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Biomedical subjects

M Leal

Publications and source records attributed to M Leal.

At least 19 recordsLinked to original sources
PubMed2006

Influence of hepatitis C and hepatitis G virus co-infection on viral and cellular dynamics in patients infected with human immunodeficiency virus following interruption of highly active anti-retroviral therapy.

This study describes the influence of hepatitis C virus (HCV) and hepatitis G virus (HGV) co-infection on CD4 cell count decline and plasma human immunodeficiency virus (HIV) viral load in HIV-infected patients during a 1-year period following interruption of highly active anti-retroviral therapy (HAART) guided by CD4 count. CD4 cell count decline and plasma HIV viral load did not differ between HIV mono-infected patients and those patients co-infected with HCV and HGV. HCV genotype 1 had no apparent influence on the cellular and viral dynamics in HIV-infected patients compared with other HCV genotypes, although the unbalanced groups make larger studies desirable.

Adult↗
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↗
PubMed2004

Consensus conference on chronic viral hepatitis and HIV infection: updated Spanish recommendations.

Chronic hepatitis B and C represent a leading cause of morbidity and mortality among human immunodeficiency virus (HIV)-infected patients worldwide. New treatment options against both hepatitis B (HBV) and C (HCV) viruses have prompted us to update previous recommendations for the management of coinfected individuals. Fifteen topics (nine related to HCV, five to HBV and one to both viruses) were selected for this purpose. A panel of Spanish experts in the field was invited to review these areas and propose specific recommendations, which were scored according to the Infectious Disease Society of America (IDSA) grading system. These guidelines represent a comprehensive and updated overview on the management of hepatitis B and C in HIV-infected patients.

Anti-HIV Agents↗
PubMed2004

Thymic volume is associated independently with the magnitude of short- and long-term repopulation of CD4+ T cells in HIV-infected adults after highly active antiretroviral therapy (HAART).

Age is one of the main factors involved in the rapidity and the magnitude of CD4(+) T cell repopulation in human immunodeficiency virus (HIV)-infected patients on highly active antiretroviral treatment (HAART). Improved thymic function has been suggested as the main factor associated with CD4(+) T cell restoration after HAART. This work was undertaken to determine, among host factors, the predictor variable at baseline involved in the magnitude of short- and long-term recovery of CD4(+) T cells after HAART. HIV-RNA levels and CD4(+) T cell numbers were determined in 54 HIV-infected adults at baseline and at weeks 4, 12, 48 and 96 after HAART. T cell subpopulations were determined by flow cytometry, thymic volume by computed tomography, T cell receptor excision circle (TREC)-bearing cells by quantitative polymerase chian reaction (PCR) and interleukin (IL)-7 levels by enzyme linked immunosorbent assay at baseline. The phenotype of patients' isolates was determined by infecting GHOST cells expressing CCR5 and CXCR4. The possible interference of phenotype with thymic function was also analysed. Baseline thymic volume was associated independently with the magnitude of short- and long-term recovery of CD4(+) T cells after HAART, despite the patients' viral phenotype. The measurement of thymic volume before therapy may predict the magnitude of T cell increase. This result could have important clinical implications not only in HIV-infected patients, but also in other scenarios of T cell depletion such as bone marrow transplantation and chemotherapy.

Adult↗
PubMed2003

Intraspecific variation in retinal cone distribution in the bluefin killifish, Lucania goodei.

Studies of visual ecology have typically focused on differences among species while paying less attention to variation among populations and/or individuals. Here, we show that the relative abundance of UV, violet, yellow, and red cones varies between two populations of bluefin killifish, Lucania goodei. Animals from a spring population (high-transmission UV/blue light) have a higher frequency of UV and violet cones and a lower frequency of yellow and red cones than animals from a swamp population (low-transmission UV/blue light). Visual sensitivity does not vary significantly between the populations, but spring animals tend to be more sensitive in the UV/blue wavelengths (360-440 nm) and less sensitive in longer wavelengths (560-600 nm) than swamp animals. The results have two important implications. First, the tight conservation of functional regions of opsin genes across taxa does not imply that visual systems are constrained in their evolution; differential sensitivity can arise through differential expression of cone classes within the retina. Second, intraspecific visual signals in this species may evolve to maximize contrast between the signaler and the background (as opposed to brightness); males with blue anal fins are most abundant in swamp habitats where animals express fewer UV and violet cones.

Dose-Response Relationship, Radiation↗
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

Structural normalization of the lymphoid tissue in asymptomatic HIV-infected patients after 48 weeks of potent antiretroviral therapy.

BACKGROUND: The hallmark of HIV infection is the involution and destruction of lymphoid tissue. However, very little information exists on the effect of highly active antiretroviral therapy (HAART) on lymphoid tissue structure. OBJECTIVE: To evaluate the effect of a HAART regimen after 48 weeks on the architecture and cell regeneration of tonsil lymphoid tissue in HIV-infected patients with CD4 T cell counts > or = 500/microl. METHODS: From June 1997 to February 1998 all asymptomatic HIV-infected patients with CD4 T cell counts > or = 500/microl seen at our unit were offered quadruple antiretroviral therapy. Tonsil biopsies were obtained at baseline and at 48 weeks. Tonsil tissue sections were examined to evaluate structural and immunohistochemical changes by two blinded and independent pathologists. Cell numbers were counted for selected markers in T-dependent zones. RESULTS: Eleven patients were evaluable, six were excluded because of insufficient or inadequate sampling in at least one of the biopsies. Cellular depletion, plasma cell accumulation and prominent vessels were observed in all cases; three excluded patients with evaluable baseline biopsies showed similar tissue lesions. Follow-up biopsies demonstrated some degree of improvement in all patients. Germinal centres appeared in seven cases that were not seen at baseline. CD4 cell counts increased and CD8 cell counts decreased significantly in lymphoid tissue. An increase in CD45RA+ cells was observed; however, the proportion of CD45+Ki67+ cells did not differ between baseline and 48 weeks. CONCLUSION: This study shows an unexpected range of moderate to severe lymphoid tissue lesions in mildly immunosuppressed HIV-infected patients, which was partly restored after 48 weeks of HAART.

Adult↗
PubMed2001

Changes in the rate of genotypic resistance to antiretroviral drugs in Spain.

Genotypic resistance to antiretroviral drugs was examined in 684 individuals attending 18 outpatient clinics distributed across Spain in June 2000. Compared with similar surveys conducted before 1998, the prevalence of resistance to nucleosides has declined significantly among naive chronic HIV carriers. In contrast, resistance among pre-treated patients has increased; resistance to all three drug families having been recognized in nearly a quarter of patients.

Anti-HIV Agents↗
PubMed2001

Drug resistance in patients experiencing early virological failure under a triple combination including indinavir.

OBJECTIVE: To assess the pattern of drug resistance mutations selected in HIV-1-infected patients failing a first line triple combination therapy including indinavir. PATIENTS AND METHODS: Plasma samples from 87 patients collected at the time of the first virological rebound (> 50 HIV-RNA copies/ml) were examined for the presence of drug-resistant genotypes. RESULTS: The mean level of plasma viraemia at rebound was 7824 HIV-1 RNA copies/ml in 73 subjects with good compliance, whereas it was 359,460 HIV-1 RNA copies/ml in 14 patients who admitted to poor adherence. Genetic sequence analysis yielded results for 51 (70%) of the patients having good adherence. More than half of them (26/51, 51%) carried primary mutations associated with resistance to nucleoside analogues. In contrast, primary protease inhibitor resistance mutations were recognized less frequently (14/51, 27%; P < 0.05). Moreover, in 23 (45%) patients there was no evidence of drug-resistant viruses at all. The most frequent drug-resistant genotypes in the reverse transcriptase gene were at codons 184 (n = 19), 215 (n = 14) and 41 (n = 8), whereas for the protease they were at codons 46 (n = 10), 82 (n = 9) and 90 (n = 7). No resistance genotypes were found among non-compliant patients. CONCLUSION: The overall rate of drug-resistant HIV genotypes was 38% (28/73) in patients with good adherence and who were experiencing a first virological failure under a triple combination regimen including indinavir; resistance to nucleoside analogues was more frequent than resistance to indinavir. Therefore, treatment intensification in those patients without resistance, or a selective substitution of nucleosides in those with resistance limited to these compounds, might be justified.

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

Usefulness of route of transmission, absolute CD8+ T-cell counts, and levels of serum tumor necrosis factor alpha as predictors of survival of HIV-1-infected patients with very low CD4 + T-cell counts.

Potential cofactors of survival in HIV-1-infected patients with CD4+ T-cell counts of < or = 100 cells/microl were investigated. All 132 patients with CD4+ T-cell counts of < or = 100 cells/microl were selected from 416 patients included in an antiretroviral therapy cohort (1989-1999). Fifty of 54 deaths were due to AIDS. There were significant associations (P<0.05) between survival and CD8+ T-cell counts, clinical AIDS stage, risk group, and antiretroviral drug regimen after baseline, but only the use of protease inhibitors had an independent effect on survival (hazard ratio [HR], 0.096; 95% confidence interval [95%CI], 0.094-0.097). A substudy restricted to the cohort of 108 patients never exposed to PIs detected independent associations between survival and CD8+ T-cell counts (P=0.0016), experience with antiretroviral therapy before baseline (HR, 2.52; 95%CI, 1.31-4.82), sexual risk group for HIV infection (HR, 3.7; 95%CI, 1.92-7.12), and levels of serum tumor necrosis factor alpha (P=0.02). This study confirms that the use of PI-containing antiretroviral regimens strongly predicts survival of HIV-1-infected patients with very low CD4+ T-cell counts. When the study was restricted to patients never exposed to PIs, the parenteral route of disease transmission, high absolute CD8 + T-cell counts, and low serum levels of tumor necrosis factor alpha were independent predictors of survival in extremely advanced HIV-1 disease.

Acquired Immunodeficiency Syndrome↗
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↗
PubMed2001

Primary HIV-1 drug resistance in Spain before and after the introduction of protease inhibitors.

The prevalence of genotypic resistance to nucleoside analogues was examined in 150 naive individuals with chronic HIV-1 infection acquired before June 1996, when protease inhibitors began to be used in Spain, and in a group of 52 recent seroconverters infected since 1997. Overall, the prevalence of subjects carrying nucleoside-resistant genotypes was similar in both groups (12.6% and 15.4%, respectively). A polymorphism at codon 70 accounted for more than half of cases (63.1%) in naive individuals infected before protease inhibitors became available, in contrast most recent seroconverters carried genotypes with one or more key nucleoside resistance mutations, mainly associated with lack of sensitivity to zidovudine or lamivudine (prevalence 9.6% and 5.9%, respectively). When only key mutations were considered in each of the two periods, the prevalence of nucleoside-resistant genotypes was increased significantly among recent seroconverters (13.5% vs. 4.7%; P<0.05). The relatively high rate of resistance to nucleosides in Spain justifies the introduction of drug resistance testing in naive recent seroconverters before beginning antiretroviral therapy.

Anti-HIV Agents↗
PubMed2001

[Poikilodermis].

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Adult↗