Topics in antiviral medicine最新文献

At the 2019 Conference on Retroviruses and Opportunistic Infections (CROI), a plan for ending the HIV epidemic in the United States was presented. More rapid HIV diagnosis and treatment is a key component needed nationwide. In international settings, substantial scale up of HIV testing and treatment has led to substantial declines in HIV incidence. U=U (undetectable equals untransmittable) is a powerful concept that can reduce stigma and encourage engagement in testing and care, but raises a number of clinical questions. HIV testing remains a gateway to HIV prevention and treatment, and innovative testing strategies, including HIV self-testing, show promise. Opioid overdose deaths are on the rise, highlighting the need for comprehensive prevention efforts. Molecular data are being used to identify rapidly growing clusters of infections for intervention. Rates of sexually transmitted infections have increased substantially in recent years. A new preexposure prophylaxis (PrEP) combination, tenofovir alafenamide/emtricitabine (FTC), was demonstrated to be non inferior to tenofovir disoproxil fumarate/FTC, with improved bone and renal safety. PrEP uptake is increasing globally, but use is lower in several populations, including African Americans, cis- and transgender women, and youth. Same-day PrEP initiations are a promising approach to increasing access, but PrEP discontinuations remain a challenge.

At the 2019 Conference on Retroviruses and Opportunistic Infections (CROI), there was a major focus on hepatitis C virus (HCV) elimination and improving each component of the hepatitis C care cascade. Many interventions showed promising improvements in diagnosis and linkage to care. Settings with robust access to direct-acting antivirals (DAAs) continue to demonstrate the role of HCV treatment as prevention. However, substantial barriers to accessing curative therapy remain. Reinfection after treatment presents an important barrier to elimination, particularly in some populations of men who have sex with men (MSM). MSM without HIV infection are at an elevated risk for sexual acquisition of HCV, and several studies reported HCV rates that were as high as those seen in MSM living with HIV. There was also a focus on HCV and HBV in pregnant women. Rates of HCV infection in women of child-bearing potential have increased, making prenatal diagnosis a priority. In the first study of HCV treatment during pregnancy, sofosbuvir/ledipasvir started at 28 weeks of gestation led to cure in 8 pregnant women. Hepatitis B virus (HBV)-active antiretrovirals are generally effective in suppressing HBV but have low rates of surface antigen loss despite long term treatment. Initial results from novel laboratory assessments of intrahepatic HBV viral infection events were presented, hopefully paving the way for more effective HBV treatment strategies to control and potentially cure HBV.

The annual Conference on Retroviruses and Opportunistic Infections remains the preeminent venue for the sharing and dissemination of research advances in the field of HIV and AIDS research. The 26th conference in Seattle featured highlights including news of additional individuals who experienced long-term virologic remission following a bone marrow transplant. The factors driving reservoir persistence gathered a lot of interest, as well as data presented on new factors involved in regulating HIV-1 latency. The effectiveness of the conference in disseminating new findings is further enhanced through themed discussions that focus the attention of participants on abstracts with a common theme. In addition, the Program Committee workshops provide an outstanding venue, directed to new investigators, fellows, and students, to receive updates on different aspects of HIV and AIDS research. These sessions add to the information-sharing environment provided by the conference.

Investigators reported many new neuroHIV research findings at the 2019 Conference on Retroviruses and Opportunistic Infections (CROI). These findings included confirmation that HIV-associated neurocognitive disorder (HAND) remains common with an increasingly recognized role for comorbidities (eg, obesity) and neurodegenerative conditions (eg, Alzheimer's disease), especially as persons living with HIV (PLWH) advance into their seventh decade of life and beyond. HAND is increasingly recognized as a heterogeneous disorder that differs between individuals (eg, by sex) in the trajectory of specific neurocognitive abilities (eg, executive functioning). A more recent focus at this year's conference was toxicity of combination antiretroviral therapy: neurocognitive performance and neuroimaging data from several studies were presented but did not consistently support that integrase strand transfer inhibitors are associated with worse neurologic outcomes. Neuroimaging studies found that white matter changes reflect a combination of the effects of HIV and comorbidities (including cerebrovascular small vessel disease) and best correlate with blood markers of inflammation. The pathogenesis of HIV in the central nervous system (CNS) was the focus of a plenary lecture and numerous presentations on HIV compartmentalization in the CNS and cerebrospinal fluid viral escape. Novel findings were also presented on associations between HIV-associated neurologic complications and glycomics, neuron-derived exosomes, and DNA methylation in monocytes. This summary will review findings from CROI and identify new research and clinical opportunities.

The 2019 Conference on Retroviruses and Opportunistic Infections included many exciting advances in antiretroviral therapy (ART). Investigators presented a case report of a second patient possibly cured of HIV through an allogeneic hematopoietic stem cell transplant from a CC chemokine receptor 5-delta 32 donor. Two clinical trials of long-acting injectable cabotegravir and rilpivirine showed promising safety, efficacy, and tolerability as maintenance ART. Test-and-treat and rapid-ART-start strategies show promise in advancing progress toward the HIV care cascade 90-90-90 Joint United Nations Programme on HIV/AIDS/World Health Organization targets. However, late diagnosis and mortality after ART initiation remain high, even in the context of HIV service scale-up, and mortality from unintentional opioid overdose in people living with HIV in the United States is on the rise. In vitro studies were presented that identified and evaluated the effect of resistance-associated mutations on ART susceptibility and elucidated mechanisms of resistance. Epidemiologic data were reported on the prevalence, impact, regional variation, and changes over time of resistance-associated mutations. Decreasing regional and national rates of resistance may be a benefit of increasing use of integrase strand transfer inhibitors (InSTIs). New findings were presented on maternal and fetal health outcomes in women of reproductive potential, drug-drug interactions between hormonal contraception and ART, and further exploration of the association between InSTIs and birth defects.

The 2019 Conference on Retroviruses and Opportunistic Infections provided a considerable amount of new information on the progress in implementation of strategies to reduce morbidity and mortality from complications and coinfections that occur in people with HIV infection, and on the clinical management of these important problems. This review will address new insights into the prevention and treatment of tuberculosis, fungal infections, sexually transmitted infections, malignancies, and a range of metabolic complications and noncommunicable diseases.

Individuals with HIV infection are living longer, and are at risk of autoimmune disorders and cancers associated with aging. Many of these conditions are treated with immunobiologic agents that affect immune function and may increase risk of opportunistic infections (OIs) and other immune disorders in individuals with HIV infection. For example, tumor necrosis factor-alpha inhibitors, used to treat such disorders as Crohn's disease, are associated with risk of tuberculosis and histoplasmosis. Rituximab, used to treat lymphoma, has been associated with progressive multifocal leukoencephalopathy due to JC virus and reactivation of other viral infections. Idealisib, used to treat chronic lymphocytic leukemia, has been associated with Pneumocystis pneumonia, and immune checkpoint inhibitors used to treat a variety of cancers have been associated with a wide range of immune-related adverse effects. Practitioners must maintain high vigilance for OIs and other immune-related disorders in patients with HIV infection who are receiving biologic therapies. This article summarizes a presentation by Peter Chin-Hong, MD, at the IAS-USA continuing education program held in Chicago in May 2018.

Direct-acting antiviral (DAA) regimens now allow treatment of previously untreated or treated (including prior DAA failures) patients with chronic hepatitis C virus (HCV) infection with 8 or 12 week regimens, largely without the use of ribavirin. Newer next-generation pan-genotypic regimens with activity against resistance-associated substitutions include glecaprevir/pibrentasvir (GLE/PIB), a combination of a nonstructural protein (NS)3 protease inhibitor and an NS5A inhibitor, and sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX), a combination of an NS5B polymerase inhibitor, NS5A inhibitor, and NS3 protease inhibitor. Both regimens have indications in DAA-experienced patients. GLE/PIB is approved for treatment of patients with genotype 1, 2, 3, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis and for the treatment of patients with genotype 1 infection previously treated with a regimen containing an NS5A inhibitor or an NS3/4A protease inhibitor, but not the combination. SOF/VEL/VOX is approved for retreatment of patients without cirrhosis or with compensated cirrhosis with genotype 1, 2, 3, 4, 5, or 6 infection previously treated with an NS5A inhibitor-containing regimen, or with genotype 1a or 3 previously treated with a SOF-containing regimen without an NS5A inhibitor. This article summarizes an IAS-USA webinar given by Susanna Naggie, MD, MHS, on August 30, 2018.

The recent hepatitis A virus (HAV) outbreak in San Diego was driven by homelessness, associated sanitation conditions, and illicit drug use. As with an outbreak in Michigan, fueled by similar factors, morbidity and mortality were higher than what has been observed with post-vaccine era foodborne HAV outbreaks. Control of the outbreak in San Diego was accomplished with vaccine, sanitation, and education initiatives that targeted those at highest risk. Mass vaccination events and mobile foot teams and vans brought education and vaccine to high-risk individuals in affected areas. The homelessness crisis in San Diego and in many locales throughout the United States poses risk of increasing numbers of outbreaks of HAV and other infectious illnesses. This article summarizes an IAS-USA continuing education webinar given by Darcy A. Wooten, MD, on July 19, 2018.

Hepatitis B virus (HBV) infection is a lifelong dynamic disease that can be controlled with treatment but cannot yet be cured. Risk of end-stage liver disease and hepatocellular carcinoma (HCC) increases with ongoing inflammation and HBV viremia. Initial treatments consist of tenofovir or entecavir. Patients who require treatment include those with chronic hepatitis, cirrhosis, HCC, or HIV coinfection; patients receiving immunosuppressive treatments; and women in the third trimester of pregnancy who have elevated HBV DNA level. A number of virologic and host immune approaches are being investigated with the aim of achieving HBV eradication. This article summarizes an IAS-USA webinar given by Marion G. Peters, MD, on June 14, 2018.