Topics in antiviral medicine最新文献

The introduction of effective antiretroviral therapy (ART) has converted HIV infection from a lethal disease to a manageable chronic condition for most people. The drastic improvement in life expectancy of people with HIV has led to an expansion of the aging population of people with HIV globally. Recent research indicates that people with HIV on suppressive ART still sustain persistent, albeit alleviated, systemic and cerebral immune activation that can facilitate age-related causes of cognitive impairment (CI), including neurodegenerative and cerebrovascular diseases. Although HIV-associated neurocognitive disorder remains prevalent in older people with HIV on suppressive ART, the co-occurrence of other age-related causes of CI makes the investigation and management of CI more challenging. More importantly, it remains unknown if the neuropsychiatric manifestations of HIV-associated neurocognitive disorder are modified by the presence of age-related causes of CI, such as Alzheimer disease, and vice versa. This article will review findings regarding the interaction between HIV-1 infection and age-related comorbidities, namely atherosclerosis and neurodegenerative diseases, followed by cognitive outcomes of people with HIV in longitudinal studies. Cognitive symptoms of people with HIV on stable ART will be discussed. The review will go through the latest recommendations for cognitive screening in different HIV management guidelines, as well as the usefulness of various screening tools in the setting of stable viral suppression.

Chronic pain is common among older people with HIV. Etiologies of chronic pain are multifactorial in this population. A careful and thorough initial assessment of pain is important. Associated conditions that can contribute to pain should be explored and managed as indicated. Special consideration is warranted for some of the unique aspects of pain in people with HIV. Chronic pain management is multimodal; a variety of pharmacologic and nonpharmacologic strategies are effective. Among medications, opioids can be used but carry a risk of significant harms. The use and monitoring of opioids is discussed here, and recommendations are made for the safe prescribing of opioids for chronic pain.

Comorbid conditions have a major impact on the health, quality of life, and survival of people with HIV, particularly as this population ages. The 2022 Conference on Retroviruses and Opportunistic Infections (CROI) featured excellent science related to specific comorbidities, such as cardiovascular disease, type 2 diabetes, cancer, and frailty. The role of systemic inflammation in the pathogenesis of cardiovascular disease was an important theme, with strong evidence regarding the impact of microbial translocation. Other studies examined functional impairment, frailty, and potential important contributors, such as concomitant medications and sleep disturbances. The ANCHOR (Anal Cancer/High-grade Squamous Intraepithelial Lesions Outcomes Research) study provided crucial evidence that treatment of high-risk anal lesions reduces the incidence of anal cancer, which has important implications in the prevention of this devastating comorbidity. In addition, numerous presentations demonstrated the importance of comorbid conditions in COVID-19 outcomes in people with HIV and described persistent symptoms after acute SARS-CoV-2 infection has resolved. This review focuses on the abstracts presented at CROI 2022 in these areas, highlighting those with the most clinical impact.

The 2022 edition of the IAS-USA drug resistance mutations list updates the Figure last published in September 2019. The mutations listed are those that have been identified by specific criteria for evidence and drugs described. The Figure is designed to assist practitioners to identify key mutations associated with resistance to antiretroviral drugs, and therefore, in making clinical decisions regarding antiretroviral therapy.

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.