clinical stage, HIV-1 p24 antigen, virus phenotype and viraemia) upon the time to development of mutation at codon 215. The presence of serum p24 antigen, syncytium-inducing (S1) phenotype, a HIV-1 RNA load greater than the median (32495 RNA copies/ml), CD4 cell counts lower than 200/mm3 and clinical CDC category C were all baseline features associated with more rapid development of the mutant RT215 genotype in the univariate analysis. However, a multivariate Cox proportional hazard stepwise regression analysis showed that only baseline p24 antigenaemia, SI phenotype and a HIV-1 RNA load greater than 32495 RNA copies/ml were sequentially selected as independent predictive factors for the development of the mutant genotype. The present study suggests that baseline HIV-1 RNA load is an independent predictive factor for the development of a zidovudine resistance genotype. Likewise, it reinforces the independent predictive value of serum p24 antigenaemia and SI phenotype, even when viraemia is taken into account.

Acquired Immunodeficiency Syndrome↗