Topics in antiviral medicine最新文献

The 2022 Conference on Retroviruses and Opportunistic Infections provided a rich source of new data and comprehensive reviews on antiviral therapy. For COVID-19, intramuscular sotrovimab was noninferior to intravenous sotrovimab, serostatus did not predict the efficacy of sotrovimab, and molnupiravir appeared safe and modestly effective in decreasing hospitalization rates. Trials from low- and middle-income countries provided data to support transitioning those on first-line therapy with or without virologic suppression and those virologically suppressed on second-line therapy to dolutegravir-based regimens. Additional data supported the use of lenacapavir as a long-acting antiretroviral drug. Data across the United States demonstrate the negative impact of the COVID-19 pandemic on the HIV care continuum, although enhanced outreach efforts and decentralization of antiretroviral therapy delivery were associated with improvements in care engagement outcomes. Researchers described potential mechanisms for the emergence of integrase strand transfer inhibitor resistance. Studies on proviral genotyping high-lighted the limitations of its use in predicting clinically significant resistance. Several studies looked at the epidemiology and treatment of hepatitis C and B and the status of current hepatitis C virus elimination efforts. Data presented on HIV, COVID-19, and maternal and pediatric health included 2-year virologic outcome data of very early antiretroviral therapy in potentially reducing the latent HIV reservoir in infants with HIV. Data presented on COVID-19 and HIV therapeutics in children included SARS-CoV-2-neutralizing monoclonal antibodies in children younger than 12 years of age, remdesivir in hospitalized infants and children, and long-acting therapies for HIV treatment in children.

Despite substantial advances in the field, liver disease morbidity and mortality remain serious issues among people with HIV. The causes of liver disease are often multifactorial and include hepatitis viruses, hepatic steatosis and oxidative stress, bacterial translocation with activation of hepatic macrophages and stellate cells, and direct toxicities from alcohol and drugs of abuse. Biopsychosocial factors including a high prevalence of psychiatric disorders, food insecurity, insufficient access to care and medications, and social stigma all play roles in the persistence of liver injury and hepatic fibrosis development among people with HIV. Rising rates of hepatocellular carcinoma have been observed, suggesting that the epidemiology of liver disease is evolving.

The 2022 Conference on Retroviruses and Opportunistic Infections featured new and important findings about the neurologic complications of HIV-1, COVID-19, and other infections. Long-term analyses identified that cognitive decline over time, phenotypic aging, and stroke are associated with various comorbidities in people with HIV. Neuroimaging studies showed greater neuroinflammation, white matter damage, demyelination, and overall brain aging in people with chronic HIV infection. Childhood trauma and exposure to environmental pollutants contribute to these neuroimaging findings. Studies of blood and cerebrospinal fluid biomarkers showed that systemic inflammation, neurodegeneration, endothelial activation, oxidative stress, and iron dysregulation are associated with worse cognition in people with HIV. Some animal studies focused on myeloid cells of the central nervous system, but other animal and human studies showed that lymphoid cells also contribute to HIV neuropathogenesis. The deleterious central nervous system effects of polypharmacy and anticholinergic drugs in people with HIV were demonstrated. In contrast, a large randomized controlled trial showed that integrase strand transfer inhibitor therapy was not associated with neurotoxicity. Studies of cryptococcal meningitis demonstrated he cost-effectiveness of single high-dose liposomal amphotericin and the prognostic value of the cryptococcal antigen lateral flow assay. People hospitalized with COVID-19 had more anxiety over time after discharge. The SARS-CoV-2 nucleocapsid antigen is present in cerebrospinal fluid in the absence of viral RNA. Systemic inflammation, astrocyte activation, and tryptophan metabolism pathways are associated with post-COVID-19 neurologic syndromes. Whether these processes are independent or intertwined during HIV-1 and COVID-19 infections requires further study.

Adolescents with HIV are growing into adulthood and are at risk for comorbidities. Comorbidities in adolescents often go unrecognized, increasing morbidity and mortality, and contributing to poorer outcomes for youth with HIV. Youth with perinatally and nonperinatally acquired HIV are at risk of developing HIV-associated and non-HIV comorbidities, including cardiovascular diseases, diabetes, mental health disorders, renal diseases, and bone disorders. Youth with HIV are also at risk for altered fat distribution and weight gain associated with certain classes of antiretroviral therapy. Sexually transmitted infections from inconsistent condom use pose a sexual health challenge for youth with HIV. Prompt interventions through comprehensive history taking, physical exams, regular screening, and prevention and treatment of clinically evident comorbid conditions are needed to prevent progression and complications.

Early treatment of anal high-grade squamous intraepithelial lesions compared with active monitoring reduced the risk of anal cancer by 57% in persons with HIV in a landmark randomized trial of 4446 participants. In a multi- country randomized trial, an entirely oral combination regimen consisting of bedaquiline, pretomanid, linezolid, and moxifloxacin for 24 weeks outperformed the World Health Organization-recommended 36- to 96-week standard of care regimen for multidrug-resistant tuberculosis (TB), ushering in a new era of shorter multidrug-resistant TB treatment. These and other studies of TB and coinfections in persons with HIV presented at the 2022 Conference on Retroviruses and Opportunistic Infections pro vided new insights and are summarized herein.

The 2022 outbreak of monkeypox virus infection has expanded far beyond regions in which the disease was previously endemic. Monkeypox has a wide range of manifestations, some of which are unique to this outbreak. Novel clinical presentations, testing limitations, and a lack of available treatments have contributed to delays in recognition, diagnosis, and treatment of monkeypox. As health care workers and governments fight this rare viral infection, which may become a routine diagnosis, early recognition of potential signs and symptoms along with appropriate testing is essential to prevent continuing spread and potential endemicity.

Depressive disorders are the most common psychiatric disorders among people with HIV. Depressive disorders cause great suffering and disability and, among people with HIV, are associated with numerous negative HIV outcomes, including nonadherence to antiretroviral medication and increased morbidity and mortality. This article is focused on the detection, differential diagnosis, and management of depressive disorders among adults in HIV primary care settings in the United States. Because of the siloed nature of HIV primary health care and behavioral health care in the United States, this paper is geared toward clinicians who are not behavioral health specialists and who are working in HIV care settings that have limited access to behavioral health services and still seek to treat depressive disorders. In clinical settings that are fortunate enough to have well-integrated behavioral health services, HIV primary care clinicians may be able to depend on this specialist workforce, but these settings tend to be the exception and not the rule.

Tuberculosis (TB) remains the leading cause of death among people with HIV, and annual risk of progression from latent TB infection to active disease in this population is 10%. Diagnostic tests for latent and active TB remain suboptimal for people with HIV who have a CD4+ count below 200 cells/μL, and there is an urgent need for assays that predict progression from latent to active disease, monitor treatment response, and test for cure after latent and active TB treatment. Traditional treatment duration for latent infection and active TB disease has been onerous for patients; however, shorter-course regimens are increasingly available across the spectrum of TB, including for drug-resistant TB. Simultaneous treatment of HIV and TB is complicated by drug-drug interactions, although trials are ongoing to better understand the magnitude of these interactions and guide clinicians in how to use short-course regimens, particularly for people with HIV.

At the 2022 Conference on Retroviruses and Opportunistic Infections, several speakers discussed disparities in HIV and COVID-19 infections and outcomes. Although the lifetime risk of HIV infection in the United States is higher overall in males than females, Black females have higher risk than White males. In 12 countries in sub-Saharan Africa, women aged 15 to 34 years accounted for more than half of all infections. Because knowledge of HIV serostatus is important for treatment and for prevention, several novel strategies were evaluated in the distribution of HIV self-test kits to undertested populations in the United States and sub-Saharan Africa. Data were presented on new products in the pre-exposure prophylaxis (PrEP) pipeline, including long-acting injectable cabotegravir, islatravir, vaginal rings, and in-situ forming implants. Challenges remain in the rollout of oral PrEP, and a number of innovative strategies to address barriers were discussed. Models suggest that the greatest impact of novel PrEP agents would be to increase the pool of persons using PrEP, rather than through improved efficacy. COVID-19 caused substantial declines in HIV and sexually transmitted infection prevention and treatment services, which have started to rebound, but are not yet at prepandemic levels in several settings.

The Conference on Retroviruses and Opportunistic Infections (CROI) 2022, which was held as a virtual conference, continues to serve as the preeminent forum that features research advances in HIV-1 and its associated coinfections. The conference has extended its area of coverage to include research advances in SARS- CoV-2. As pointed out in the presentation from Hatziioannou in the New Investigators workshop, there has been an explosion in research activity on SARS-CoV-2 that has eclipsed that for HIV-1. In the past 12 months, there were approximately 6600 publications on HIV-1 and approximately 64,000 on SARS-CoV-2. Although these numbers include review articles, they reveal the tremendous response by researchers to the existential threats posed by lentiviruses and coronaviruses. This poses challenges for any conference committee tasked with selecting abstracts for presentation from the large number submitted for consideration. CROI organizers have consistently been able to assemble a program that, through invited presentations, abstract-driven talks, posters, interactive sessions, workshops, and symposia, showcases the most recent research advances.