Impact of HIV status on prognosis of malignancies among people living with HIV in Japan.

BACKGROUND: Antiretroviral therapy has reduced the incidence and mortality of AIDS-defining malignancies (ADM); however, non-AIDS-defining malignancies (NADM) are a major cause of death among people living with HIV (PLWH) today. Though current guidelines suggest that PLWH should receive the same treatment as the general population, there are limited studies focused on how HIV status affects the prognosis of cancers. The present study aimed to investigate the characteristics and prognosis of malignant diseases among PLWH in Japan. METHODS: Patients with HIV diagnosed with malignant diseases at our institution between 2011 and 2021 were retrospectively reviewed. RESULTS: There were 205 patients who were diagnosed with malignancies. Of these, 87 (42.4%) were diagnosed with ADM and 118 (57.6%) were diagnosed with NADM. Among 69 patients who received chemotherapy for ADM, 24 (34.8%) developed AIDS-defining opportunistic infections during treatment. In contrast, only one (1.8%) of the 56 patients administered chemotherapy for NADM developed AIDS-defining opportunistic infections. Complications of opportunistic infections at diagnosis of malignancies, low CD4+ T-cell count, positive HIV RNA, and nonadministration of antiretroviral therapy were associated with 5-year overall survival among patients with malignant lymphomas. However, the variables associated with HIV did not affect NADM prognosis. CONCLUSIONS: In this analysis, HIV status had a small impact on the prognosis of malignant diseases in PLWH. Few patients with NADM developed AIDS-defining opportunistic infections after receiving chemotherapy.

Impact of sustained viral response for hepatitis C virus on the outcomes of liver transplantation in hemophilic patients with human immunodeficiency virus/hepatitis C virus co-infection: A nationwide survey in Japan.

AIM: Human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infection from blood products for hemophilia has been a social problem in Japan, and liver transplantation (LT) for these patients has been a challenging procedure. However, with the advent of the direct-acting antiviral agent for HCV and change in the policy for prioritization of deceased donor LT, the results of LT for patients co-infected with HCV/HIV may have improved. METHODS: This study was conducted to provide updated results of our nationwide survey of LT for patients co-infected with HCV/HIV, from January 1997 to December 2019. We collected data on 17 patients with HIV/HCV co-infection who underwent either deceased donor LT (n = 5) or living donor LT (n = 12). RESULTS: All the patients were men with hemophilia, and the median age was 41 (range, 23-61) years. The median CD4 count before LT was 258 (range, 63-751). Most patients had poor liver function before surgery with Child-Pugh grade C and a Model for End-stage Liver Disease score of 20 (range, 11-48). The right lobe was used for most grafts for living donor liver transplantation (n = 10). Overall survival was significantly better with a sustained viral response (SVR) than without an SVR, and a univariate analysis indicated that SVR after direct-acting antiviral or interferon/ribavirin showed the highest hazard ratio for patient survival after LT. A multivariate analysis was not possible because of the limited number of cases. CONCLUSION: SVR for HCV showed the highest impact on the outcome of LT for patients with hemophilia co-infected with HIV/HCV. SVR for HCV should be achieved before or after LT for patients with hemophilia co-infected with HIV/HCV for a better outcome.

Surgical management of appendicitis in patients with human immunodeficiency virus (HIV) positivity: a propensity score-matched analysis in a base hospital for HIV treatment in Japan.

PURPOSE: To investigate the impact of human immunodeficiency virus (HIV) infection on surgical outcomes after appendectomy. METHODS: Data on patients who underwent appendectomy for acute appendicitis between 2010 and 2020 at our hospital were investigated retrospectively. The patients were classified into HIV-positive and HIV-negative groups using propensity score-matching (PSM) analysis, adjusting for the five reported risk factors for postoperative complications: age, sex, Blumberg's sign, C-reactive protein level, and white blood cell count. We compared the postoperative outcomes of the two groups. HIV infection parameters, including the number and proportion of CD4 + lymphocytes and the HIV-RNA levels were also compared before and after appendectomy in the HIV-positive patients. RESULTS: Among 636 patients enrolled, 42 were HIV-positive and 594 were HIV-negative. Postoperative complications occurred in five HIV-positive patients and eight HIV-negative patients, with no significant difference in the incidence (p = 0.405) or severity of any complication (p = 0.655) between the groups. HIV infection was well-controlled preoperatively using antiretroviral therapy (83.3%). There was no deterioration in parameters and no changes in the postoperative treatment in any of the HIV-positive patients. CONCLUSION: Advances in antiviral drugs have made appendectomy a safe and feasible procedure for HIV-positive patients, with similar postoperative complication risks to HIV-negative patients.

Genetic and cytometric analyses of subcutaneous adipose tissue in patients with hemophilia and HIV-associated lipodystrophy.

BACKGROUND: The authors recently performed plastic surgeries for a small number of patients with hemophilia, HIV infection, and morphologic evidence of lipodystrophy. Because the pathophysiological mechanism of HIV-associated lipodystrophy remains to be elucidated, we analyzed subcutaneous adipose tissues from the patients. METHODS: All six patients had previously been treated with older nucleoside analogue reverse-transcriptase inhibitors (NRTIs; stavudine, didanosine or zidovudine). Abdominal and inguinal subcutaneous fat samples were obtained from the HIV+ patients with hemophilia and HIV- healthy volunteers (n = 6 per group), and analyzed via DNA microarray, real-time PCR, flow cytometry and immunohistochemistry. RESULTS: The time from initial NRTI treatment to collecting samples were 21.7 years in average. Cytometric analysis revealed infiltration of inflammatory M1 macrophages into HIV-infected adipose tissue and depletion of adipose-derived stem cells, possibly due to exhaustion following sustained adipocyte death. Genetic analysis revealed that adipose tissue from HIV+ group had increased immune activation, mitochondrial toxicity, chronic inflammation, progressive fibrosis and adipocyte dysfunction (e.g. insulin resistance, inhibited adipocyte differentiation and accelerated apoptosis). Of note, both triglyceride synthesis and lipolysis were inhibited in adipose tissue from patients with HIV. CONCLUSIONS: Our findings provide important insights into the pathogenesis of HIV-associated lipodystrophy, suggesting that fat redistribution may critically depend on adipocytes' sensitivity to drug-induced mitochondrial toxicity, which may lead either to atrophy or metabolic complications.

Indications and waiting list priority for deceased donor liver transplantation in HIV/HCV co-infected hemophilic patients in Japan through contaminated blood product.

HIV/HCV co-infection from blood products for hemophilia has been a social problem in Japan. Liver transplantation (LT) is an important treatment option for hepatic failure and cirrhosis of the liver in co-infected patients, and appropriate indications for LT, especially organ form deceased donors, are required by society. The aim is to propose priority status for the waiting list for deceased donor (DD) LT in HIV/HCV co-infected patients in Japan based on medical and scientific considerations. Since 2009, we have been working on the subject in research projects under grants-in-aid for health and labour sciences research on AIDS measures provided by the Ministry of Health, Labour and Welfare (the Kanematsu project and Eguchi project). Our research showed that hepatic fibrosis is advanced in HIV/HCV co-infected Japanese patients, especially those with hemophilia who became infected from blood products at a faster rate than HCV mono-infected patients. In addition, those patients who developed portal hypertension had a poor prognosis at a young age. The results of our research contributed to increasing the priority score of those patients on the deceased donor liver transplantation (DDLT) waiting list in 2013 and to establishing a scoring system for DDLT corresponding to the Model for End-stage Liver disease (MELD) score in 2019. This paper introduces changes in priority and the current state of priority of the DDLT waiting list for HIV/HCV co-infected patients in Japan.

Underestimated Amoebic Appendicitis among HIV-1-Infected Individuals in Japan.

Entamoeba histolytica is not a common causative agent of acute appendicitis. However, amoebic appendicitis can sometimes be severe and life threatening, mainly due to a lack of awareness. Also, its frequency, clinical features, and pathogenesis remain unclear. The study subjects were HIV-1-infected individuals who presented with acute appendicitis and later underwent appendectomy at our hospital between 1996 and 2014. Formalin-fixed paraffin-embedded preserved appendix specimens were reexamined by periodic acid-Schiff (PAS) staining and PCR to identify undiagnosed amoebic appendicitis. Appendectomies were performed in 57 patients with acute appendicitis. The seroprevalence of E. histolytica was 33% (14/43) from the available stored sera. Based on the medical records, only 3 cases were clinically diagnosed as amoebic appendicitis, including 2 diagnosed at the time of appendectomy and 1 case diagnosed by rereview of the appendix after the development of postoperative complications. Retrospective analyses using PAS staining and PCR identified 3 and 3 more cases, respectively. Thus, E. histolytica infection was confirmed in 9 cases (15.8%) in the present study. Apart from a significantly higher leukocyte count in E. histolytica-positive patients than in negative patients (median, 13,760 versus 10,385 cells/µl, respectively, P = 0.02), there were no other differences in the clinical features of the PCR-positive and -negative groups. In conclusion, E. histolytica infection was confirmed in 9 (15.8%) of the appendicitis cases. However, only 3, including one diagnosed after intestinal perforation, were diagnosed before the present analyses. These results strongly suggest there is frequently a failure to detect trophozoites in routine examination, resulting in an underestimation of the incidence of amoebic appendicitis.

Protease inhibitor-associated bone mineral density loss is related to hypothyroidism and related bone turnover acceleration.

BACKGROUND: Clinical and experiments evidence indicate that protease inhibitors (PI) can cause bone mineral density (BMD) loss. However, the mechanism of such loss remains obscure. METHODS: This single-center, cross-sectional study included 184 HIV-infected patients treated with PI who underwent dual-energy X-ray absorptiometry scan. Serum phosphorus, percentage of tubular reabsorption of phosphate (%TRP), thyroid and parathyroid function (iPTH), vitamin D, osteocalcin (OC), urinary deoxypyridinoline (DPD), and urinary cross-linked N-telopeptide of type I collagen (u-NTx) were measured. RESULTS: The rate of hypothyroidism in PI-users [32/117 (27%)] was double that in non-PI users [8/67 (12%), p = 0.016] and was significantly associated with PI use in multivariate analysis [odds ratio (OR) 11.37, 95% confidence interval (CI) 1.358-95.17, p = 0.025]. Spine BMD was significantly lower in hypothyroid patients than euthyroid, for both total population (-1.37 vs. -1.00, p = 0.041) and PI users (-1.56 vs. -1.13, p = 0.029). Multivariate regression analysis identified inverse correlation between hypothyroidism and spine BMD [estimate -0.437, 95% CI -0.858 to -0.024, p = 0.042]. OC, DPD and u-NTx were significantly higher in PI users than in non-PI users (p = 0.01, 0.05, and 0.01, respectively). CONCLUSIONS: PI use is associated with hypothyroidism as well as bone turnover acceleration, which worsens PI-associated BMD loss. In PI-treated patients, thyroid function tests are warranted to prevent further progression of PI-associated BMD loss.

HIV infection/AIDS.

In 2015, 36.7 million people globally were estimated to be living with HIV. As well as reduc- ing the morbidity and mortality of HIV-infected persons associated with HIV infection, effec- tive antiretroviral therapy has been demonstrated to reduce the risk of HIV transmission to sexual partners from HIV-infected person dramatically. Current treatment guidelines recom- mend antiretroviral therapy for all HIV-infected individuals, regardless of CD4 cell count.

Single-nucleotide polymorphisms in the UDP-glucuronosyltransferase 1A-3' untranslated region are associated with atazanavir-induced nephrolithiasis in patients with HIV-1 infection: a pharmacogenetic study.

OBJECTIVES: Ritonavir-boosted atazanavir (atazanavir/ritonavir) is a widely used antiretroviral drug, though it can potentially cause nephrolithiasis. The aim of this study was to determine the relationship between polymorphisms in genes encoding proteins involved in metabolism and transportation of atazanavir, and atazanavir/ritonavir-induced nephrolithiasis in HIV-1-infected patients treated with atazanavir/ritonavir. METHODS: Nineteen SNPs in the ABCB1, NR1I2, UGT1A1, SLCO1B1 and CYP3A5 genes were examined in case patients with atazanavir/ritonavir-induced nephrolithiasis (n = 31) and controls (n = 47). Case patients were those with a clinical diagnosis of nephrolithiasis while on atazanavir/ritonavir, based on new-onset acute flank pain plus one of the following: (i) new-onset haematuria; (ii) documented presence of stones by either abdominal ultrasonography or CT; or (iii) confirmed stone passage. Control patients were consecutively enrolled among those with >2 years of atazanavir/ritonavir exposure free of nephrolithiasis. Genotyping was performed by allelic discrimination using TaqMan 5'-nuclease assays with standard protocols. Associations between alleles and atazanavir/ritonavir-induced nephrolithiasis were tested by univariate and multivariate logistic regression analyses. RESULTS: Multivariate analysis showed a significant association between atazanavir/ritonavir-induced nephrolithiasis and genotype T/C versus C/C at position c.211 (adjusted OR = 3.7; 95% CI, 1.13-11.9; P = 0.030), genotype G/C versus C/C at 339 (adjusted OR = 5.8; 95% CI, 1.56-21.3; P = 0.009) and genotype G/G or G/C versus C/C at 440 (adjusted OR = 5.8; 95% CI, 1.56-21.3; P = 0.009) of the UGT1A-3' untranslated region (UTR). CONCLUSIONS: This is the first known study to identify the association between SNPs in the UGT1A-3'-UTR and atazanavir-induced nephrolithiasis. Further studies are warranted to confirm this association and to elucidate how these SNPs might influence atazanavir exposure.

Skin rash induced by ritonavir-boosted darunavir is common, but generally tolerable in an observational setting.

Ritonavir-boosted darunavir (DRV/r) is a protease inhibitor widely used in the treatment of HIV-1 infection. However, skin rash is a well-known adverse event of DRV, and limited data are available from observational settings. This observational study examined the characteristics of DRV-induced skin rash in treatment-naïve patients who commenced once-daily DRV/r-containing antiretroviral therapy (ART). Of the 292 study patients, DRV rashes developed in 31 (11%) patients with a median latency of 10 days (developing from 7 to 14 days in 93%) from initiation of ART. DRV skin rash was generally mild, as only one patient (3%) had grade 3 rash whereas 24 (77%) patients had grade 2 and 6 (19%) patients had grade 1. Only two patients (7%) discontinued DRV/r due to skin rash, and the other continued DRV/r and their rashes disappeared completely without any complications. Interestingly, DRV rash occurred more frequently to patients with less advanced HIV-1 infection than those with advanced infection. The incidence of DRV rash was not significantly different between patients with and without history of sulfonamide allergy (p = 0.201). Furthermore, when we exclude patients without history of sulfonamide use and only examine patients with sulfonamide use (n = 145), the result was similar (p = 0.548). In conclusion, DRV rashes were frequently observed but the prognosis was benign. Most patients tolerated DRV rashes with use of oral steroid or antihistamine without discontinuation of DRV. To date, there is no clear clinical evidence to suggest that DRV should be avoided in patients with history of sulfonamide allergy.

Urinary beta-2 microglobulin and alpha-1 microglobulin are useful screening markers for tenofovir-induced kidney tubulopathy in patients with HIV-1 infection: a diagnostic accuracy study.

Kidney tubulopathy is a well-known adverse event of antiretroviral agent tenofovir. A cross-sectional study was conducted to compare the diagnostic accuracy of five tubular markers, with a collection of abnormalities in these markers as the reference standard. The study subjects were patients with HIV-1 infection on ritonavir-boosted darunavir plus tenofovir/emtricitabine with suppressed viral load. Kidney tubular dysfunction (KTD) was predefined as the presence of at least three abnormalities in the following five parameters: ß2-microglobulinuria (ß2M), α1-microglobulinuria (α1M), high urinary N-acetyl-ß-D-glucosaminidase (NAG), fractional excretion of phosphate (FEIP), and fractional excretion of uric acid (FEUA). Receiver operating characteristic curves and areas under the curves (AUC) were estimated, and the differences between the largest AUC and each of the other AUCs were tested using a nonparametric method. The cutoff value of each tubular marker was determined using raw data of 100% sensitivity with maximal specificity. KTD was diagnosed in 19 of the 190 (10%) patients. The AUCs (95% CIs) of each tubular marker were ß2M, 0.970 (0.947-0.992); α1M, 0.968 (0.944-0.992); NAG, 0.901 (0.828-0.974); FEIP, 0.757 (0.607-0.907), and FEUA, 0.762 (0.653-0.872). The AUCs of ß2M and α1M were not significantly different, whereas those of the other three markers were smaller. The optimal cutoff values with 100% sensitivity were 1,123 µg/gCr (ß2M, specificity 89%), 15.4 mg/gCr (α1M, specificity 87%), 3.58 U/gCr (NAG, specificity 46%), 1.02% (FEIP, specificity 0%), and 3.92% (FEUA, specificity 12%). Urinary ß2M and α1M are potentially suitable screening tools for tenofovir-induced KTD. Monitoring either urinary ß2M or α1M should be useful in early detection of tenofovir nephrotoxicity.

High incidence of renal stones among HIV-infected patients on ritonavir-boosted atazanavir than in those receiving other protease inhibitor-containing antiretroviral therapy.

BACKGROUND: Little information is available on the incidence of renal stones with ritonavir-boosted atazanavir (ATV/r) use. METHODS: In a single-center study, the incidence of renal stones was compared between human immunodeficiency virus (HIV)-infected patients who commenced ritonavir-boosted atazanavir (ATV/r)-containing antiretroviral (ARV) therapy (the ATV/r group) and those who were receiving other protease inhibitors (the other PIs group). The effects of ATV/r were estimated by univariate and multivariate Cox proportional hazards regression models. Other possible risk factors were evaluated by univariate analysis, and those found to be significant were entered into multivariate analysis. RESULTS: Renal stones were diagnosed in 31 patients (23.7 cases per 1000 person-years) in the ATV/r group (n = 465) and 4 in patients (2.2 cases per 1000 person-years) in the other PIs group (n = 775). ATV/r use was significantly associated with renal stones, by univariate and multivariate analyses (adjusted hazard ratio, 10.44; 95% confidence interval [CI], 3.685-29.59; P < .001). ATV/r remained a significant risk factor for renal stones in all subgroups stratified by the median values of baseline variables. In the 31 patients receiving ATV/r who developed renal stones, the median time from commencement of ATV/r to diagnosis was 24.5 months (interquartile range, 14.7-34.6 months). Of the 18 patients who continued ATV/r despite the diagnosis of renal stones, 6 (33.3%) experienced recurrence. No patient who discontinued ATV/r experienced recurrence during the observation period (250.6 person-months). CONCLUSIONS: The incidence of renal stones was substantially higher among patients in the ATV/r group, compared with patients in the other PIs group. Continuation of ATV/r after diagnosis of renal stones was associated with a high rate of recurrence. Switching ATV/r to other ARVs is warranted in patients who develop renal stones.

Chronic hepatitis B in patients coinfected with human immunodeficiency virus in Japan: a retrospective multicenter analysis.

A nationwide survey in Japan revealed that about 6 % of human immunodeficiency virus (HIV)-positive patients are coinfected with hepatitis B virus (HBV). To further analyze the features of liver disease in HIV/HBV-coinfected patients, we analyzed 252 patients from six hospitals in the HIV/AIDS (acquired immunodeficiency syndrome) Network of Japan. The mean age was 39.5 years, and the proportion of male patients was very high (243 of 252; 96 %). The main transmission route was male homosexual contact (186 of 252; 74 %), followed by heterosexual contact. The HBV genotype was determined in 77 patients. Among them, genotype A HBV was the most frequent (58 of 77; 75 %) and was detected almost exclusively in homosexual patients. Acute hepatitis B was documented in 21 patients (8 %). Three of the 252 HIV/HBV-coinfected patients developed advanced liver disease with the complication of ascites, hepatic encephalopathy, or hepatocellular carcinoma. A comparison between patients not treated and those treated with antiretroviral drugs including anti-HBV drugs revealed that the baseline liver function was worse in treated patients. However, the serum albumin levels and platelet counts in both groups increased after treatment and were similar. Liver disease-associated death was not observed. Here, we characterize the clinical features of liver disease in HIV/HBV-coinfected patients in Japan for the first time. The findings suggest that antiretroviral therapy with anti-HBV drugs may retard the progression of a liver disease and prevent liver disease-associated death in such patients.

[Integrase inhibitors and CCR5 receptor antagonists].

Integrase inhibitors and CCR5 receptor antagonists, novel class of antiretrovirals, were introduced into clinical practice in late 2000s. Currently available drugs in these classes, raltegravir and maraviroc, show good tolerability and have little impact on lipid or glucose metabolism compared to traditional classes. Disadvantage of these two drugs is the need for twice-daily dosing. The usefulness of raltegravir in both treatment-naïve and treatment-experienced setting has been well established through clinical trials and five years' clinical use, whereas the usefulness of maraviroc in treatment-naïve setting is still unclear. These drugs will be utilized as a key component of NRTI-sparing regimens in the future.

Outcomes following cholecystectomy in human immunodeficiency virus-positive patients treated with antiretroviral therapy: A retrospective cohort study.

The number of the human immunodeficiency virus (HIV)-positive patients are increasing worldwide, and more HIV-positive patients are undergoing urgent or elective cholecystectomy. There is still insufficient evidence on the relationship between surgical complications of cholecystectomy and antiviral status in HIV-positive patients. The purpose of the present study is to evaluate surgical outcomes after cholecystectomy in HIV-positive patients. Records of consecutive HIV-positive patients who underwent cholecystectomy between January 2010 and December 2020 were reviewed retrospectively. Patients were divided into urgent and elective surgery groups. Urgent surgery was defined as surgery within 48 hours of admission. Postoperative complications were evaluated according to the Clavien-Dindo classification. A total of 30 HIV-positive patients underwent urgent (n = 7) or elective (n = 23) cholecystectomy. Four complications (13.3%) occurred, and the rate was significantly higher in the urgent group than in the elective group (p = 0.008). However, all complications were minor (3 cases of grade I and one case of grade II), and there were no severe postoperative complications. There was no significant difference in CD4+ lymphocyte status in all patients and between the 2 groups before and after surgery (p = 0.133). No cases of postoperative deterioration in the control of HIV infection were observed. In conclusion, cholecystectomy in HIV-positive patients with controlled HIV under recent antiretroviral therapy may be performed safely even in an emergency situation.

Characteristics of 2-drug regimen users living with HIV-1 in a real-world setting: A large-scale medical claim database analysis in Japan.

BACKGROUND: Regimen simplification to 2-drug antiretroviral therapy (2-ART) may address potential tolerability issues, increase adherence, and reduce toxicity and potential drug-drug-interactions among people living with HIV-1 (PLWH). However, real-world treatment patterns and characteristics of 2-ART users are unclear. METHODS: This retrospective observational cohort study employed a large-scale medical claim database of Japanese hospitals to extract data on 4,293 PLWH aged ≥18 years with diagnosis of HIV and treated with any ART regimens between April 2008 and April 2019. A 2-ART cohort was compared with a 3-drug antiretroviral therapy (3-ART) cohort in terms of population characteristics, comorbid conditions, and treatment patterns. Treatment switching rates were calculated for each cohort followed by sensitivity analysis to confirm the robustness of the findings. RESULTS: There were 94 individuals identified in the 2-ART cohort. Compared to the standard 3-ART cohort (n = 3,993), the 2-ART cohort was older (median age 53 [IQR 44-64] vs 42 years [IQR 35-50]), with a lower proportion of males (87.2% vs 93.8%), higher Charlson Comorbidity Index (CCI) (median score 6 [IQR 5-8] vs 5 [IQR 4-6]), more co-medications (median 6 [IQR 4-11] vs 3 [IQR 2-7]), and a higher percentage of AIDS-defining conditions (66.0% vs 42.8%). The most common 2-ART were protease inhibitor (PI) + integrase strand transfer inhibitor (INSTI) and non-nucleoside reverse transcriptase inhibitor (NNRTI) + INSTI (33.0% and 31.9%, respectively). Overall, most of the regimens were nucleoside reverse transcriptase inhibitor (NRTI)-sparing (71.3%), with a decreasing trend over time (76.2% to 70.2%). ART regimen switch occurred more often in the 2-ART cohort than in the 3-ART cohort (33.0% vs 21.2%). CONCLUSION: The profiles of individuals on 2-ART in Japan were demonstrated to be complex. Most were treated with NRTI-sparing regimens which may reflect an effort to reduce treatment-related toxicities.

Progressive Cytopenia Developing during Treatment of Cryptococcosis in a Patient with HIV Infection and Bone Marrow Cryptococcal Infection.

Cytopenia is a common complication in patients with human immunodeficiency virus (HIV) infection. Identifying the cause is demanding because of the wide range of possible diagnoses. We herein report an HIV-infected patient with disseminated cryptococcosis involving multiple organs including the blood, brain, lungs, and bone marrow, who developed progressive pancytopenia after initiation of anti-fungal treatment with liposomal amphotericin-B (L-AMB) and flucytosine (5FC). The pancytopenia persisted despite early 5FC discontinuation. A bone marrow biopsy revealed cryptococcal infiltration and the blood examination findings recovered quickly after resuming L-AMB. Thus, this HIV-infected patient's pathological findings and clinical course suggested that the primary cause of the pancytopenia was bone marrow cryptococcosis.

Unmasking latent extrapulmonary tuberculosis with newly diagnosed HIV-1 infection in a COVID-19 patient with prolonged fever.

Prolonged fever is a common symptom of COVID-19 infection. However, other febrile diseases continue during the pandemic. Herein, we report a COVID-19-infected patient with prolonged fever despite the lack of oxygen requirement, who was finally diagnosed with tuberculotic lymphadenitis and HIV-1 infection. All symptoms improved rapidly after the initiation of antituberculosis medications. Tuberculosis is an important differential diagnosis for patients with prolonged fever during the COVID-19 pandemic. It is possible that COVID-19 infection could serve to unmask latent infections via a cytokine storm.

Anal human papillomavirus infection and its relationship with abnormal anal cytology among MSM with or without HIV infection in Japan.

Anal high-risk human papillomavirus (hr-HPV) infection is widely considered a cause of anal cancer. However, epidemiological data are quite limited in Japan. This study investigated anal HPV infections and cytological abnormalities among MSM with or without HIV infection. Anal swabs were obtained, and cytological results were examined. Hybrid capture-based methodology was used for hr-HPV genotyping. The exclusion criterion was a history of vaccination against HPV. 644 subjects participated, and the overall prevalence of hr-HPV was 59.7% (95% CI 54.7-62.3), HIV-infected had higher prevalence than HIV-uninfected (68.9% vs 40.6%) p < .001. Among hr-HPV-infected participants, 82.8% (312/377) were infected with at least one of 9 valent vaccine-covered hr-HPV genotypes. From regression analysis, detection of abnormal cytology correlated positively with HIV infection (OR 2.17 [95% CI 1.51-3.13]), number of hr-HPV genotypes infected (OR 1.83 [1.59-2.10]), history of STI (OR 1.58 [1.14-2.22]) and No. of lifetime sexual partners (OR 1.56 [1.10-2.21]), albeit multivariate analysis identified the number of detected hr-HPV genotypes (adjusted OR 1.78 [1.54-2.06]) as the independent risk factor for abnormal cytology. High rates of anal hr-HPV infection, especially 9-valent HPV vaccine-preventable hr-HPV were detected among our MSM participants in Japan. HPV vaccination should also be encouraged for MSM in Japan.