Latency to initiation of antiretroviral therapy in people living with HIV in Japan.

Rapid initiation of antiretroviral therapy (ART) in HIV infection is recommended because it increases care retention rate and reduces the time to viral suppression. In Japan, although ART initiation is delayed, there is little information on the latency to ART initiation (time from HIV diagnosis to ART initiation). The present study was designed to obtain information on the latency to ART initiation in individuals with 1) acute or recent HIV infection (ARH), and with 2) advanced HIV diseases. Questionnaires were sent to 379 regional AIDS facilities requesting information on the people living with HIV (PLWH) who visited their facilities during 2020. Among 1098 new PLWH visitors, 706 were treatment-naïve patients, including 111 (15.7%) with ARH and 304 (43.1%) with advanced HIV diseases. Among those with ARH, only 8.2% received rapid ART initiation (latency to ART <2 weeks) and the time from diagnosis to virological suppression was longer than 14 weeks in 40.4%. Among those with advanced HIV diseases, 36.2% received late ART initiation (latency to ART ≧6 weeks). Our data showed that only a small proportion of PLWH with ARH in Japan received rapid ART. Furthermore, in PLWH with advanced HIV diseases in Japan, current latency to ART seems too long, though the timing of ART commencement should be tailored according to the presence/lack of opportunistic infections and accessibility to medical care. Further investigation is required to identify barriers to rapid ART initiation in Japan.

Young age is a key determinant of body weight gain after switching from tenofovir disoproxil fumarate to tenofovir alafenamide in Japanese people living with HIV.

BACKGROUND: Treatment with tenofovir alafenamide fumarate (TAF) is associated with body weight gain. However, little or no information is available on this issue in Asian populations. METHODS: This single-center retrospective study included Japanese people living with HIV (PLWH) who satisfied the following criteria; 1) switching from TDF to TAF after HIV-suppression, 2) follow-up for ≥2 years while on TDF and TAF, and 3) no switching of the third antiretroviral agent. Changes in annual body weight and lipid profiles were compared between the TDF and TAF periods. RESULTS: Of 328 patients, dolutegravir (DTG) was used in 118 PLWH. Overall, no significant difference in weight gain was observed between TDF and TAF (0.76 vs. 0.9 kg/year, p = 0.331). In TAF-period, younger (<50 years of age) group showed significantly greater weight gain than older group (1.03 vs. 0.12 kg/year, p = 0.037). In DTG group, weight gain was larger in TAF-period (0.74 vs. 1.31 kg/year, p = 0.046), especially in younger subgroup (1.43 kg/year) compared with older one (-0.12 kg/year). Multivariate regression analysis showed that TAF was not associated with weight gain (estimates 0.201, p = 0.170) except for DTG group, whereas young age was associated with weight gain in all subjects (estimates -0.033/1 year older, p < 0.001), DTG, RAL, and EFV groups. CONCLUSION: In Japanese PLWH, annual body weight change was comparable in TDF- and TAF-period, while TAF plus DTG correlated with weight gain. Since young age was a key determinant of weight change, careful interpretation is needed for TAF-associated weight gain.

Long-term administration of pegylated liposomal doxorubicin at almost twice the recommended lifetime dose in 10 years without cardiotoxicity in a Japanese patient with HIV-associated Kaposi sarcoma.

We report a Japanese patient with HIV-associated Kaposi sarcoma (KS) who had many cutaneous KS lesions with extensive bilateral groin edema. As the KS was refractory to antiretroviral therapy and pegylated liposomal doxorubicin (PLD), he was administered PLD up to a cumulative dose of 940 mg/m2 in 10 years, which exceeded the recommended lifetime dose (550 mg/m2). However, the patient showed no major adverse events, including cardiotoxicity, and he eventually died of pancreatic cancer.

[Undetectable anti-platelet factor 4/heparin antibodies with IgG-specific chemiluminescent immunoassays in a heparin-induced thrombocytopenia patient].

A 51-year-old man with a 9-month history of narrowing of visual fields and papilledema was admitted to the Department of Neurosurgery. Upon admission, glycerol was intravenously administered and heparin flushes were initiated to maintain intravenous access. Brain MRI revealed right transverse and sigmoid sinus thrombosis on hospital day 2, and the patient was treated with unfractionated heparin. On hospital day 9, the patient had a seizure and impaired mental status. Moreover, on hospital day 10, the platelet count decreased to less than half compared with that documented upon admission. The patient was then switched from heparin to argatroban because thrombosis exacerbation due to heparin-induced thrombocytopenia (HIT) was suspected. Despite negative IgG-specific chemiluminescent immunoassay for anti-platelet factor 4 (PF4) /heparin antibodies, positive functional assay led to the diagnosis of HIT. Warfarin was initiated and the platelet count was restored. Because maintaining the patient's PT-INR within the therapeutic range was difficult probably due to concomitant antimicrobial administration for complicating pneumonia, anticoagulation was switched to rivaroxaban. No bleeding or thrombotic complications developed. Thus, the presentation and clinical course should be considered for an accurate diagnosis of HIT. This is particularly important when the immunological assay is negative for anti-PF4/heparin antibodies. Furthermore, anticoagulation with rivaroxaban can be useful in the management of the subacute phase of HIT.

[Investigation of the Pathophysiology and Diagnostic Methods Through a Case of Acute HIV Infection in which the Western Blot Method Remained Negative Over the Long Term and the 4th Generation Screening Assay Became Negative for a Certain Period of Time after Initiating Antiretroviral Therapy].

Confirmatory tests using Western blot (WB) and HIV-1 nucleic acid testing (HIV-1 RNA) following a positive screening test are required for the diagnosis of HIV-1 infection according to the current Japanese guidelines for HIV-1/2 diagnosis. We report herein on a rare case in a patient who remained negative for WB over 10 months in spite of being positive by fourth-generation immunoassays (4thGIA) and who subsequently seroreverted by 4thGIA for three months after initiating antiretroviral therapy. Case: A man in his early twenties previously visited a hospital because of fever in October 2012. Laboratory data revealed leukocytopenia, thrombocytopenia and increased serum ferritin, suggesting hemophagocytic syndrome (HPS). During that visit, he tested positive for a 4thGIA, but negative for HIV-1 WB and his result of HIV-1 RNA result was detected invalid because of the presence of some inhibitory material in his RNA preparation. Thereafter, he was diagnosed as having cytomegalovirus-associated HPS treatment was for which initiated. In January 2013, he developed Pneumocystis jirovecii pneumonia, and his HIV-1 RNA viral load was 7.7 × 105 copies/mL in February 2013. Acute HIV infection was suspected, because the HIV-1 WB remained negative. He was started on antiretroviral therapy in April 2013. His 4thGIA was converted to negative in May 2013 and was reconverted to positive in August 2013. HIV-1 WB, however, continued to be indeterminant until February 2014, in which it turned positive for the first time according to the CDC criteria. Methods and Results: The genetic analyses of HIV-1 were done on the gag, env, nef and pol region of the HIV-1 gene from the patient. There was no clear element to delay antibody production on the virus side. Preserved specimens of the patient were measured with eight kinds of HIV screening assay. It was thought that the fourth generation assay was positive only by the presence of the antigen until March 2013 because the antibody had not been detected. Discussion: We encountered a case of acute HIV infection in which the WB result was negative for 10 months after the first positive response of the 4thGIA. The 4thGIA is essential for the early diagnosis and early treatment of HIV infection; therefore, the 4thGIA should be strictly recommended to avoid the use of older generations of immunoassay in the diagnostic guidelines. The role of the WB test should be examined closely from various aspects for use as a confirmatory test under recent laboratory situations in which highly sensitive and specific methods, e.g. the 4th GIA, have become available. In addition, unnecessary confusion due to the diversities of antibody formation should be avoided. The antibody detection tests for HIV are still necessary and indispensable for the confirmation of the disease or the diagnosis of the acute infection stage. Therefore development of a newer antibody measuring method which could achieve an easier operation and should have a higher sensitivity and specificity for HIV confirmation is strongly expected.

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.

[Syphilis Testing and High Rate of Infection Among HIV-infected Patients].

Background: The incidence of syphilis has globally increased over the last decade, particularly among men who have sex with men coinfected with the human immunodeficiency virus (HIV). HIV infection may make the clinical symptoms and seroreactivity of syphilis atypical, which requires careful consideration in terms of diagnoses and treatments by clinicians. Syphilis is known as a great imitator, and is often difficult to be diagnosed or it can be overlooked if clinicians depend only on its symptoms or signs. It is also highly contagious and could be transmitted without sexual intercourse, and reinfection is common. Guidelines recommend that all HIV-infected persons be provided with STD screening, including syphilis, at least annually. However, to our knowledge, there are no published data on the actual frequency of testing and instances of syphilis among HIV-infected persons in Japan. Materials and Methods: We collected data from HIV infected male patients who had sex with men (MSM) at Tokyo Medical University Hospital from June 2011 to June 2012. Data from the patients, who had been tested with the rapid plasma reagin assay (RPR) at least once during the study period, were retrospectively obtained from clinical records and were analyzed. Results: Among 1000 patients with HIV infection, 935 patients were MSM. 723 patients (77.4%) were tested using the Treponema pallidum latex agglutination test (TPLA) and RPR more than once during the study period. Out of the 723 patients, 443 patients (61.3%) were reactive for TPLA and 238 patients (32.9%) had reactive tests for RPR. All patients who were reactive for RPR were reactive for TPLA. Among the patients who were reactive for RPR, 93 patients (12.9%) were considered newly diagnosed or with a repeat infection. In this cohort, all patients were MSM with a median age of 37 years, and a median CD4+T-lymphocyte cell count of 465/uL. A total of 76 patients had been prescribed antiretroviral therapy, and 61 patients had a documented HIV-1 RNA viral load of <40 copies/mL at their most recent test. Two patients both developed two episodes of syphilis during the study period. Of the 95 episodes, 44% were symptomatic syphilis and the most common symptom among them was a skin rash at the second stage. Nearly half of the patients (47%) were diagnosed at regular screenings. Two thirds (67%) had syphilis infections before the study period, whereas at least 20% of them were newly diagnosed during the study period. Conclusions: A substantial percentage of the participants were newly or recurrently diagnosed with syphilis during the study period. More public health awareness should be encouraged regarding the current epidemic of syphilis among HIV-infected persons in Japan. It is also important for clinicians to provide HIV-infected persons with periodical syphilis screening, regardless of the apparent clinical signs or symptoms to achieve earlier treatment intervention.

[Status of use and side effects of atovaquone for the treatment and prevention of pneumocystis pneumonia in HIV infected patients in Japan--from 1997 to 2012--The Clinical Study Group for AIDS Drugs, supported by Health and Labor Science Grants from the Ministry of Health, Labor and Welfare, Japan].

PURPOSE: Atovaquone is effective and well-tolerated for the treatment of mild or moderate Pneumocystis pneumonia (PCP) and the prevention of PCP. When atovaquone was not yet approved in Japan, it was supplied by the Clinical Study Group for AIDS Drugs, which has been supported by the Japan Health Science Foundation since 1997. We investigated the status of use and the reported side effects, since atovaquone has recently been approved and made available in Japan. METHOD: We retrospectively examined the application and adverse events associated with atovaquone use between January 1997 and March 2012. RESULTS: During this period, there were 721 new applications, increasing over time, with the highest rate of increase observed in recent years. Fifty-seven adverse events in 39 patients were reported. Drug eruption was the most common side effect (20 cases), followed by cytopenia (11 cases), fever (10 cases), and liver dysfunction (8 cases). Two deaths were reported (one with an unknown correlation, another with no comments provided). One case of liver dysfunction attributable to atovaquone was severe. In this case, the AST and ALT levels increased to 1,921 IU/L, and 1,062 IU/L, respectively on day 4 of atovaquone administration, but these levels improved after atovaquone discontinuation. No other severe side effects were reported. DISCUSSION: This study revealed that as in other countries, few side effects caused by atovaquone were reported in Japan. Moreover, there were no side effects unique to the Japanese population. However, caution is required when administering atovaquone, because a low incidence of severe atovaquone-induced liver dysfunction has been reported.

[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.

Mutations to the probe of Cobas TaqMan HIV-1 ver. 1.0 assay causing undetectable viral load in a patient with acute HIV-1 infection.

We encountered a human immunodeficiency virus (HIV)-1 in which the viral load was undetectable with the Cobas TaqMan HIV-1 ver. 1.0 (CTM v.1.0) in a patient with acute HIV-1 infection. The CTM v.1.0 assay showed more than 1,000-fold underestimation compared with the subsequent Cobas Amplicor Monitor v.1.5 assay. Because five mismatches to the CTM v.1.0 assay probe in the HIV-1 virus in the patient were disclosed by the manufacturer, partial gag regions of the HIV genome were directly sequenced from the patient's plasma viral RNA. The detected single nucleotide point mutations were located near the 5'-end of the Cobas Amplicor Monitor probe. Clinicians should be very careful in making interpretations when indeterminate Western blot analysis results and a low or even undetectable HIV-1 viral load are encountered with the CTM HIV-1 ver. 1.0 assay in patients with suspected acute HIV infection. Repeating Western blot analysis is essential before considering a low HIV-1 viral load to be a false-positive result.

Whole brain radiation alone produces favourable outcomes for AIDS-related primary central nervous system lymphoma in the HAART era.

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.

[Utilities and limitations of a real-time PCR based assay for HIV-1 RNA quantification].

OBJECTIVE: This study evaluated the clinical utilities and limitations of HIV 1 RNA quantification using a real time PCR based assay, COBAS AmpliPrep/COBAS Taqman HIV 1 Test(TaqMan), since higher viral loads or wider fluctuations in viral loads have been demonstrated after this assay replaced COBAS AmpliPrep/AMPLICOR HIV-1 Monitor Version 1.5 Ultrasensitive (AMPLICOR). DESIGN AND RESULTS: We conducted a clinical study analyzing HIV-1 RNA levels measured by AMPLICOR assay and by TaqMan assay, CD4+ lymphocyte counts (CD4) and regimens of highly active antiretroviral therapy among patients who were treated in Tokyo Medical University Hospital. HIV 1 RNA levels were measured by an independent clinical laboratory (SRL, Inc.) outside the hospital. More than 50 copies/ml of HIV-1 RNA were demonstrated by TaqMan assay in 47% of 58 specimens in which HIV 1 RNA levels were undetectable (< 50 copies/ml) by AMPLICOR assay. TaqMan assay showed higher levels of HIV-1 RNA in comparison with AMPLICOR assay on correlation analysis. However, there was no tendency toward deterioration of either the serum HIV-1 RNA load or CD4 in patients showing discrepancies between the two assays. There was no correlation between the detection of HIV-1 RNA and the use of certain antiretroviral agents. Repeated assay of specimens from the same collection tube showed large discrepancies. CONCLUSION: HIV 1 RNA quantification assay is essential to monitor the effects of antiretroviral therapy. Physicians must remain aware that the TaqMan assay is not yet sufficiently reliable.

[High-titer idiopathic acquired factor V inhibitor patient showing decreased activities of multiple coagulation factors].

A 72-year-old male presented with oral bleeding resulting from acquired factor V (FV) inhibitor. We observed abnormalities in prothrombin time (PT) (8%) and activated partial thromboplastin time (APTT) (>200 seconds). FV activity was less than 3%, and a mixing test did not correlate with PT. FV inhibitor assay demonstrated 240 Bethesda units/ml. The patient also showed markedly decreased activity of Factors II (13%) and X (14%). Oral bleeding disappeared and coagulation abnormalities improved with prednisolone therapy. High titer FV inhibitor might affect coagulation assays even in a patient with normal factor activity.

[Asymmetric peripheral neuropathy following reduced-intensity cord blood transplantation].

A 57-year-old male patient in the first remission of acute erythroid leukemia underwent reduced-intensity umbilical cord blood transplantation. He developed grade III acute graft-versus-host disease (GVHD) on day 29. Although the acute GVHD was resolved with tacrolimus and steroid therapy, weakness developed in the left upper extremity on day 59. Neurological examination demonstrated asymmetric muscular weakness of the extremities with the proximal part of the left upper extremity being markedly affected. Neurophysiological studies suggested that this was due to immune-mediated demyelinating neuropathy. Intravenous immunoglobulin (IVIG) therapy was administered at a dose of 0.4 g/kg/day for 5 days and worsening of clinical symptoms ceased. While the patient developed diarrhea and chronic GVHD of the skin and cytomegalovirus (CMV) antigenemia was repeatedly positive, neurological exacerbation was stabilized. Neurological symptoms did not immediately improve after the second and third dose of IVIG. Approximately 50 days after the third dose of IVIG, neurological symptoms improved with the gradual resolution of diarrhea and CMV reactivation. Although the pathophysiology of polyneuropathies after allo-SCT is not well understood, some reports suggest an association with GVHD or alloreactive T cell expansion following antecedent infection. This case provides valuable information regarding the pathophysiology of peripheral neuropathy following allo-SCT.

HIV positivity may not have a negative impact on survival in Epstein-Barr virus-positive Hodgkin lymphoma: A Japanese nationwide retrospective survey.

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.

[Primary diffuse large B-cell lymphoma of the bone marrow complicated with autoimmune hemolytic anemia and erythroid hypoplasia].

A 75-year-old woman was admitted for general fatigue. Diagnostic investigations showed no lymphadenopathy or hepatosplenomegaly. Laboratory examinations revealed severe anemia and an undetectable level of haptoglobin in the peripheral blood. A direct Coombs test was positive. Bone marrow examination showed abnormal, large, CD20-positive lymphocytes and erythroid hypoplasia. Accordingly, a diagnosis of primary diffuse large B-cell lymphoma (DLBCL) of the bone marrow with autoimmune hemolytic anemia (AIHA) and erythroid hypoplasia was made. The patient was treated with prednisolone and 3 courses of rituximab, followed by 6 courses of R-CHOP. AIHA and erythroid hypoplasia subsided after prednisolone and 3 courses of rituximab. Treatment with 6 courses of R-CHOP resulted in complete remission. Isolated bone marrow disease as a presenting feature of DLBCL is very rare. Although malignant lymphomas are often associated with immunologic disorders, this is the first report of diffuse large B-cell lymphoma with isolated bone marrow disease and simultaneous autoimmune hemolytic anemia and erythroid hypoplasia. This case provides valuable information concerning the pathophysiology of an immunologic anomaly with malignant lymphoma.

[Varicella-zoster virus meningoencephalitis without skin manifestation in an allogeneic bone marrow transplantation patient successfully treated with aciclovir].

This report describes a 56-year-old man who developed meningoencephalitis as a result of varicella-zoster virus (VZV) without dermatomal manifestations. The patient received an allogeneic bone marrow transplantation for malignant lymphoma, and during treatment for chronic graft-versus-host disease, he presented with a fever and headache. Cerebrospinal fluid analysis revealed an increased cell count with lymphocyte predominance and an extremely high amount of VZV DNA, and an MRI study showed multiple lesions of increased T2 intensity within deep white matter regions. Meningoencephalitis was diagnosed and the patient was successfully treated with aciclovir administered at a dose of 30 mg/kg/day for four weeks.

Clinical and pathological aspects of human immunodeficiency virus-associated plasmablastic lymphoma: analysis of 24 cases.

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.