Topics in antiviral medicine最新文献

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.

International guidelines recommend lifelong nucleos(t)ide analogue (NA) treatment in individuals with chronic hepatitis B (CHB) infection who are hepatitis B e antigen (HBeAg) seronegative, because hepatitis B surface antigen (HBsAg) seroconversion is rarely achieved. However, after terminating therapy, sustained responses and HBsAg loss have been observed. Clinical characteristics identifying persons with favorable outcomes after discontinuing NA therapy have not yet been defined. This case series describes outcomes of 6 individuals with HBeAg-seronegative CHB infection without cirrhosis and low plasma levels of HBsAg who discontinued long-term NA treatment. All individuals had a virologic relapse and 4 of 6 had a biochemical relapse; but 5 of 6 later developed a sustained virologic and biochemical response and a marked reduction of quantitative HBsAg (qHBsAg). Two of the 6 individuals experienced HBsAg loss. Only 1 patient was retreated, and none showed signs of hepatic decompensation. NA treatment can be safely stopped in selected HBeAg-seronegative patients. Sustained offtreatment responses seem to be frequently preceded by a virologic and biochemical flare. Loss of HBsAg possibly reflects restoration of antiviral immunity during prolonged NA treatment. Predictive factors, such as qHBsAg, may be valuable in selecting patients who could benefit from NA discontinuation.

Viral resistance to direct-acting antiviral drugs may impact their effectiveness during treatment of hepatitis C virus (HCV) infection. Most data on HCV drug resistance concern genotypes 1 and 3. The clinical impact of resistance to HCV nonstructural protein 5A (NS5A) inhibitors and a practical approach to indications and methods for resistance testing are discussed.

Neurologic complications in persons with HIV infection are less severe in the era of potent antiretroviral therapy but remain highly prevalent. Prior to the use of antiretroviral therapy, opportunistic infections of the central nervous system (CNS) and CNS malignancy were common. Progressive multifocal leukoencephalopathy (PML), however, remains a diagnostic challenge in HIV-infected individuals, and no effective antiviral treatment for PML is currently available. Primary neurologic complications of acute HIV infection include aseptic meningitis and acute inflammatory demyelinating polyneuropathy. Among the neurologic complications of chronic HIV infection, HIV-associated neurocognitive disorders (HAND) remain most prevalent. The use of antiretroviral therapy has greatly reduced the severity of HAND, under which progressive HIV-associated dementia once predominated, to a milder chronic form of potentially disabling neurocognitive impairment. The persistence of HAND in individuals with virologic suppression suggests a need for adjunctive therapies for limiting its morbidity. This article summarizes a presentation by Dennis Kolson, MD, PhD, at the IAS-USA continuing education program, Improving the Management of HIV Disease, held in Chicago, Illinois, in May 2017.

Restrictive policies on access to new, curative hepatitis C treatments represent a substantial barrier to treating patients infected with hepatitis C. This case series demonstrates challenges experienced by patients and practitioners in accessing these treatments and highlights several strategies for navigating the treatment preauthorization process.

At the 2017 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle, Washington, hepatitis C virus (HCV) infection was a major focus in the context of HIV-associated liver disease. Well-tolerated direct-acting antiviral (DAA) regimens have enabled effective treatment of the populations that are hardest to cure, including those with decompensated cirrhosis, and many studies examined the impact of HCV cure on hepatitis and extrahepatic outcomes. Scaling up access to DAA, and the impact that their universal availability can have on reducing prevalence were key topics. There was much discussion of what is needed to eliminate HCV on local and global levels and a focus on ensuring that the populations hardest to reach can access treatment. Prevention of new infections and reinfection will be key to sustaining the benefits of scaled-up HCV treatment, with particular attention to populations at elevated risk for HCV reinfection, including HIV-infected men who have sex with men (MSM) as well as some HIV-uninfected MSM on preexposure prophylaxis. In the hepatitis B virus (HBV) arena, a landmark phase III trial demonstrated that tenofovir disoproxil fumarate given to HBV-infected pregnant women at week 28 of gestation, in combination with postpartum HBV vaccination and hepatitis B immunoglobulin, resulted in zero mother-to-child transmissions of HBV.

The brain is a major target for HIV infection and is a potential viral reservoir even in virologically well-controlled HIV-infected individuals. Data presented at the 2017 Conference on Retroviruses and Opportunistic Infections (CROI) suggested that during early HIV infection, CD4+ T cells in the meninges and choroid plexus serve as an important early site of HIV infection in the central nervous system (CNS), with brain macrophages and microglial cells becoming an important source of viral replication with advancing disease. Longitudinal evaluations of HIV-associated neurocognitive disorder (HAND) demonstrated that cognitive changes occur during early HIV infection and may remain during chronic infection despite virologic control by antiretroviral therapy. Cerebrospinal fluid escape during treatment was noted in numerous cohorts and pathogenetically evaluated as a state of persistent CNS HIV infection despite antiretroviral therapy. Non-HIV risk factors identified for cognitive impairment were depression and frailty. Questions remain concerning appropriate cognitive screening tests to evaluate for HAND. Additional studies highlighted the increasing role of neuroimaging to longitudinally assess potential changes in brain integrity in individuals on systemically suppressive therapy, and provided new CNS considerations in antiretroviral regimens.