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Background & Aims: Treatment of chronic hepatitis B virus (HBV) infection with entecavir suppresses virus replication and reduces disease progression, but could require life-long therapy. To investigate clinical outcome events and safety associated with long-term treatment with entecavir, we followed up patients treated with entecavir or another standard-of-care HBV nucleos(t)ide analogue for up to 10 years. We assessed long-term outcomes and relationships with virologic response., Methods: Patients with chronic HBV infection at 299 centers in Asia, Europe, and North and South America were assigned randomly to groups that received entecavir (n = 6216) or an investigator-selected nonentecavir HBV nucleos(t)ide analogue (n = 6162). Study participants were followed up for up to 10 years in hospital-based or community clinics. Key end points were time to adjudicated clinical outcome events and serious adverse events. In a substudy, we examined relationships between these events and virologic response., Results: There were no significant differences between groups in time to event assessments for primary end points including malignant neoplasms, liver-related HBV disease progression, and death. There were no differences between groups in the secondary end points of nonhepatocellular carcinoma malignant neoplasms and hepatocellular carcinoma. In a substudy of 5305 patients in China, virologic response, regardless of treatment group, was associated with a reduced risk of liver-related HBV disease progression (hazard ratio, 0.09; 95% CI, 0.038-0.221) and hepatocellular carcinoma (hazard ratio, 0.03; 95% CI, 0.009-0.113). Twelve patients given entecavir (0.2%) and 50 patients given nonentecavir drugs (0.8%) reported treatment-related serious adverse events., Conclusions: In a randomized controlled trial of patients with chronic HBV infection, we associated entecavir therapy with a low rate of adverse events over 10 years of follow-up evaluation. Patients receiving entecavir vs another nucleos(t)ide analogue had comparable rates of liver- and non-liver-related clinical outcome events. Participants in a China cohort who maintained a virologic response, regardless of treatment group, had a reduced risk of HBV-related outcome events including hepatocellular carcinoma. ClinicalTrials.gov identifier no: NCT00388674., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

We describe a previously healthy adult who had a solitary cerebellar brain abscess diagnosed. This infection occurred 4 weeks after the patient underwent a tongue piercing procedure that was complicated by an apparent local infection. The clinical history, abscess culture results, and lack of an alternative explanation suggest that infection of the tongue piercing site was the source of the cerebellar abscess.

The course of human immunodeficiency virus (HIV) disease is characterized by a progressive decline in immune function. The advent of highly active antiretroviral therapy (HAART) has allowed patients to experience a significant degree of immune restoration when compared with the era before the availability of HAART. Multiple studies, which have employed sophisticated in vitro measures of immune function, have demonstrated improvement in CD4(+) lymphocyte (T4) responses to various opportunistic pathogens. In addition, for patients treated during acute HIV infection, HIV-specific T4 responses have been restored. By contrast, there are a limited number of in vivo measures of T4 function available to assess immune recovery following initiation of HAART. The primary measurement is an increase in CD4 lymphocyte count, the significance of which may be underappreciated. Delayed-type hypersensitivity testing to recall antigens and serological response to prophylactic vaccines may also have a role. This review discusses available markers of immune function and offers suggestions regarding their use in HAART recipients.

Actinomycosis has been rarely reported in patients with HIV/AIDS in contrast to other opportunistic and common pathogens. We report a case of esophageal ulcer disease, secondary to actinomycosis occurring in a patient with recurrent odynophagia. The diagnosis was made histologically only after repeated upper endoscopy with biopsies.

Purpose: To describe an unusual concurrence of acute retinal necrosis and progressive outer retinal necrosis in fellow eyes of a patient with acquired immunodeficiency syndrome (AIDS)., Methods: Interventional case report. In a 37-year-old man with AIDS and herpes zoster keratitis in the right eye, progressive outer retinal necrosis developed in the right eye and acute retinal necrosis developed in the left eye., Results: Disparate presentations of retinitis persisted in each eye, and retinal detachment and vision loss ensued in both eyes despite antiviral therapy., Conclusion: Distinct features of acute retinal necrosis and progressive outer retinal necrosis do not necessarily reflect systemic factors, and they may be variant manifestations of the same underlying infection.

Background: Pharmacokinetic interactions complicate and potentially compromise the use of antiretroviral and other HIV therapeutic agents in patients with HIV disease. This may be particularly so among those receiving treatment for substance abuse., Objective: We describe seven cases of opiate withdrawal among patients receiving chronic methadone maintenance therapy following initiation of therapy with the non-nucleoside reverse transcriptase inhibitor, nevirapine., Design: Retrospective chart review., Results: In all seven patients, due to the lack of prior information regarding a significant pharmacokinetic interaction between these agents, the possibility of opiate withdrawal was not anticipated. Three patients, for whom methadone levels were available at the time of development of opiate withdrawal symptoms, had subtherapeutic methadone levels. In each case, a marked escalation in methadone dose was required to counteract the development of withdrawal symptoms and allow continuation of antiretroviral therapy. Three patients continued nevirapine with methadone administered at an increased dose; however, four chose to discontinue nevirapine., Conclusion: To maximize HIV therapeutic benefit among opiate users, information is needed about pharmacokinetic interactions between antiretrovirals and therapies for substance abuse.

The effect of interleukin (IL)-12 on T lymphocyte function was assessed in 47 human immunodeficiency virus (HIV)-infected persons of different disease stages and 16 seronegative controls. Lymphoproliferative responses (LPR) were measured to various HIV and non-HIV antigens and mitogens using peripheral blood mononuclear cells cultured with or without IL-12. Without exogenous IL-12, 96% of HIV-seropositive persons responded to mitogens, 77% to >=1 non-HIV antigen, and 11% to >=1 HIV antigen. Supplementation with IL-12 augmented LPR of HIV-seropositive persons to non-HIV antigens; however, the effect was greatest for those with higher CD4 cells (40% vs. 9% for those with >200 vs. <=200 CD4 cells/mm3). Addition of IL-12 also enhanced LPR to HIV antigens in 30% of subjects. This effect was most pronounced for those with>500 CD4 cells/mm3 (56% [P<. 05]). These findings suggest that impaired T lymphocyte recognition of foreign antigen, including HIV, can be reconstituted in part for selected HIV-seropositive persons.

Objective: This study aimed to describe a recently recognized and rare presentation of varicella zoster virus (VZV) retrobulbar optic neuritis preceding retinitis in patients with acquired immune deficiency syndrome and to identify factors that may relate to improved visual outcome., Methods: Diagnosis, treatment, and clinical course are described for three eyes of two patients with this viral infection., Results: Patients had decreased vision, headache, and recent zoster dermatitis. Varicella zoster virus retrobulbar optic neuritis was diagnosed on the bases of clinical, laboratory, and electrophysiologic examination results. Profound vision loss and peripheral retinitis ensued despite intravenous antiviral treatment. Combination intravenous and intravitreous antiviral injections were administered with dramatic visual recovery., Conclusions: Varicella zoster virus retrobulbar optic neuritis should be considered in immunocompromised patients with visual loss. Early diagnosis and aggressive combination therapy via systemic and intravitreous routes may enable return of useful vision.

Streptococcus pneumoniae is an infrequent cause of infectious endocarditis in adults. In the past 2 years, however, we have encountered several cases at our institution, and additional cases have been reported in the literature. This infection typically follows pneumonia in the setting of chronic alcoholism and may additionally be complicated by meningitis. Less commonly, pneumococcal endocarditis occurs in other hosts or follows primary infection at other extrapulmonary sites. In such cases, the diagnosis may be initially missed, with a resultant delay in institution of appropriate therapy. Moreover, there are controversies regarding the optimal therapy for infections of this nature in the era of penicillin resistance. Since a comprehensive review of this topic has not been published since 1990, we reviewed cases of pneumococcal endocarditis in the penicillin era, with particular attention to disease recognition, the role of echocardiography, and the dilemmas surrounding medical and surgical therapeutic interventions.

Transmission studies have suggested that an optimal human immunodeficiency virus type 1 (HIV-1) vaccine should induce both neutralizing antibodies and cytolytic T cells to eliminate free virus and infected cells. A phase I trial in healthy HIV-1-seronegative persons was conducted with a combination HIV-1 vaccine regimen (strain IIIB) consisting of priming with a recombinant vaccinia (vac/env) virus expressing HIV-1 envelope and boosting with a gp160 glycoprotein derived from a recombinant baculovirus (rgp160). T-cell and antibody responses detected after immunization with either vac/env alone or rgp160 alone were generally of low magnitude and transient, and no subject developed neutralizing antibodies. In contrast, recipients of the combination regimen demonstrated in vitro T-cell proliferative responses to homologous HIV-1 antigens that were 3- to 10-fold higher than responses with either vaccine alone, and these responses were sustained for > 18 months in 75% of recipients. Moreover, both CD8+ and CD4+ cytolytic T cells were detected. Antibody responses (titer, 1:800 to 1:102,400) to homologous HIV envelope developed in all recipients of the combination regimen, and neutralizing antibodies were detected in 7 of 13. Thus, immunization with a live virus vaccine followed by boosting with a soluble protein offers promise for inducing the broad immunity needed in an HIV vaccine.

In a randomised phase I trial of a recombinant vaccina virus vaccine expressing the gp160 envelope gene of the human immunodeficiency virus (HIVAC-1e) 35 healthy, HIV-seronegative males, 31 of whom had a history of smallpox immunisation and 4 of whom were vaccinia naive, were vaccinated and then boosted 8 weeks later with HIVAC-1e or standard NY strain vaccinia virus. The frequency, duration, and titre of virus isolation from the vaccination site and occurrence of local side-effects were similar between the two groups of vaccinees. Vaccinia-naive (vac-n) subjects shed virus from the vaccination site for longer and at a higher titre than did vaccinia-primed (vac-p) individuals (19 vs 7 days and 10(7) vs 10(5) pfu/ml, respectively). In-vitro T-cell proliferative responses to one or more HIV antigen preparations developed in 13 of 16 vaccinia-primed subjects inoculated with HIVAC-1e. T-cell responses were, however, transient and in no subject did antibodies to HIV become detectable. The 2 vaccinia-naive subjects vaccinated with HIVAC-1e showed strong T-cell responses to homologous and heterologous strains of whole virus and to recombinant gp160 protein that remained detectable for over a year; antibodies to HIV envelope also developed in both. Recombinant vaccinia virus vaccines induce T-cell priming to the foreign gene products in most individuals. If used as the sole immunising agent they will be most efficacious in vaccinia-naive individuals.