Outcomes in Kaposi's sarcoma-associated herpesvirus -associated primary effusion lymphoma and multicentric Castleman's disease in patients with human immunodeficiency virus (HIV) in a safety-net hospital system.

OBJECTIVE: To describe cases of Kaposi's sarcoma-associated herpesvirus (KSHV)-associated multicentric Castleman's disease (MCD) and primary effusion lymphoma (PEL) in patients with HIV from a large, safety-net hospital system in Dallas, Texas, USA. METHODS: We conducted a retrospective review of patients with HIV-associated PEL and/or MCD. RESULTS: Twelve patients with PEL and 10 patients with MCD were identified. All patients were male and 17 of 20 were men who have sex with men; 66.7% of PEL patients and 50% of MCD patients had concurrent KS at the time of diagnosis; 42% of patients with PEL and 20% of patients with MCD died during the follow-up period. We noted improved survival in our cohort compared to previous studies, particularly in our PEL patients with a median survival of 11.4 months compared to 3-6-month median survival historically. Median follow-up time for MCD patients was 17.5 months. This improved survival is despite suboptimal antiretroviral therapy (ART) adherence at diagnosis, with only 50% of patients on ART at the time of MCD/PEL diagnosis. CONCLUSION: These data highlight the importance of early recognition of PEL and MCD, and the larger-scale efforts needed to better understand the pathogenetic drivers of clinical outcomes in patients affected by KSHV-related diseases.

Prevalence, Incidence, and Predictors of Kaposi Sarcoma-associated Herpesvirus Infection Among Young Men Who Have Sex with Men in the Southern United States.

Kaposi Sarcoma (KS) continues to cause substantial morbidity and mortality in populations at risk in the southern US. Utilizing biospecimens from the Houston site of the Young Men's Affiliate Project, 351 men who have sex with men had blood tested for Kaposi Sarcoma-associated herpesvirus (KSHV) IgG. Measuring seroprevalence, seroconversion between timepoints, and demographic and clinical correlates, KSHV prevalence was 36.7% and incidence was 8.9 per 100 person-years, prevalence and incidence were higher among Black individuals, people living with HIV, and those with a history of syphilis. Further research on KSHV risk may improve health disparities in KS diagnosis and outcomes.

Severe Mpox Infections in People With Uncontrolled Human Immunodeficiency Virus.

In the current mpox outbreak, infections are usually self-limited. We describe 3 patients with uncontrolled HIV and mpox infections lasting months, causing debilitating lesions, complications, and death, despite initiating anti-mpox and antiretroviral therapy. Delayed treatment of mpox with antiviral agents may contribute to poor outcomes in severely immunocompromised patients.

High Seroprevalence of Kaposi Sarcoma-Associated Herpesvirus in Men Who Have Sex With Men With HIV in the Southern United States.

Background: Disparities in mortality in human immunodeficiency virus (HIV)-associated Kaposi sarcoma have been described, particularly in Black men in the southern United States. It is unclear if there are racial/ethnic differences in the seroprevalence of Kaposi sarcoma-associated herpesvirus (KSHV) that may be contributing. Methods: This is a cross-sectional study of men who have sex with men (MSM) and transgender women with HIV. Participants were recruited from an outpatient HIV clinic in Dallas, Texas, for a 1-time study visit and were excluded from analysis if they had any history of KSHV disease. Plasma was tested for antibodies to KSHV K8.1 or ORF73 antigens, and KSHV DNA was measured in oral fluids and blood by polymerase chain reaction. KSHV seroprevalence and viral shedding in blood and oral fluids were calculated. Additionally, independent risk factors for KSHV seropositivity were assessed by multivariable logistic regression analysis. Results: Two hundred five participants were included in our analysis. Overall, KSHV seroprevalence was high (68%) with no significant difference between racial/ethnic groups. Among seropositive participants, KSHV DNA was detected in 28.6% of oral fluids and 10.9% of peripheral blood specimens, respectively. The factors most strongly associated with KSHV seropositivity were oral-anal sex (odds ratio [OR], 3.02), oral-penile sex (OR, 4.63), and methamphetamine use (OR, 4.67). Conclusions: High local seroprevalence of KSHV is likely a key driver of the high burden of KSHV-associated diseases regionally, though it does not explain the observed disparities in KSHV-associated disease prevalence among racial/ethnic groups. Our findings support that KSHV is primarily transmitted via exchange of oral fluids.

Mortality disparities among patients with HIV-associated Kaposi's sarcoma in the southern United States.

OBJECTIVE: To describe risk factors for mortality in HIV-associated Kaposi's sarcoma in an urban population in Dallas, Texas. DESIGN: Retrospective electronic medical record review of patients with HIV-associated Kaposi's sarcoma. METHODS: Electronic medical records were reviewed from 1 January 2009 to 31 December 2018 for patients with a diagnosis of HIV and Kaposi's sarcoma by ICD-9 or ICD-10 codes. Demographics, HIV history, Kaposi's sarcoma history, treatment, and mortality data were collected. Mortality data was supplemented by an inquiry from the National Death Index (NDI). Survival analyses were performed using Cox proportional hazards analysis to determine independent predictors of mortality. RESULTS: Black patients had higher mortality than white or Hispanic patients (hazard ratio 2.07, 95% confidence interval 1.12-3.82), even after adjusting for covariates. This mortality difference correlates with higher rates of advanced Kaposi's sarcoma disease and KS-IRIS in black patients compared with other groups and is not explained by differences in CD4+ cell count, HIV viral load, engagement in care, or ART adherence at the time of cancer diagnosis. CONCLUSION: Despite nationwide trends showing decreased incidence and decreased mortality in Kaposi's sarcoma in the ART era, a high number of Kaposi's sarcoma cases and disparities in Kaposi's sarcoma outcomes persist in certain populations in the United States.

Toxoplasmosis Encephalitis: A Cross-Sectional Analysis at a U.S. Safety-Net Hospital in the Late cART Era.

Despite decreasing incidence of toxoplasmosis encephalitis(TE) among people living with HIV(PLWH) in the late antiretroviral era, U.S. safety-net hospitals still see significant numbers of admissions for TE. Little is known about this population, their healthcare utilization and long-term outcomes. We conducted an 8-year retrospective review of PLWH with TE at a safety-net hospital. Demographics, clinical characteristics, treatments, readmissions, and outcomes were collected. We used chi-squared test to evaluate 6-month all-cause readmission and demographic/clinical characteristics. Of 38 patients identified, 79% and 40% had a new diagnosis of TE and HIV respectively. 59% had 6-month all-cause readmission. Social factors were associated with readmission (uninsured (p = 0.036), Spanish as primary language (p = 0.017), non-adherence (p = 0.030)) and not markers of clinical severity (ICU admission, steroid-use, concomitant infections, therapeutic adverse events). Despite high readmission rates, at follow-up, 60% had a complete response, 30% had a partial response. Improving TE outcomes requires focus on culturally competent, coordinated care.

Mouse and Human Monoclonal Antibodies Protect against Infection by Multiple Genotypes of Japanese Encephalitis Virus.

Japanese encephalitis virus (JEV) remains a leading cause of viral encephalitis worldwide. Although JEV-specific antibodies have been described, an assessment of their ability to neutralize multiple genotypes of JEV has been limited. Here, we describe the development of a panel of mouse and human neutralizing monoclonal antibodies (MAbs) that inhibit infection in cell culture of four different JEV genotypes tested. Mechanism-of-action studies showed that many of these MAbs inhibited infection at a postattachment step, including blockade of virus fusion. Mapping studies using site-directed mutagenesis and hydrogen-deuterium exchange with mass spectrometry revealed that the lateral ridge on domain III of the envelope protein was a primary recognition epitope for our panel of strongly neutralizing MAbs. Therapeutic studies in mice demonstrated protection against lethality caused by genotype I and III strains when MAbs were administered as a single dose even 5 days after infection. This information may inform the development of vaccines and therapeutic antibodies as emerging strains and genotypic shifts become more prevalent.IMPORTANCE Although Japanese encephalitis virus (JEV) is a vaccine-preventable cause of viral encephalitis, the inactivated and live attenuated platforms available are derived from strains belonging to a single genotype (GIII) due to its historical prevalence in areas of JEV epidemics. Related to this, studies with vaccines and antibodies have focused on assessing the in vitro and in vivo protective responses to homologous or heterologous GIII strains. An epidemiological shift in JEV genotype distribution warrants the induction of broadly neutralizing antibody responses that inhibit infection of multiple JEV genotypes. Here, we generated a panel of mouse and human neutralizing monoclonal antibodies and evaluated their inhibitory activity, epitope location, and capacity for protection against multiple JEV genotypes in mice.