Topics in antiviral medicine最新文献

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.

Our increased understanding of the human microbiome has brought insight into the role it plays in health and disease, including HIV infection. Studies have shown that the gut microbiome is less diverse in individuals with HIV infection than in noninfected control subjects. Efforts to modify the microbiome to bolster immune reconstitution in people with HIV infection have so far been unsuccessful. The vaginal microbiome affects risk of HIV acquisition, with Lactobacillus dominance being protective compared with vaginosis characterized by larger populations of Gardnerella. The vaginal microbiome might also affect efficacy of topical tenofovir disoproxil fumarate preexposure prophylaxis. This article summarizes a presentation by Robert T. Schooley, MD, at the IAS-USA continuing education program held in San Francisco in May 2018.

The incidence of HIV-related opportunistic infections (OIs) has dramatically declined with the ability to achieve viral suppression and immune reconstitution with potent antiretroviral therapy. However, a large number of patients remain at risk for OIs because they are diagnosed at late stages of HIV disease, fail to stay in treatment, or fail to maintain viral suppression. Clinicians should remain vigilant for OIs and for changes in recommended management strategies. Issues that often arise in this regard include how to interpret polymerase chain reaction diagnostic results in individuals with HIV infection; whether primary prophylaxis for Mycobacterium avium complex is still needed; whether clinicians should screen asymptomatic patients for cryptococcal antigen; and need for amphotericin B in treatment regimens for cryptococcal meningitis. This article summarizes a presentation by Henry Masur, MD, at the IAS-USA continuing education program held in Washington, DC, in April 2018.

Available data indicate that opioid substitution treatment can successfully reduce rates of HIV transmission and that patients receiving such treatment can adhere to therapies for HIV, hepatitis C, and tuberculosis infection. Integration of opioid substitution treatment into the HIV clinic setting can make such treatment easier and improve retention in treatment. This article summarizes a presentation by R. Douglas Bruce, MD, MA, MS, at the IAS-USA continuing education program held in Chicago, Illinois, in May 2018.