Topics in antiviral medicine最新文献

The conference on Retroviruses and Opportunistic Infections represents the most important venue for the dissemination of research advances in HIV and AIDS. The 25th conference, held in Boston, featured presentations that provided insight into the mechanisms of HIV-1 spread in tissues as well as new information on mechanisms of HIV-1 persistence in individuals on effective antiretroviral treatment. The ability of the conference to convey research findings for a general audience is enhanced, to a large part, by preconference workshops. These workshops feature leading researchers who aim to present cutting edge research to a general audience. These sessions rank highly in terms of education and professional value.

This year marked the 25th Conference on Retroviruses and Opportunistic Infections (CROI), and although there is much progress to celebrate in terms of treatment of HIV infection and expanding ART globally, many challenges remain. Tuberculosis is still the leading cause of death among people with HIV infection globally. This year, the results of investments in research to improve the prevention and treatment of tuberculosis were a highlight of the meeting. Noninfectious causes remain an important source of morbidity. Progress in identifying risk factors for non-AIDS complications and improvements in screening and monitoring for such conditions continue to be reported, but to date, despite the efforts of many investigators around the globe, interventions to effectively reduce HIV-related inflammation beyond effective and safer antiretroviral therapy (ART) remain elusive. This section will review highlights of the meeting on tuberculosis and cryptococcal infection as well as complications of long-term ART.

The 2018 Conference on Retroviruses and Opportunistic Infections (CROI) showcased exciting data on new investigational agents including MK-8591 and tri-specific antibody targeting 3 highly conserved epitopes on HIV-1 in a single antibody. Clinical trials of initial antiretroviral therapy (ART) and switch studies involving bictegravir/emtricitabine/tenofovir alafenamide were presented. Intensification of initial ART with integrase strand transfer inhibitors did not increase the risk of immune reconstitution inflammatory syndrome. Pharmacokinetic issues were discussed, including the substantial drug-drug interactions between efavirenz-based ART and hormonal contraception delivered via a vaginal ring. Studies on pre-ART drug resistance and emergence of drug resistance after initial and second-line ART in different settings and populations were highlighted. Novel technologies to identify drug resistance included a free, cloud-based web service for HIV genotyping analysis and a promising technology for point-of-care drug resistance mutations testing. New strategies to improve the HIV care continuum included home-based testing with initiation of same-day ART and stratified care with specialized clinics to serve those disengaged in care, but the data on financial incentives were not encouraging. Several studies provided insights into the impact of early ART on decreasing the size of the HIV reservoir in HIV-infected infants. Pertinent conference findings relating to women's health issues included similar clinical outcomes between breastfeeding and formula feeding HIV-infected women, the problem of viral rebound and ART nonadherence in pregnancy and postpartum.

At the 2018 Conference on Retroviruses and Opportunistic Infections, trends in and risk factors for in HIV infection were highlighted. In the United States, new HIV diagnoses are highest in the South and among African Americans and are increasing in rural areas. Youth remain highly vulnerable to HIV infection globally. The epidemiology of HIV infections among people who inject drugs is changing, with overdose deaths, a major public health concern. Phylogenetics are being used to identify HIV transmission clusters and hotspots, which can inform prevention efforts. Vaginal microbial dysbiosis and proteomic alterations are associated with increased risk of HIV acquisition, as are the pregnancy and postpartum periods. HIV testing is a central first step for the HIV care and treatment continua, and several innovative strategies to expand HIV testing coverage and frequency show promise. Preexposure prophylaxis (PrEP) uptake is rapidly increasing in some cities, with reductions of new infections at the population level, but use is lower among African Americans and Latinos, youth, cis- and transgender women, and people who inject drugs. PrEP continuation remains a challenge. Two open-label extension studies of the dapivirine vaginal ring demonstrated high uptake, adherence, and reduced HIV infections. Several novel systemic and topical prevention agents show promise in non-human primates.

At the 2018 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. Several countries and cohorts have demonstrated the remarkable impact that universal HCV testing and unrestricted access to hepatitis C treatment can have on markedly reducing incident HCV infections and HCV infection prevalence, including in people who inject drugs and HIV/HCV-coinfected populations. However, in many settings, substantial barriers to widespread HCV treatment remain, including undiagnosed HCV infection, particularly in populations outside the standard "baby boomer" birth cohort (ie, born 1945-1965); restricted access to hepatitis C treatment in those with known HCV infection; reinfection with HCV; and migration of HCV-infected populations. Many innovative programs have successfully implemented HCV testing and treatment outside of traditional care settings, expanding access for harder-to-reach populations, which will be crucial to successful elimination efforts. Outbreaks of hepatitis A virus (HAV) infection continue to occur in among men who have sex with men and homeless populations in the United States, Europe, and Southeast Asia, highlighting the need for improved HAV vaccination programs for populations at risk.

Preexposure prophylaxis (PrEP) with tenofovir/emtricitabine (slash indicates coformulation) is highly effective in preventing new HIV infections. PrEP efficacy is strongly associated with adherence. In clinical trials, PrEP has been more effective in men who have sex with men and HIV-serodiscordant heterosexual couples than in women, likely reflecting pharmacokinetic differences between levels of tenofovir disoproxil fumarate in vaginal and rectal tissues, and poorer adherence in studies in women. Current guidelines recommend daily PrEP for men and women; however, PrEP taken at least 4 days per week for men may be as effective as daily PrEP, and women must take PrEP 6 to 7 days per week to maximize efficacy. Data are accumulating on the effectiveness of pericoital PrEP for men who have sex with men, but it is not yet recommended in the United States. PrEP is underprescribed for younger individuals, black individuals, and Hispanic and Latino individuals. This article summarizes a presentation by Susan P. Buchbinder, MD, at the IAS-USA continuing education program, Improving the Management of HIV Disease, held in Chicago, Illinois, in May 2017.

Achieving cure of HIV infection requires eliminating all replication-competent virus from the reservoir of latently infected cells or completely inhibiting infected cells from emerging from latency. Strategies include very early use of antiretroviral therapy; hematopoietic stem cell transplantation; "shock-and-kill" approaches; immune therapy with immune checkpoint inhibitors; gene therapy, including use of CC chemokine receptor 5-modified CD4+ T cells; and broadly neutralizing antibody therapy. Success is likely to require a combination of approaches. This article summarizes a presentation by Daniel C. Douek, MD, PhD, at the IAS-USA continuing education program held in Berkeley, California, in May 2017.

Over the past 30 years, antiretroviral drug regimens for treating HIV infection have become more effective, safer, and more convenient. Despite 31 currently approved drugs, the pipeline of investigational HIV drugs remains full. Investigational antiretroviral drugs include the nucleoside analogue reverse transcriptase translocation inhibitor (NRTTI) MK-8591, a long-acting compound that could be dosed once weekly. Investigational nonnucleoside analogue reverse transcriptase inhibitors (NNRTIs) include doravirine, which is active in vitro against NNRTI-resistant HIV and was potent and well-tolerated when used in combination with a dual-nucleoside analogue RTI (nRTI) backbone in treatment-naive individuals.New integrase strand transfer inhibitors (InSTIs) include recently approved bictegravir, which is active against InSTI-resistant viral strains in vitro and was potent and well-tolerated in combination regimens in treatment-naive individuals, and investigational cabotegravir, which is being studied with monthly parenteral dosing for HIV maintenance treatment and with bimonthly dosing for HIV preexposure prophylaxis (PrEP). Investigational HIV entry inhibitors include the new CD4 attachment inhibitor fostemsavir, which targets HIV envelope glycoprotein 120, and recently approved ibalizumab, which binds the CD4 receptor. This article summarizes presentations by Roy M. Gulick, MD, MPH, at the IAS-USA continuing education program, Improving the Management of HIV Disease, held in Los Angeles, California, in April 2017, and at the 2017 Ryan White HIV/AIDS Program Clinical Conference, held in San Antonio, Texas, in August 2017.

HIV-infected individuals on effective antiretroviral therapy experience a number of non-AIDS noncommunicable diseases, such as cardiovascular disease, more frequently than uninfected individuals. Common pathways for such diseases are chronic immune activation and inflammation, including the prolonged inflammation associated with lower nadir CD4+ cell count. Prevention and treatment of non-AIDS conditions include treatment of traditional risk factors, lifestyle interventions, earlier initiation of antiretroviral therapy, and potentially therapies specifically targeting inflammation and immune activation (eg, statins). This article summarizes a presentation by Judith S. Currier, MD, at the IAS-USA continuing education program, Improving the Management of HIV Disease, held in New York, New York, in February 2017.

HIV-infected persons are more likely to have chronic pain, receive opioid analgesic treatment, receive higher doses of opioids, and to have substance use disorders and mental illness compared with the general population, putting them at increased risk for opioid use disorder. Management of opioid use in HIV-infected individuals can be complex, and the limited data on opioid treatment in this population are conflicting with regard to its effect on HIV outcomes. Buprenorphine treatment for opioid use disorder improves HIV outcomes and other outcomes. This article summarizes a presentation by Chinazo O. Cunningham, MD, MS at the IAS-USA continuing education program, Improving the Management of HIV Disease, held in Atlanta, Georgia, in March 2017.