Search

Antiretroviral therapy(ART)has been associated with reduced AIDS- and non-AIDS-related morbidity and mortality in people living with HIV/AIDS(PLWH). Nevertheless, the incidence of many comorbid conditions remains higher in PLWH than in the general population, including AIDS-defining malignancies(ADM)as well as several non-AIDS-defining malignancies (NADM). It's important to prevent ADM/NADM, like periodic health checkup for early diagnosis, to quit smoking, and cooperation with cancer and HIV specialists.

We herein report the case of a 25-year-old man who was referred to our hospital due to acute cytomegalovirus (CMV) colitis. The initial blood tests showed that the patient had concurrent primary human immunodeficiency virus (HIV) infection and severe thrombocytopenia. Raltegravir-based antiretroviral therapy (ART) was initiated without the use of ganciclovir or corticosteroids and resulted in a rapid clinical improvement. Platelet transfusions were only necessary for a short period, and subsequent colonoscopy revealed a completely healed ulcer. This case implies that ART alone could be effective for treating severe thrombocytopenia during primary HIV and CMV coinfection.

We present 3 cases of ocular syphilis in patients who had been newly diagnosed as having HIV. All the patients had only complained of ophthalmologic symptoms at the time of their initial visit. Treatment with penicillin was successful, resulting in no significant sequelae. Ocular syphilis may lead to reduced visual acuity or even blindness if left untreated. However, the diagnosis may be challenging, since patients may lack symptoms that are commonly observed in cases with primary and secondary syphilis. Considering the recent increase in the number of syphilis patients, clinicians should be aware of ocular syphilis and should have a high index of suspicion for syphilis in any patient at risk so as to ensure a prompt diagnosis.

We report a case of a 63-year-old HIV-positive Japanese male with a CD4 cell count of 127/μL who was admitted to our hospital because of suspected malignant lymphoma. Initial blood tests revealed anemia, thrombocytopenia, hypoalbuminemia, and hypergammaglobulinemia. Imaging tests revealed a lung nodule, bilateral pleural effusion, hepatosplenomegaly and generalized lymphadenopathy. No evidence of malignant lymphoma or multicentric Castleman's disease was noted on biopsy specimens; however, Kaposi sarcoma-associated herpesvirus (KSHV)-encoded latency-associated nuclear antigen-1-positive cells were observed as well as an elevated interleukin (IL)-6, IL-10 and KSHV viral load. He fulfilled the novel diagnostic criteria for KSHV-associated inflammatory cytokine syndrome (KICS). After initiating antiretroviral therapy, his symptoms and radiological abnormalities drastically improved. After 1-year follow-up, his HIV was well controlled without any relapsing symptoms.

Background Chronic kidney disease (CKD) has become one of the common comorbid conditions affecting the human immunodeficiency virus (HIV) population. Human immunodeficiency virus-infected individuals are at increased risk of developing CKD, and they are likely to experience faster progression of renal dysfunction compared with HIV-uninfected individuals. Albuminuria represents not only kidney damage but also manifests metabolic syndrome and vascular dysfunction. Methods We conducted a multicenter, cross-sectional study involving 2135 HIV-infected individuals in Japan to test the prevalence of CKD and proteinuria/albuminuria. Urine sample was analyzed by both dipstick test and albumin-to-creatinine ratio (ACR) assay. Chronic kidney disease was classified according to the Kidney Disease Outcomes Quality Initiative (K/DOQI) and Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. The diagnostic performance of dipstick test to detect albuminuria (ACR ≥30 mg/g) was evaluated. Results The prevalence of CKD, evaluated by K/DOQI and KDIGO guidelines, was 15.8% and 20.4%, respectively. Age, total cholesterol level, prevalence of hypertension, diabetes mellitus, and hepatitis C infection tended to increase, whereas levels of hemoglobin, serum albumin, and CD4 cell count tended to decrease as CKD risk grades progressed. Proteinuria and albuminuria were present in 8.9% and 14.5% of individuals, respectively. Dipstick test ≥1+ to detect albuminuria had an overall sensitivity of 44.9% and specificity of 97.2%. Conclusions The KDIGO guideline may enable physicians to capture HIV-infected patients at increased risk more effectively. The sensitivity of dipstick proteinuria to detect albuminuria is so poor that it may not serve as an alternative in HIV-infected individuals., This multicenter study demonstrated that the new CKD guideline that used albuminuria targeted more patients at high risk than the previous guideline that used dipstick proteinuria, and the sensitivity of dipstick proteinuria to detect albuminuria is poor among HIV-infected individuals.

There has been no comparative clinical study focused on differences in the clinical features of Epstein-Barr virus (EBV)+ Hodgkin lymphoma (HL) between HIV-positive and -negative cases. In a nationwide survey from 511 institutions in Japan, the present study investigated 16 EBV+ HIVpositive HL patients. To further clarify their characteristics in comparison with EBV+ HIVnegative HL (n=34) in the combination antiretroviral therapy era in Japan, the present study was performed. Results indicated that EBV+ HIVpositive HL frequently occurred in a younger population compared with EBV+ HIVnegative HL (P=0.0295), and that the EBV+ HIVpositive HL group was not associated with the nodular sclerosis subtype in the population who were below the age of 40. Notably, the EBV+ HIVpositive HL group had a significantly higher frequency of extra-nodal involvement (P=0.0214), including marrow invasion. In the advanced stage, 80% of those with EBV+ HIVpositive HL did not require dose-reduction and in the majority of cases, chemotherapy was completed. There were no significant differences in the complete remission rate (P=0.1961), overall survival (P=0.200) and progression-free survival (P=0.245) between EBV+ HIVpositive HL (median observational period, 23.5 months) and EBV+ HIVnegative HL (median observational period, 64.5 months), suggesting that HIV positivity may not have a negative impact on the clinical outcome of EBV+ HL. Notably, standard chemotherapy is effective and tolerable for EBV+ HL, regardless of HIV infection.

Lung cancer has become a crucial problem among individuals living with the human immunodeficiency virus (HIV) and causes high mortality in Western countries. Japan has an increasing number of newly infected HIV patients, and lung cancer is becoming a theme in this population. However, clinical factors of this particular population in East Asian are unclear given the identification of ethnic differences in lung cancer in the general population.From 1986 to 2013, a retrospective nationwide study involving Japanese patients living with HIV and diagnosed with lung cancer was undertaken.Forty-three lung cancer patients with HIV were identified (median age, 60.0 years; males, 97.7%; early-stage cancer, 37.2%; metastatic cancer, 34.9%), 41 (95.3%) of whom developed lung cancer in the antiretroviral era. The median CD4-positive T-cell count was 326 cells/µL. Adenocarcinoma was the most frequent histology (55.8%), followed by squamous cell carcinoma (27.9%). Epidermal growth factor receptor (EGFR) status was examined in 14 patients; five (35.7%) had EGFR mutations. The median overall survival time was 25.1 months for all stages and 7.9 months for advanced-stage cancer. Using univariate analysis, the only favorable prognostic factor for overall survival was cancer stage (p = 0.02).The incidence of lung cancer among HIV patients in Japan has been increasing in the past decade. The present Japanese cohort showed similar EGFR mutation status similar to that of general population. The ethnic differences known in the general population were seen even in the population living with HIV, implying distinct clinical characteristics and outcomes from those reported in Western countries.

Objective: Acquired immunodeficiency syndrome-related non-Hodgkin lymphoma is treated similarly to non-acquired immunodeficiency syndrome lymphoma, but it is not clear whether highly intensive regimens are beneficial for acquired immunodeficiency syndrome-related Burkitt lymphoma. We conducted a multicenter retrospective survey to clarify the clinical outcomes of acquired immunodeficiency syndrome-related Burkitt lymphoma in the combined antiretroviral therapy era in Japan. Methods: We retrospectively analyzed the outcome of 33 patients with acquired immunodeficiency syndrome-related Burkitt lymphoma, who were diagnosed at five regional hospitals for human immunodeficiency virus/acquired immunodeficiency syndrome in Japan between January 2002 and December 2010. Results: The median follow-up period was 20.0 months (range 0.5–92.7 months). Six (18.2%) patients were treated with cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate, ifosphamide, etoposide and high-dose cytarabine, and 23 (69.7%) patients were treated with hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, high-dose methotrexate and high-dose cytarabine. The overall response rate for all patients was 78.8%, with a complete response rate of 72.7%. The two-year overall survival rate was 68.1%. There was no significant difference in overall survival between chemotherapeutic regimens with rituximab (n ¼ 20) and without rituximab (n ¼ 13) (P ¼ 0.49). The two-year overall survival rate was 66.7% for patients receiving cyclophosphamide, vincristine, doxorubicin, dexamethasone, etoposide, ifosfamide and cytarabine, and was 72.6% for patients receiving cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate and cytarabine (P ¼ 0.72). There was one treatment-related death. Conclusions: Highly intensive chemotherapy would bring a high remission rate and prolonged overall survival for patients with acquired immunodeficiency syndrome-related Burkitt lymphoma.

A 19-year-old Filipino man was admitted to our hospital because of persisting fever and back pain. He had recognized his symptoms 6 months previously, but a definite diagnosis was not made. Image testing demonstrated a compressed fracture of the thoracic vertebrae accompanied with a perivertebral abscess. A biopsy specimen revealed granuloma compatible with tuberculosis (TB). Anti-TB drugs were initiated, and his clinical symptoms steadily improved. However, he developed neuropathic symptoms due to exacerbation of the abscess two months after starting the anti-TB drugs. An immediate laminectomy was performed resulting in symptom relief; however severe kyphosis remained. Polymerase chain reaction testing of the abscess collected during the operation was positive for Mycobacterium tuberculosis, confirming the diagnosis of spinal TB. The diagnosis of spinal TB has been a challenge world-wide. Clinicians should be aware of the demographic background as well as the clinical and laboratory features of spinal tuberculosis, facilitating earlier diagnosis.

We report herein on a 20-year-old Japanese man who was referred to our hospital for fever and diarrhea after returning from Indonesia. On admission, his blood test was essentially normal, besides a slight elevation in inflammatory markers. After excluding malaria and dengue fever, empiric use of ceftriaxone was initiated for suspected enteric fever, which was unsuccessful. However, drastic clinical improvement was observed after initiation of minocycline. The polymerase chain reaction test for Rickettsia typhi was positive from serum samples on admission, confirming the diagnosis of murine typhus. Although rarely seen in Japan, clinicians should be aware of this disease when examining patients with fever coming back from murine typhus endemic areas.

We report on a previously healthy 56-year-old woman who was referred to our hospital with fever and progressive left foot pain. She had been bitten by a cat 7 days previously, and cephalosporins had been prescribed for treatment. However, her clinical symptoms deteriorated, and physical examination on admission was compatible with necrotizing fasciitis. Treatment with ampicillin-sulbactam and clindamycin was initiated. In addition, immediate surgical debridement was performed, resulting in therapeutic success. Culture of the necrotizing tissue grew multiple organisms, including Pasteurella multocida and Bacteroides caccae. Administration of appropriate antibiotics after a cat bite is essential for the prevention of potentially fatal complications.

We describe herein two cases of sick sinus syndrome possibly due to lopinavir-ritonavir in HIV-infected individuals. The heart rate dropped to 30 to 40 beats per minute in both cases, but patients remained asymptomatic and recovered promptly after discontinuation of lopinavir-ritonavir. The time until onset varied; one patient developed bradyarrhythmia 9 days after the initial dose, and another 4 hours after. Since lopinavir-ritonavir is a frequently used antiretroviral agent, clinicians must be aware of this potentially lethal adverse effect.

We herein report a 52-year-old man infected with human immunodeficiency virus (HIV) who was referred to our hospital due to the development of severe neurocognitive disorders and bilateral leukoencephalopathy. He has been treated with antiretroviral agents for 17 years, but low-level viremia has been detected consistently prior to admission. Drug resistant testing of the serum and the cerebrospinal fluid (CSF) both demonstrated a M184V mutation. A brain biopsy revealed perivascular CD8(+) T-lymphocyte infiltration, leading to the diagnosis of CD8 encephalitis. The clinical symptoms improved drastically after changing to a nucleoside reverse transcriptase inhibitor sparing regimen, which subsequently decreased the HIV viral load to an undetectable level in both the serum and CSF.

Plasmablastic lymphoma (PBL) is a rare AIDS-related malignancy with a poor prognosis. Little is known about this entity, and no standard treatment regimen has been defined. To establish an adequate treatment strategy, we investigated 24 cases of PBL arising in human immunodeficiency virus-positive individuals. Most of the patients were in the AIDS stage, with a median CD4 count of 67.5/µL. Lymph nodes (58 %), gastrointestinal tract (42 %), bone marrow (39 %), oral cavity (38 %), and CNS (18 %) were the most commonly involved sites. Histology findings for the following were positive at varying rates, as follows: CD10 (56 %); CD30 (39 %); CD38 (87 %); MUM-1 (91 %); CD138 (79 %); EBER (91 %); and LMP-1 (18 %). There was a marked increase in patients in 2011–12, and the cases found in that period appeared to be more aggressive, showing a higher rate of advanced-stage PBL. Fourteen cases were treated with CHOP, while the others were treated with more intensive regimens, including bortezomib and hematopoietic stem cell transplantation. The overall median survival time was 15 months. A CD4 count of >100/µL at diagnosis and attaining complete remission in the first-line chemotherapy were associated with better outcomes (P = 0.027 and 0.0016, respectively). Host immune status and chemosensitivity are associated with improved prognosis in PBL.

Background: The number of HIV-infected patients who require palliative or end-of-life care is increasing, and the status of end-of-life care for HIV patients with malignancies is unclear. Aim: This study aimed to evaluate the end-of-life care provided to HIV patients with malignancies in Japan. Design: National cross-sectional questionnaire-based survey. Setting/participants: Questionnaires were delivered to the medical staff of 378 regional core hospitals/core hospitals for AIDS and 285 palliative care units in Japan. Data were collected between August and October 2013. Results: Overall, 226 regional core hospitals/core hospitals for AIDS (59.8%) responded. A total of 55 institutions (24.3%) provided end-of-life care to HIV patients with malignancies. Regarding the place of death of the patients, 69.1% died at the institution whereas 18.2% were transferred to palliative care units. The requests of 16 (29.1%) institutions to transfer patients to palliative care units were rejected. Of the 378 palliative care units, 179 (62.8%) responded. While 13 palliative care units (4.6%) provided care to hospitalized HIV patients with malignancies, 20 (11.2%) refused to accept these patients for treatment because of a lack of experience in treating these patients and a lack of knowledge regarding HIV infection. Conclusion: Our findings suggest that in Japan, HIV patients with malignancies have difficulties obtaining hospitalization at a palliative care unit, which is likely due to a lack of experience among the professionals in treating such patients as well as a lack of knowledge about HIV.

We report a case of a 45-year-old Japanese man with AIDS-associated Kaposi's sarcoma (KS) involving skin, liver, and lungs. Antiretroviral therapy was started in conjunction with pegylated liposomal doxorubicin (PLD). A clinical response was observed initially, but symptoms recurred following cessation of medication. The chemotherapeutic agent was changed to paclitaxel (PTX), since the therapeutic response to PLD was reduced and the total dose reached the maximum dose of 500 mg/m2. The patient had a good response to PTX and tolerated the medication well. Symptoms did not recur after completing 8 courses of chemotherapy. PTX should be considered as an alternative agent in treating KS when there are problems with the use of PLD.

We report on a 26-year-old Japanese man who was referred to our hospital because of anal pain and hematochezia. On admission, in addition to his gastrointestinal symptoms, a generalized maculopapular rash was observed, involving the palms of his hands and soles of his feet. His history and physical examination were compatible with syphilis, confirmed by a high syphilis titer on blood examination. Further tests revealed the presence of HIV infection, with a CD4 cell count of 227/microL. Colonoscopy demonstrated a deep ulcer in the lower rectum, although biopsy specimens did not reveal any syphilis spirochetes, or any other specific microorganisms. Intravenous penicillin G was initiated, resulting in a dramatic improvement of the ulcers along with the skin lesions confirming the diagnosis of syphilis proctitis. A rapid plasma reagin titer test performed 3 months after treatment demonstrated significant decrease, indicating successful treatment.

Lung cancer has emerged as a crucial problem among human immunodeficiency virus (HIV)-infected patients, contributing to significant mortality in Western countries. Japan has an increasing number of newly infected HIV patients, but clinical characteristics of lung cancer have not been well investigated in Asian populations with HIV. We retrospectively analyzed patients diagnosed with HIV and lung cancer simultaneously in our institution between 1985 and 2010. Data regarding HIV status, characteristics, treatment, and prognosis of lung cancer were evaluated. We identified 13 consecutive patients (all men; mean age, 59.0 ± 10.2 years) since 1985, 7 of whom had been diagnosed since 2008. Mean CD4 cell count was 332 ± 159 cells/μL, and HIV viral loads were undetectable in 8 patients (61.5%) at the time of lung cancer diagnosis. The mean latency from HIV diagnosis to detection of lung cancer was 4.0 years. Histological examination demonstrated adenocarcinoma in 9 patients (69.2%), followed by squamous cell carcinoma (23.1%), and small cell carcinoma (7.7%). Among the 7 patients available for examination, 2 patients (28.6%) harbored EGFR mutation. Six patients had stage IA–IIIA, and 7 patients had stage IIIB/IV. Among 6 patients treated with chemotherapy for unresectable stages, 5 (83.3%) achieved a partial response. Median overall survival was 17 months for all stages and 14 months for advanced stages. Toxicities for treatment modalities were largely acceptable. Clinical characteristics of Japanese HIV-infected patients with lung cancer resemble those of Western populations. The prognosis for patients in the metastatic stage was better than previously reported.

Human immunodeficiency virus (HIV)-infected individuals have concurrent risk factors for chronic kidney disease (CKD), but there are no prediction models to quantify the effect of multiple factors on the development of incident CKD.A 1-year prognostic model was developed using prospective data between January 2008 and March 2009, from a derivation cohort of 623 patients with an estimated glomerular filtration rate (eGFR) exceeding 60 ml/min/1.73 m(2) at baseline. Incident CKD was defined as both an eGFR falling below 60 ml/min/1.73 m(2) and a decrease in eGFR of at least 25% during the period. Continuous variables were divided into categories using the mean value of the whole cohort. Multivariate logistic regression was used to determine baseline categories associated with incident CKD. The model was tested with prospective data between April 2009 and March 2010, from a validation cohort of 534 patients exceeding 60 ml/min/1.73 m(2) at baseline, consisting of part of the derivation cohort and newly enrolled patients. The discriminative ability was evaluated using the area under the receiver operating characteristic (AROC) curve.Eighteen subjects developed incident CKD (2.9%). In a multivariate logistic regression analysis of the derivation cohort, 5 variables (age, CD4 cell count, diabetes, proteinuria, and eGFR at baseline) were independently associated with the incidence of CKD. The AROC curve was 0.841 (95% CI 0.799-0.894) in the validation cohort.This prediction model may be a useful tool for identifying HIV-infected individuals with a high likelihood of new-onset CKD.

We report a case of pathologically confirmed malignant syphilis in an HIV-infected patient. Physical examinations revealed ulceronecrotic skin lesions. Skin biopsies demonstrated syphilis spirochetes on immunohistochemical stain, and syphilis serological titers were positive. Treatment with intravenous penicillin G was begun, and complete resolution of the skin lesions was observed. A rapid plasma reagin titer test performed 3 months after treatment revealed a 4-fold reduction in the titer, indicating successful treatment.

Subjective adverse reactions to metronidazole were analyzed in 111 patients with amebiasis. Metronidazole was administered to 36 patients at a daily dose of 2250 mg and 75 patients at daily doses lower than 2250 mg. The reactions reported included nausea without vomiting in 11 (9.9%) patients, nausea with vomiting in 2 (1.8%), dysgeusia in 2 (1.8%), diarrhea in 1 (0.9%), headache in 1 (0.9%), numbness in 1 (0.9%), dizziness in 1 (0.9%), urticaria in 1 (0.9%), exanthema in 1 (0.9%), and discomfort in 1 (0.9%). Nausea was reported by 28% (10/36) of the patients receiving metronidazole at a daily dose of 2250 mg and 4% (3/75) of the patients receiving lower daily doses. The duration of the metronidazole administration in days was not associated with the appearance of nausea. No life-threatening adverse reactions were identified, and good clinical therapeutic effects were observed in 96% (107/111) of the patients. While metronidazole appears to be a safe anti-protozoal agent for patients with amebiasis, our results indicate that a daily metronidazole dose of 2250 mg is excessive for amebiasis, as it often induces nausea.

Primary central nervous system lymphoma (PCNSL) related to acquired immunodeficiency syndrome (AIDS) is a lethal disorder, but the recent application of highly active antiretroviral therapy (HAART) has significantly improved prognosis. This retrospective cohort study of AIDS-related PCNSL examined the actual clinical outcomes and prognostic variables affecting overall survival (OS) in the HAART era. Twenty-three newly diagnosed AIDS-related PCNSL at 12 regional centre hospitals for HIV/AIDS in Japan between 2002 and 2008 were consecutively enrolled. The estimated 3-yr OS rate of the entire cohort was 64% (95%CI, 41.0-80.3%). Whole brain radiation therapy (WBRT) had an independent positive impact on survival (WBRT >or=30 Gy vs. others, P = 0.02). Nine of 10 patients with a good performance status (PS) (0-2) remained alive with complete response, whereas 10 (77%) of 13 of those with a poor PS (3-4) died mostly after a short period. The estimated 3-yr OS rate of the groups with a good and poor PS was 100% and 38% (95%CI, 14-63%), respectively (P = 0.01). Leukoencephalopathy (grade >or= 2) developed in 21% of those that survived more than 12 months after radiation. The patients receiving a curative intent radiation dose (>or=30 Gy) of WBRT achieved prolonged survival while maintaining a good quality of life in the HAART era, especially among patients with a favourable PS.

Highly active antiretroviral therapy（HAART）によりhuman immunodeficiency virus（HIV）感染者の生命予後は改善したが，長期生存に伴う合併症として慢性腎臓病（chronic kidney disease：CKD）や末期腎不全（end-stage renal disease：ESRD）が問題となりつつある．本研究では，長期にわたる治療期間中にCKDからESRDに至ったHIV感染者の臨床的特徴を報告することを目的とした．都立駒込病院外来に通院しているHIV感染者の中で，2009年8月時点でESRDに至った10症例を対象とした．患者の臨床的特徴，透析導入までの期間，HIV感染コントロール状態，合併症，腎毒性を有する薬剤の曝露歴を診療録を用いて検討した．性別は全て男性，透析導入時の平均年齢は50.7±9.1歳，末梢血CD4陽性リンパ球数は340±185 cells/μL，HIV-RNA量は全例50 copies/mL未満であった．導入時血清クレアチニン値は6.6±1.6 mg/dL，eGFRは8.7±2.6 mL/min/1.73 m2であった．HAART開始から透析導入までの平均期間は8.1±2.9年であり，HAART開始時にCKDを有した3例は，その他の患者よりも4年早く透析導入に至った．透析導入後の死亡例は3例で1例は3年後，2例は数か月後に死亡した．HAART導入後に糖尿病は5例（50％）から7例（70％），高血圧は3例（30％）から9例（90％），高脂血症は1例（10％）から6例（60％）に増加した．腎毒性を有する抗レトロウイルス薬の代表であるTenofovir disoproxil fumarate（TDF）の内服歴は1例もなく，Indinavir（IDV）の内服歴は2例にあった．その他の腎毒性のある薬剤では，trimethoprim-sulfamethoxazole（ST）合剤の内服歴が4例，nonsteroidal anti-inflammatory drugs（NSAIDs）の内服歴が3例にあった．ESRDに至ったHIV感染者10例は，HAART開始前から半数に糖尿病を合併しており，平均約8年で透析導入となった．TDF内服歴を持つ患者は皆無であった．既存の糖尿病とHAARTによる代謝性合併症の増加がCKD進行に関係している可能性がある．

Kidney disease is a significant cause of morbidity and mortality among persons infected with the human immunodeficiency virus (HIV). However, epidemiologic and clinical variables regarding kidney disease have not been determined among HIV-infected patients in Japan.A cross-sectional study of 788 HIV-infected outpatients including 706 men was conducted in 2009. The patient's mean age and CD4+ T cell count were 46.2 +/-11.8 years and 418 +/- 202/microL, respectively. Of them, 677 patients (86%) had an undetectable HIV-RNA level (50 copies/mL). Random urine and blood samples were collected to study the coexistence of chronic kidney disease (CKD). In addition, serum cystatin C was measured since it is considered to be an alternative marker of early kidney dysfunction in the HIV population. The estimated glomerular filtration rate (eGFR) based on serum creatinine was calculated using the 3-variable equation, proposed by the Japanese Society of Nephrology [eGFR (mL/ min/1.73m2) = 194 x Serum creatinine (-1.094) x Age (-0.287 x 0.739 (if female)]. CKD stages were classified based on the National Kidney Foundation guidelines.The prevalence of CKD and that of CKDor = stage 3 was 14.9% and 9.4%, respectively. The pro-portion of each stage was as follows: stage 1, 15 patients (1.9%); stage 2, 28 patients (3.6%); stage 3, 66 patients (8.4%); stage 4, 1 patient (0.1%); stage 5, 1 patient (0.1%); and stage 5D, 6 patients (0.8%). Elevation of serum cystatin C (or = 0.9 mg/L) was found in 23.3%. Comorbidities such as hypertension and diabetes were found in 55.4% and 27.0% in patients with CKDor = stage 3, respectively. Urinalysis showed 71 patients (9.1%) with proteinuria and 44 patients (5.6%) with hematuria.CKD has become an important comorbidity for HIV-infected patients in Japan, a point that should be given more emphasis from public health perspective.

症例は37歳同性愛の男性で, 2002年3月下旬, 腹痛, 下痢を主訴に前医を受診, 小潰瘍を主体とした非特異的大腸炎と多発性肝膿瘍を認め, 赤痢アメーバ症が臨床的に強く疑われ, メトロニダゾールにて治療されていた. Human immunodeficiency virus (以下, HIV) 抗体陽性が判明したため, 4月初旬当院感染症科緊急入院, CD4陽性リンパ球数が224/ulとHIVによる低免疫状態が疑われた. 入院翌日, 右下腹部痛の急性増悪あり緊急CTにて遊離ガス像と多量の腹水を認めアメーバ性大腸炎の穿孔と診断し緊急手術を施行した. 穿孔部位は盲腸で, 穿孔部を利用した人工肛門造設術を施行した. 肝膿瘍は保存的に治療し, 1年後に人工肛門を閉鎖した.近年アメーバ性大腸炎, HIV感染とも増加傾向にあり, これらを念頭においた早期診断および治療が劇症化の阻止と救命に重要であると考えられた

To describe the clinical features of dengue cases in Japan, a retrospective study was conducted on 62 laboratory-confirmed Japanese dengue cases presented to Tokyo Metropolitan Komagome Hospital between 1985 and 2000. Age distribution was from 18 to 62 years old (mean, 31.5 years). All cases were imported from abroad and diagnosed as dengue fever. Clinical manifestations included fever (100%), headache (90%), and skin rash (82%). Laboratory examinations revealed leukocytopenia (71%), thrombocytopenia (57%), elevated levels of serum aspartate aminotransferase (78%), and lactate dehydrogenase (71%). Antibody responses were consistent with that of secondary flavivirus infection in 60% of cases. Severity of symptoms in patients with primary dengue antibody response and those with secondary flavivirus antibody responses didn't show statistical significance. Dengue virus infection should be taken into consideration in the differential diagnosis of febrile patients who recently entered Japan from tropical or subtropical countries.

Objective To assess DNA polymorphisms in mycobacterial isolates obtained from human immunodeficiency virus (HIV)-seropositive patients with tuberculosis in Japan from 1996 to 2003. Methods Restriction fragment length polymorphisms (RFLP) from Mycobacterium tuberculosis and Mycobacterium avium isolates obtained from individual seropositive patients with tuberculosis ( n =78) were analysed with the use of IS 6110 and (CGG) 5 or IS 1245 and IS 1311 , respectively, as markers. As a control, the same procedures were applied to isolates from HIV-seronegative tuberculosis patients ( n =87). Results Of 86 mycobacterial strains, M. tuberculosis , M. avium and Mycobacterium chelonae were identified in 48 (55.8%), 36 (41.9%) and 2 (2.3%) isolates, respectively. The obtained RFLP patterns of M. tuberculosis isolates from both the HIV-seropositive and -seronegative groups were variable, suggesting no obvious clustering among the isolates. Similar results were obtained in isolates of M. avium . Conclusions This is the first report on the molecular epidemiology of Mycobacterium spp. isolated from HIV-seropositive patients in Japan. The results indicate that no particular clones of M. tuberculosis or M. avium prevail in HIV-seropositive patients in Japan. Further monitoring of mycobacterial infection associated with HIV infection in Japan should be continued.

Human herpesvirus 8 (HHV-8) can be classified into distinct subtypes on the basis of sequence polymorphisms in several open reading frames (ORFs). We analyzed the subtypes of HHV-8 in 59 human immunodeficiency virus-infected Japanese patients by using polymorphisms in ORF26 and found that over two-thirds of the HHV-8 isolates fell into major subtype A. We also found that single nucleotide polymorphisms (SNPs) at nucleotide positions 1032 (C-to-A substitution) and 1055 (G-to-T substitution) in HHV-8 ORF26 were correlated with increased susceptibility to Kaposi's sarcoma, compared to the results obtained with HHV-8 with wild-type nucleotides at these positions ( P = 0.0106). This observation suggests that molecular heterogeneity of the HHV-8 genome affects the biological properties of HHV-8, resulting in different clinical phenotypes of HHV-8 infection. Since sensitive PCR of ORF26 allowed us to analyze the SNPs by using peripheral blood from HHV-8-infected patients, the ORF26 SNPs will be a potent tool for investigating the pathogenesis of HHV-8 infection.

Four patients infected with Cyclospora cayetanensis who sought medical care at the Tokyo Metropolitan Komagome Hospital are herein presented. All were Japanese males, and their ages ranged from 22 to 50 years of age. One patient, who was HIV-positive with a CD4+ lymphocyte count of 141/microliter, demonstrated no AIDS-defining illness. This patient acquired HIV in some Southeast Asian country/countries through heterosexual contact. This patient presented with watery diarrhea with a frequency of up to 18 times a day for more than two months. The other three cases were not considered to be debilitated hosts. Diarrhea occurring from one to ten times a day continued for 6 to 26 days in all of these three patients. The presumed origin of the infection was considered to be Southeast Asian countries and the season of onset of diarrhea was March to July in all four cases. Treatment with a sulfamethoxazole/trimethoprim compound was performed for both the HIV-infected patient and the other non-debilitated patient. Both symptomatic and parasitologic improvements were quickly observed in these patients. A prospective study was performed using fecal specimens from the diarrheal patients to identify the presence of C. cayetanensis during the period from 1996 to 2001. Protozoa-positive specimens were found in 3 of 410 (0.7%) specimens from patients who had traveled overseas, is one of 148 (0.7%) for HIV-infected (the C. cayetanensis-positive patient also acquired the protozoa in Southeast Asia), and in none of 513 (0%) patients who developed diarrhea in Japan. In summary, C. cayetanensis infection is rare in Japan and most patients infected with this pathogen tend to be overseas travelers and HIV-infected individuals at present.

Background Cystatin C is an overall biomarker of pathophysiologic abnormalities that accompany chronic kidney disease (CKD). The utility of cystatin C is not fully understood in an HIV-infected population. Methods This prospective study investigated 661 HIV-infected individuals for 4 years to determine the incidence of adverse outcomes, including all-cause mortality, cardiovascular disease, and renal dysfunction. The risk of developing the outcomes was discriminated with a 4 color-coded classification in a 3 × 6 contingency table, that combined 3 grades of dipstick proteinuria with 6 grades of estimated glomerular filtration rate (eGFR) calculated using either serum creatinine (eGFRcr) or cystatin C (eGFRcy): green, low risk; yellow, moderately increased risk; orange, high risk; and red, very high risk. The cumulative incidence of the outcomes was assessed by the Kaplan–Meier method, and the association between color-coded risk and the time to outcome was evaluated using multivariate proportional hazards analysis. Results Compared with eGFRcr, the use of eGFRcy reduced the prevalence of risk ≥orange by 0.8%. The adverse outcomes were significantly more likely to occur to the patients with baseline risk category ≥orange than those with ≤yellow, independent of risk categories based on eGFRcr or eGFRcy. However, in multivariate analysis, risk category ≥orange with eGFRcy-based classification was significantly associated with adverse outcomes, but not the one with eGFRcr. Conclusions Replacing creatinine by cystatin C in the CKD color-coded risk classification may be appropriate to discriminate HIV-infected patients at increased risk of a poor prognosis.

BACKGROUND HIV-associated neurocognitive disorders (HAND) have emerged as a problem among HIV-infected individuals in the era of antiretroviral therapy. However, there are insufficient data on HAND regarding its prevalence and clinical features in Japan. METHODS A test battery composed of eight neuropsycological tests proposed by the Ministry of Health, Labour and Welfare (MHLW test battery) was applied to assess 30 subjects at Tokyo Metropolitan Komagome Hospital. Among them, 5 subjects were excluded due to central nervous system complications. The background of each patient along with the results of head magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis and neuropsychological tests were compared to each HAND category. In addition, the clinical utility of a combination of neuropsychological tests as an abbreviated test battery of HAND was evaluated. RESULTS A total of 19 (76%) subjects were diagnosed as having a HAND. Among them, HIV-associated dementia, mild neurocognitive disorders and asymptomatic neurocognitive disorders were diagnosed in 7, 8, and 4 subjects, respectively. Neither the patient's background nor the results of the head MRI and CSF analysis showed relevance to disease severity. The conventional International HIV Dementia Scale with the Digit Symbol Substitute Test was capable of detecting 94.7% cases of HAND. CONCLUSIONS Most HIV-infected subjects clinically suspected as having neurocognitive disorders were diagnosed as having a HAND. Neuropsychological tests of the MHLW test battery were in some part useful to diagnose HAND. However, more precise neuropsychological tests are warranted to screen and diagnose HAND, based on the current criteria.

AIDS-related lymphoma (ARL) remains a significant burden for specialists in HIV/AIDS medicine. Pathological findings of ARL are often non-typical in various histological types. Diagnosis of correct histological type of ARL by the skilled pathologist is essential. Therapy of patients with ARL is the challenge of integrating treatment appropriate for the stage and histological subset of non-Hodgkin lymphoma. In addition to chemotherapy, essential components of an optimal ARL treatment strategy include antiretroviral therapy and prophylaxis for opportunistic infections.

We report a case of a 60-year-old man infected with human immunodeficiency virus (HIV) who was transferred to our hospital for management of multiple non-healing, painful ulcers on the lower extremities. The histological findings of the biopsy specimen were compatible with the diagnosis of pyoderma gangrenosum (PG). An association between HIV infection and the development of PG was considered after a thorough investigation. Antiretroviral therapy without the use of adjunctive immunosuppressive agents resulted in clinical improvement. Our case implies that antiretroviral therapy alone could heal PG in untreated HIV-infected patients.

Distinguishing life-threatening toxoplasmic encephalitis (TE) from brain lymphoma in patients with acquired immunodeficiency syndrome (AIDS) may be difficult. Empiric anti-toxoplasmosis treatment is often initiated because of the reluctance in performing brain biopsies, which may delay the diagnosis and treatment of brain lymphoma in Japan. In this study, we retrospectively examined the clinical characteristics of 13 AIDS patients with TE in Japan, including magnetic resonance imaging and thallium 201 (201TI) single photon emission computed tomography (SPECT) findings, cerebral spinal fluid analysis, serology, and polymerase chain reaction (PCR) results. All patients improved on anti-toxoplasmosis treatment. Of the 11 patients who underwent serological testing, 6 (55%) had a positive serological result. Of the 7 patients who underwent PCR testing, 3 (42.9%) had a positive PCR result. Nine of 11 patients with TE (81.8%) had multiple lesions. Analysis of the sites of TE lesions did not reveal a difference in site predilection between TE and brain lymphoma. Uptake was negative in all 9 patients who underwent 201Tl SPECT. The study findings suggest that toxoplasma serostatus and PCR may be used to discriminate TE from brain lymphoma. No focal accumulation of 201TI is strongly suggestive of TE in patients with AIDS in Japan.

To assess the characteristics of CD4 and CD8 T cells specific for HIV-1 and cytomegalovirus (CMV) antigens in untreated and treated HIV-1-infected patients.Antigen-specific T cell frequencies were determined by flow cytometric detection of antigen-induced intracellular cytokines.In untreated patients, HIV-1-specific CD4 T cell counts in peripheral blood were less than one tenth of CMV-specific CD4 T cell counts, while the number of specific CD8 T cells was approximately the same for both HIV-1 and CMV. In patients treated with highly active antiretroviral therapy (HAART) for less than 1.5 years, HIV-1-specific CD4 and CD8T cell counts were significantly lower than those in untreated patients. Perforin expression in HIV-1-specific CD8 T cells was significantly lower than that in CMV-specific CD8 T cells.These data indicate that HIV-1-specific T cells in HIV-1-infected patients have quantitative and qualitative abnormalities.

OBJECTIVES To investigate the prevalence and relative titre of TT virus (TTV) DNA, and to examine the relationship between the extent of TTV viraemia and the immune status among 144 patients with HIV infection; 178 age- and sex-matched healthy individuals were also studied. METHODS TTV DNA was detected quantitatively by two distinct polymerase chain reaction (PCR) methods [untranslated region (UTR) and N22]. UTR PCR detects all TTV genotypes, and N22 PCR can primarily detect four major TTV genotypes (1-4). RESULTS Using UTR PCR and N22 PCR, respectively, TTV DNA was detected significantly more frequently in HIV-infected patients than in controls (99 versus 91%, P < 0.001; 56 versus 27%, P < 0.0001), and the relative titre (10N/ml) was significantly higher in HIV-infected patients [4.5 +/- 1.2 (mean +/- SD) versus 3.1 +/- 0.9, P < 0.0001; 2.6 +/- 1.5 versus 1.5 +/- 0.9, P < 0.0001]. Age, sex, co-infection with hepatitis B or C virus, and risk factors for HIV transmission did not appear to be significant factors associated with the titre of TTV viraemia. However, the titre of TTV DNA was significantly higher in HIV-infected patients with AIDS (P < 0.0001), those with low CD4 T cell count (P < 0.0001), or those with high HIV viral loads (P = 0.0047). CONCLUSION TTV is highly prevalent and high-titred in HIV-infected patients. The TTV viral load may reflect the degree of immune status of these immunocompromised hosts.

Patients with typhoid fever presenting to the Tokyo Metropolitan Komagome Hospital during the period 1975-1998 were retrospectively investigated. All cases were diagnosed by a positive culture for Salmonella typhi in either of their clinical specimens. Of the total number of 130 patients, 57% contracted the disease abroad; this population increased in later years as the total numbers of cases decreased. The period from disease onset to diagnosis averaged 14 days with 20% of the cases requiring over three weeks to establish a diagnosis. As for symptomatology relative bradycardia was seen in less than half of the cases, and rose spots or splenomegaly in less than one third. A positive blood culture was the most frequent test establishing the diagnosis followed by a positive stool culture. Intestinal bleeding was recognized in as many as 35 cases (27%) and even intestinal perforation occurred in two cases (1.5%). Chloramphenicol was most commonly employed during the early study period, however, during the late period it was replaced by fluoroquinolones. The clinical cure rate was 98% with regimens that include fluoroquinolones/quinolone; however it was 87% with the other antimicrobial regimens. Bacteriological relapse occurred in 25% of the non-fluoroquinolone group while only in 2.0% in the fluoroquinolone/quinolone group. Four strains of Salmonella typhi that were multi-resistant to chloramphenicol, ampicillin and cotrimoxazole were isolated in travelers from Asia. Early diagnosis by appropriate bacteriological examination regardless of classical symptomatology should be stressed and the use of fluoroquinolones is warranted in the treatment of typhoid fever.

The emergence of syncytium-inducing (SI) variants of human immunodeficiency virus type 1 (HIV-1) in infected individuals is an indicator of poor prognosis and is often correlated with faster CD4+cell depletion and rapid disease progression. Interleukin-4 (IL-4) is a pleiotropic cytokine with various immune-modulating functions including induction of immunoglobulin E (IgE) production in B cells, down-regulation of CCR5 (a coreceptor for HIV-1 non-SI [NSI] strains), and up-regulation of CXCR4 (a coreceptor for HIV-1 SI variants). Here we show that homozygosity of a polymorphism in the IL-4 promoter region, IL-4 −589T, is correlated with increased rates of SI variant acquisition in HIV-1-infected individuals in Japan. This mutation was also shown to be associated with elevated serum IgE levels in HIV-1-infected individuals, especially in those at advanced stages of disease. In contrast, neither a triallele polymorphism in IL-10, another Th2 cytokine, nor a biallele polymorphism in the RANTES promoter affected acquisition of the SI phenotype. This finding suggested that IL-4-589T increases IL-4 production in the human body and thus accelerates the phenotypic switch of HIV-1 from NSI to SI and possibly disease progression of AIDS.

Varicella has been thought to be one of the representative infectious disease in childhood, but recently we are under the impression that adults contracting varicella are increasing in number. On the other hand, they say that varicella generally causes a serious illness in adult patients. So we investigated signs and symptoms of varicella, source of infection, occupations of adult patients, except those who were immunologically compromised, by means of medical records, to know the characteristics of varicella in adulthood. According to the varicella severity score proposed by Nagai et al., varicella in the hospitalized adult patient was found to be much severer than that in children. The most remarkable symptoms, were high fever and sore throat, and these were the main reason of hospitalization in most of our patients. Although severity scores were very high in admitted adult patients with varicella, their clinical courses were not serious, and most of them recovered with only supportive therapy. These patients rarely suffered from complications, like pneumonia. If adult patients with varicella hospitalized in the early stage and received supportive care, they could recover without any complications. In most cases of adult varicella the source of infection was unknown. In the case of married persons, however, many of them were infected through their child. When adults contract varicella, not only the patients themselves suffer from high fever and sore throat, but also they act as the source of infection, if they are medical care workers. Furthermore, in public, the contraction of varicella results a socioeconomic loss from suspension of business caused by the illness. Prophylaxis with varicella vaccine, therefore, should be considered, when there are people who have never contracted varicella, whether or not they are medical staff.

BACKGROUND In 2012, the number of rubella cases sharply increased in Japan. It continued to rise in 2013. Between October 2012 and May 2013, 10 cases of congenital rubella syndrome (CRS) were reported nationwide. This current rubella outbreak comprised mainly males who were between 20 to 39 years of age, and had not received the rubella vaccine. Data have been lacking on the clinical characteristics of adults infected with the rubella virus. METHODS Using medical charts, we collected data from 27 patients who were diagnosed with clinically or laboratory-confirmed rubella infection at Tokyo Metropolitan Komagome Hospital from January 2012 to April 2013. RESULTS Of the 27 patients studied, their median age was 34.5 years and 70.4% were male between 21-56 years of age. For the 11 cases with known vaccination status, 9 (81.8%) occurred in persons who had not received a rubella vaccine. A total of 33.3% of the patients were hospitalized, due to persistent fever, poor oral intake, or dehydration. Major clinical symptoms were fever (96.3% of cases), lymphadenopathy (92.6%), rash (85.2%), conjunctivitis (77.8%), and headache (63.0%). The mean duration of fever was 5 days (range, 3-9). The exanthema consisted of punctate, pink maculopapules; however, the rash became confluent in 37.0%, and pigmented in 18.5% of the patients. Initial laboratory data were as follows:white cells, 3,800/microL (range: 2,000-8,300); platelets, 129,000/microL (range, 63,000 - 230,000); aspartate aminotransferase, 27IU/L (range, 16 - 49); lactase dehydrogenase, 279IU/L (range, 168-440) [all described in medians]. Rubella-specific immunoglobulin M antibodies from the serum sample obtained at the initial visit were detected in 17 cases (65.4%). Likewise, measles-specific immunoglobulin M antibodies were detected in 7 cases (26.9%), all of which were false-positive. CONCLUSIONS The clinical characteristics of rubella in adults resembled measles in some part, which may cause difficulty for physicians to differentiate between the two diseases. Vaccinating rubella-susceptible individuals now is critical to interrupt rubella virus transmission, and to prevent further CRS cases.