Prophylaxis Of Opportunistic Infections Research Articles

Vaccination in children living with HIV – review of Polish recommendations

Vaccines are an extremely effective primary prevention tool recommended for routine use in children worldwide. Vaccination is crucial for patients with underlying diseases, including children living with HIV, because of their increased risk of morbidity and mortality from various vaccine-preventable diseases. Complex care for patients living with HIV includes antiretroviral therapy (which has dramatically improved survival), prophylaxis and treatment of common infections, prophylaxis and treatment of opportunistic infections, and vaccination. Immunisation is generally safe and beneficial for children living with HIV, although HIV-induced immune suppression reduces the benefits. All inactivated vaccines, whether killed whole organism or subunit, recombinant, toxoid, polysaccharide or conjugate (which includes diphtheria, tetanus, pertussis, poliomyelitis, Haemophilus influenzae type b, hepatitis B, hepatitis A, Streptococcus pneumoniae vaccines, Neisseria meningitidis, influenza, HPV), can be administered safely. Live attenuated measles–mumps–rubella and varicella vaccines are indicated in children without severe immunodeficiency. The Bacillus Calmette–Guérin vaccine is contraindicated due to the risk of disseminated BCG infection. Although a live attenuated influenza vaccine is available, it is contraindicated for people living with HIV because of the paucity of safety data and the availability of alternative vaccines. The study reviews the current paediatric immunisation recommendations in HIV infection in Poland. Additionally, we focus on vaccine effectiveness, especially HBV protection based on anti-Hbs antibodies.

Treatment patterns and outcomes of high-grade immune checkpoint inhibitor-related pneumonitis in an oncology hospitalist service.

Immune checkpoint inhibitors (ICI) have become standard of care for some types of lung cancer. Along with expanding usage comes the emergence of immune-related adverse events (irAEs), including ICI-related pneumonitis (ICI-P). Treatment guidelines for managing irAEs have been developed; however, how clinicians manage irAEs in the real-world setting is less well known. We aimed to describe the outcomes and care patterns of grade ≥ 3 ICI-P in an onco-hospitalist service. We included patients with lung cancer treated with ICI who were admitted to an oncology hospitalist service with a suspicion of ICI-P. We described the hospitalization characteristics, treatment patterns, discharge practices, and clinical outcomes of patients with confirmed ICI-P. The primary outcome was time to start treatment for ICI-P. Among 49 patients admitted with a suspicion of ICI-P, 31 patients were confirmed to have ICI-P and subsequently received ICI-P directed treatment. Pulmonology was consulted in 97% of patients. Median time to start treatment for ICI-P was 1day (IQR 0-3.5days). All 31 patients received corticosteroids. Inpatient mortality was 32%. Majority of patients discharged with steroids were prescribed prophylaxis for gastritis and opportunistic infections. Thirty-eight percent of patients were seen by pulmonology and 86% were seen by the oncology team post-discharge. Our study confirms prior findings of high mortality among patients with high-grade ICI-P. Early diagnosis and treatment are key to improving clinical outcomes. Understanding the care patterns and adherence to treatment guidelines of clinicians caring for this patient population may help identify ways to further standardize management practices and improve patient outcomes.

Molecular Analysis of Dihydropteroate Synthase Gene Mutations in Pneumocystis jirovecii Isolates among Bulgarian Patients with Pneumocystis Pneumonia

Pneumocystis jirovecii pneumonia (PCP) is a significant cause of morbidity and mortality in immunocompromised people. The widespread use of trimethoprim-sulfamethoxazole (TMP-SMZ) for the treatment and prophylaxis of opportunistic infections (including PCP) has led to an increased selection of TMP-SMZ-resistant microorganisms. Sulfa/sulfone resistance has been demonstrated to result from specific point mutations in the DHPS gene. This study aims to investigate the presence of DHPS gene mutations among P. jirovecii isolates from Bulgarian patients with PCP. A total of 326 patients were examined via real-time PCR targeting the P. jirovecii mitochondrial large subunit rRNA gene and further at the DHPS locus. P. jirovecii DNA was detected in 50 (15.34%) specimens. A 370 bp DHPS locus fragment was successfully amplified in 21 samples from 19 PCP-positive patients, which was then purified, sequenced, and used for phylogenetic analysis. Based on the sequencing analysis, all (n = 21) P. jirovecii isolates showed DHPS genotype 1 (the wild type, with the nucleotide sequence ACA CGG CCT at codons 55, 56, and 57, respectively). In conclusion, infections caused by P. jirovecii mutants potentially resistant to sulfonamides are still rare events in Bulgaria. DHPS genotype 1 at codons 55 and 57 is the predominant P. jirovecii strain in the country.

1565. Antiretroviral Stewardship: Protocol Development and Implementation at an Academic Medical Center.

Abstract Background 1.2 million people are living with HIV (PLWH) in the USA. As this population grows older (47% of PLWH were over age 50 in 2018) and more medically complex, the risk of medication errors increases. This population has not been prioritized for stewardship efforts, but experts have called for ARV stewardship programs to be developed. We developed a protocol to systematically review patients on ARVs during inpatient admissions to reduce and prevent medication errors, improve patient safety, and improve equity of care for PLWH. Methods We implemented a pharmacist-driven intervention over a 3-month period and compared it to usual practice in the 3 months prior to launch. Patients with active ARV prescriptions were identified using a novel automated patient report generated within the EMR. Then, a pharmacist reviewed the ARV regimen and opportunistic infection prophylaxis for accuracy, completeness, potential DDIs or administration issues. A standardized consult note was developed to communicate pharmacist recommendations to the care team. We evaluated qualitative features of the ARV-related interventions and calculated the proportion of hospital days with and without medication errors. Results The baseline period included 52 patients with an average age of 52 years and LOS of 6.6 days. The intervention period included 60 patients with an average age of 53 years and LOS of 5.4 days. During the intervention, automated pharmacy review led to medication intervention on 49% of patients, compared with 36% of patients in the baseline period. Similarly, the average time to pharmacy intervention decreased from 3 days after admission in the baseline period to 2.5 days in the intervention period. The most common interventions were resuming an ARV regimen and management of DDIs. The most common clinical rationales for interventions were DDIs, acute changes in renal function, and non-formulary medication restrictions. Automated patient identification and pharmacist review reduced the prevalence of medication errors related to ART from 17% of inpatient days to 2% of inpatient days. Conclusion There is a need for ARV stewardship. Expanding, automating, and standardizing these capabilities improved patient safety by reducing medication errors and improving continuity of care in the inpatient setting. Disclosures All Authors: No reported disclosures

Assessing sex differences in viral load suppression and reported deaths using routinely collected program data from PEPFAR-supported countries in sub-Saharan Africa

BackgroundIn sub-Saharan Africa, more women than men access HIV testing and treatment and may have better viral load suppression (VLS). We utilized routinely reported aggregated HIV program data from 21 sub-Saharan African countries to examine sex differences in VLS and death rates within antiretroviral therapy (ART) programs supported by the United States President's Emergency Plan for AIDS Relief (PEPFAR).MethodsWe included VLS and reported death data for persons aged 15 + years on ART from October–December 2020 disaggregated by sex and age for each subnational unit (SNU). We used linear mixed-model regression to estimate VLS proportion and negative binomial mixed-model regression to estimate the rates of death and death plus interruptions in treatment (IIT). All models were weighted for SNU-level ART population size and adjusted for sex, age, HIV/tuberculosis coinfection, country, and SNU; models for reported deaths and deaths plus IIT were also adjusted for SNU-level VLS.ResultsMean VLS proportion was higher among women than men (93.0% vs. 92.0%, p-value < 0.0001) and 50 + than 15–49 age group (93.7% vs. 91.2%, p-value < 0.0001). The mean rate of reported deaths was higher among men than women (2.37 vs. 1.51 per 1000 persons, p-value < 0.0001) and 50 + than 15–49 age group (2.39 vs. 1.50 per 1000, p-value < 0.0001); the mean rate of reported deaths plus IIT was higher among men (30.1 in men vs. 26.0 in women per 1000, p-value < 0.0001) and higher among 15–49 than 50 + age group (34.7 vs. 22.6 per 1000, p-value < 0.0001).ConclusionsThe mean rate of reported deaths was higher among men in most models despite adjusting for VLS. Further exploration into differences in care-seeking behaviors; coverage of screening, prophylaxis, and/or treatment of opportunistic infections; and more extensive testing options for men to include CD4 is recommended.

Examining HIV Essential Medicines Access in Nigeria: A Comparative Study of South-South and North-East Regions through WHO Health Systems Framework

Availability and accessibility of essential medicines for HIV recipients of care varies across regions in Nigeria. This study seeks to compare access and availability of medicines for HIV in the South south and Northeast regions of Nigeria. Data were collected from 120 health facilities and 385 respondents using structured questionnaires and analysed using descriptive statistics and thematic analysis. The study methodology included an exploratory sequential mixed of quantitative and qualitative methods, including facility assessments, in-depth interviews, client satisfactory questionnaire conducted amongst HIV program stakeholders and HIV recipients of care. The study found that the HIV program in the regions have made progress in improving the accessibility of essential medicines for HIV patients. The North-East had an average access rate of 87.1%, while the South-South had a slightly higher average access rate of 85.6%. The North-East had a prescription rate of 100% for antiretroviral therapy (ART) for adolescents and for the preventive treatment for tuberculosis (INH + Pyridoxine). On the other hand, access to micronutrient supplementation was higher in the South-South region at 94.7%, compared to the North-East region with a rate of 74.2%. In conclusion, this study highlights that the availability of essential medicines such as ART drugs, micronutrients and prophylaxis for opportunistic infections, medicine supply, storage and documentation has improved overtime with support from donor agencies, though still challenged with electronic management systems and need for adequate procurement, quantification, additional technical assistance, funding and supply chain infrastructure is recommended to be addressed towards achievement of HIV epidemic control in Nigeria. Keywords: Essential medicines, Health systems, HIV, North-East, South-South.

Advanced HIV disease: A review of diagnostic and prophylactic strategies.

Despite expanded access to antiretroviral therapy (ART) and the rollout of the World Health Organization's (WHO) 'test-and-treat' strategy, the proportion of people with HIV (PWH) presenting with advanced HIV disease (AHD) remains unchanged at approximately 30%. Fifty percent of persons with AHD report prior engagement to care. ART failure and insufficient retention in HIV care are major causes of AHD. People living with AHD are at high risk for opportunistic infections and death. In 2017, the WHO published guidelines for the management of AHD that included a comprehensive package of care for screening and prophylaxis of major opportunistic infections (OIs). In the interim, ART regimens have evolved: integrase inhibitors are first-line therapy globally, and the diagnostic landscape is evolving. The objective of this review is to highlight novel point-of-care (POC) diagnostics and treatment strategies that can facilitate OI screening and prophylaxis for persons with AHD. We reviewed the WHO guidelines for recommendations for persons with AHD. We summarized the scientific literature on current and emerging diagnostics, along with emerging treatment strategies for persons with AHD. We also highlight the key research and implementation gaps together with potential solutions. While POC CD4 testing is being rolled out in order to identify persons with AHD, this alone is insufficient; implementation of the Visitect CD4 platform has been challenging given operational and test interpretation issues. Numerous non-sputum POC TB diagnostics are being evaluated, many with limited sensitivity. Though imperfect, these tests are designed to provide rapid results (within hours) and are relatively affordable for resource-poor settings. While novel POC diagnostics are being developed for cryptococcal infection, histoplasmosis and talaromycosis, implementation science studies are urgently needed to understand the clinical benefit of these tests in the routine care. Despite progress with HIV treatment and prevention, a persistent 20%-30% of PWH present to care with AHD. Unfortunately, these persons with AHD continue to carry the burden of HIV-related morbidity and mortality. Investment in the development of additional POC or near-bedside CD4 platforms is urgently needed. Implementation of POC diagnostics theoretically could improve HIV retention in care and thereby reduce mortality by overcoming delays in laboratory testing and providing patients and healthcare workers with timely same-day results. However, in real-world scenarios, people with AHD have multiple comorbidities and imperfect follow-up. Pragmatic clinical trials are needed to understand whether these POC diagnostics can facilitate timely diagnosis and treatment, thereby improving clinical outcomes such as HIV retention in care.

Comparative Safety and Changes in Immunologic and Virologic Parameters of Dolutegravir versus Efavirenz-Based Antiretroviral Therapies Among HIV Patients: A Retrospective Cohort Study.

In combination with other two antiretroviral drugs, an efavirenz (EFV) or dolutegravir (DTG)-based regimen is the treatment of choice for human immunodeficiency virus (HIV) infection. This study aimed to determine the safety and changes in immunologic and virologic parameters of DTG compared with EFV-based ART as first-line HIV treatment among HIV patients. A retrospective hospital-based cohort study was carried out from September 1, 2019 to August 30, 2020 at HIV clinics of three selected hospitals in North-West-East Ethiopia, Amhara Region. All HIV patients ≥3 years old, who had been on either DTG or EFV-based combination anti-retroviral therapy (cART), and had detectable viral load (VL) were included. Descriptive and multivariate Cox regression analyses were used. Overall, 990 HIV patients were included in the analysis (DTG n=694, EFV n=296). A VL of <50 copies/mL was observed in 69% of patients in the DTG group and 66% in the EFV group (crude hazard ratio [CHR] =1.28, 95% CI: 1.08-1.51; p=0.004). Out of the total, 289 (42%) of the patients in the DTG group reported adverse drug events (ADEs) compared with 147 (50%) in the EFV group (p=0.020). Younger age, opportunistic infections (OIs), bed-ridden condition, no prophylaxis for OIs, low baseline cluster of differentiation 4 (CD4) count, high baseline VL, poor adherence, and ADEs were predictors of poor survival, and younger age, OIs, low baseline CD4, DTG-based initial regimen, poor adherence with cART, naïve treatment history, and student job type were predictors of poor safety outcomes. The DTG-based regimen demonstrates an improved viral suppressionand CD4 cell recovery, and better safety profile compared with the EFV-based regimen for the treatment of HIV-infected patients. A baseline CD4+ T-cell count <200 cells/mm3, OIs, and poor adherence with therapy were factors associated with poor survival and safety outcomes. HIV patients with these risk factors should be treated and monitored regularly.

Late Onset of Pneumocystis jirovecii Pneumonia in Kidney Transplant: How Long is too Long in Opportunistic Infection Prophylaxis?

Late Onset of Pneumocystis jirovecii Pneumonia in Kidney Transplant: How Long is too Long in Opportunistic Infection Prophylaxis?

Late Onset of Pneumocystis jirovecii Pneumonia in Kidney Transplant: How Long is too Long in Opportunistic Infection Prophylaxis?

Pneumocystis jirovecii (PJ) opportunistic infections occur in immunocompromised patients impacting significantly hospitalizations and mortality. Trimethoprim-sulfamethoxazole (TMP-SMX) is universally used as prophylaxis of Pneumocystis jirovecii pneumonia (PJP) and therefore, this infection is rare condition in solid organ transplant (SOT) recipients. We present a case of a 46-years-old male, who received an ABO-incompatible transplant with prior desensitization protocol with plasmapheresis, rituximab, and anti-CMV immunoglobulin. IgG anti-B title pre-desensitization was 1:128. The patient had 6 ABDR mismatches, without HLA antibodies, and the CDC crossmatch for T and B cells was negative. Both recipient and donor were CMV positive (D+/R+). The patient received induction immunosuppression with corticosteroids, basiliximab, calcineurin inhibitor, and mycophenolate mofetil. Immediate kidney function was verified, and three additional plasmapheresis sessions were performed. At discharge serum creatinine (sCr) was 1.38 mg/dL, but kidney function declined during the first 6 months (sCr 2.5 mg/dL). Urinalysis was unremarkable. A kidney biopsy was declined by the patient. Unit protocol maintained the prophylaxis for PJP and cytomegalovirus (CMV) infection with TMP-SMX and valganciclovir. The patient was admitted to the emergency department 20 months after the transplant with respiratory symptoms and was diagnosed with PJP. Bronchoalveolar lavage fluid was also positive for CMV. Intensive care unit (ICU) admission was necessary due to clinical deterioration, with subsequent good evolution without mechanical ventilation. At discharge, prophylaxis with TMP-SMX and valganciclovir was maintained for more than six months. Here we discuss the late onset of PJP, and the main risk factors related to severe infection. Transplant subgroups in which longer PJP prophylaxis could be beneficial and the indication to re-start PJP prophylaxis is still under discussion.

Impact of Bridging Therapy on Infectious Complications Post CAR T-Cell Therapy: The UT Southwestern Experience

Background: CAR T-cell therapy (CAR T) has become a powerful new tool in the treatment of relapsed/refractory (r/r) hematologic malignancies. Infections are well-recognized risks of CAR T. Bridging therapy is often employed to allow patients to reach successful infusion but may also further immunosuppress this already vulnerable group. This study aims to identify patterns of infections post-CAR T and the potential impact of bridging therapy. Methods: Medical records of patients who underwent apheresis for CAR T from 2018-2022 for r/r lymphomas or multiple myeloma (MM) at UT Southwestern were analyzed. Demographics, treatment characteristics and infection data were collected via retrospective chart review. Post-CAR T infections were identified by reviewing patient hospitalizations after CAR T infusion for infectious complications confirmed by positive diagnostic studies during admission. Infections were categorized as bacterial, viral, fungal, or multi-pathogenic. Time-to-infection was calculated from lymphodepletion (LD) date. Categorical variables were compared using Fisher's exact test. Continuous variables were compared using Mann-Whitney U test. Overall- and progression-free survival (OS and PFS) were calculated from CAR T infusion date, estimated by the Kaplan-Meier method, and compared using a log-rank test. Results: Data were collected on 75 total patients, 44 with lymphoma and 31 with MM, who underwent apheresis and 74 (98.7%) underwent CAR T. Baseline patient characteristics are shown in Table 1. All patients received standardized opportunistic infection (OI) prophylaxis and intravenous immunoglobulin (IVIG) and growth factor support based on institutional guidelines. Thirty-eight patients (51%) had a post-CAR T infection. Post-CAR T infections manifested at a median of 117 days (range: 12 - 1344 days) after LD. Patients who received bridging therapy had an earlier median incidence of post CAR T infections (92 vs 113 days post-LD, p = 0.03). Number of prior lines of therapy did not predict infection rates or time to infection. Time-to-infection did not vary by lymphoma versus MM or by cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity (ICANS) grade. MM patients had a numerically higher rate of viral infections (77% vs 41%) while lymphoma patients had a higher bacterial infection rate (65% vs 55%). A majority (58%) of these patients had infectious events between 31- and 100-days post lymphodepletion [Figure 2]. Infection rates were not significantly associated with tocilizumab or steroid usage during CAR T. In our cohort, 77% of patients received bridging. Bridging therapy was associated with a significantly higher neutropenic fever rate (73% vs 37%, p = 0.006), which persisted after adjusting for prior lines of therapy. All patients with neutropenic fever received broad-spectrum antibiotic coverage. In lymphoma patients, bridging therapy was associated with higher grades of CRS (p = 0.018). Being hospitalized for infection within 6 months (p=0.01) or receiving antibiotics in the month (p=0.02) prior to lymphodepletion, were associated with grade ≥3 CRS. One-year PFS and OS were 55% and 74% for the entire cohort. Four patients died due to infectious complications after successful CAR T infusion at a median of 163 days post infusion. Patients who had post-CAR T infections trended towards worse progression-free survival (1-year PFS 65% vs 46%, p = 0.1) and had similar OS (1-year OS 70% vs 77%, p = 0.75). Conclusions: Bridging therapy prior to CAR T may increase the risk of neutropenic fever and be associated with earlier infectious risk. Febrile neutropenia and high-grade CRS drive more intensive resource utilization, which may be mitigated with more intentional patient selection for bridging therapy.Our findings show that post-CAR T infections contribute to significant morbidity, and thus calls for personalizing bridging strategies, peri-CAR T OI prophylaxis and infection management. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Cutaneous adverse drug reactions among people living with human immunodeficiency virus in a tertiary care hospital in Johor, Malaysia.

Cutaneous adverse drug reactions (cADRs) among people living with HIV (PLWH) are common. Data on drug eruptions among PLWH in Malaysia are limited. Thus, our study aimed to determine the clinical patterns of cADRs among PLWH and the risk factors associated with severe cutaneous adverse reactions (SCAR). A cross-sectional study was conducted among PLWH who developed cADRs presenting to our dermatology clinic from June 2020 to December 2020. The Naranjo scale was used for drug causality assessment. A total of 78 PLWH were recruited with a male-to-female ratio of 12:1. The maculopapular eruption was the commonest type of cADRs (75.6%), followed by drug reaction with eosinophilia and systemic symptoms (DRESS) (15.4%). SCAR is defined as a potentially life-threatening, immunologically mediated, drug-induced disease, accounting for 17.9% of the cases. Most of the patients were on antiretroviral therapy (ART) (85.9%), with efavirenz + tenofovir/emtricitabine being the most common combination (80.6%). Efavirenz (51.3%) was the main culprit drug implicated, followed by trimethoprim/sulfamethoxazole (23.1%) and nevirapine (11.5%). CD4 T-cell count <100 cells/μL (p = 0.006) was the independent risk factor for SCAR. Most cases had probable causal relationships with the culprit drugs (84.6%) and were not preventable (93.6%). The commonest cADR seen in PLWH was maculopapular eruption, while efavirenz, trimethoprim/sulfamethoxazole, and nevirapine were the three main implicated drugs. Most of the cases had probable drug causality and were not preventable. PLWH with CD4 count <100 cells/μL were particularly at risk of developing SCAR. Overall, this study showed that immune suppression and polypharmacy as a consequence of opportunistic infection prophylaxis are important factors contributing to the increased risk of ADRs among PLWH.

POS1179 SYSTEMATIC LITERATURE REVIEW ON THE SCREENING AND PROPHYLAXIS OF CHRONIC AND OPPORTUNISTIC INFECTIONS

BackgroundOpportunistic and chronic infections can arise in the context of treatment used for Autoimmune Rheumatic Diseases (ARDs). Although it is recognized that screening procedures and prophylactic measures must be followed, clinical practice is largely heterogeneous, with relevant recommendations not currently developed or disparately located across the literature.ObjectivesTo conduct a systematic literature review (SLR) focusing on the screening and prophylaxis of opportunistic and chronic infections in ARDs. This is preparatory work done by members of the respective EULAR task force (TF).MethodsFollowing the EULAR standardised operating procedures, we conducted an SLR with the following 5 search domains; 1) Infection: infectious agents identifed by a scoping review and expert opinion (TF members), 2) Rheumatic Diseases: all ARDs, 3) Immunosuppression: all immunosuppressives/immunomodulators used in rheumatology, 4) Screening: general and specific (e.g mantoux test) terms, 5) Prophylaxis: general and specific (e.g trimethoprim) terms. Articles were retrieved having the terms from domains 1 AND 2 AND 3, plus terms from domains 4 OR 5. Databases searched: Pubmed, Embase, Cochrane. Exclusion criteria: post-operative infections, pediatric ARDs, not ARDs (e.g septic arthritis), not concerning screening or prophylaxis, Covid-19 studies, articles concerning vaccinations and non-Εnglish literature. Quality of studies included was assessed as follows: Newcastle Ottawa scale for non-randomized controlled trials (RCTs), RoB-Cochrane tool for RCTs, AMSTAR2 for SLRs.Results5641 studies were initially retrieved (Figure 1). After title and abstract screening and removal of duplicates, 568 full-text articles were assessed for eligibility. Finally, 293 articles were included in the SLR. Most studies were of medium quality. Reasons for exclusion are shown in Figure 1. Results categorized as per type of microbe, are as follows: For Tuberculosis; evidence suggests that tuberculin skin test (TST) is affected by treatment with glucocorticoids and conventional synthetic DMARDs (csDMARDs) and its performance is inferior to interferon gamma release assay (IGRA). Agreement between TST and IGRA is moderate to low. Conversion of TST/IGRA occurs in about 10-15% of patients treated with biologic DMARDs (bDMARDs). Various prophylactic schemes have been used for latent TB, including isoniazide for 9 months, rifampicin for 4 months, isoniazide/rifampicin for 3-4 months. For hepatitis B (HBV): there is evidence that risk of reactivation is increased in patients positive for hepatitis B surface antigen. These patients should be referred for HBV treatment. Patients who are positive for anti-HBcore antibodies, are at low risk for reactivation when treated with glucocorticoids, cDMARDs and bDMARDs but should be monitored periodically with liver function tests and HBV-viral load. Patients treated with rituximab display higher risk for HBV reactivation especially when anti-HBs titers are low. Risk for reactivation in hepatitis C RNA positive patients, treated with bDMARDs is low. However, all patients should be referred for antiviral treatment and monitored periodically. For pneumocystis jirovecii: prophylaxis with trimethoprim/sulfamethoxazole (alternatively with atovaquone or pentamidine) should be considered in patients treated with prednisolone: 15-30mg/day for more than 4 weeks. Few data exist for screening and prophylaxis from viruses like EBV, CMV and Varicella Zoster Virus. Expert opinion supports the screening of rare bugs like histoplasma and trypanosoma in patients considered to be at high risk (e.g living in endemic areas).Figure 1.SLR flowchartConclusionThe risk of chronic and opportunistic infections should be considered in all patients prior to treatment with immunosuppressives/immunomodulators. Different screening and prophylaxis approaches are described in the literature, partly determined by individual patient and disease characteristics. Collaboration between different disciplines is important.AcknowledgementsWe would like to thank all members of the EULAR Task Force for the screening and prophylaxis of chronic and opportunistic infections in Autoimmune Rheumatic Diseases.Disclosure of InterestsNone declared

Oral and maxillofacial manifestations of human immunodefficiency virus infection

Oral manifestations occur at all stages of human immunodeficiency virus (HIV) infection. Their clinical expressions and severity depend on the evolution of the infection and become critical at the stage of acquired immunodeficiency (AIDS). They are essentially infectious, tumoral, and, starting a few years ago, iatrogenic. Infections are mostly fungal (candidiasis), viral (herpes, zoster, human papillomavirus infections, etc.), and less frequently bacterial (streptococcemia). Cases of sexually transmitted diseases, particularly syphilis, are multiplying preoccupyingly. The most frequently observed tumors are Kaposi's sarcoma. Drug intolerance is common; the symptoms are mostly dermatological, but also oral (Stevens-Johnson syndrome and toxic epidermal necrolysis) when sulfonamides and certain antiretrovirals are used. The advent of prolonged Highly Active Anti-Retroviral Therapies (HAARTs) has led to a decline in the incidence of most opportunistic conditions, infections and tumors (except for multiple oral warts and zoster). HAARTs also provoke adverse reactions such as lipodystrophy syndromes (signs of peripheral atrophy and central hypertrophy, associated in varying degrees with metabolic syndromes). Extended survival and the new methods for prophylaxis of opportunistic infections have gradually modified diagnostic and therapeutic strategies for oral manifestations of HIV infections.

Advanced HIV disease management practices within inpatient medicine units at a referral hospital in Zambia: a retrospective chart review

BackgroundZambia recently achieved UNAIDS 90-90-90 treatment targets for HIV epidemic control; however, inpatient facilities continue to face a large burden of patients with advanced HIV disease and HIV-related mortality. Management of advanced HIV disease, following guidelines from outpatient settings, may be more difficult within complex inpatient settings. We evaluated adherence to HIV guidelines during hospitalization, including opportunistic infection (OI) screening, treatment, and prophylaxis.MethodsWe reviewed inpatient medical records of people living with HIV (PLHIV) admitted to the University Teaching Hospital in Lusaka, Zambia between December 1, 2018 and April 30, 2019. We collected data on patient demographics, antiretroviral therapy (ART), HIV biomarkers, and OI screening and treatment—including tuberculosis (TB), Cryptococcus, and OI prophylaxis with co-trimoxazole (CTX). Screening and treatment cascades were constructed based on the 2017 WHO Advanced HIV Guidelines.ResultsWe reviewed files from 200 charts of patients with advanced HIV disease; of these 92% (184/200) had been on ART previously; 58.1% (107/184) for more than 12 months. HIV viral load (VL) testing was uncommon but half of VL results were high. 39% (77/200) of patients had a documented CD4 count result. Of the 172 patients not on anti-TB treatment (ATT) on admission, TB diagnostic tests (either sputum Xpert MTB/RIF MTB/RIF or urine TB-LAM) were requested for 105 (61%) and resulted for 60 of the 105 (57%). Nine of the 14 patients (64%) with a positive lab result for TB died before results were available. Testing for Cryptococcosis was performed predominantly in patients with symptoms of meningitis. Urine TB-LAM testing was rarely performed.ConclusionsAt a referral hospital in Zambia, CD4 testing was inconsistent due to laboratory challenges and this reduced recognition of AHD and implementation of AHD guidelines. HIV programs can potentially reduce mortality and identify PLHIV with retention and adherence issues through strengthening inpatient activities, including reflex VL testing, TB-LAM and serum CrAg during hospitalization.

Immunosuppressors and immunomodulators in Neurology - Part I: a guide for management of patients underimmunotherapy.

For patients with autoimmune diseases, the risks and benefits of immunosuppressive or immunomodulatory treatment are a matter of continual concern. Knowledge of the follow-up routine for each drug is crucial, in order to attain better outcomes and avoid new disease activity or occurrence of adverse effects. To achieve control of autoimmune diseases, immunosuppressive and immunomodulatory drugs act on different pathways of the immune response. Knowledge of the mechanisms of action of these drugs and their recommended doses, adverse reactions and risks of infection and malignancy is essential for safe treatment. Each drug has a specific safety profile, and management should be adapted for different circumstances during the treatment. Primary prophylaxis for opportunistic infections and vaccination are indispensable steps during the treatment plan, given that these prevent potential severe infectious complications. General neurologists frequently prescribe immunosuppressive and immunomodulatory drugs, and awareness of the characteristics of each drug is crucial for treatment success. Implementation of a routine before, during and after use of these drugs avoids treatment-related complications and enables superior disease control.

IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME AFTER USE OF ANTI-RETROVIRAL THERAPY IN COVID-19

TOPIC: Chest Infections TYPE: Global Case Reports INTRODUCTION: COVID-19 is still an emerging topic and co-existence in HIV patients presents its unique challenge. These patients can range from elite controllers to Acquired immunodeficiency syndrome (T cell CD4 < 200). Throughout our management, we noticed certain trends in our population. Those patients with CD4 T cell < 200 were rarely admitted to hospital with severe cases of COVID-19, requiring if anything minimal oxygen requirements. However, HIV patients who were admitted did not fare well after initiating their anti-retroviral therapy (ART) therapy during index hospitalization. We describe two such cases one in which ART was maintained and one in which ART was help with different outcomes. CASE PRESENTATION: Both patients on admission were admitted for progressive dyspnea with COVID PCR positive, started on ART therapy, given a 10-day course of Dexamethasone 6mg and 5 doses of Remdisivir.Case 1 - 55year old Hispanic male with a history of non-compliance on Triumeq (CD4 count of 34), lymphoma in remission after chemotherapy, and sulfa allergy. On admission he was started on Triumeq, Azithromycin, Clindamycin, Primaquine. Over next 3 days he experienced progressive hypoxia and worsening chest imaging eventually requiring mechanical ventilation.Case 2 - 66year old female non-compliant on ART, and polysubstance abuse. She was also noted to have MSSA pneumonia. She was started on Emricitabine, Tenofovir, Ritonavir, and Atazanorvir. Within 48 hours of ART initiation her oxygen requirement increased. At this time, her antiretrovirals were stopped and started on Solumedrol 40mg twice daily for suspected IRIS. Her respiratory status improved and her oxygen requirements were back to baseline. Upon restarting ART 2 weeks post treatment for IRIS, patient again required an increase in oxygen supplementation. ART was held for an extended period while maintaining opportunistic infection prophylaxis. DISCUSSION: We pose this discussion for the community, as COVID-19 pathophysiology has been hypothesized to be an inflammatory response mitigated by Interleukins and Interferon-gamma, released by CD4 and CD8 T cells {3} Theoretically those with lower CD4 T cells, such as those with AIDs, should produce a lesser inflammatory response;and therefore, be less symptomatic. IRIS is typically determined from clinical context and is seen more frequently in those with CD4 < 100. {1} Treatment is typically steroids with a prolonged taper, with an ongoing discussion on whether ART should be held. {4} CONCLUSIONS: Currently there are no guidelines regarding utilization of ART in HIV patients infected with COVID;which leads to following questions of whether ART be held transiently until the COVID-19 pneumonia has been sufficiently treated? When should ART be restarted in these patients? If a patient's condition is deteriorating, should the patient's ART be held and started on opportunistic infection prophylaxis? REFERENCE #1: Bosamiya, S.S. The immune reconstitution inflammatory syndrome (2011) 56(5) 476-9, Indian J Dermatology. doi : 10.4103/0019-5154.87114 REFERENCE #2: Brown, L.B, Spinelli, M.A., and Gandhi, M. The interplay between HIV and COVID-19: summary of the data and responses to date. (2021) 16(1) 63-73, Current opinion of HIV and AIDs. REFERENCE #3: Kalfaoglu, B., Almeida-Santos, J., Tye, C.A., Satou, Y., and Ono, M. T cell dysregulation in COVID-19 (2020) 29(530) 204-210, Biochem Biophys Res Commun. doi: 10.1016/j.bbrc.2020.10.079 DISCLOSURES: No relevant relationships by Obed Adarkwah, source=Web Response no disclosure on file for Anjali Bakshi;No relevant relationships by Louis Gerolemou, source=Web Response No relevant relationships by Aneeta Kumari, source=Web Response No relevant relationships by Nabil Mesiha, source=Web Response No relevant relationships by Steven Miller, source=Web Response No relevant relationships by Kunal Nangrani, source=Web Response No relevant relationships by Jose Orsini, source=Web Response No relevant relationships by Gaurav Parhar, source=We Response no disclosure on file for Dhruv Patel;No relevant relationships by Jason Ravidas, source=Web Response No relevant relationships by jad sargi, source=Web Response No relevant relationships by Viswanath Vasudevan, source=Web Response No relevant relationships by Kiran Zaman, source=Web Response No relevant relationships by John Zeibeq, source=Web Response

Quality assessment of selected co-trimoxazole suspension brands marketed in Nairobi County, Kenya.

IntroductionQuality of medicines in both developed and developing countries is sometimes compromised due to infiltration of counterfeit, substandard or degraded medicines into the markets. It is a public health concern as poor quality medicines endanger public health where patients are exposed to chemical toxins and/or sub-therapeutic doses. This could lead to reduced treatment efficacy and promote development of drug resistance. Co-trimoxazole, a fixed dose combination of sulfamethoxazole and trimethoprim, is a broad spectrum for bacterial diseases and is also used as a prophylaxis for opportunistic infections in HIV infected individuals. This study evaluated quality of selected co-trimoxazole suspension brands marketed in Nairobi County, Kenya.MethodsA total of 106 samples were collected, categorized into 15 brands and evaluated for active pharmaceutical ingredient content (API) and pH following United States Pharmacopeia. Assay for API was conducted using High Performance Liquid Chromatography. Results were compared with pharmacopeia references. Visual examination of labels and confirmation of retention status of the brands with Pharmacy and Poisons Board retention register was carried out.ResultsThe samples were primarily of local origin (86.7%). On October 23, 2019, retention status of six of the fifteen brands documented were no longer listed in the Pharmacy and Poisons Board retention register. Of the 106 samples tested 70.6% and 86.8% were compliant with United States Pharmacopeia (USP) specifications for pH and API respectively while 84.0% adhered to packaging and labelling requirements.ConclusionThis study has demonstrated that majority of co-trimoxazole suspensions tested were compliant with USP requirements. Additionally, it has provided evidence of poor quality co-trimoxazole medicines that could compromise treatment of infectious diseases in children. This emphasizes the need for regular quality assurance tests to ensure only quality medicines are in the market.

Improved detection and management of advanced HIV disease through a community adult TB-contact tracing intervention with same-day provision of the WHO-recommended package of care including ART initiation in a rural district of Mozambique.

IntroductionAIDS‐mortality remains unacceptably high in sub‐Saharan Africa, largely driven by advanced HIV disease (AHD). We nested a study in an existing tuberculosis (TB) contact‐tracing intervention (Xpatial‐TB). The aim was to assess the burden of AHD among high‐risk people living with HIV (PLHIV) identified and to evaluate the provision of the WHO‐recommended package of care to this population.MethodsAll PLHIV ≥14 years old identified between June and December 2018 in Manhiça District by Xpatial‐TB were offered to participate in the study if ART naïve or had suboptimal ART adherence. Consenting individuals were screened for AHD. Patients with AHD (CD4 < 200 cells/μL or WHO stage 3 or 4) were offered a package of interventions in a single visit, including testing for cryptococcal antigen (CrAg) and TB‐lipoarabinomannan (TB‐LAM), prophylaxis and treatment for opportunistic infections, adherence support or accelerated ART initiation. We collected information on follow‐up visits carried out under routine programmatic conditions for six months.ResultsA total of 2881 adults were identified in the Xpatial TB‐contact intervention. Overall, 23% (673/2881) were HIV positive, including 351 TB index (64.2%) and 322 TB contacts (13.8%). Overall, 159/673 PLHIV (24%) were ART naïve or had suboptimal ART adherence, of whom 155 (97%, 124 TB index and 31 TB‐contacts) consented to the study and were screened for AHD. Seventy percent of TB index‐patients (87/124) and 16% of TB contacts (5/31) had CD4 < 200 cells/µL. Four (13%) of the TB contacts had TB, giving an overall AHD prevalence among TB contacts of 29% (9/31). Serum‐CrAg was positive in 4.6% (4/87) of TB‐index patients and in zero TB contacts. All ART naïve TB contacts without TB initiated ART within 48 hours of HIV diagnosis. Among TB cases, ART timing was tailored to the presence of TB and cryptococcosis. Six‐month mortality was 21% among TB‐index cases and zero in TB contacts.ConclusionsA TB contact‐tracing outreach intervention identified undiagnosed HIV and AHD in TB patients and their contacts, undiagnosed cryptococcosis among TB patients, and resulted in an adequate provision of the WHO‐recommended package of care in this rural Mozambican population. Same‐day and accelerated ART initiation was feasible and safe in this population including among those with AHD.

Pooled Safety Analysis from Phase I and II Studies for Patients with Relapsed Indolent Non-Hodgkin's Lymphoma Treated with Intravenous Copanlisib

Pooled Safety Analysis from Phase I and II Studies for Patients with Relapsed Indolent Non-Hodgkin's Lymphoma Treated with Intravenous Copanlisib