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

Convalescence of atypical reversible posterior leukoencephalopathy syndrome in human immunodeficiency virus infection

Reversible Posterior Leukoencephalopathy Syndrome (RPLS) is an uncommon neurological disorder which shows the diffuse edema in white matter of occipital lobe of brain. In this report, we describe a RPLS case with Human Immunodeficiency Virus (HIV) infection, whose lesion was improved with Highly Active Antiretroviral Therapy (HAART). A HIV-infected man, who was diagnosed as a mental deterioration with Central Pontine Myelinolysis (CPM) appearing high intensity pontine lesion in brain Magnetic Resonance Imaging (MRI), improved with HAART. No episode of hyponatremia or hypertension was observed in his clinical course. Evaluation of apparent diffusion coefficient (ADC) mapping in diffusion weight imaging (DWI) was performed in brain MRI at the onset and four months after commencement of HAART. ADC mapping enabled to interpret the pontine lesion as RPLS. HAART improved the mental deterioration within two weeks and the elevated ADC value at the onset was normalized at four-month clinical course

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

Problems in three Japanese drug users with Human Immunodeficiency Virus infection

Numbers of individuals infected with Human Immunodeficiency Virus (HIV) are increasing in Japan. The majority of them are Men who have sex with men and a part of them take drugs as ‘Sex drug’ at their sexual intercourse. Especially, Amyl nitrite, Methamphetamine, 5-methoxy-N, N-diisopropyltryptamine (5-MeO-DIPT Foxy), and 3, 4- methylenedioxy- methamphetamine (MDMA Ecstasy) are used, and they sometimes cause the physical and mental disorders. However, the actual drug inducing troubles among Japanese HIV-infected drug users had not yet been discussed enough. In this report, we describe three cases with HIV infection a case developed severe neuroleptic malignant syndrome (NMS) after taking 5-MeO-DIPT, a case with persistent convulsion due to multiple drug intake and a case with rhabdomyolysis due to the nonsubjective methamphetamine intake. Through these cases, we raise and discuss several underlying problems associated with drug use among HIV-infected individuals

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

Impact of UGT1A1 gene polymorphisms on plasma dolutegravir trough concentrations and neuropsychiatric adverse events in Japanese individuals infected with HIV-1

Abstract Background Dolutegravir (DTG) is metabolized mainly by uridine diphosphate (UDP)-glucuronosyltransferase 1A1 (UGT1A1), and partly by cytochrome P450 3A (CYP3A). Therefore, we focused on UGT1A1 gene polymorphisms (*6 and *28) in Japanese individuals infected with human immunodeficiency virus (HIV)-1 to examine the relationship between their plasma trough concentration of DTG and gene polymorphisms. Recently, neuropsychiatric adverse events (NP-AEs) after the use of DTG have become a concern, so the association between UGT1A1 gene polymorphisms and selected NP-AEs was also investigated. Methods The study subjects were 107 Japanese patients with HIV-1 infections who were receiving DTG. Five symptoms (dizziness, headache, insomnia, restlessness, and anxiety) were selected as NP-AEs. The subjects were classified by their UGT1A1 gene polymorphisms for the group comparison of DTG trough concentration and the presence or absence of NP-AEs. Results The subjects consisted of eight (7%) *6 homozygotes, three (3%) *28 homozygotes, four (4%) for *6/*28 compound heterozygotes, 23 (21%) *6 heterozygotes, 18 (17%) *28 heterozygotes, and 51 (48%) patients carrying the normal allele. The plasma DTG trough concentration of the *6 homozygous patients was significantly higher than that of the patients carrying the normal allele (median, 1.43 and 0.82 μg/mL, respectively, p = 0.0054). The *6 and *28 heterozygous patients also showed significantly higher values than those shown by patients with the normal allele. Multivariate analysis revealed that carrying one or two UGT1A1*6 gene polymorphisms, one UGT1A1*28 polymorphism, and age of < 40 years were independent factors associated with high DTG trough concentrations. The median DTG trough concentration was significantly higher in the patients with NP-AEs (1.31 μg/mL) than in those without NP-AEs (1.01 μg/mL). Consistent with these results, subjects carrying UGT1A1*6, UGT1A1*28, or both alleles showed a higher cumulative incidence of having selected NP-AEs than those carrying the normal alleles (p = 0.0454). Conclusion In addition to younger age, carrying UGT1A1*6 and/or UGT1A1*28 was demonstrated to be a factor associated with high DTG trough concentrations. Our results also suggest a relationship between plasma DTG trough concentrations and NP-AEs, and that carrying UGT1A1*6 and/or UGT1A1*28 alleles might be a risk factor for NP-AEs