Evaluation of human herpesvirus-8 viremia and antibody positivity in patients with HIV infection with human herpesvirus-8-related diseases.

Human herpesvirus-8 (HHV-8) viremia is associated with refractory conditions in patients infected with HIV-1. Therefore, we evaluated the factors related to plasma HHV-8-DNA. Participants included patients infected with HIV-1 who visited our hospital. Plasma HHV-8-DNA levels were measured using real-time polymerase chain reaction, and anti-HHV-8 antibodies were assessed through enzyme immunoassays using multiple antigens (K8.1, ORF59, ORF65, and LANA). Factors related to plasma HHV-8-DNA were examined using Fisher's exact test or Mann-Whitney U test. The study involved 36 patients infected with HIV-1, of whom 19 were histologically diagnosed with Kaposi's sarcoma (KS), two had multicentric Castleman's disease (MCD), and 15 did not exhibit HHV-8-related disease. Before the introduction of antiretroviral therapy (ART), plasma HHV-8-DNA was detected in 44% (7/16) of patients with KS and in 9% (1/11) of patients without HHV-8-related disease. Among patients with KS, elevated plasma HHV-8-DNA levels (≥0.05 copies/µL) correlated with the presence of CDC category C diseases other than KS (p = 0.0337), anti-HHV-8 antibody negativity (p = 0.0337), anemia (p = 0.0474), and thrombocytopenia (p = 0.0146). Following ART initiation, the percentage of patients positive for plasma HHV-8-DNA decreased from 44% (7/16) to 6% (1/17), and the percentage of patients positive for anti-HHV-8 antibodies increased from 44% (7/16) to 88% (15/17). Finally, plasma HHV-8-DNA positivity and anti-HHV-8 antibody negativity were observed in two patients with MCD. Our findings suggest that insufficient production of anti-HHV-8 antibodies was associated with HHV-8 viremia, and that anti-HHV-8 antibody production was recovered with ART; thus, indicating the possibility of involvement of humoral immunity in suppressing HHV-8 viremia.

Evaluation of plasma doravirine concentrations in patients with HIV-1 undergoing hemodialysis.

The pharmacokinetics of doravirine (DOR) have not been clarified in patients undergoing hemodialysis (HD). In this study, we evaluated the pharmacokinetics of DOR in four HIV-1-infected patients undergoing HD who were administered DOR. The participants were patients undergoing HD for end-stage renal disease and were administered DOR. DOR was administered once daily (one tablet of 100 mg), every evening. On days of HD treatment, DOR was administered after the end of the procedure. After administration of DOR for at least 1 week, the plasma DOR concentration was measured. The median plasma trough DOR concentration was 766.9 ng/mL (range: 509-1085 ng/mL). The median DOR clearance by HD, DOR elimination rate, half-life (T1/2) of plasma DOR concentration during HD, and T1/2 during the non-HD period were 85.04 mL/min, 73.12%, 7.71 h, and 13.76 h, respectively. The T1/2 during the HD period was significantly shorter than the T1/2 during the non-HD period (p = 0.0030). In this study, elimination of DOR by HD was confirmed. Viral suppression was maintained in all patients undergoing HD, and none had adverse events or safety problems. As DOR is eliminated by HD, monitoring its plasma concentration is considered necessary for clinical use.

Observational study of skin and soft-tissue Staphylococcus aureus infection in patients infected with HIV-1 and epidemics of Panton-Valentine leucocidin-positive community-acquired MRSA infection in Osaka, Japan.

BACKGROUND: In patients infected with human immunodeficiency virus (HIV)-1 at our hospital, we observed increases in skin and soft-tissue infections (SSTIs) by community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). Therefore, we analyzed factors related to CA-MRSA infection and performed a molecular epidemiological investigation. METHODS: HIV-1-infected patients were diagnosed with SSTIs related to S. aureus between 2007 and 2017, and MRSA was classified into community and hospital-acquired types according to published criteria. Information was collected retrospectively from clinical records, and multivariate analysis by logistic regression was performed concerning factors related to CA-MRSA infection. We evaluated the staphylococcal cassette chromosome mec (SCCmec) type, multilocus sequence type, and the presence of genes encoding Panton-Valentine leucocidin (PVL) in 27 MRSA samples isolated during and after 2015. RESULTS: We found 218 episodes of SSTIs in 169 patients, and among initial episodes of SSTIs, the MRSA ratio was higher from 2015 to 2017 relative to that from 2007 to 2014 (88% vs. 44%; p < 0.0001). Multivariate analysis showed that in men having sex with men [MSM; odds ratio (OR): 13] and exhibiting onset during and after 2015 (OR: 5.4), CD4+ cell count ≥200 cells/µL (OR: 5.6) and the presence of lesions in the lower abdomen or buttocks (OR: 9.5) were independent factors related to CA-MRSA infection. Additionally, PVL+/ST8/SCCmec type IV MRSA was the predominant pathogen (22 cases; 81%). CONCLUSIONS: These data describe an increased prevalence of SSTIs due to PVL-positive ST8-MRSA-IV, not previously considered epidemic in Japan, in MSM infected with HIV-1 in Osaka, Japan.

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

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.

Cross-sectional and longitudinal investigation of human herpesvirus 8 seroprevalence in HIV-1-infected individuals in Osaka, Japan.

INTRODUCTION: High human herpesvirus 8 (HHV-8) seroprevalence has been reported in men who have sex with men (MSM) and are infected with HIV-1. However, it is unclear when they become infected with HHV-8. Thus, we conducted cross-sectional and longitudinal investigations of HHV-8 seroprevalence in HIV-1-infected individuals in Osaka, Japan. PATIENTS AND METHODS: Plasma was collected from 121 individuals infected with HIV-1 and the anti-HHV-8 antibody titer was measured using an enzyme-linked immunosorbent assay with whole virus lysate. Subjects were classified into those with and without a past medical history of HHV-8-associated disease; the latter group was then classified into 3 subgroups based on the assumed route of HIV-1 infection: blood products, homosexual contact, and other routes. HHV-8 seroprevalence was compared among the groups and measured again approximately 3 years after the baseline measurement. The relationship between HHV-8 seropositivity and possible associated factors was also investigated. RESULTS: All 15 subjects with HHV-8-associated disease were seropositive, and all 11 subjects in the blood product group were seronegative. In the MSM group, 25 (30%) of 79 subjects were HHV-8 seropositive and, in the non-MSM group, 1 (6%) of 16 subjects was (p < 0.0001). In the longitudinal investigation, seroconversion was observed in 10 (19%) of 52 subjects in the MSM group who were seronegative at baseline. A correlation was observed between seroconversion and symptomatic syphilis (p = 0.0432). CONCLUSIONS: HHV-8 seropositivity and seroconversion rates were high in HIV-1-infected MSM, suggesting that, currently, HHV-8 is an epidemic pathogen in this population.

[A case of Wegener's granulomatosis with pachymeningitis].

A 49-year-old man was admitted to our hospital because of headache, rhinorrhea, and general fatigue. Chest CT revealed some lung nodules bilaterally, and laboratory data were positive for C-ANCA. Brain MRI revealed the findings of pachymeningitis. Wegener's granulomatosis (WG) was diagnosed by the pathological findings of his paranasal sinuses and kidneys. Most of his symptoms remarkably improved with oral corticosteroids and cyclophosphamide. A MEDLINE search about WG with pachymeningitis obtained only 15 cases previously reported in Japan. Considering those reports about WG with pachymeningitis in both Japan and overseas, in some cases pachymeningitis preceded WG, and relatively more cases than normal WG were negative for C-ANCA, furthermore the pathological findings of pachymeningitis were mainly necrotizing granuloma. Therefore pachymeningitis with WG might be mainly composed of granuloma rather than angitis and which might be a expansion of granulomatous inflammation of upper respiratory tract.

[A case of pulmonary amebiasis].

A 57-year-old man was admitted to our hospital because of dyspnea and right abdominal pain. Chest X-ray radiogram showed right massive pleural effusion. Ultrasonic echogram of abdomen showed a unilocular liver cyst. He was treated with intravenous infusion of meropenem, and percutaneous pleural and liver drainage were performed. At the time of drainage, we injected contrast medium into the liver cyst and confirmed a fistula connecting to the right pleural space. Initially we made a diagnosis of bacterial empyema and liver abscess, yet there was no response to the initial treatment. Cultures of pleural effusion and liver abscess were confirmed to be negative. A few days after admission, the patient stated that he was a homosexual. Liver amebiasis and its perforation became the most likely diagnosis, and metronidazole was administered. On admission day 21, tests for anti-amebic antibody were positive. Finally he fully recovered. We must be aware of the rare pulmonary manifestation of amebiasis. We report this case and review the literature.