Topics in antiviral medicine最新文献

Liver disease remains a key contributor to morbidity and mortality among people with HIV. Although substantial progress has been made in terms of a cure for hepatitis C, increased life expectancy is associated with emerging issues associated with steatotic liver disease. Hepatitis B and D are still prevalent and often underrecognized as a cause of indolent liver injury leading to inflammation and fibrosis. Barriers to care exist in many subpopulations that reduce the use of potentially lifesaving therapies. Hepatocellular carcinoma continues to be a factor in advanced hepatic fibrosis.

The 2025 Conference on Retroviruses and Opportunistic Infections (CROI) showcased advances in understanding neuropsychiatric complications among people with HIV (PWH). This review synthesizes key findings related to central nervous system (CNS) reservoirs, neuropathogenesis, and biomarkers of brain health. Emerging data underscore the persistence of HIV in brain tissues despite antiretroviral therapy (ART), with compartmentalization occasionally observed in the spinal cord and brain, and evidence suggesting that HIV-infected cells may contribute to chronic inflammation in the CNS. Single-cell and epigenetic profiling of cerebrospinal fluid cells revealed immune dysregulation in myeloid and B cells, suggesting ongoing CNS dysfunction during suppressive ART. Longitudinal neuroimaging and cognitive studies reinforced that incomplete or unstable HIV suppression correlates with worse brain outcomes. Notably, higher blood phosphorylated tau 217 and systemic inflammation predicted cognitive decline in aging PWH. Promising therapeutic avenues included observations that glucagon-like peptide-1 receptor agonists, such as semaglutide, improve visuospatial performance in PWH and cannabinoid receptor 2 agonists reduced neuroinflammatory pathways in preclinical models. Additionally, early initiation of ART was associated with normalization of brain volumes and attenuation of neuronal injury markers. Together, these findings highlight the complexity of neuro-HIV interactions and underscore the need for targeted interventions to protect brain health in PWH.

At the 2025 Conference on Retroviruses and Opportunistic Infections (CROI), investigators presented updates on the global HIV epidemic. Although new HIV infections have been declining globally, new infections are expanding in Eastern Europe and central Asia, the Middle East and North Africa, and Latin America. HIV incidence remains high among key populations and their partners. Initiation of oral preexposure prophylaxis (PrEP) is increasing globally, with 91% of PrEP starts funded by the US President's Emergency Plan for AIDS Relief, and large rises in new HIV infections are predicted to occur due to international funding cuts. Several presentations focused on strategies to increase HIV testing, including home HIV self-testing, couples HIV testing, and use of digital strategies. Substance use continues to be a driver of new HIV infections. Implementation of harm reduction and opiate agonist therapy significantly reduced new infections among people who inject drugs in Malaysia, and other person-centered approaches tailored for people who use drugs are being investigated. The uptake of PrEP has been increasing in a number of priority populations; however, persistence on oral PrEP remains sub-optimal. Although the use of long-acting injectable cabotegravir (CAB-LA) remains low in the US, several programs have demonstrated high persistence. When provided choice, many individuals choose CAB-LA over other available options, and adherence to follow-up injections has been high. Several interventions to increase PrEP uptake and adherence show promise, including pharmacy-based refills and incentives, point-of-care urine tenofovir testing with counseling, and use of mobile health tools. PrEP with emtricitabine/tenofovir alafenamide was shown to reduce HIV infections in cisgender women adherent to PrEP. A single once-yearly injection with lenacapavir showed promising pharmacokinetic results and a phase III trial is planned. Interest in doxycycline postexposure prophylaxis is high, and real-world implementation has been associated with significant declines in bacterial sexually transmitted infections.

Stimulant use disorder poses substantial challenges to the health and well-being of people with HIV, contributing to increased HIV transmission risk and poor clinical outcomes. This article highlights the cultural significance of stimulant use, its epidemiology, and the latest evidencebased interventions for stimulant use disorder among individuals with HIV. Contingency management has emerged as the most effective treatment, with harm-reduction approaches serving as vital tools for improving the health of individuals unable or unwilling to achieve abstinence. Integrated care models that combine behavioral interventions, pharmacotherapy, and harm reduction offer a promising framework to improve health outcomes for people with HIV who use stimulants, addressing the intersection of stimulant use and HIV in care settings.

Weight gain among persons with HIV PWH) on contemporary antiretroviral therapy (ART) can extend beyond an initial return-to-health phenomenon and lead to overweight/obesity in the first 1 to 2 years, resulting in enhanced cardiometabolic risk. Factors that may contribute to increased weight gain include specific ART regimens (those initiating dolutegravir and tenofovir alafenamide or withdrawing tenofovir disoproxil and efavirenz), women with HIV, and certain virologic factors including lower baseline CD4 count and higher HIV viral load. Weight reduction starting at 5% body weight confers metabolic protection, such as improved hypertension and dysglycemia. Even greater metabolic impact has been shown with weight reduction in the approximate range of 15% body weight, as evidenced by decreases in cardiovascular disease mortality. Effective weight management is essential to reducing cardiometabolic risk, may not be achieved with lifestyle changes alone, and requires other therapeutic strategies. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are well recognized to provide potent weight reduction among persons with overweight/obesity; in addition, studies have shown cardiovascular benefit among those with established cardiovascular disease. Recent studies have permitted us to begin to understand the potential role of GLP-1 RAs among PWH and overweight/obesity. This review highlights weight gain specific to PWH and discusses current evidence and key clinical considerations for GLP-1 RA use among PWH.

People with HIV (PWH) are living longer and experiencing a greater burden of morbidity from non-AIDS-defining conditions. Chronically treated HIV disease is associated with ongoing systemic inflammation that contributes to the development of chronic conditions (eg, cardiovascular disease) and geriatric syndromes (eg, frailty). Apart from HIV disease, a progressive increase in systemic inflammation is a characteristic feature of biologic aging, a process described as "inflammaging." Inflamm-aging is driven by persistent antigen stimulation and stress, leading to an immune profile characterized by elevated levels of blood inflammatory markers and cellular activation and senescence. Chronic HIV disease is hypothesized to accentuate the immune profile of inflamm-aging, in part through viral persistence in lymphatic tissues, permanent injury impairing immune recovery, the presence of copathogens, gut dysbiosis and microbial translocation, and chromosomal and genetic alterations associated with immune activation. Few strategies exist for safe and effective modulation of systemic inflammation among older PWH. The strongest current evidence supports aggressive management of modifiable risk factors such as lipids, blood pressure, and levels of physical activity. Future inflamm-aging research should be directed toward advancing the implementation of proven approaches, such as physical activity, as well as studying novel mechanisms of, and treatments for, inflamm-aging among PWH.

Data on the HIV care cascade demonstrated challenges in achieving Ending the HIV Epidemic (EHE) targets across all 18 EHE focus metropolitan areas, but innovative adherence interventions using point-of-care tenofovir testing and motivational interviewing support care cascade outcomes in Namibia and South Africa, respectively. Data on treatment with long-acting injectable (LAI) antiretroviral therapy (ART) demonstrated high acceptability, retention, and virologic suppression including in groups that were not well represented in clinical trials including persons born female and persons with detectable viral loads. The adjuvanted hepatitis B vaccine appeared to be safe and appeared to be superior to conventional hepatitis B vaccines in persons with HIV (PWH) who were prior nonresponders to the hepatitis B vaccine. New therapies are in the pipeline for LAI hepatitis C medication that may cure hepatitis C with 1 injection. ACTG (AIDS Clinical Trials Group) A5359 showed that long-acting cabotegravir/rilpivirine (LA CAB/RPV) can be used effectively in PWH experiencing adherence challenges to oral ART and suggested a paradigm for treating this population with an unmet medical need. Studies on resistance mutations in SARS COV-2 show that treatmentrelated emergent resistance does not appear to contribute to viral rebound or have the potential for transmitted drug resistance. The data presented on HIV and maternal and pediatric health included findings from studies on the implementation of first-line dolutegravir-based ART in pregnant and postpartum women and children, along with results of a phase I/II trial involving LA CAB/RPV in adolescents. Additionally, various abstracts addressed hypertensive disorders in HIV during pregnancy and postpartum periods, as well as the intersection of HIV and mental health in women and youth.

Studies of acute and post-acute COVID-19, including their biology, prevention, and treatment, were presented at the 2024 Conference on Retroviruses and Opportunistic Infections. Numerous studies reported on the impact of hybrid immunity (ie, from a combination of prior infection and vaccination) on the natural history, pathogenesis, and outcomes of infection with modern SARS-CoV-2 variants. Several studies demonstrated the continued benefit of SARS-CoV-2 vaccination and the effect of treatment, particularly in the setting of severe disease. New data regarding persistent RNA shedding in immunocompromised populations were presented, demonstrating the potential challenges that this phenomenon poses with regard to viral evolution. In addition, there was a continued focus on post-acute sequelae of SARS-CoV-2 including its clinical manifestations and potential underlying biology. These and other studies are summarized here.

The 2024 Conference on Retroviruses and Opportunistic Infections featured new and impactful findings about neuropsychiatric complications in people with HIV and other infections. Reports included new evidence from low- and middleincome countries, HIV persistence in the central nervous system, aging-related complications (including cerebrovascular disease), additional data relevant to pathogenesis, and therapeutics. Also included were new evidence of active HIV RNA transcription in cells from cerebrospinal fluid and the brain during virally suppressive antiretroviral therapy as well as links between neuropsychiatric complications or brain imaging findings in people with HIV and a) carotid artery inflammation and cerebrovascular disease, b) Alzheimer's disease genetic risk, c) social determinants of health, including exposure to pollution, and d) epigenetic aging. New therapeutic findings were presented on the cerebrospinal fluid inhibitory quotient, the effects of polypharmacy, and clinical trials of tesamorelin and telmisartan. This review summarizes these and other new findings and highlights new research directions for the neuro-HIV field.