Topics in antiviral medicine最新文献

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.

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.

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.

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.

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.