[Current Topics of Cancer and HIV].

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.

End-of-life care for HIV-infected patients with malignancies: A questionnaire-based survey.

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.

[Kaposi's Sarcoma Herpesvirus-associated Inflammatory Cytokine Syndrome (KICS) Improved by Antiretroviral Therapy in an HIV-infected Patient].

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.

[Ocular Syphilis Complicated with HIV Infection: A Report of 3 Cases].

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.

Comparison of cystatin C and creatinine to determine the incidence of composite adverse outcomes in HIV-infected individuals.

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.

The prevalence of opportunistic infections and malignancies in autopsied patients with human immunodeficiency virus infection in Japan.

BACKGROUND: Opportunistic infections and malignancies such as malignant lymphoma and Kaposi sarcoma are significant complications of human immunodeficiency virus (HIV) infection. However, following the introduction of antiretroviral therapy in Japan in 1997, the incidence of clinical complications has decreased. In the present study, autopsy cases of HIV infection in Japan were retrospectively investigated to reveal the prevalence of opportunistic infections and malignancies. METHODS: A total of 225 autopsy cases of HIV infection identified at 4 Japanese hospitals from 1985-2012 were retrospectively reviewed. Clinical data were collected from patient medical records. RESULTS: Mean CD4 counts of patients were 77.0 cells/µL in patients who received any antiretroviral therapy during their lives (ART (+) patients) and 39.6 cells/µL in naïve patients (ART (-) patients). Cytomegalovirus infection (142 cases, 63.1%) and pneumocystis pneumonia (66 cases, 29.3%) were the most frequent opportunistic infections, and their prevalence was significantly lower in ART (+) patients than ART (-) patients. Non-Hodgkin lymphoma and Kaposi sarcoma were observed in 30.1% and 16.2% of ART (-) patients, and 37.9% and 15.2% of ART (+) patients, respectively. Malignant lymphoma was the most frequent cause of death, followed by cytomegalovirus infection regardless of ART. Non-acquired immunodeficiency syndrome (AIDS)-defining cancers such as liver and lung cancer caused death more frequently in ART (+) patients (9.1%) than in ART (-) patients (1.5%; P = 0.026). CONCLUSIONS: The prevalence of infectious diseases and malignancies were revealed in autopsy cases of HIV infection in Japan. The prevalence of cytomegalovirus infection and pneumocystis pneumonia at autopsy were lower in ART (+) patients than ART (-) patients. Higher prevalence of non-AIDS defining malignancies among ART (+) patients than ART (-) patients suggests that onsets of various opportunistic infections and malignancies should be carefully monitored regardless of whether the patient is receiving ART.

Clinical outcomes of AIDS-related Burkitt lymphoma: a multi-institution retrospective survey in Japan.

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 = 20) and without rituximab (n = 13) (P = 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 = 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.

Classification of human immunodeficiency virus-infected patients with chronic kidney disease using a combination of proteinuria and estimated glomerular filtration rate.

BACKGROUND: In 2012, the Kidney Disease: Improving Global Outcomes (KDIGO) updated the 2002 Kidney Disease Outcomes Quality Initiative (KDOQI) clinical practice guideline for chronic kidney disease (CKD). The 2012 KDIGO guideline elaborated the identification and prognosis of CKD by combining albuminuria with estimated glomerular filtration rate (eGFR). Identification of CKD with a high risk for a poor prognosis was investigated in human immunodeficiency virus (HIV)-infected individuals by applying the new guideline. METHODS: A total of 1,447 HIV-infected patients (1,351 male, 96 female; mean age 44.4 ± 11.5 years) were classified using a combination of eGFR and dipstick proteinuria, as a convenient alternative to albuminuria. Proteinuria was classified into 3 grades-(A1) - and +/- , (A2) 1+ and 2+ , and (A3) 3+ and 4+. eGFR was classified into 6 grades-(G1) ≤90, (G2) 60-89, (G3a) 45-59, (G3b) 30-44, (G4) 15-29, and (G5) <15 mL/min/1.73 m(2). RESULTS: Mean CD4 cell count was 487 ± 214 /µL, with 80.7 % of patients having an undetectable HIV-RNA level. The prevalence of CKD stage ≤2 and stage ≥3 classified according to KDOQI staging was 93.4 and 6.6 %, respectively. Using the new KDIGO classification, the prevalence of CKD with either a low (green) or moderately increased (yellow) risk was 96.9 %, while the prevalence for a high (orange) and very high (red) risk was 3.1 %. CONCLUSION: The use of the new KDIGO classification may reduce the prevalence of HIV-infected CKD individuals who are at high risk for a poor prognosis by nearly a half.

Pyoderma gangrenosum successfully treated with antiretroviral therapy alone in a human immunodeficiency virus-infected individual.

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.

[A case of spinal tuberculosis in a young Filipino man].

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.

[Murine typhus in a Japanese traveler returning from Indonesia: a case report].

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.

[Evaluation of HIV-infected patients suspected as having HIV-associated neurocognitive disorders].

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.

[Immunodeficiency related malignant lymphoma: diagnosis and therapy of AIDS-related lymphoma].

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.

[Necrotizing fasciitis after a cat bite: a case report].

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.

[Medical study of cases diagnosed as rubella in adults].

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.

[Sick sinus syndrome possibly due to lopinavir-ritonavir: report of two cases].

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.

[Prevalence of chronic kidney disease among HIV-infected individuals in Japan--a report from two tertiary hospitals].

BACKGROUND: The improved survival of subjects with human immunodeficiency virus (HIV) has been accompanied by an increased prevalence of chronic kidney disease (CKD). Epidemic of CKD among those with HIV has not yet been evaluated in multiple tertiary hospitals in Japan. METHODS: A cross-sectional study was conducted in 2011 at Tokyo Metropolitan Komagome Hospital (TMKH) and Tokyo Medical University Hospital (TMUH). A total of 1482 HIV-infected subjects (1384 men, 98 female, mean age: 44.2 +/- 11.4 years old) were consecutively enrolled in the study. Random urine and blood samples were collected to study prevalence of CKD. CKD was diagnosed as a decrease in glomerular function and/or proteinuria and classified into 5 stages based on National Kidney Foundation guidelines. The estimated glomerular filtration rate based on serum creatinine was calculated using the 3-variable equation, constructed by the Japanese Society of Nephrology. Proteinuria was defined as > or = 1+ on urine dipstick examination. All electronic medical charts were reviewed to determine comorbidities, including hypertension and diabetes mellitus (DM). The proportion of subjects receiving tenofovir disoproxil fumarate (TDF) was investigated. Risk factors for CKD were determined using multivariate logistic regression analysis. RESULTS: The mean CD4 cell count was 487 +/- 216/microL and 80.5% had undetectable HIV-RNA level in the combined cohort. Of the 90.2% of subjects taking antiretroviral agents, 61.5% was using TDF. The prevalence of overall CKD and CKD > or = stage 3 was 12.9% and 6.7%, respectively, both of which were nearly 3-fold higher in the TMKH cohort (p < .0001). Mean age and proportional prevalent hypertension and DM were significantly higher in the TKMH cohort than in the TMUH cohort. Multivariate analysis showed significant CKD to be associated with age > or =50 years (odds ratio [OR], 2.81), hypertension (OR, 3.04), and DM (OR, 2.05). CONCLUSIONS: CKD prevalence was 12.9% among combined cohorts, but differed significantly between them. Differences in age distribution and the proportion of comorbidities, including hypertension and DM, are likely involved.

Successful dual antiviral therapy with remdesivir and ensitrelvir in a case of prolonged COVID-19 following B-cell depleting immunotherapy for malignant lymphoma.

Prolonged COVID-19 following B-cell depleting immunotherapy for malignant lymphoma is characterized by repeated cycles of remission followed by symptom recurrence, persistent detection of SARS-CoV-2, and profound humoral immunodeficiency. To the best of our knowledge, the present report is the first to describe dual antiviral therapy with remdesivir and ensitrelvir for prolonged COVID-19 following B-cell depleting immunotherapy for malignant lymphoma. A 59-year-old, female patient with a history of follicular lymphoma treated with obinutuzumab and bendamustine contracted COVID-19 despite receiving a single course of standard remdesivir therapy. She received dual antiviral therapy with remdesivir following a five-day course of oral ensitrelvir, which improved her clinical symptoms and chest radiology findings and cleared SARS-CoV-2 from respiratory samples. Dual antiviral therapy with remdesivir and ensitrelvir may be sufficient to stop viral replication and promote clinical resolution in prolonged COVID-19 following B-cell depleting immunotherapy for malignant lymphoma.

Clinical characteristics of Japanese lung cancer patients with human immunodeficiency virus infection.

BACKGROUND: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[Syphilis proctitis complicated with HIV infection: a case report].

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.