Discontinuation Of Prophylaxis Research Articles

Point-of-care urine tenofovir test predicts future HIV preexposure prophylaxis discontinuation among young users.

Young men who have sex with men and transgender women (YMSM/TGW) have disproportionately high HIV incidence and lower preexposure prophylaxis (PrEP) adherence. Point-of-care (POC) urine tenofovir (TFV) rapid assay (UTRA) testing permits real-time monitoring for nonadherence within clinical settings. We performed UTRA testing among PrEP users to examine the relationship between low PrEP adherence and future PrEP discontinuation, and the accuracy of POC testing compared to gold-standard liquid chromatography tandem mass spectrometry (LC/MS/MS). YMSM/TGW participants ( n = 100) were recruited during a daily PrEP visit. Logistic regression models analyzed the relationship between the primary predictor of urine POC assay results (cutoff 1,500 ng/ml) and the primary outcome of PrEP discontinuation, defined as no PrEP follow-up or prescription within 120 days. Overall, 19% of participants had low urine TFV and 21% discontinued PrEP, while 11% of participants self-reported low PrEP adherence (<4 pills per week), which was only 43% sensitive/84% specific in predicting low TFV levels and was not associated with PrEP discontinuation. Low urine TFV level predicted PrEP discontinuation [adjusted odds ratio (AOR) 6.1; 95% confidence interval (CI): 1.4-11; P = 0.005] and was 71% sensitive/90% specific for discontinuation after 120 days. Compared to LC/MS/MS, UTRA testing had a 98% positive and 100% negative predictive value. In a sample of YMSM/TGW on daily PrEP, POC UTRA testing predicted PrEP discontinuation more accurately than self-reported adherence, with high predictive values compared to LC/MS/MS. UTRA testing may be a clinical tool for directing preventive interventions towards those likelier to discontinue PrEP despite ongoing HIV vulnerability.

Real-world experience with letermovir for cytomegalovirus-prophylaxis after allogeneic hematopoietic cell transplantation: A multi-centre observational study

Efficacy and safety of letermovir as prophylaxis for clinically significant cytomegalovirus infections (csCVMi) was evaluated in randomised controlled trials while most of the real-world studies are single-centre experiences. We performed a retrospective, multi-centre case-control study at six German university hospitals to evaluate clinical experiences in patients receiving CMV prophylaxis with letermovir (n=200) compared to controls without CMV prophylaxis (n=200) during a 48-week follow-up period after allogeneic hematopoietic cell transplantation (aHCT). The incidence of csCMVi after aHCT was significantly reduced in the letermovir (34%, n=68) compared to the control group (56%, n=112; p<0.001). Letermovir as CMV prophylaxis (OR 0.362) was found to be the only independent variable associated with theprevention of csCMVi. Patients receiving letermovir showed significantly better survival compared to the control group (HR = 1.735, 95% CI: 1.111-2.712; p=0.014). Of all csCMVi, 46% (n=31) occurred after discontinuation of letermovir prophylaxis. Severe neutropenia (<500 neutrophils/µL) on the day of the stem cell infusion was the only independent variable for an increased risk of csCMVi after the end of letermovir prophylaxis. Our study highlights the preventive effects of letermovir on csCMVi after aHCT. A substantial proportion of patients developed a csCMVi after discontinuation of letermovir. In particular, patients with severe neutropenia require specific attention after drug discontinuation.

Letermovir as secondary prophylaxis of cytomegalovirus infection after allogeneic hematopoietic cell transplantation: A single center experience.

Letermovir, a novel anti-cytomegalovirus (CMV) agent acts by inhibiting the viral terminase complex and is approved for primary prophylaxis in CMV seropositive patients post allogeneic hematopoietic cell transplantation (HCT). The favorable efficacy and safety profile make it an attractive option for use as secondary prophylaxis in patients at high-risk for CMV reactivation. In this study, we report the efficacy and safety of letermovir secondary prophylaxis after at least one treated episode of CMV reactivation in a cohort of 39 high-risk patients. Thirty two (82%) patients received anti-thymocyte globulin (ATG), 27 (69%) received a combination of ATG and post-transplant cyclophosphamide for graft-versus-host disease (GVHD) prophylaxis. Twenty one patients (54%) received CMV seronegative grafts. In addition, 18 (46%) patients had HLA mismatched unrelated or haploidentical donors while 18 (46%) had active GVHD requiring immunosuppression at the time of commencing secondary prophylaxis. Letermovir was initiated at a median of 47 days (range, 41-56) after HCT and was administered for a median duration of 77 days (range, 46-90). A single breakthrough CMV reactivation was noted in this high-risk cohort. Four additional episodes of CMV reactivation occurred at a median of 28 days (range, 23-59 days) after discontinuation of secondary prophylaxis. The drug was well tolerated and 77% of the cohort completed the planned duration of secondary prophylaxis. None of the patients discontinued treatment due to treatment-related adverse effects. In conclusion, letermovir is effective and well tolerated and may be considered for secondary prophylaxis in patients at high risk for CMV reactivation. Prospective studies are required to validate these findings.

Tailoring cytomegalovirus prophylaxis based on T cell immunity panel assessment in kidney transplant patients at high risk of cytomegalovirus.

Valganciclovir prophylaxis against cytomegalovirus (CMV) is recommended for solid organ transplant recipients, but is associated with drawbacks, including expense and leukopenia. Our center adopted a strategy of serial assessment with a CMV-specific T cell immunity panel (CMV-TCIP) and cessation of valganciclovir prophylaxis upon demonstration of adequate CD4+ responses in kidney transplant patients at high risk of CMV disease. We retrospectively reviewed adult recipients of a kidney or pancreas transplant between August 2019 and July 2021 undergoing serial CMV-TCIP monitoring. Included patients were considered high risk for CMV, defined by donor positive (D+)/recipient negative (R-) CMV IgG serostatus, or recipient positive (R+) patients who received induction with a lymphocyte-depleting agent. Prophylaxis was discontinued after a patient's first CMV-specific CD4+ T cell value of ≥0.20%. Risk of clinically significant CMV infection (csCMVi) in those who underwent early discontinuation of CMV prophylaxis and predictors of CMV T cell immunity were analyzed. Of 54 included patients, 22 stopped prophylaxis early due to CMV-specific CD4+ T cell immunity at a median of 4.7 (IQR: 3.8-5.4) months after transplant. No instances of csCMVi were observed in the 22 patients who had prophylaxis discontinued early, of whom 19/22 were CMV R+ and 3/22 were CMV D+/R-. Donor/recipient CMV serostatus was predictive of immunity (p <.001). Early discontinuation of valganciclovir prophylaxis in patients with CMV CD4+ T cellular immunity appears safe and potentially beneficial in this preliminary series, especially in R+ patients. Further study is warranted, given that truncated prophylaxis may yield patient-level benefits.

RETRACTION: A predictive model of herpes zoster after allogeneic hematopoietic stem cell transplantation: VZV reactivation following antiviral prophylaxis discontinuation.

Retraction: Feng, C-J. , Zhao, P. , Fu, H-X. , Yan, C-H. , Wang, C-C. , Zhu, X-L. , He, Y. , Wang, F-R. , Zhang, Y-Y. , Mo, X-D. , Kong, Y. , Han, W. , Wang, J-Z. , Wang, Y. , Chen, H. , Chen, Y-H. , Zhao, X-Y. , Chang, Y-J. , Xu, L-P. , Liu, K-Y. , Huang, X-J. , Zhang, X-H. (2023) A predictive model of herpes zoster after allogeneic hematopoietic stem cell transplantation: VZV reactivation following antiviral prophylaxis discontinuation. American Journal of Hematology. https://doi.org/10.1002/ajh.27090. The above article, published online on 29 September 2023 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief Carlo Brugnara and Wiley Periodicals LLC. The retraction has been agreed following notification by a third party who identified methodological errors in the published article. The journal conducted an investigation including post-publication review by an independent expert, who confirmed that the errors were substantial. The authors provided a point-for-point response to the journal about these concerns. However, the journal concluded that while some errors could be corrected, the methodology and data still would contain fundamental errors that invalidate the conclusions. The authors disagree with this retraction."

Mortality in recipients of allogeneic haematopoietic cell transplantation in the era of cytomegalovirus primary prophylaxis: a single-centre retrospective experience

ObjectivesAllogeneic haematopoietic cell transplant (allo-HCT) recipients who are cytomegalovirus (CMV)-seronegative have better post-transplant outcomes than CMV-seropositive recipients. Letermovir (LTV) is approved for CMV primary prophylaxis in adults who are CMV-seropositive after allo-HCT, and its use is associated with improved long-term post-transplant outcomes. We analysed whether LTV has affected the relationship between CMV serostatus and post-transplant outcomes. MethodsWe conducted a retrospective single-centre cohort study of allo-HCT recipients, stratified according to donor (D) and recipient (R). CMV serostatus and the use of LTV: D−/R−, R+/LTV−, and R+/LTV+. Outcomes measured were all-cause and non-relapse mortality, clinically significant CMV infection, graft-versus-host disease, and relapse up to week 48 after allo-HCT. The D−/R− group served as the reference for comparisons in univariate, competing risk regression, and cumulative incidence functions. ResultsThe analysis included 1071 consecutive allo-HCT recipients: 131 D−/R−, 557 R+/LTV−, and 383 R+/LTV+. All-cause mortality by day 100 was 6.1% for the D−/R− group, compared with 14.0% (p 0.024) and 7.8% (p 0.7) for the R+/LTV− and R+/LTV + groups, respectively. Non-relapse mortality by day 100 was 11.0%, 6.8% and 3.8% for R+/LTV−, R+/LTV+, and D−/R− groups, respectively, without significant difference. When including relapse as a competing event, the hazard ratio for non-relapse mortality was 1.83 (95% CI: 1.12–2.99, p 0.017) for R+/LTV− compared with D−/R− and 1.05 (95% CI 0.62–1.77, p 0.85) for R+/LTV + compared with D−/R−. DiscussionCMV primary prophylaxis with LTV abrogated the mortality gap based on CMV serostatus, a protective effect that persisted after discontinuation of primary prophylaxis.

A Review of Hepatitis B Reactivation Risk on Immunosuppressants with a Focus on Newer Immunomodulators

Abstract Purpose of Review Hepatitis B virus reactivation (HBVr) can complicate the use of immunosuppressive, antiviral, and chemotherapeutic medications in individuals with a history of prior exposure to HBV or chronic infection. Timely management is crucial to prevent fatalities. This review focuses on the various classes of biologics linked to the risk of HBVr, with emphasis on newer immunosuppressive and immunomodulator therapies. Recent Findings Immune checkpoint inhibitors, tyrosine kinase inhibitors, cytokine inhibitors, and chimeric antigen receptor T-cell immunotherapies are associated with a high risk of hepatitis B virus reactivation (HBVr) in patients who are hepatitis B surface antigen-positive (HbsAg-positive). This risk decreases significantly when patients start nucleoside analogue (NA) prophylaxis. It is recommended to use NA prophylaxis alongside these medications and closely monitor for reactivation upon discontinuation of NA prophylaxis. Summary To minimize the risk of reactivation when starting immunosuppressive, antiviral, and chemotherapeutic agents in individuals at high, intermediate, and low risk for hepatitis B virus reactivation (HBVr), it is crucial to employ specific strategies for risk assessment, monitoring, and management.

Impaired T cells and “memory-like” NK-cell reconstitution is linked to late-onset HCMV reactivation after letermovir cessation

AbstractAllogeneic hematopoietic stem cell transplantation (alloSCT) is the only cure for many hematologic malignancies. However, alloSCT recipients are susceptible to opportunistic pathogens, such as human cytomegalovirus (HCMV). Letermovir prophylaxis has revolutionized HCMV management, but the challenge of late HCMV reactivations has emerged. Immunological surrogates of clinically significant HCMV infection (csCMVi) after discontinuation of letermovir remain to be defined. Therefore, we studied natural killer (NK)-cell reconstitution along with the global and HCMV pp65-specific T-cell repertoire of 24 alloSCT recipients at 7 time points before (day +90) and after (days +120-270) cessation of letermovir prophylaxis. Patients who experienced csCMVi had lower counts of IFN-γ+ HCMV–specific CD4+ and CD8+ T cells than HCMV controllers. Furthermore, patients with csCMVi displayed late impairment of NK-cell reconstitution, especially suppression of “memory-like” CD159c+CD56dim NK-cell counts that preceded csCMVi events in most patients. Moreover, several surrogates of immune reconstitution were associated with the severity of HCMV manifestation, with patients suffering from HCMV end-organ disease and/or refractory HCMV infection harboring least HCMV–specific T cells and “memory-like” NK cells. Altogether, our findings establish an association of delayed or insufficient proliferation of both HCMV–specific T cells and “memory-like” NK cells with csCMVi and the severity of HCMV manifestations after discontinuation of letermovir prophylaxis.

De novo hepatitis B infection following liver transplantation with core antibody positive grafts: The role of surface antibody status in guiding long-term prophylaxis.

Liver transplantation (LT) with hepatitis B core antibody (anti-HBc) positive grafts to hepatitis B surface-antigen (HBsAg) negative recipients is safe and has likely contributed to improvements in organ access over the years. The incidence of de novo hepatitis B infection (HBV) in these instances is low with appropriate prophylaxis and is affected by recipient immunologic status. There is debate as to whether hepatitis B surface antibody (anti-HBs) positivity may safely inform prophylaxis discontinuation post-LT. In this retrospective study of all hepatitis B surface antigen (HBsAg) negative recipients of anti-HBc positive organs at three large academic centers between January 2014 and December 2019, nine LT recipients discontinued prophylaxis after developing anti-HBs antibodies 1 year or later post-LT. Three of the nine patients (33%) developed de novo HBV, defined by positive HBsAg or hepatitis B virus (HBV) DNA, during the study period. The remaining six patients had no evidence of HBV infection after a mean follow-up of 37 months. The patients without de novo HBV had higher anti-HBs titers at the time of prophylaxis discontinuation and were less likely to have negative anti-HBs at the time of transplant or negative anti-HBc at any time point. These results suggest that quantitative anti-HBs titer thresholds rather than qualitative anti-HBs positivity at 1 year or later after LT should be used to identify patients at decreased risk of de novo infection and help guide prophylaxis duration.

Cytomegalovirus Triggering Hemophagocytic Lymphohistiocytosis in a Kidney Transplant Recipient

A woman in her 70s presented four months after receiving a kidney transplant with fever, epigastric discomfort and loss of appetite. She had experienced antibody-mediated rejection ten days after transplantation, successfully treated with high doses of intravenous corticosteroids, plasma exchanges and rituximab. Two months earlier, neutropenia had led to the discontinuation of valganciclovir prophylaxis, administered in the context of a CMV-seropositive donor/seronegative recipient status. Her immunosuppressive therapy included tacrolimus, mycophenolate mofetil and corticosteroids.

Infectious diseases: what's new in 2023

The year 2023 saw the publication of several studies in various areas of infectious diseases. The administration of corticosteroids decreased mortality in severe community-acquired pneumonia. Administration of doxycycline post-exposure prophylaxis reduced the risk of bacterial sexually transmitted infections at the risk of resistance selection. An herbal preparation decreased mortality in sepsis. A meta-analysis concludes that oseltamivir does not significantly reduce the risk of hospitalisation for influenza. Discontinuation of antibiotic prophylaxis during dental procedures in Sweden did not increase the incidence of viridans group Streptococcus endocarditis. Several studies have led to the introduction of RSV (Respiratory Syncytial Virus (RSV) vaccination. 2023 also saw the resurgence of invasive Group A Streptococcal infections, of which clinicians must be wary.

Dismal prognosis of Pneumocystis jirovecii pneumonia in patients with multiple myeloma

Patients with multiple myeloma (MM) are at high risk for infections, including opportunistic infections such as Pneumocystis jirovecii pneumonia (PJP). We conducted a retrospective analysis of patients with MM developing PJP over a 6-year period between January 2016 and December 2021 at the University Hospital of Würzburg by screening cases of microbiologically documented PJP. A total of 201 positive results for P. jirovecii in respiratory specimens were retrospectively retrieved through our microbiology database. Of these cases, 13 patients with MM fulfilled the definition of probable PJP according to EORTC fungal disease definitions. We observed two peaks in PJP incidence, one after stem cell transplantation during first-line treatment (n = 5) and the other in heavily pretreated patients with six or more prior lines of therapy (n = 6). There was high morbidity with nine (69%) patients admitted to the ICU, seven of whom (78%) required mechanical ventilation, and high mortality (62%, n = 8). Notably, only two of the 13 patients (15%) had received PJP prophylaxis. The main reason for discontinuation of prophylaxis with trimethoprim-sulfamethoxazole was grade IV neutropenia. The observed morbidity and mortality of PJP in MM patients are significant and even higher than reported for patients with other hematologic malignancies. According to most current guidelines, the use of prophylaxis would have been clearly recommended in no more than three (23%) of the 13 patients. This illustrates the need to critically reconsider the indications for PJP prophylaxis, which remain incompletely defined.

Stopping antibacterial prophylaxis in pediatric allogeneic hematopoietic cell transplantation: An internal audit.

Antibacterial prophylaxis in children and adolescents undergoing allogeneic hematopoietic cell transplantation (HCT) is controversial and not recommended by international guidelines. We analyzed relevant posttransplant outcomes following discontinuation of antibacterial prophylaxis at a major European pediatric transplant center. The single-center retrospective audit included all pediatric allogeneic HCT patients (pts) transplanted between 2011 and 2020 before (≤2014) and after (≥2015) stopping routine antibacterial prophylaxis with penicillin, metronidazole, and ciprofloxacin upon start of the conditioning regimen. The primary endpoint was overall survival until the first hospital discharge. Secondary endpoints included the occurrence of fever; bacterial infections; and cumulative days with antibacterial agents until discharge. A total of 257 HCT procedures were performed in 249 pts (median age: 10 years, range, 0.2-22.5) for leukemia/lymphoma (n = 150) and nonmalignant disorders (n = 107). Of these, 104 procedures were performed before (cohort 1) and 153 after (cohort 2) stopping prophylaxis. Overall survival until discharge was 90.4% in cohort 1 and 96.1% in cohort 2 (p = .06). No differences were observed in the occurrence of fever (92.3vs. 94.1%; p = .57) and bacterial infections (34.6vs. 25.5%; p = .11). The median number of days on antibacterial agents was significantly lower in cohort 2 (39vs. 34; p = .002). Detection rates of resistant organisms were overall low. In this single-center audit, the stop of routine antibacterial prophylaxis had no effect on the occurrence of fever, bacterial infections, resistant organisms, and GVHD. Overall antibiotic use was significantly reduced, and survival was noninferior to the historical control cohort.

Real-World Efficacy and Safety of Letermovir for Cytomegalovirus Prophylaxis in Allogeneic Hematopoietic Stem Cell Transplantation: A Retrospective Analysis at a Single Center

Introduction Cytomegalovirus (CMV) infection is related with significant morbidity and mortality in the patients undergoing allogeneic hematopoietic cell transplantation (HSCT). Agents used to treat CMV infection can be associated with toxicities including renal impairment or myelosuppression. Letermovir is a novel viral terminase complex inhibitor that has efficacy in preventing clinically significant CMV infection (csCMV) in allogeneic HSCT recipients with minimal associated toxicities. Objectives This study aims to analyze the efficacy and toxicity of letermovir as CMV prophylaxis in patients with allogeneic HSCT. Letermovir was started within 5 days of stem cell infusion and was administered for a total of 100 days or until csCMV or unacceptable toxicity, whichever happens first. CMV monitoring was performed using CMV antigenemia immunocytochemical stain every week from neutrophil engraftment until the immunosuppressive agent discontinuation. Retrospective medical record review was conducted for the patients who received letermovir during allogeneic HSCT in Seoul National University Bundang Hospital. Results From September 2020 to May 2023, a total of 139 patients received letermovir for CMV prophylaxis. Median age of the patients was 54 (range, 19 - 73) years with 76 (54.7%) male patients. Diagnosis for allogeneic HSCT included acute myeloid leukemia (n = 55), acute lymphoblastic leukemia (n = 34), myelodysplastic syndrome (n = 25), lymphoma (n = 6), primary myelofibrosis (n = 5). The patient cohort included 2 aplastic anemia patients, 1 atypical chronic myeloid leukemia, and 1 chronic myelomonocytic leukemia. For our patent cohort, all the recipients were seropositive for CMV. Among the patients, 32 patients (23.0%) received HSCT from matched sibling donor, 36 patients (25.9%) from matched unrelated donor, and 54 patients (38.8%) from haploidentical donor. Rest of the patients received HSCT from mismatched unrelated donor (n = 17, 12.2%). 56 patients (40.3%) underwent myeloablative conditioning regimen. For T-cell depletion, antithymocyte globulin was administered in 133 patients (95.7%). Post-transplantation cyclophosphamide was administered in 9 patients (6.5%). Overall, median time on letermovir was 90 (range, 2 - 158) days. Thirty-three patients (23.7%) discontinued Letermovir before completing planned period. In about half of the cases, the reason for drug discontinuation was related to the underlying hematologic disease, not to the side effects or low efficacy of the drug itself (disease progression, infection, or graft-versus-host disease; n = 16). Eight patients discontinued Letermovir due to adverse events (n = 8): gastrointestinal discomfort in 6 patients, edema in 1 patient, and intolerance in 1 patient. During follow-up period, CMV antigenemia positivity was perceived in 55 patients. Cumulative incidence of CMV antigenemia positivity was 61.1%. Cumulative incidence of csCMV and CMV disease was 25.3% and 8.4%, respectively. Of the 55 CMV positive cases, 11 cases (7.9%) occurred during letermovir prophylaxis. However, only 4 cases required ganciclovir preemptive treatment. The remaining 44 cases occurred after discontinuation of the drug. Nineteen cases needed ganciclovir treatment, including 7 CMV disease cases (5 colitis, 1 retinitis, and 1 pneumonitis). Conclusions Letermovir was effective in CMV prophylaxis and well tolerated. Adherence to the drug was mostly associated with general medical condition including underlying hematologic disease and complication of HSCT. Close monitoring is warranted following discontinuation of CMV prophylaxis.

631. Using a commercially available assay that measures cytomegalovirus (CMV)-specific CD4+ and CD8+ T-cell immunity to predict protection against CMV: Results from a prospective, blinded clinical trial

Abstract Background Cytomegalovirus (CMV) infection is associated with significant morbidity and mortality among kidney transplant recipients (KTR). Given toxicities and costs of antivirals, there is growing interest in assays that measure CMV-specific T-cell immunity (TCI), which may predict protection against clinical infection. The Viracor® CMV TCI Panel (TCIP) uses flow cytometry and intracellular cytokine staining to measure %CMV-specific CD4+ and CD8+ T-cells; it is the only commercially available TCI assay in the US. In this investigator-initiated study, we evaluated the performance of the TCIP in predicting clinically significant CMV events. To our knowledge, this is the first prospective blinded clinical study of the TCIP. Methods We enrolled consecutive donor (D) or recipient (R) CMV seropositive KTR, who had TCIP testing monthly until either discontinuation of valganciclovir prophylaxis or the primary outcome. We also enrolled KTR with low-level untreated DNAemia, or after completion of valganciclovir treatment, to evaluate assay predictive values for progression or relapse of CMV infection, respectively. The primary outcome was CMV DNAemia (tested at the discretion of the treating provider for symptoms or laboratory findings), prompting treatment initiation. Secondary outcomes were any DNAemia and DNAemia &amp;gt;1000 IU/mL. Treating providers were unaware of TCIP results. Results We included 46 KTR. Median age was 50.5 (range 18-74) years. 73.6% identified as men, 10.8% Black, 8.7% Hispanic; 41.3% had CMV D+/R- status. KTR with CMV events had significantly lower %CMV-specific CD8+ T-cells (Fig. 1A, p=0.024), and the CMV protection ROC AUC was significant (Fig. 1B: AUC 0.78, 95%CI 0.55-0.99, p=0.026). The positive predictive values of both CD4+ and CD8+ T-cell positivity &amp;gt;0.2% for CMV protection were 96.3% (95%CI 81-99.9%) for the primary outcome, 92.6% (95%CI 75.7-99.1%) for any DNAemia, and 100% (one-sided 95%CI 87.2%) for DNAemia &amp;gt;1000 IU/mL.Figure 1.A. Comparison of CMV-specific %CD8+ T-cells between patients with or without (protected) CMV events. B Receiver Operating Characteristic (ROC) curve for CMV protection. Conclusion The TCIP exhibited good performance in predicting protection from CMV events and could be a useful adjunct tool in clinical decision-making, regarding initiation or extension of CMV prophylaxis or treatment, as well as adjustments in immunosuppression. Disclosures Panos Arvanitis, MS, NIH: Grant/Research Support|NIH: Brown University Summer Assistantship program and from the Brown Emerging Infectious Disease Scholars (EIDS) (5R25AI140490) Dimitrios Farmakiotis, M.D., Astellas: Grant/Research Support|Merck: Grant/Research Support|Viracor: Advisor/Consultant|Viracor: Grant/Research Support

Using a commercially available assay that measures cytomegalovirus (CMV)-specific T-cell immunity to predict protection against CMV: A prospective, blinded clinical study

The Viracor CMV-T-cell immunity Panel (TCIP) measures %CMV-specific CD4+ and CD8+ T-cells. In this blinded clinical study, we evaluated the performance of the TCIP in predicting CMV events. Prospectively enrolled donor or recipient CMV-seropositive kidney transplant recipients (KTR) were evaluated with monthly TCIP testing until either discontinuation of valganciclovir prophylaxis or CMV DNAemia prompting treatment initiation. Also, prospectively enrolled KTR with low-level untreated DNAemia or after completion of treatment were evaluated for progression or relapse of CMV infection. Among 46 KTR, those with CMV events had significantly lower %CMV-specific CD8+ T-cells (p = 0.024), and the CMV protection ROC AUC was significant (AUC 0.78, p = 0.026). The positive predictive values of CD4+ and CD8+ T-cell positivity >0.2 % for CMV protection were: 96.3 % for CMV DNAemia prompting treatment initiation, 92.6 % for any DNAemia, 100 % for DNAemia >1000 IU/mL. The TCIP could be a useful adjunct tool in individualized management of CMV infection.

Mental Health Needs of Adolescent and Young Adult PrEP Users in South Africa: Implications for Sexual and Reproductive Health Programming

PurposePoor mental health is associated with sexual and reproductive health (SRH) risks, including human immunodeficiency virus (HIV) and pre-exposure prophylaxis discontinuation. Adolescents and young people (AYP) are vulnerable to HIV and depression. This paper describes the prevalence and severity of depression and associated factors in AYP accessing SRH services in South Africa. MethodsA cross-sectional analysis of enrollment data (January 2019 to December 2021) from a cohort of individuals receiving pre-exposure prophylaxis services at eight clinics in three provinces in South Africa was conducted. Females (n = 1,074) and males (n = 231) aged 15–24 years were included. Interviewer-administered questionnaires were conducted, and the prevalence and severity of depression assessed using the Patient Health Questionnaire-9. Multivariate analysis was used to identify factors associated with depression. ResultsOver 40% of participants had experienced any depression symptoms (43.7% of females, 38.5% of males). For males, experiencing intimate partner violence was the only predictor of depression symptoms (adjusted odds ratio (AOR) 8.81, 95% confidence intervals (CI) 1.03–75.44). For females, living with both parents (AOR 1.70, 95% CI 1.15–2.51), having transactional sex (AOR 1.63, 95% CI 1.00–2.65), experiencing any intimate partner violence (AOR 1.96, 95% CI 1.34–2.89), and using drugs (AOR 1.78, 95% CI 1.03–3.11) were all positively associated with depression symptoms. Resilience was a protective factor against depression symptoms for both sexes (males: AOR 0.96, 95% CI 0.93–0.98; females: AOR 0.96, 95% CI 0.95–0.97). DiscussionThere is a high burden of depression among AYP accessing SRH services in South Africa. Mental health screening should be integrated into SRH and HIV prevention programs for AYP.

Uptake and Discontinuation of Pre-Exposure Prophylaxis Among Uninsured Transgender and Cisgender Women: A Public-Private Partnership Model in North Carolina.

HIV pre-exposure prophylaxis (PrEP) remains underutilized among cis and trans women. The PrEP Initiative Program (PIP) is a novel public-private partnership implemented at 12 local clinics in North Carolina. PIP provides HIV/sexually transmitted infection (STI) testing and clinical and laboratory monitoring for PrEP to uninsured/underinsured clients. We sought to understand service-related differences among both cis and trans women enrolled in PIP, including STIs diagnoses, clinic type, sources of referral, services needed, and reasons for PrEP discontinuation. The Kaplan-Meier curves display retention on PrEP over the duration of the program. Since 2018, 142 women (cis n = 113; trans n = 29) enrolled, and 136 started PrEP. The majority were ages 25-34 years (31.7%) or 18-24 years (29.6%), Black (57.8%) or Latinx (24.7%). Approximately 20.6% of recipients reported at least one STI while enrolled. Overall, trans women requested fewer services than cis women. After accounting for the amount of time each patient was taking PrEP, there were higher rates of trans women diagnosed with syphilis than cis women. Rates of persons with other STIs were not notably different between trans and cis women. Clinic access varied by gender: 69% of trans women were enrolled at only one site. Trans women were retained significantly longer: The Kaplan-Meier adjusted median time to discontinuation was 560 and 238 days for trans and cis women, respectively. PIP successfully reached historically marginalized and uninsured cis and trans women who may benefit from PrEP. Further investigations into factors contributing to recruitment and retention of women in HIV prevention programs are needed.

Pneumocystis jirovecii Pneumonia after Heart Transplantation: Two Case Reports and a Review of the Literature.

Post-transplant Pneumocystis jirovecii pneumonia (PcP) is an uncommon but increasingly reported disease among solid organ transplantation (SOT) recipients, associated with significant morbidity and mortality. Although the introduction of PcP prophylaxis has reduced its overall incidence, its prevalence continues to be high, especially during the second year after transplant, the period following prophylaxis discontinuation. We recently described two cases of PcP occurring more than one year after heart transplantation (HT) in patients who were no longer receiving PcP prophylaxis according to the local protocol. In both cases, the disease was diagnosed following the diagnosis of a viral illness, resulting in a significantly increased risk for PcP. While current heart transplantation guidelines recommend Pneumocystis jirovecii prophylaxis for up to 6-12 months after transplantation, after that period they only suggest an extended prophylaxis regimen in high-risk patients. Recent studies have identified several new risk factors that may be linked to an increased risk of PcP infection, including medication regimens and patient characteristics. Similarly, the indication for PcP prophylaxis in non-HIV patients has been expanded in relation to the introduction of new medications and therapeutic regimens for immune-mediated diseases. In our experience, the first patient was successfully treated with non-invasive ventilation, while the second required tracheal intubation, invasive ventilation, and extracorporeal CO2 removal due to severe respiratory failure. The aim of this double case report is to review the current timing of PcP prophylaxis after HT, the specific potential risk factors for PcP after HT, and the determinants of a prompt diagnosis and therapeutic approach in critically ill patients. We will also present a possible proposal for future investigations on indications for long-term prophylaxis.

Pre-exposure Prophylaxis Use and Discontinuation in a Federally Qualified Health Center in a Mexico-US Border City.

Latino men who have sex with men (MSM) experience disproportionately high rates of HIV diagnoses in the United States. Pre-exposure prophylaxis (PrEP) use is critical to reduce this inequity, but PrEP awareness, access, and use are low among Latino MSM. This study aims to describe patterns of PrEP persistence and discontinuation among predominately Latino MSM accessing PrEP in a federally qualified health center (FQHC) in El Paso, Texas. This retrospective cohort comprised individuals who were eligible for PrEP at a FQHC in El Paso, Texas, between January 30, 2019, and August 15, 2021. We defined hierarchical categories of PrEP use and discontinuation, which was defined as more than 120days between PrEP visits. We used Kaplan-Meier survival plots to estimate median time to first PrEP discontinuation. There were 292 patients evaluated for PrEP; 91% were Latino. The majority of PrEP patients (70%, 205/292) experienced any PrEP discontinuation, and the median time to first PrEP discontinuation was 202days (95% CI: 179-266). The proportion of patients who remained on PrEP at 3months after initiation was 82% (95% CI: 76%, 87%) and at 6months after initiation was 55% (95% CI: 46%, 62%). While 3-month PrEP retention was high in this predominately Latino MSM patient population, PrEP discontinuation was common. Interventions that enhance longer-term persistence and support for restarting PrEP are needed to reduce the persistent ethnoracial disparities in HIV incidence.