Clinical features and management of individuals admitted to hospital with monkeypox and associated complications across the UK: a retrospective cohort study.

BACKGROUND: The scale of the 2022 global mpox (formerly known as monkeypox) outbreak has been unprecedented. In less than 6 months, non-endemic countries have reported more than 67 000 cases of a disease that had previously been rare outside of Africa. Mortality has been reported as rare but hospital admission has been relatively common. We aimed to describe the clinical and laboratory characteristics and outcomes of individuals admitted to hospital with mpox and associated complications, including tecovirimat recipients. METHODS: In this cohort study, we undertook retrospective review of electronic clinical records and pathology data for all individuals admitted between May 6, and Aug 3, 2022, to 16 hospitals from the Specialist and High Consequence Infectious Diseases Network for Monkeypox. The hospitals were located in ten cities in England and Northern Ireland. Inclusion criteria were clinical signs consistent with mpox and MPXV DNA detected from at least one clinical sample by PCR testing. Patients admitted solely for isolation purposes were excluded from the study. Key outcomes included admission indication, complications (including pain, secondary infection, and mortality) and use of antibiotic and anti-viral treatments. Routine biochemistry, haematology, microbiology, and virology data were also collected. Outcomes were assessed in all patients with available data. FINDINGS: 156 individuals were admitted to hospital with complicated mpox during the study period. 153 (98%) were male and three (2%) were female, with a median age of 35 years (IQR 30-44). Gender data were collected from electronic patient records, which encompassed full formal review of clincian notes. The prespecified options for data collection for gender were male, female, trans, non-binary, or unknown. 105 (71%) of 148 participants with available ethnicity data were of White ethnicity and 47 (30%) of 155 were living with HIV with a median CD4 count of 510 cells per mm3 (IQR 349-828). Rectal or perianal pain (including proctitis) was the most common indication for hospital admission (44 [28%] of 156). Severe pain was reported in 89 (57%) of 156, and secondary bacterial infection in 82 (58%) of 142 individuals with available data. Median admission duration was 5 days (IQR 2-9). Ten individuals required surgery and two cases of encephalitis were reported. 38 (24%) of the 156 individuals received tecovirimat with early cessation in four cases (two owing to hepatic transaminitis, one to rapid treatment response, and one to patient choice). No deaths occurred during the study period. INTERPRETATION: Although life-threatening mpox appears rare in hospitalised populations during the current outbreak, severe mpox and associated complications can occur in immunocompetent individuals. Analgesia and management of superimposed bacterial infection are priorities for patients admitted to hospital. FUNDING: None.

A phase IV, open-label three-arm study investigating the impact of a combination of tenofovir disoproxil fumarate/emtricitabine with raltegravir or dolutegravir or elvitegravir/cobicistat on renal function in HIV-1 antiretroviral naïve patients.

Objectives: Tenofovir DF (TDF) remains one of the preferred backbone agents for naïve HIV patients starting antiretroviral treatment (ART). The impact of TDF on renal function and metabolic parameters may vary by anchor agent. We investigated the impact of TDF in combination with 3 different integrase inhibitors on tubular and glomerular function, and metabolic parameters in ART-naïve patients.Methods: Sixty patients with normal renal function were randomised (20 per arm) to TDF/emtricitabine (FTC) plus either raltegravir (RAL) (400 mg b.d.), dolutegravir (DTG) or elvitegravir/cobicistat (EVG/c) for 48 weeks.Results: 57 patients completed the study. Significant increases in RBP/creatinine ratio at week 24 were seen in all arms [RAL +4.7 µg/mmol (CI 0.43 to 8.98, p = 0.032); DTG +4.96 µg/mmol (CI 0.77 to 9.15, p = 0.021); EVG/c +6.95 µg/mmol (CI 2.53 to 11.36, p = 0.002)], although this was not sustained to week 48 in the RAL arm. Similar changes across the arms were observed for urinary α1microglobulin (RAL +6.20 mg/L, p = 0.030; DTG +6.30 mg/L, p = 0.025; EVG/c +8.15 mg/L, p = 0.003). Urinary ß2microglobulin significantly increased at week 24 with DTG and EVG/c but remained unchanged in the RAL arm. Glomerular filtration measured with CKD-EPI creatinine-cystatin C increased significantly in the RAL arm at week 24 through 48 but declined modestly in other two arms. Total and LDL cholesterol decreased in the RAL arm, but increased in the EVG/c arm, with no significant changes in the DTG arm. Weight increased significantly from baseline with DTG but not RAL or EVG/c.Conclusion: INSTIs in combination with TDF/FTC impact differently on tubular microproteinuria, eGFR, metabolic markers and weight. Use of TDF/FTC with RAL had the least tubular effects and the most favorable metabolic profile.

A case of pulmonary nodules in a patient living with HIV diagnosed with secondary syphilis.

We discuss a case of secondary syphilis with pulmonary involvement in a 45-year-old man who tested positive for HIV. He presented with dyspnoea, chest pain and a rash on his limbs and torso. A CT showed multiple bilateral necrotic lung nodules. A diagnosis of pulmonary syphilis was made due to his respiratory symptoms and imaging, his serological, histopathology findings, and the resolution of symptoms on treatment with benzathine penicillin.

Recent advances in HIV-associated Kaposi sarcoma.

Kaposi sarcoma (KS) is a mesenchymal tumour caused by KS-associated herpesvirus and is an AIDS-defining illness. Despite a decline in incidence since the introduction of combination anti-retroviral therapy, KS remains the most common cancer in people living with HIV in sub-Saharan Africa, where it causes significant morbidity and mortality. This review reflects on recent epidemiological data as well as current management, unmet needs and future perspectives in the treatment of HIV-associated KS with particular emphasis on the potential role of immune checkpoint inhibitors.

High Incidence of Infections in HIV-positive Patients Treated for Lymphoproliferative Disorders.

BACKGROUND: Lymphoproliferative disorders are frequently diagnosed in HIV-positive patients and severe infections may occur during antineoplastic treatments: the incidence and impact of such events are not well-characterized. OBJECTIVE: To describe the occurrence and mortality of incident infections in HIV-positive individuals treated for lymphoproliferative disorders. METHODS: A retrospective study in HIV-positive adults with lymphoproliferative disorders (2000- 2012) who were hospitalised to receive antineoplastic chemotherapy; antimicrobial prophylaxis with alternate day co-trimoxazole (800/160 mg) was administered to all individuals. RESULTS: 103 patients were included: mostly males (81, 78.6%), Caucasians (101, 98.1%), with a median age of 43 years (39-51). Fifty-eight (56.3%) patients had non-Hodgkin's lymphoma (NHL), thirty-two (29.1%) had Hodgkin's lymphoma (HL) and ten patients (9.7%) had Burkitt's lymphoma (BL). Five year survival was 63.1%: the best survival rates were reported in HL (78.1%), followed by NHL (58.6%) and BL (50%). Forty-four patients (42.7%) developed 82 infections during follow up: identified causative agents were bacteria (35, 42.7%), viruses (28, 34.1%), mycobacteria (7, 8.5%), protozoa (7, 8.5%) and fungi (5, 6.1%). Cytomegalovirus infections (n=17, including 5 endorgan diseases) emerged 53 days after the diagnosis: multivariate analysis showed CD4+ cell count <100/uL as the only independently associated factor (p<0.001, aOR=23.5). Two factors were associated with mortality risk: an IPI/IPS-score of >2 (p=0.004, aOR=6.55) and the presence of CMV disease (p=0.032, aOR=2.73). CONCLUSION: HIV positive patients receiving treatment for lymphoproliferative disorders suffer from a high incidence of infections and associated mortality risk. Tailored prophylactic strategies need to be considered in this setting.

Cerebrospinal fluid inhibitory quotients of antiretroviral drugs in HIV-infected patients are associated with compartmental viral control.

BACKGROUND: Despite the efficacy of highly active antiretroviral treatment (HAART), a large proportion of human immunodeficiency virus (HIV)-infected patients may develop moderate neurocognitive impairment. Antiretroviral drug passage into the central nervous system may be relevant for preventing and treating HIV-associated neurocognitive disorder; nevertheless, clear cerebrospinal fluid (CSF) pharmacodynamic targets are not known. METHODS: HAART-treated adults with wild-type HIV were prospectively enrolled. CSF concentrations (measured by mass spectrophotometric methods) and inhibitory quotients (CSF concentrations divided by in vitro 50% and 95% inhibitory concentrations) were compared among different drugs and related to CSF HIV RNA levels. CSF escape was defined as CSF HIV RNA >50 copies/mL despite contemporary plasma HIV RNA below that threshold. RESULTS: One hundred twenty-seven patients (91 male [71.7%], 93 white [73.2%], with a median age of 46 years [interquartile range, 40.5-54.5 years]) provided 174 paired CSF and plasma samples. Twice-daily darunavir, once-daily darunavir, and efavirenz had the highest CSF 95% inhibitory quotients (18.5, 8.2, and 6.4, respectively). Higher nadir CD4 cell count (P = .01) and plasma HIV RNA <50 copies/mL (P < .001) were independent predictors of controlled CSF HIV RNA. Optimal drug exposure (CSF detectable drugs and 95% inhibitory quotient >1) was protective for CSF escape (P = .01). CONCLUSIONS: Cerebrospinal fluid 95% inhibitory quotients may be used to compare antiretroviral drug compartmental exposure; they deserve longitudinal studies to assess the adequacy of CSF drug concentrations in treated HIV-infected patients.