Topics in antiviral medicine最新文献

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.

Comorbid conditions have a major impact on the health, quality of life, and survival of people with HIV (PWH), particularly as they age. The 2024 Conference on Retroviruses and Opportunistic Infections (CROI) featured many excellent reports related to specific comorbidities, most notably cardiovascular disease, cancer, fatty liver disease, and hypertension. Major themes included hypertension management strategies used in low- and middle-income countries, important insights from the REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) study that focused on cardiometabolic outcomes, studies investigating metabolic-associated fatty liver disease, and the use of glucagon-like peptide-1 receptor agonists in PWH. This review focuses on the abstracts presented at CROI 2024 that discussed these areas, highlighting those with the most clinical impact.

Scientists from around the world gathered in Denver for the Conference on Retroviruses and Opportunistic Infections (CROI). The conference maintained its existing format and used a combination of plenary lectures, workshops, oral abstract sessions, themed discussions, and interactive symposia to deliver the latest advances in HIV/AIDS research to the almost 4000 delegates in attendance. As with previous CROI meetings, the conference provided a fertile environment for early-stage investigators who were interested in getting updates in areas of research outside of their particular domain. This was exemplified by the Scott M. Hammer Workshop for New Investigators and Trainees. Here, leading investigators helped orient new investigators and trainees to the various scientific presentations in the different thematic areas being covered at CROI. The meeting organizers did a great job of minimizing conflicts and made sure that talks in similar thematic areas would not end up in parallel sessions. The conference continues to focus on research related to HIV/AIDS and comorbidities. Approximately 20% of the accepted abstracts featured research on SARS-CoV-2 and 3% on mpox. CROI continues to serve as a "1-stop-shop" conference to educate and update infectious disease researchers on the latest developments in the field.

Several novel antituberculosis agents, including long-acting injectable agents in mouse models, have shown promise in preclinical and early clinical studies. This encouraging news is offset by the failures of a tuberculosis (TB) vaccine to prevent disease recurrence and a 3-month clofazimine-based treatment regimen for drug-susceptible TB. Clinically focused insights regarding TB, mpox, and other HIV-associated infectious complications that were presented at the 2024 Conference on Retroviruses and Opportunistic Infections (CROI) are summarized in this review.

At the 2024 Conference on Retroviruses and Opportunistic Infections (CROI), investigators presented updates on the global HIV epidemic, focusing on ongoing disparities by race/ethnicity in the US, the ongoing concentration of new infections among men who have sex with men (MSM) and transgender women in the Americas, and a shift to a greater total number of infections now in low versus high prevalence countries globally. HIV testing, the gateway to prevention and to treatment, has not fully rebounded from the substantial declines seen during the early COVID-19 pandemic in some settings, although innovative strategies including home testing and opt-out testing in clinical settings appear to be reaching populations in need of testing. Several investigators reported on the efficacy and effectiveness of doxycycline used as postexposure prophylaxis (doxy-PEP) to prevent bacterial sexual transmitted infections in MSM and transgender women in clinical trials and clinic settings; citywide rates of chlamydia and syphilis have decreased in San Francisco after the rollout of the first doxy-PEP guidelines in the US. Lack of doxy-PEP efficacy in cisgender women in Kenya appears due to low adherence in that trial. Rollout and persistence on oral HIV preexposure prophylaxis (PrEP) are associated with reduced seroincidence on a population and individual level. The rollout of long-acting injectable cabotegravir (CAB-LA) PrEP is proceeding slowly in the US. New, longer-acting oral and injectable agents are in development, with preclinical and early clinical trial data presented at CROI. Oral PrEP uptake among populations in sub-Saharan Africa remains low in most settings, suggesting the need for more options and more support; point-of-care tenofovir testing appear acceptable in various populations and may improve adherence and identify PrEP users needing more support. Choice of PrEP or PEP including CAB-LA combined with clinical support substantially increased biomedical prevention coverage in East Africa. Novel approaches to PrEP rollout, including delivery using mobile services and in nonclinical settings appear to show promise. HIV PEP continues to be underutilized.