Topics in antiviral medicine最新文献

A high proportion of individuals with HIV infection currently are diagnosed at an advanced stage of disease (late presenters), increasing their risk for immune reconstitution inflammatory syndrome (IRIS). IRIS typically occurs within 6 months of initiation of antiretroviral therapy (ART) in patients with low CD4+ cell counts and can occur before any marked elevation in CD4+ count is achieved on ART. In addition to low CD4+ count at ART initiation, 2 other major clinical predictors of IRIS are preexisting opportunistic infection (including subclinical infection) and shorter treatment period for opportunistic infection prior to starting ART. Mycobacterial infection-associated IRIS, including tuberculosis (TB)-associated IRIS, and cryptococcal infection-associated IRIS are the most common forms of the syndrome. Corticosteroid prophylaxis and early treatment can be effective in reducing incidence of TB-IRIS and severity of symptoms in select patients. Sterilization of the cerebrospinal fluid should be achieved prior to starting ART in patients with TB meningitis and cryptococcal meningitis. This article summarizes a presentation by Irini Sereti, MD, MHS, at the International Antiviral Society-USA (IAS-USA) continuing education program held in Washington, DC, in April 2019.

Effective antiretroviral therapy has extended life expectancy for individuals with HIV. Estimates from 2015 indicate that 47% of persons with HIV in the US were older than 50 years of age and 16% were older than 65 years. These older patients are at increased risk of age-related diseases and conditions. Further, there is substantial evidence that patients with HIV infection accumulate age-related conditions earlier than do those in the general population. There is risk for increased comorbidities and polypharmacy in the aging HIV-infected population. Specific measures for assessing and reducing the risk of cardiovascular disease and other age-related conditions in the aging HIV population are needed. This article summarizes a presentation by Judith A. Aberg, MD, at the International Antiviral Society-USA (IAS-USA) annual continuing education program held in Chicago, Illinois, in May 2019.

Achieving a cure for HIV remains a priority in HIV research. Two cases of 'sterilizing cure' have been observed-in Timothy Ray Brown and the "London" patient; both patients received allogeneic hematopoietic stem cell transplantation (HSCT) from donors homozygous for the CCR5-delta 32 deletion, which impairs function of an HIV coreceptor on host cells. Other strategies that have been evaluated for achieving sterilizing cure or functional cure--ie, sustained virologic remission in the absence of antiretroviral therapy (ART)-include: HSCT with wild-type CC chemokine receptor (CCR5); early ART to limit size of the HIV latent reservoir; shock and kill strategies using latency reversing agents and/or anti-HIV broadly neutralizing antibodies; and gene therapy, including attempts to modify CCR5 genes, HIV proviruses in autologous host cells, or enhanced T cells. This article summarizes a presentation by Jonathan Li, MD, MMSc, at the International Antiviral Society-USA (IAS-USA) continuing education program held in Atlanta, Georgia, in March 2019.

The 2019 edition of the IAS-USA drug resistance mutations list updates the Figure last published in January 2017. The mutations listed are those that have been identified by specific criteria for evidence and drugs described. The Figure is designed to assist practitioners in identifying key mutations associated with resistance to antiretroviral drugs, and therefore, in making clinical decisions regarding antiretroviral therapy.

Available data indicate that 55% of women and 20% of men living with HIV infection experience intimate parter violence (IPV) and that 24% of women experience abuse by their partners after disclosing their HIV serostatus. IPV increases the risk of HIV acquisition and often interferes with victims' engagement in and adherence to HIV care. The processes of integrating IPV screening as part of a health-centered approach in the HIV clinic are discussed. This article is based on a presentation by Tami P. Sullivan, PhD, at the 2018 Clinical Conference at the National Ryan White Conference on HIV Care and Treatment in December 2018.

Rates of syphilis and other sexually transmitted infections are on the rise in the United States. The lesions of early syphilis can be mistaken for those of other infections and conditions, and syphilis should be suspected in all sexually active patients presenting with a new skin rash or an oral or genital lesion. Rapid diagnosis and treatment of syphilis as well as rapid identification and treatment of sexual contacts are needed to reverse the trend of increasing incidence. Available data indicate success in reducing acquisition of syphilis with doxycyclinepre- and postexposure prophylaxis. This article is based on a presentation by Jeffrey D. Klausner, MD, MPH, at the 2018 Clinical Conference at the National Ryan White Conference on HIV Care and Treatment in December 2018.

The leading cause of non-HIV-related mortality is liver disease. Fatty liver disease can be characterized as alcoholic or nonalcoholic in nature. Alcohol use is prevalent among individuals with HIV infection and can lead to medication nonadherence, lower CD4+ cell count, inadequate viral suppression, and disease progression. The pathogenesis of nonalcoholic fatty liver disease (NAFLD) in individuals with HIV infection includes metabolic syndrome, hyperuricemia, HIV-related lipodystrophy, genetic polymorphisms, medications, HIV itself, and the gut microbiome. The prevalence of NAFLD in persons with HIV infection ranges from 30% to 65% depending on the modality of diagnosis. Individuals with HIV infection and NAFLD are at higher risk of cardiovascular disease; however, there is a dearth of longitudinal outcomes studies on this topic. Current therapies for NAFLD, such as vitamin E and pioglitazone, have not been studied in persons with HIV infection. There are several drugs in phase II and III clinical trials that specifically target NAFLD in HIV, including CC chemokine receptor 5 inhibitors, growth hormone-releasing factor agonists, and stearoyl-CoA desaturase inhibitors. Persons with HIV should be screened for NAFLD while pursuing aggressive risk factor modification and lifestyle changes, given the increased risk of cardiovascular mortality.

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.