CROI 2024 Abstract eBook

Abstract eBook

Invited Session

communities, healthcare providers, and pregnant women about syphilis risks, the importance of antenatal care, and available preventive measures is crucial to increase awareness and enable early intervention in CS cases. Syphilis, despite being an ancient infection, presents ongoing challenges that require strategic approaches to enhance the healthcare network's capacity and improve the quality of care provided to pregnant women.

and aligned with emotional well-being (Terminal Illness vs. Chronic Condition), psychological well-being (Innocence vs Culpability), and social well-being (Visibility vs. Invisibility). These findings suggest that historic narratives of the HIV epidemic, and its many iterations, have enduring effects on individual narratives of mental well-being among a welcomed generation of adults living with PHIV. Cardiometabolic Risks and Complications: Adolescents and Young Adults With Perinatally Acquired HIV Sahera Dirajlal-Fargo Ann and Robert Lurie Children's Hospital, Chicago, IL, USA Background: Antiretroviral therapy (ART) scale-up has dramatically reduced rates of pediatric HIV mortality and morbidity. Children living with perinatally acquired HIV (PHIV) are living through adolescence and well into adulthood, such that adolescents now represent the largest growing population living with HIV. This presentation aims to discuss the literature describing the prevalence of cardiometabolic complications and the research gaps that remain, as well as opportunities to optimize research and care. There are continued challenges in determining the risk of cardiometabolic co-morbidities in adolescents and young adults with PHIV, and their risk factors differ compared to adults with horizontally acquired HIV. Data suggest evidence for subclinical cardiometabolic complications in PHIV in the setting of newer ART and include: 1) Cardiovascular: evidence of functional cardiac abnormalities, subclinical vascular disease and endothelial dysfunction; 2) Metabolic: evidence of alterations in adipose tissues, dyslipidemia and insulin resistance. In addition, previous exposure to thymidine analogues continue to cause increase risk of metabolic complications in this population. Novel techniques available techniques in imaging and omics may help identify early cardiometabolic abnormalities in this population as well as mechanistic pathways. Further studies are needed to understand the long term risk and management strategies in adolescents with PHIV to prevent complications to avoid diabetes and cardiovascular disease. Background: Congenital syphilis (CS) is transmitted from an infected mother to her unborn child during pregnancy, leading to severe health complications such as stillbirth, miscarriage, infant death, and maternal and infant morbidity. These adverse outcomes can be prevented through timely screening and treatment during antenatal care. The increasing prevalence of CS is associated with several challenges, requiring a comprehensive approach involving improved healthcare infrastructure, enhanced access to antenatal care, strong testing and screening programs, and extensive education initiatives to mitigate the impact on maternal and child health. Addressing the underdiagnosis of syphilis in pregnancy, especially in regions with limited healthcare access, is essential to avoid missed opportunities for screening and early detection. While reliable and accessible syphilis testing during pregnancy, including treponemal and non-treponemal tests, is essential for early detection, challenges may arise due to limited testing facilities, cultural stigma, and the complexity of implementing comprehensive screening programs. Ensuring that infected pregnant women receive timely and appropriate penicillin treatment is another critical measure to prevent CS, as penicillin is the only effective treatment during pregnancy. However, challenges such as limited healthcare access, potential allergic reactions, and penicillin shortages in some countries must be addressed. The stigma surrounding sexually transmitted infections and societal attitudes can discourage pregnant women from seeking testing, treatment, and follow-up care. Therefore, addressing these sociocultural factors is essential to create an environment where pregnant women feel comfortable accessing healthcare services. Despite specific recommendations from the World Health Organization aligned with sustainable development goals, CS remains a public health concern in many countries, with higher rates in developing countries and emerging cases in developed nations. Educating Why Can't We Do Better at Diagnosing Syphilis? Ina Park University of California San Francisco, San Francisco, CA, USA Background: This session will utilize challenging case studies to review methods for syphilis diagnosis, including direct detection, serology (non treponemal and treponemal tests), molecular diagnostics and point of care testing. The Burgeoning Epidemic of Congenital Syphilis Angelica Espinosa Miranda Ministry of Health of Brazil, Brasilia, Brazil

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Syphilis: Management Conundrums Khalil G Ghanem The Johns Hopkins University, Baltimore, MD, USA

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Background: As the rates of syphilis continue to increase, clinicians are caring for patients with complex clinical presentations, and they are facing challenging management dilemmas. In this session, we will answer the following questions: How do we approach rapid plasma reagin (RPR) titers that fail to decline appropriately following therapy? RPR titers that increase following treatment? What is the optimal management of patients with neurosyphilis, ocular, and otic syphilis? Are additional doses of benzathine penicillin G necessary in patients with these complications? How could DOXY-PEP impact the management of syphilis? Approaches that provide consistency in the care of patients with complex presentations of syphilis are feasible despite a paucity of data. HIV Assembly, Maturation Inhibitors, and Drug Resistance Eric O Freed National Cancer Institute, Frederick, MD, USA Background: HIV-1 particle assembly is driven by the viral Gag polyprotein precursor, which initiates assembly by forming an immature Gag lattice at the inner leaflet of the infected cell plasma membrane. Following completion of immature particle assembly and virus budding, the viral protease (PR) cleaves the Gag precursor at a number of sites to generate the mature Gag proteins matrix (MA), capsid (CA), nucleocapsid (NC), p6, and two small spacer peptides SP1 and SP1. PR-mediated Gag cleavage triggers a morphological transformation of the nascently released virion (known as maturation) during which the newly liberated CA protein assembles to form the viral capsid, into which are packaged the viral RNA genome and the viral enzymes reverse transcriptase (RT) and integrase (IN). Our work and that of others has demonstrated that the finely tuned stability of the immature Gag lattice is essential for particle assembly and subsequent maturation, and proper capsid stability is essential for early post-entry events. The stability of immature and mature Gag lattices is modulated by the cellular polyanion inositol hexakisphosphate (IP6). From a translational perspective, two classes of HIV-1 inhibitors - maturation inhibitors and capsid inhibitors (including the recently FDA-approved drug lenacapavir) - act by tipping the stability/ instability balance of the immature Gag lattice and the mature capsid, respectively. Thus, elucidating the determinants of Gag complex stability is crucial for both achieving a basic understanding of HIV-1 replication and also for moving forward drug discovery efforts that target assembly, maturation, or capsid-mediated post-entry events, including nuclear import. In a separate line of investigation, our recent work has shown that the lipid composition of the HIV-1 virion plays a key role in HIV-1 maturation, as disrupting the cellular lipid biosynthesis enzyme neutral sphingomyelinase 2 (nSMase2) blocks Gag processing, particle maturation, and virus replication. In all of the above described studies, drug resistance selections and forced evolution experiments have provided key mechanistic insights. Accelerating Tuberculosis Elimination: Short-Course Prevention and Treatment Vidya Mave Center for Infectious Diseases in India, Johns Hopkins India, Pune, India Background: Tuberculosis (TB) is among the leading cause of morbidity and mortality from an infectious disease, among patients with and without HIV, worldwide. Despite cost-free 6- months anti-TB therapy (ATT), the cure rates for TB have been suboptimal due to inadequate exposure/ adherence to ATT, causing a higher risk of failure, relapse, or acquired drug resistance, particularly in the setting of HIV. Recent research developments demonstrated that highly potent ATT regimens can allow shortening of TB treatment for both drug-sensitive and drug resistant TB in adult, adolescent and paediatric populations. In addition, shortened TB preventive therapy containing highly potent rifamycins and isoniazid is as good as the traditional 6-9 months of isoniazid prophylaxis among at-risk populations. Furthermore, emerging evidence shows that shortened course TB treatment and prevention regimens

Invited Session

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CROI 2024