Liposomal amphotericin B for a case of intractable cryptococcal meningoencephalitis and immune reconstitution syndrome

We examined the efficacy of liposomal amphotericin B (L-AMB) for intractable cryptococcal meningoencephalitis in a patient with acquired immunodeficiency syndrome (AIDS) and the presence of immune reconstitution syndrome (IRS) caused by the treatment. A 34-year-old patient presented with meningitis. Cryptococcal organisms were detected microscopically in the cerebrospinal fluid (CSF) with Indian ink staining, and were then cultured from the CSF. Initial treatment with amphotericin B and flucytosine (5-FC) or voriconazole and/or fluconazole failed to eradicate cryptococcal organisms from the CSF. Secondary treatment with L-AMB and 5-FC following seven months of antiretroviral therapy was successful. Simultaneously, treatment with L-AMB caused severe brain edema likely due to IRS. There were large differences in immune function improvement and liposomalization of the fungicide between the initial and secondary treatments. In conclusion, differences in immune status should be considered when administering L-AMB, in order to prevent IRS-related complications

Cellular HIV-1 DNA levels in patients receiving antiretroviral therapy strongly correlate with therapy initiation timing but not with therapy duration

<p>Abstract</p> <p>Background</p> <p>Viral reservoir size refers to cellular human immunodeficiency virus-1 (HIV-1) DNA levels in CD4⁺T lymphocytes of peripheral blood obtained from patients with plasma HIV-1-RNA levels (viral load, VL) maintained below the detection limit by antiretroviral therapy (ART). We measured HIV-1 DNA levels in CD4⁺lymphocytes in such patients to investigate their clinical significance.</p> <p>Methods</p> <p>CD4⁺T lymphocytes were isolated from the peripheral blood of 61 patients with a VL maintained at less than 50 copies/ml for at least 4 months by ART and total DNA was purified. HIV-1 DNA was quantified by nested PCR to calculate the copy number per 1 million CD4⁺lymphocytes (relative amount) and the copy number in 1 ml of blood (absolute amount). For statistical analysis, the Spearman rank or Wilcoxon signed-rank test was used, with a significance level of 5%.</p> <p>Results</p> <p>CD4 cell counts at the time of sampling negatively correlated with the relative amount of HIV-1 DNA (median = 33 copies/million CD4⁺lymphocytes; interquartile range [IQR] = 7-123 copies/million CD4⁺lymphocytes), but were not correlated with the absolute amounts (median = 17 copies/ml; IQR = 5-67 copies/ml). Both absolute and relative amounts of HIV-1 DNA were significantly lower in six patients in whom ART was initiated before positive seroconversion than in 55 patients in whom ART was initiated in the chronic phase, as shown by Western blotting. CD4 cell counts before ART introduction were also negatively correlated with both the relative and absolute amounts of HIV-1 DNA. Only the relative amounts of HIV-1 DNA negatively correlated with the duration of VL maintenance below the detection limit, while the absolute amounts were not significantly correlated with this period.</p> <p>Conclusions</p> <p>The amounts of cellular HIV-1 DNA in patients with VLs maintained below the detection limit by the introduction of ART correlated with the timing of ART initiation but not with the duration of ART. In addition, CD4⁺T lymphocytes, which were newly generated by ART, diluted latently infected cells, indicating that measurements of the relative amounts of cellular HIV-1 DNA might be underestimated.</p

Analysis of the Hepatic Functional Reserve, Portal Hypertension, and Prognosis of Patients With Human Immunodeficiency Virus/Hepatitis C Virus Coinfection Through Contaminated Blood Products in Japan

Background As the survival of human immunodeficiency virus (HIV)-infected individuals has improved due to the widespread use of antiretroviral therapy, the mortality rate due to hepatitis C virus (HCV)-related liver disease has increased in HIV/HCV-coinfected patients. Aim The aims of this study were to establish the appropriate therapeutic strategy for HIV/HCV-coinfected patients by evaluating the liver function, including the hepatic functional reserve and portal hypertension, and to investigate the prognosis of HIV/HCV-coinfected patients in Japan. Patients and Methods In addition to regular liver function tests, the hepatic functional reserve of 41 patients with HIV/HCV coinfection was evaluated using the indocyanine green retention rate and liver galactosyl serum albumin-scintigraphy. The data for 146 patients with HIV/HCV coinfection through blood products were extracted from 4 major HIV centers in Japan. In addition to liver function tests, the platelet counts (PLT) were evaluated as a marker of portal hypertension. Results In spite of the relatively preserved general liver function test results, approximately 40% of the HIV/HCV-coinfected patients had an impaired hepatic functional reserve. In addition, while the albumin and bilirubin levels were normal, the PLT was <150,000/μL in 17 patients. Compared with HCV mono-infected patients with a PLT <150,000/μL, the survival of HIV/HCV-coinfected patients was shorter (HCV, 5 years, 97%; 10 years, 86% and HIV/HCV, 5 years, 87%; 10 years, 73%; P <.05). Conclusion These results must be taken into account to establish an optimal therapeutic strategy, including the appropriate timing of liver transplantation in HIV/HCV-coinfected patients in Japan

Clinical characteristics of HIV-1-infected patients with high levels of plasma interferon-γ: a multicenter observational study

Abstract Background Circulating interferon-γ (IFN-γ) concentration may be sustained at a high level regardless of the initiation of antiretroviral therapy (ART) in some patients with HIV-1 infection. In the present study, we examined the clinical characteristics of HIV-1-infected patients with high levels of plasma IFN-γ. Methods The study subjects were patients infected with HIV-1 who were either naïve to ART with CD4+ cell count > 200 cells/μL (n = 12), or had achieved viral suppression after ART for over a year (n = 188). The levels of plasma IFN-γ and interleukin-6 (IL-6) were measured by the enzyme-linked immunosorbent assay. Patients were divided into high IFN-γ and low IFN-γ groups based on a cutoff level of 5 pg/mL. Results The high IFN-γ group included 41 patients (21%). Compared to the patients on ART with low IFN-γ levels, those on ART in the high IFN-γ group were more likely to be younger than 50 years of age (P = 0.0051) and less likely to have dyslipidemia (P = 0.0476) or to be on a protease inhibitor (P = 0.0449). There was no significant difference between groups in the median increase of CD4+ cell counts from the initiation of ART for up to 3 years. However, after 4 years, the increase in CD4+ cell counts was significantly lower in the high IFN-γ group compared with that in the low IFN-γ group. There were no such significant differences between patients with low and high (> 2 pg/mL) levels of plasma IL-6. Conclusion We concluded that HIV-1-infected patients with high levels of circulating IFN-γ did not have a higher rate of comorbidities related to immune activation. However, they exhibited lower CD4+ cell count recovery after 4 years of being on ART. This deficit could be a consequence of persistent immune activation

Lack of association between intact/deletion polymorphisms of the APOBEC3B gene and HIV-1 risk.

The human APOBEC3 family of proteins potently restricts HIV-1 replication APOBEC3B, one of the family genes, is frequently deleted in human populations. Two previous studies reached inconsistent conclusions regarding the effects of APOBEC3B loss on HIV-1 acquisition and pathogenesis. Therefore, it was necessary to verify the effects of APOBEC3B on HIV-1 infection in vivo.Intact (I) and deletion (D) polymorphisms of APOBEC3B were analyzed using PCR. The syphilis, HBV and HCV infection rates, as well as CD4(+) T cell counts and viral loads were compared among three APOBEC3B genotype groups (I/I, D/I, and D/D). HIV-1 replication kinetics was assayed in vitro using primary cells derived from PBMCs.A total of 248 HIV-1-infected Japanese men who have sex with men (MSM) patients and 207 uninfected Japanese MSM were enrolled in this study. The genotype analysis revealed no significant differences between the APOBEC3B genotype ratios of the infected and the uninfected cohorts (p = 0.66). In addition, HIV-1 disease progression parameters were not associated with the APOBEC3B genotype. Furthermore, the PBMCs from D/D and I/I subjects exhibited comparable HIV-1 susceptibility.Our analysis of a population-based matched cohort suggests that the antiviral mechanism of APOBEC3B plays only a negligible role in eliminating HIV-1 in vivo

Demographics of the cohorts.

a<p>IQR denotes interquartile range.</p>b<p>NA, Not applicable.</p