Topics in antiviral medicine最新文献

At the 2020 Conference on Retroviruses and Opportunistic Infections, held virtually as a result of the emerging COVID-19 pandemic, trends in the HIV epidemic were highlighted, with decreasing HIV incidence reported across several countries, although key regions remain heavily impacted, including the US South. Adolescent girls and young women, men who have sex with men (MSM), transgender persons, and people who inject drugs continue to experience a high burden of new infections. Sexually transmitted infections during pregnancy can lead to a number of adverse outcomes in infants; novel strategies to detect and treat these infections are needed. Innovative HIV testing strategies, including self-testing and assisted partner services, are expanding the reach of testing; however, linkage to care can be improved. Novel preexposure prophylaxis (PrEP) delivery strategies are increasing uptake of PrEP in different groups, although adherence and persistence remain a challenge. Use of on-demand PrEP is increasing among MSM in the US. Strategies are needed to address barriers to PrEP uptake and persistence among cis- and transgender women. Several novel regimens for postexposure prophylaxis show promise.

Therapeutic vaccines and broadly neutralizing antibodies (bNAbs) represent potential approaches to antiretroviral-free treatment of HIV. Although therapeutic vaccines have been able to produce transient reductions in viral load during analytic treatment interruptions (ATIs), thus far none has been able to induce long-term remission. Pairing with latency reversal agents and immune modulators may improve vaccine efficacy. The bNAbs are investigated as a promising approach to achieving durable virologic control in the absence of antiretroviral therapy. Combinations of antibodies are necessary for increasing overall breadth and potency of coverage and preventing emergence of resistance. The next generation of antibodies includes engineered bispecific and trispecific antibodies that target 2 or 3 independent viral sites. This article is based on a presentation by Magdalena E. Sobieszczyk, MD, MPH, at the International Antiviral Society-USA (IAS-USA) continuing education program held in New York in March 2019.

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 Ryan White HIV/AIDS Program (RWHAP) has been effective in serving people living with HIV (PLWH). Our goal was to examine the impact of the implementation of the Affordable Care Act (ACA) on the program's role in HIV care and its clients. We utilized critical review to synthesize the literature on the anticipated effects of the ACA, and assess the evidence regarding the early effects of the ACA on the program and on PLWH who receive RWHAP services. To date, research on the impact of ACA on RWHAP has been fragmented. Despite the expected benefits of the ACA to PLWH, access and linkage to care, reducing inequity in HIV risk and access to care, and coping with comorbidities remain pressing challenges. There are additional gaps following ACA implementation related to immigrant care. RWHAP's proven success in addressing these challenges, and the political threats to ACA, highlight the need for maintaining the program to meet HIV care needs. More evidence on the role and impact of RWHAP in this new era is needed to guide policy and practice of care for PLWH. Additional research is needed to explore RWHAP care and its clients' health outcomes following ACA implementation, with a focus on at-risk groups such as immigrants, transgender women, homeless individuals, and PLWH struggling with mental health problems.

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.