Topics in antiviral medicine最新文献

Approximately 10% of patients who survive COVID-19 will proceed to have lasting, often debilitating effects, known as "long COVID." These symptoms can take various forms, most commonly including postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, heart palpitations, diminished sexual desire or capacity, loss of smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Here, 2 physician-patients present their own experiences with long COVID and share their perspectives on the experience. One key insight is that patients who are not familiar with long COVID may not attribute ongoing symptoms to their illness. Diagnosis requires an astute, compassionate physician who understands long COVID and can appropriately situate the symptoms within the evolving understanding of the condition, leading the patient toward recovery.

Limited therapeutic options are available for patients with multidrug-resistant HIV. This report describes a 38-year-old female who was perinatally infected with HIV-1 and treated with 14 different antiretroviral regimens over 27 years, gradually leading to 4-class drug resistance. Despite various attempts to obtain sustained viral suppression, including the off-label administration of intravenous foscarnet and enfuvirtide, and thorough follow-up with 16 viral genotyping/phenotyping from 1999 to 2021, viral control was not maintained. Recently, the introduction of a regimen with fostemsavir and lenacapavir resulted in long-term viral suppression.

Vaccinations are an important part of primary care for people with HIV (PWH) and can protect against viral hepatitis and some sexually transmitted infections, as well as respiratory bacterial and viral infections. Vaccinations for influenza, COVID-19, herpes zoster (shingles), hepatitis B, meningococcal disease, mpox, and human papillomavirus are recommended for PWH. Additionally, the Advisory Committee on Immunization Practices has released recommendations incorporating the newer formulations of the pneumococcal pneumonia and respiratory syncytial virus vaccines. Additional considerations for the timing of vaccinations are de-scribed, including whether to delay vaccination until improvement of the immune status. Live vaccines (other than nonreplicating) are contraindicated for PWH with CD4+ counts less than 200 cells/μL or uncontrolled HIV.

Over the past several years, messenger RNA (mRNA) vaccine has evolved from a term familiar only to vaccine scientists into one easily recognized by much of the general population. This change occurred because of the remarkable success of effective and safe mRNA vaccines during the COVID-19 pandemic that saved countless lives. Although mRNA vaccine technology has a clear use for combating future emerging diseases, its role in fighting currently known pathogens, such as HIV-1, is not well defined. This review summarizes mRNA vaccine technology, highlighting its success during the COVID-19 pandemic. It then addresses past and current efforts to develop a vaccine for HIV-1, including how mRNA vaccine technology has created opportunities in the ongoing search for an effective HIV-1 vaccine.

People with HIV (PWH) are at higher risk for cardiovascular disease (CVD) than people without HIV. As antiretroviral therapy (ART) and the natural history of HIV have evolved, so have the pathogenesis and manifestations of HIV-associated CVD. Epidemiologic data from several cohorts demonstrate that PWH have an approximately 50% higher risk than people without HIV for CVD, including, but not limited to, myocardial infarction and heart failure. This elevated CVD risk is not universal among PWH; for instance, the risk is higher among individuals with a history of sustained unsuppressed viremia, diminished CD4+ cell count recovery, or hepatitis C virus coinfection. Specific antiretroviral drugs may also associate differently with CVD risk. Regarding management, the recent REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) study results demonstrated a 35% relative risk reduction in atherosclerotic CVD for PWH at low to moderate predicted risk taking pitavastatin; this is a larger reduction than for comparable moderate-intensity statins in the general population. Whether these higher-than-expected reductions in CVD risk among PWH also extend to higher-intensity statins and into secondary prevention settings for people with existing CVD merits further study. Nonlipid approaches to CVD risk reduction in PWH-ranging from antithrombotic therapy to inflammation-modulating therapy-remain under active investigation. Results of these studies will provide essential information to further guide CVD management in PWH.

Doxycycline postexposure prophylaxis (doxy-PEP) is a novel strategy now demonstrated in several clinical trials to dramatically reduce incidence rates of gonorrhea, chlamydia, and syphilis in some key populations at high risk of sexually transmitted infections. Even so, much remains unknown about the long-term consequences of doxy-PEP, and several concerns, including the potential for the development of antibiotic resistance and disturbances to the microbiome, balance the benefits. This review highlights the history of antibiotic prophylaxis for sexually transmitted infections, and the rationale, current evidence, and future directions for doxy-PEP.

The US Department of Health and Human Services guidelines on infant feeding among people with HIV have changed in response to (1) evidence of low risk of transmission via breast milk among individuals with consistent viral suppression, (2) considerations of equity and cultural norms, and (3) community desires. The 2023 guidelines recommend patient-centered shared decision-making. Individuals with HIV who are receiving antiretroviral therapy (ART) and have consistent viral suppression should be counseled on the options of for-mula feeding, feeding with banked donor milk, or breast (or chest) feeding, and nonjudgmentally supported in their decision. Individuals who choose to breastfeed should be counseled on and supported in adherence to ART, viral suppression, and engagement in postpartum care for themselves and their babies. Exclusive breastfeeding is recommended, with the understanding that brief periods of replacement feeding may be necessary. Data are lacking on ideal infant prophylaxis regimens.

The 2023 Conference on Retroviruses and Opportunistic Infections (CROI) featured new and impactful findings about neuropsychiatric complications in people with HIV and other infections. Reports included new evidence of (a) the importance of myeloid cells in the pathogenesis of HIV disease in the central nervous system, including as an HIV reservoir; (b) eukaryotic and prokaryotic viruses in cerebrospinal fluid during suppressive antiretroviral therapy; (c) the influence of sex on pathogenesis, including in novel neuropsychiatric biotypes identified by machine learning and other methods;(d) premature aging in people with HIV, including the brain-age gap observed on magnetic resonance imaging; (e) cellular and soluble biomarkers of neuropsychiatric complications in people with HIV; and (f) the neurotoxicity of certain antiretroviral drugs. This review summarizes these and other new findings and highlights new research directions for the neuro-HIV field.

Novel implementation strategies to increase uptake and adherence to tuberculosis (TB) preventive therapy hold promise for reducing TB incidence in persons with HIV in high-burden settings. In persons who develop drug-susceptible TB, progress to shorten TB treatment continues to be made with the introduction of new drugs and novel treatment strategies that could allow for treatment shortening to 2 months for most people. A global case series provided powerful evidence that mpox should be considered an HIV-related opportunistic infection given its severe manifestations and poor outcomes. Studies of TB and infectious complications in people with HIV presented at the 2023 Conference on Retroviruses and Opportunistic Infections (CROI) are summarized herein.

The 2023 Conference on Retroviruses and Opportunistic Infections (CROI) represented the first fully in-person conference since the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic began. CROI continues as the premier conference in which delegates can appraise themselves of almost every facet of HIV/AIDS research as well as emerging and re-emerging pathogens such as SARS-CoV-2 and mpox. The return to an in-person format is particularly important for early-stage investigators, who were faced with challenges of advancing their independent research careers during the SARS-CoV-2 pandemic. The personnel interactions and face-to-face meetings between junior investigators and their peers enable collaboration that is important in the academic development process. A very packed program showcased research advances in basic research, clinical, and epidemiology/public health endeavors around HIV and other pandemic viruses. Session presentation summaries, themed discussion sessions, and scientific workshops condense and assimilate specific areas of research that are particularly useful for delegates who want to see the state of research in areas that may be outside their specific areas of interest. The conference organizers drew on more than 1000 accepted abstracts to assemble a dynamic and engaging program that was appealing to infectious disease researchers worldwide.