Rapid progression to liver cirrhosis of toxic hepatitis due to ebrotidine.
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Adult↗
Biomedical subjects
E Lissen
Publications and source records attributed to E Lissen.
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↗
Multiple dideoxynucleoside analogue-resistant (MddNR) HIV-1 strains isolated from patients from different European countries.
OBJECTIVE: To study the prevalence of multiple dideoxynucleoside (ddN)-resistant (MddNR) HIV-1 in European patients under treatment with multiple ddN analogues, and to characterize MddNR strains genotypically and phenotypically. DESIGN AND METHODS: Blood samples from patients after > or = 6 months of treatment with multiple ddN were screened for the MddNR mutation Q151M. After confirmation of MddNR in 15 patients from five European countries, genotypic resistance was evaluated by DNA sequencing of the reverse transcriptase (RT) gene. Phenotypic resistance was measured by the recombinant virus assay. Results were compared with the clinical evolution of the patients. RESULTS: The prevalence of MddNR strains in European patients treated with multiple ddN analogues was 3.5%. Viruses typically contained amino acid substitutions V75F, F77L, F116Y and Q151M in the RT gene. A new mutation, S68G, was frequently associated with MddNR. Phenotypically, viruses displayed high-level resistance to zidovudine (ZDV), didanosine (ddl), zalcitabine (ddC), stavudine (d4T) and partial resistance to lamivudine (3TC) once multiple mutations were present. Under in-vivo treatment pressure, some MddNR strains additionally developed resistance to protease inhibitors or non-nucleoside RT inhibitors (NNRTI). Clinically, most patients had advanced HIV disease with low CD4 cell counts, high viral loads and a rapid progression, but two patients harbouring MddNR virus responded well to dual protease inhibitor associations. CONCLUSIONS: MddNR resistant HIV-1 can be found in European patients. MddNR is characterized by a specific set of drug resistance mutations, cross-resistance to most ddN analogues and a fast clinical progression. MddNR can be associated with protease inhibitor or NNRTI resistance.
Amino Acid Sequence↗
Tumor necrosis factor beta and soluble APO-1/Fas independently predict progression to AIDS in HIV-seropositive patients.
The relationship between serum concentration of different components of the nerve growth factor/tumor necrosis factor (TNF) receptor family, including soluble APO-1/Fas (sAPO-1/Fas) and progression of HIV infection, was analyzed in a case-control study of individuals selected from a cohort of HIV-seropositive patients who were progressing or not progressing to AIDS while being treated with nucleoside analogs. HIV-seronegative healthy controls were also analyzed. The results showed that, despite close matching for immunologic (CD4 cell count, beta2-microglobulin concentration) and virologic (p24 antigen, detection of HIV syncytium-inducing phenotype, plasma HIV viremia) parameters, the baseline serum concentrations of TNF-beta and sAPO-1/Fas were statistically different between progressing and nonprogressing patients. In addition, serum concentrations of TNF-beta and sAPO-1/Fas showed the strongest independent predictive power for progression to AIDS in a multivariate conditional logistic regression model. Because TNF-beta and Fas were suggested to be mediators of antigen-induced cell death (AICD) in HIV infection and sAPO-1/Fas was hypothesized to protect lymphocyte against AICD, these data suggest an important pathogenetic role for AICD in the progression of HIV infection.
Acquired Immunodeficiency Syndrome↗
[Antiretroviral treatment with nucleoside analogs does not decrease the viremia of the hepatitis C virus in patients with HIV-1 infection].
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Anti-HIV Agents↗
Short-term evolution of HIV-1 viraemia and CD4+ cell counts in patients who have a primary mutation to zidovudine.
OBJECTIVE: To investigate the different responses to antiretroviral treatment including zidovudine, of patients harbouring HIV with primary resistance to zidovudine, serum viral load, and CD4+ cell counts, for 24 weeks in a group of antiretroviral-naive patients with the codon 215 mutation of the HIV pol gene and in a control group at the start of treatment. DESIGN: A case-control retrospective study (1989-1996). METHOD: Nineteen out of 210 patients previously studied harboured the codon 215 mutation, had a self-reported compliance with treatment, a minimum follow-up of 24 weeks, and were treated with zidovudine alone or in combination with other nucleoside analogues. These patients were matched with 19 patients with wild-type strains at entry by initial CD4+ cell counts, clinical status, and antiretroviral treatment. RESULTS: During the first 12 weeks, CD4+ cell counts increased (76+/-26 and 64+/-26 x 10(6)/l in wild-type and mutant virus-infected groups, respectively), decreasing slightly until week 24, although no significant differences were found between the two groups studied. Serum viral load decreased in both groups (change in serum viral load of 0.80+/-0.11 log10 and 0.87+/-0.26 log10 copies/ml, wild-type and mutant virus-infected, respectively), although no significant differences were found between groups. CONCLUSION: No significant differences were found between patients with the primary mutation to zidovudine and control patients harbouring wild-type virus in terms of short-term response measured by serum viral load and CD4+ cell counts.
Adult↗
[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↗
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↗
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↗
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↗
Regression of invasive AIDS-related Kaposi's sarcoma following antiretroviral therapy.
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Acquired Immunodeficiency Syndrome↗
Low sensitivity of peripheral blood smear for diagnosis of subclinical visceral leishmaniasis in human immunodeficiency virus type 1-infected patients.
The peripheral blood smear is an easy method for the diagnosis of symptomatic visceral leishmaniasis (VL) in human immunodeficiency virus type 1 (HIV-1)-infected patients. However, its efficiency in diagnosing subclinical VL remains unknown. In this study, Leishmania amastigotes were seen in blood smears from 1 of 13 HIV-1-positive individuals with subclinical VL. This shows that this procedure is not suitable for subclinical-VL diagnosis.
AIDS-Related Opportunistic Infections↗
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↗
The role of serology in the diagnosis and prognosis of visceral leishmaniasis in patients coinfected with human immunodeficiency virus type-1.
To define the possible role of serology in the diagnosis and prognosis of visceral leishmaniasis (VL) in patients with human immunodeficiency virus type-1 (HIV-1) infection, the dynamics of humoral immune responses was investigated in 20 coinfected patients. Sequential sera obtained before, during, and after VL diagnosis were analyzed by an indirect immunofluorescent antibody test (IFAT), a recombinant ELISA (using the rK39 protein), and immunoblotting. During the active course of the disease, positive results were found by IFAT or ELISA in 22% of the cases and by immunoblotting in 78% of the cases. A great variability in the response was observed during the follow-up with a trend to more positive results near the time of VL diagnosis. Forty-six percent of the patients were positive by IFAT or ELISA on at least one time point before VL and 37.5% were positive during the period following treatment. These results confirm the limited usefulness of the IFAT and ELISA in the diagnosis of VL in coinfected patients and demonstrate their low ability to predict the development or the outcome of disease. In these patients, immunoblotting could be a useful tool for studying the natural course of leishmaniasis, although it has limited value for diagnosis or treatment control.
Acute Disease↗
Increase in the frequency of mutation at codon 215 associated with zidovudine resistance in HIV-1-infected antiviral-naive patients from 1989 to 1996.
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Anti-HIV Agents↗
Is hepatitis G virus transmitted sexually?
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Flaviviridae↗
Significance of indeterminate reactivity to human T-cell lymphotropic virus in western blot analysis of individuals at risk.
Current tests to confirm human T-cell lymphotropic virus (HTLV) infection in individuals at risk of retroviral infection commonly yield indeterminate results. To assess the significance of HTLV-seroindeterminate reactivities in a high-risk population, 16 at-risk individuals who had this serologic pattern by Western blot were studied using a polymerase chain reaction (PCR) assay. Human T-cell lymphotropic virus type II infection was confirmed by the presence of virus-specific nucleic acid in four patients. However, PCR analysis was negative in the remaining 12 individuals. These results indicate strongly that all specimens from at-risk individuals with nondiagnostic HTLV reactivity by current Western blot assay should continue to be considered inconclusive, requiring further testing by more sensitive tests.
Antibodies, Viral↗
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↗