Immunogenicity, effectiveness, and safety of SARS-CoV-2 vaccination in people with HIV.

OBJECTIVES: People with HIV (PWH) experience a greater risk of morbidity and mortality following COVID-19 infection, and poorer immunological responses to several vaccines. We explored existing evidence regarding the immunogenicity, effectiveness, and safety of SARS-CoV-2 vaccines in PWH compared with controls. METHODS: We conducted a systematic search of electronic databases from January 2020 until June 2022, in addition to conference databases, to identify studies comparing clinical, immunogenicity, and safety in PWH and controls. We compared results between those with low (<350 cells/µl) and high (>350 cells/µl) CD4 + T-cell counts where possible. We performed a meta-analysis of seroconversion and neutralization responses to calculate a pooled risk ratio as the measure of effect. RESULTS: We identified 30 studies, including four reporting clinical effectiveness, 27 immunogenicity, and 12 reporting safety outcomes. PWH were 3% [risk ratio 0.97, 95% confidence interval (95% CI) 0.95-0.99] less likely to seroconvert and 5% less likely to demonstrate neutralization responses (risk ratio 0.95, 95% CI 0.91-0.99) following a primary vaccine schedule. Having a CD4 + T-cell count less than 350 cells/µl (risk ratio 0.91, 95% CI 0.83-0.99) compared with a CD4 + T-cell count more than 350 cells/µl, and receipt of a non-mRNA vaccine in PWH compared with controls (risk ratio 0.86, 95% CI 0.77-0.96) were associated with reduced seroconversion. Two studies reported worse clinical outcomes in PWH. CONCLUSION: Although vaccines appear well tolerated in PWH, this group experience poorer immunological responses following vaccination than controls, particularly with non-mRNA vaccines and low CD4 + T-cell counts. PWH should be prioritized for mRNA COVID-19 vaccines, especially PWH with more advanced immunodeficiency.

Human immunodeficiency virus and solid organ transplantation: a 15-year retrospective audit at a tertiary Australian transplant centre.

BACKGROUND: The incidence of end-stage organ disease in people living with human immunodeficiency virus (HIV) (PLWH) is increasing, as people live longer due to potent, tolerable antiretroviral therapy (ART). Consequently, the number of PLWH who would benefit from solid organ transplant (SOT) is rising. The SOT experience in PLWH in Australia remains limited. Aim To retrospectively review the outcomes for SOT in PLWH at our service, in Victoria, Australia. METHODS: A retrospective cohort study of PLWH undergoing SOT over a 15-year period was performed. Adult PLWH age >18 years were eligible and identified from the Victorian HIV Service database. Descriptive statistics were used to summarise baseline demographics and clinical data, and outcomes following SOT. RESULTS: Nine virologically suppressed PLWH underwent SOT from HIV-negative donors (five kidneys, two livers and two bilateral sequential lung transplants). All patients were male, with a median age of 57.3 years (interquartile range (IQR) = 54.3-60.1) and CD4 count of 485 (IQR = 342-835) at transplantation, and comorbidities were common at baseline. After a median follow up of 3.9 years (IQR = 2.7-7.6), 8 (89%) patents were alive, 7 (78%) had functioning grafts, although 5 (56%) experienced organ rejection. Infections were common. Two patients required modification to their ART due to significant drug-drug interactions prior to transplant, while 5 (56%) had modifications post-SOT. No patients experienced HIV virologic failure. CONCLUSION: PLWH with end-stage organ disease experience good clinical and functional outcomes and should be considered for SOT where indicated. However, multidisciplinary planning and care is essential to optimise care in this patient group.

Treatment of invasive IMP-4 Enterobacter cloacae infection in transplant recipients using ceftazidime/avibactam with aztreonam: A case series and literature review.

Infections caused by carbapenemase-producing Enterobacteriaceae (CPE) are an emerging threat in both solid organ and stem cell transplant recipients. Invasive CPE infections in transplant recipients are associated with a high mortality, often due to limited therapeutic options and antibacterial toxicities. One of the most therapeutically challenging group of CPE are the metallo-ß-lactamase (MBL)-producing Gram-negative bacteria, which are now found worldwide, and often need treatment with older, highly toxic antimicrobial regimens. Newer ß-lactamase inhibitors such as avibactam have well-established activity against certain carbapenemases such as Klebsiella pneumoniae carbapenemases (KPC), but have no activity against MBL-producing organisms. Conversely, aztreonam has activity against MBL-producing organisms but is often inactivated by other co-existing ß-lactamases. Here, we report four cases of invasive MBL-CPE infections in transplant recipients caused by IMP-4-producing Enterobacter cloacae who were successfully treated with a new, mechanism-driven antimicrobial combination of ceftazidime/avibactam with aztreonam. This novel antimicrobial combination offers a useful treatment option for high-risk patients with CPE infection, with reduced drug interactions and toxicity.

Sufentanil Sublingual Tablet System for the Management of Postoperative Pain after Knee or Hip Arthroplasty: A Randomized, Placebo-controlled Study.

BACKGROUND: Complications with IV patient-controlled analgesia include programming errors, invasive access, and impairment of mobility. This study evaluated an investigational sufentanil sublingual tablet system (SSTS) for the management of pain after knee or hip arthroplasty. METHODS: This prospective, randomized, parallel-arm, double-blind study randomized postoperative patients at 34 U.S. sites to receive SSTS 15 µg (n = 315) or an identical placebo system (n = 104) and pain scores were recorded for up to 72 h. Adult patients with American Society of Anesthesiologists status 1 to 3 after primary total unilateral knee or hip replacement under general anesthesia or with spinal anesthesia that did not include intrathecal opioids were eligible. Patients were excluded if they were opioid tolerant. The primary endpoint was the time-weighted summed pain intensity difference to baseline over 48 h. Secondary endpoints included total pain relief, patient and healthcare professional global assessments, and patient and nurse ease-of-care questionnaires. RESULTS: Summed pain intensity difference (standard error) was higher (better) in the SSTS group compared with placebo (76 [7] vs. -11 [11], difference 88 [95% CI, 66 to 109]; P < 0.001). In the SSTS group, more patients and nurses responded "good" or "excellent" on the global assessments compared with placebo (P < 0.001). Patient and nurse ease-of-care ratings for the system were high in both groups. There was a higher incidence of nausea and pruritus in the SSTS group. CONCLUSION: SSTS could be an effective patient-controlled pain management modality in patients after major orthopedic surgery and is easy to use by both patients and healthcare professionals.

Intracystic Breast Carcinoma with Giant Axillary Metastasis: A Case Report.

Cystic breast disease is the most frequent cause of benign breast masses. While breast cysts are common, intracystic lesions, especially intracystic carcinomas, are rare. Furthermore, while breast carcinoma is the most common cancer in women, intracystic breast cancers are rare. Most intracystic breast carcinomas have been described as either papillary or medullary subtypes with infiltrating ductal carcinomas being much less common. The literature has shown their incidence to range from 0.3% to 7% of all breast carcinomas. We describe an interesting case of a premenopausal woman with a large cystic breast carcinoma and review the literature.