Topics in antiviral medicine最新文献

Individuals with HIV have elevated risks for cardiovascular diseases (CVDs) ranging from myocardial infarction to heart failure. Our understanding of this heightened HIV-associated cardiovascular risk has evolved over the past 2 decades. In the early era of antiretroviral therapy (ART), concern existed that ART was the primary driver of cardiovascular risk. However, it has become increasingly apparent that HIV-related viremia, immune dysregulation, and inflammation are primary drivers of HIV-associated cardiovascular risk, along with traditional cardiovascular risk factors such as tobacco smoking. Indeed, early and effective ART blunts risk for CVDs among individuals with HIV. Despite these improvements in HIV-associated cardiovascular risk, questions remain regarding how to optimally predict, prevent, and treat CVDs among individuals with HIV. Efforts are underway to define more precisely which diagnostic and therapeutic strategies will be most effective in curbing HIV-associated CVDs.

Despite major advances in the HIV prevention toolbox in the past decade, there remain substantial social, economic, and structural barriers to access to preexposure prophylaxis (PrEP) that prevent a universal, population-level reduction in HIV incidence. Daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) has been the flagship PrEP regimen, and data support a pericoital/on-demand "2-1-1" dosing schedule for men who have sex with men. Daily oral PrEP with tenofovir alafenamide combined with emtricitabine (TAF/FTC) was approved by the US Food and Drug Administration (FDA) in 2019 for all routes of exposure other than vaginal exposures. The effectiveness of daily oral TDF/FTC has not been consistent in cisgender women outside of serodifferent couples, likely owing to differences in vaginal tissue penetration of PrEP agents resulting in less "forgiveness" of nonadherence. These observations have highlighted the need for additional choices of HIV prevention strategies. Injectable long-acting cabotegravir was recently shown to be superior to daily oral TDF/FTC across risk populations. PrEP studies of islatravir are underway for a monthly oral formulation and a drug-eluting subdermal implant. Lenacapavir, with a novel mechanism of action, is under investigation as a subcutaneous injection at 6-month intervals.

Because individuals with HIV are living longer, comorbidities are moving to the forefront of HIV patient care. People with HIV have a higher risk for HIV-related and non-HIV-related cancers than the general population, making cancer screening vital for this population. Immunizations are another important element of primary care for older adults with HIV, including a COVID-19 vaccine, about which data continue to evolve. This article summarizes a presentation by Steven C. Johnson, MD, at the International Antiviral Society-USA (IAS-USA) virtual HIV course Aging and HIV: Issues, Screening, and Management in Individuals with HIV as They Age in June 2021.

At the 2021 Conference on Retroviruses and Opportunistic Infections, there was a focus on progress toward hepatitis C virus (HCV) microelimination in geographic regions and targeted populations. HCV elimination is facilitated by well-tolerated, highly effective HCV treatment that requires essentially no on-treatment monitoring in most patients, as highlighted by the MINMON (Minimal Monitoring Study or A5360) study, and that should be increasingly available to children with new data supporting feasible treatment in younger patients. Challenges to HCV elimination include HCV reinfection via sexual exposure in men who have sex with men (MSM) and continued barriers to diagnosis and access to HCV treatment. Hepatitis B virus (HBV) suppression may take years in HIV/HBV-coinfected patients. This may have important consequences as the risk for hepatocellular carcinoma was associated in a dose-dependent manner with HBV viral load and was lowest in those with sustained undetectable HBV, highlighting the need for HBV DNA monitoring during therapy. Public health programs should prioritize improving hepatitis A and hepatitis B vaccination in at-risk populations, including people with HIV, as vaccinations rates for these preventable diseases continue to be suboptimal in many settings. Fatty liver disease, heavy alcohol use, antiretroviral therapy, and COVID-19 infection were also examined as drivers of hepatic disease in HIV infection.

Although there is extensive literature around the biologic correlations of neurocognitive function in HIV/AIDS, less is known about the impact in everyday living. We conducted a systematic review of the association of neurocognitive impairment with everyday life functions in people with HIV on antiretroviral therapy. We specifically focused on attention, executive function, processing speed, and the central executive component of the working memory. We considered 3 domains of everyday functions: (1) autonomy, (2) decision making and adherence to treatment, and (3) quality of life and psychologic wellbeing. The relationship between neurocognitive impairment and mental health was examined, given its correlation with everyday life functions. Results indicate that people with HIV do experience problems with autonomy of daily living (especially if aged older than 50 years) and with decision making, and neurocognitive impairment plays a role in this regard. Psychologic wellbeing is associated with executive function and processing speed. These patients may also have a reduced quality of life, but the relationship between quality of life and cognition is uncertain or could be mediated by other factors. Neurocognitive impairment correlates with depression and anxiety; however, the relationship of cognitive performance with apathy is still controversial.

The Conference on Retroviruses and Opportunistic Infections (CROI) serves as one of the most highly visible platforms upon which researchers gather to share the most recent findings on HIV/AIDS and, recently, on SARS-CoV-2 research. Research presentations on the novel coronavirus SARS-CoV-2 have become an increasing fixture at the conference since it was first covered at last year's conference. Although CROI 2021 was virtual, the organizers coordinated a seamless platform for presentations and poster sessions that effectively engaged the audience. CROI 2021 had a strong showing in terms of basic science presentations on HIV-1 and on SARS-CoV-2. Highlights included new insights into some of the more elusive steps in the viral replication cycle as well as new findings on immune escape strategies employed by SARS-CoV-2. The new investigator workshop has become a valuable resource that can be used by early stage and established investigators alike to receive state-of-the-art updates on research areas that might be outside their immediate areas of research. The new investigator workshop featured engaging presentations on novel aspects of HIV-1 and SARS-CoV-2 replication, impact of host immunity on HIV-1 and SARS-CoV-2, and approaches to assessing viral reservoir dynamics and strategies for viral reservoir elimination.

The 2021 Conference on Retroviruses and Opportunistic Infections included advances in therapy for HIV as well as for SARS-CoV-2. Data presented on COVID-19 therapies included trials showcasing the use of monoclonal antibodies for prevention and treatment of COVID-19. Promising new data were presented on lenacapavir, an investigational HIV capsid inhibitor given as a subcutaneous injection every 6 months. Although encouraging data from settings across the globe reported achievement of 90-90-90 HIV care cascade targets, disparities exist in care engagement and viral suppression, particularly for people of color and young people with HIV. Several interventions were associated with improved care cascade outcomes. The COVID-19 pandemic has impacted HIV care engagement, but mitigation strategies can allow programs to continue to serve people with HIV during the pandemic. Studies examining the resistance patterns of existing antiretroviral therapy (ART) agents were presented, as were resistance mechanisms of novel agents such as lenacapavir and resistance patterns among individuals who seroconverted while on preexposure prophylaxis. Data from large observational cohorts were presented on patterns of ART uptake and trends in mortality and in virologic failure. Pertinent findings relating to pediatric and maternal health issues included data on dolutegravir-based ART in children and adolescents with HIV; safety and tolerability of dolutegravir-based ART in children and pregnant women; similarly high maternal viral suppression at 50 weeks postpartum in women receiving certain ART regimens; weight gain in pregnant women receiving dolutegravir plus tenofovir alafenamide/emtricitabine; and viral suppression with dolutegravir-based ART when started during the third trimester of pregnancy.

Tuberculosis (TB) remains a main driver of morbidity and mortality among people with HIV along with other opportunistic infections. This review summarizes key highlights related to TB, and other opportunistic infections in HIV as well as studies from the virtual 2021 Conference on Retroviruses and Oppoprtunitstic Infections evaluating outcomes among HIV-COVID-19 coinfected patients.

The 2021 Conference on Retroviruses and Opportunistic Infections (CROI) featured a timely review of the neurologic complications of COVID-19 as well as new research findings on mechanisms by which SARS-CoV-2 may affect the brain. CROI included new and important findings about the neurologic complications of HIV-1, human polyomavirus 2 (also known as JC Virus), and cryptococcus. New long-term analyses of cognition in people with HIV-1 identified that cognitive decline over time is associated with multimorbidity, particularly diabetes, chronic lung disease, and vascular disease risk conditions. These conditions are associated with aging, and the question of whether people with HIV are at risk for premature aging was addressed by several reports. New findings from large analyses of resting state networks also provided valuable information on the structural and functional networks that are affected by HIV-1 infection and cognitive impairment. Several reports addressed changes after initiating or switching antiretroviral therapy (ART). Findings that will improve understanding of the biologic mechanisms of brain injury in people with HIV were also presented and included evidence that host (eg, myeloid activation, inflammation, and endothelial activation) and viral (eg, transcriptional activity and compartmentalization) factors adversely affect brain health. Other research focused on adjunctive therapies to treat HIV-1 and its complications in the central nervous system. This summary will review these and other findings in greater detail and identify key gaps and opportunities for researchers and clinicians.