Sexual behaviors and access to HIV services during the COVID-19 pandemic among cisgender men who have sex with men in Lima, Peru.

Background: The COVID-19 pandemic significantly impacted sexual behaviors, access to health services, and other factors related to HIV vulnerability among sexual and gender minority populations globally. This study investigates such changes among men who have sex with men (MSM) in Lima, Peru.

Methods: We analyzed data from a cross-sectional survey that was conducted initially in 2018–2019 (‘pre-pandemic’ period,  = 382) and then repeated in 2020–2021 (‘mid-pandemic’ period,  = 387).

CD4-mimetics sensitize HIV-infected cells to ADCC mediated by plasma from persons with early-stage HIV-1 infection.

Unlabelled: The viral reservoir in long-lived memory CD4+ cells, established in the early stages of HIV infection, represents the main obstacle to an HIV cure. Some strategies being developed to target the reservoir rely on rendering HIV-1 envelope glycoproteins (Env) visible to the immune system. Small molecule CD4-mimetics (CD4mcs) expose vulnerable Env epitopes, which can be targeted by non-neutralizing antibodies (nnAbs) that are abundant in the plasma of people living with HIV (PLWH) and can mediate antibody-dependent cellular cytotoxicity (ADCC).

ULACNet-301, OPTIMO protocol: optimizing HPV vaccination regimen for cancer prevention in children and adolescents living with HIV.

Background: Persistent infection with human papillomavirus (HPV) is associated with most cervical and anal cancer cases and a large fraction of other anogenital and oropharyngeal cancers. The prophylactic HPV vaccines are known to prevent HPV infections and HPV-associated disease, although there is evidence of reduced response to the HPV vaccination among individuals living with HIV. Prior studies among individuals without HIV suggest that a single HPV vaccine dose induces humoral immune responses that, while lower than those induced by two or three doses, still confer protection against HPV infection.

Cytomegalovirus immunity in high-risk liver transplant recipients following preemptive antiviral therapy versus prophylaxis.

CMV-specific T cells, NK cells, and neutralizing antibodies (nAbs) were assessed in a randomized trial of CMV prevention with preemptive antiviral therapy (PET) versus prophylactic antiviral therapy (PRO) in donor-seropositive/recipient-seronegative (D+R-) liver transplant recipients (LTxR) at 100 days (end of intervention) and at 6 and 12 months after transplant. The PET group had significantly increased numbers of circulating polyfunctional T cells, NK cells, and nAbs compared with the PRO group at day 100, and several CMV immune parameters remained significantly higher by 12 months after transplant. Among PET recipients, preceding CMV viremia (vs.

Viral Load Dynamics in Plasma and Semen When Antiretroviral Therapy Is Initiated During Early HIV-1 Infection.

We assessed human immunodeficiency virus (HIV) load in plasma and semen during primary HIV infection using serial samples of semen and plasma during the first 24 weeks after diagnosis in untreated participants and those who started antiretroviral therapy (ART) immediately at diagnosis. In the absence of treatment, semen viral load was >1000 copies/mL in almost all specimens (83%) collected 2-10 weeks after the estimated date of HIV acquisition and remained >1000 copies/mL in 35% of untreated participants at the last observed time point. Thus, in the absence of ART, semen viral load remained at a level consistent with transmissibility throughout primary infection.

Impact of youth lay health workers on HIV service delivery in South Africa: A pragmatic cluster randomized trial of the Youth Health Africa program.

Background: Innovative approaches are needed to increase lay health workers in HIV programs. The Youth Health Africa (YHA) program is a novel approach that places young adults seeking work experience in one-year internships in health facilities to support HIV-related programming (e.g.

Association of Cytomegalovirus (CMV) DNAemia With Long-Term Mortality in a Randomized Trial of Preemptive Therapy and Antiviral Prophylaxis for Prevention of CMV Disease in High-Risk Donor Seropositive, Recipient Seronegative Liver Transplant Recipients.

In a post-hoc analysis of the association of CMV DNAemia with long-term mortality in a randomized trial of CMV preemptive therapy vs. antiviral prophylaxis in D+R- liver transplant recipients, post-intervention CMV DNAemia was associated with increased mortality after adjusting for study arm.

Protocol for evaluating mechanistic pathways associated with HIV acquisition via nested Least Absolute Shrinkage and Selective Operator analysis.

Statistical analysis to evaluate mechanistic pathways can be limited by non-causal associations as well as co-linearity of high-dimensional data. Here, we present a protocol evaluating statistical associations between multiple exposure variables (sociodemographic and behavioral), immune biomarkers, and HIV acquisition. We describe steps for study setup, combining Least Absolute Shrinkage and Selective Operator with the standard regression approach, and building nested models.

A Systematic Review and Meta-analysis of Optimized CMV Preemptive Therapy and Antiviral Prophylaxis for CMV Disease Prevention in CMV High-Risk (D+R-) Kidney Transplant Recipients.

Unlabelled: The optimal strategy for cytomegalovirus (CMV) disease prevention in CMV donor/recipient kidney transplant recipients remains uncertain. Conclusions of prior meta-analyses that CMV disease rates with preemptive therapy (PET) and universal prophylaxis (UP) were comparable may have been affected by inclusion of studies lacking key determinants of efficacy of the respective strategies.

Methods: We conducted a systematic review and meta-analysis of PET with weekly CMV polymerase chain reaction monitoring for ≥3 mo and UP with 6 mo of valganciclovir.

Does a youth intern programme strengthen HIV service delivery in South Africa? An interrupted time-series analysis.

Introduction: Since 2018, Youth Health Africa (YHA) has placed unemployed young adults at health facilities across South Africa in 1-year non-clinical internships to support HIV services. While YHA is primarily designed to improve employment prospects for youth, it also strives to strengthen the health system. Hundreds of YHA interns have been placed in programme (e.

Dynamic immune markers predict HIV acquisition and augment associations with sociobehavioral factors for HIV exposure.

Prior studies attempting to link biomarkers of immune activation with risk of acquiring HIV have relied on cross sectional samples, most without proximity to HIV acquisition. We created a nested case-control study within the study in Peru, and assessed a panel of plasma immune biomarkers at enrollment and longitudinally, including within a month of diagnosis of primary HIV or matched timepoint in controls. We used machine learning to select biomarkers and sociobehavioral covariates predictive of HIV acquisition.

Immune Activation in Primary Human Immunodeficiency Virus: Influence of Duration of Infection, Treatment, and Substance Use.

Background: Primary human immunodeficiency virus (HIV) is characterized by dynamic changes in viral load and innate and adaptive immune responses; it is unclear the extent to which time from acquisition to antiretroviral therapy (ART) initiation and substance use impact these immunologic changes.

Methods: We studied plasma immune activation biomarkers, viral load, and CD4 and CD8 cell counts in participants from the Sabes primary infection study in Peru, who had been randomized to begin ART immediately after diagnosis vs 24 weeks later. We modeled influence of substance use and duration of HIV infection on biomarkers at baseline and over 24 weeks.

Long-term effects of early antiretroviral initiation on HIV reservoir markers: a longitudinal analysis of the MERLIN clinical study.

Background: Early antiretroviral therapy (ART) initiation (ie, within 3 months of infection) limits establishment of the HIV reservoir. However, the effect of early ART initiation on the long-term dynamics of the pool of infected cells remains unclear.

Methods: In this longitudinal analysis, we included cisgender men who have sex with men (MSM) and transgender women (aged 18-54 years) at high risk for HIV infection, enrolled in the ongoing longitudinal MERLIN study in Peru between Oct 28, 2014, and Nov 8, 2018.

Pathogen-Specific Humoral Immunity and Infections in B Cell Maturation Antigen-Directed Chimeric Antigen Receptor T Cell Therapy Recipients with Multiple Myeloma.

Chimeric antigen receptor (CAR) T cell therapy targeting B cell maturation antigen (BCMA-CARTx) is an emerging treatment for relapsed or refractory multiple myeloma (R/R MM). Here we characterize the epidemiology of infections, risk factors for infection, and pathogen-specific humoral immunity in patients receiving BCMA-CARTx for R/R MM. We performed a retrospective cohort study in 32 adults with R/R MM enrolled in 2 single-institution phase 1 clinical trials of BCMA-CARTx administered after lymphodepleting chemotherapy alone (n = 22) or with a gamma secretase inhibitor (GSI).

HIV transmission patterns among transgender women, their cisgender male partners, and cisgender MSM in Lima, Peru: A molecular epidemiologic and phylodynamic analysis.

Background: Transgender women (TW) in Peru are disproportionately affected by HIV. The role that cisgender men who have sex with TW (MSTW) and their sexual networks play in TW's risk of acquiring HIV is not well understood. We used HIV sequences from TW, MSTW, and cisgender men who have sex with men (MSM) to examine transmission dynamics between these groups.

Brief Report: Self-Reported Knowledge of HIV Status Among Cisgender Male Sex Partners of Transgender Women in Lima, Peru.

Background: Knowledge of HIV status is a critical first step in the HIV care cascade. Cisgender male sex partners of transgender women (MSTW) are at a disproportionately high risk of HIV, but little is known about their access to HIV testing or knowledge of HIV status.

Methods: We used cross-sectional data from a respondent-driven sampling study to analyze self-reported HIV status and predictors of knowledge of HIV status among MSTW in Lima, Peru.

Genomic attributes of homology-directed DNA repair deficiency in metastatic prostate cancer.

Cancers with homology-directed DNA repair (HRR) deficiency exhibit high response rates to poly(ADP-ribose) polymerase inhibitors (PARPi) and platinum chemotherapy. Though mutations disrupting BRCA1 and BRCA2 associate with HRR deficiency (HRRd), patterns of genomic aberrations and mutation signatures may be more sensitive and specific indicators of compromised repair. Here, we evaluated whole-exome sequences from 418 metastatic prostate cancers (mPCs) and determined that one-fifth exhibited genomic characteristics of HRRd that included Catalogue Of Somatic Mutations In Cancer mutation signature 3.

Long-term effects of early antiretroviral initiation on HIV reservoir markers: a longitudinal analysis of the MERLIN clinical study.

Background: Early antiretroviral therapy (ART) initiation (ie, within 3 months of infection) limits establishment of the HIV reservoir. However, the effect of early ART initiation on the long-term dynamics of the pool of infected cells remains unclear.

Methods: In this longitudinal analysis, we included cisgender men who have sex with men (MSM) and transgender women (aged 18-54 years) at high risk for HIV infection, enrolled in the ongoing longitudinal MERLIN study in Peru between Oct 28, 2014, and Nov 8, 2018.

Bayesian validation framework for dynamic epidemic models.

Complex models of infectious diseases are used to understand the transmission dynamics of the disease, project the course of an epidemic, predict the effect of interventions and/or provide information for power calculations of community level intervention studies. However, there have been relatively few opportunities to rigorously evaluate the predictions of such models till now. Indeed, while there is a large literature on calibration (fitting model parameters) and validation (comparing model outputs to data) of complex models based on empirical data, the lack of uniformity in accepted criteria for such procedures for models of infectious diseases has led to simple procedures being prevalent for such steps.

HIV Disease Dynamics and Markers of Inflammation and CNS Injury During Primary HIV Infection and Their Relationship to Cognitive Performance.

Introduction: Early systemic and central nervous system viral replication and inflammation may affect brain integrity in people with HIV, leading to chronic cognitive symptoms not fully reversed by antiretroviral therapy (ART). This study examined associations between cognitive performance and markers of CNS injury associated with acute HIV infection and ART.

Methods: HIV-infected MSM and transgender women (average age: 27 years and education: 13 years) enrolled within 100 days from the estimated date of detectable infection (EDDI).

Exploring HIV risk behavior and sexual/gender identities among transgender women and their sexual partners in Peru using respondent-driven sampling.

HIV prevalence is high among transgender women, but little is known about cisgender men who have sex with transgender women (MSTW). The objective of this study was to investigate characteristics and behavior of MSTW compared to transgender women and men who have sex with men (MSM) using a modified respondent-driven sampling design. Seed participants completed a survey and invited up to three sex partners.

Antibodies against vaccine-preventable infections after CAR-T cell therapy for B cell malignancies.

BACKGROUNDLittle is known about pathogen-specific humoral immunity after chimeric antigen receptor-modified T (CAR-T) cell therapy for B cell malignancies.METHODSWe conducted a prospective cross-sectional study of CD19-targeted or B cell maturation antigen-targeted (BCMA-targeted) CAR-T cell therapy recipients at least 6 months posttreatment and in remission. We measured pathogen-specific IgG against 12 vaccine-preventable infections and the number of viral and bacterial epitopes to which IgG was detected ("epitope hits") using a serological profiling assay.