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A significant proportion of human immunodeficiency virus (HIV) infected patients are coinfected with hepatitis B virus (HBV). Currently available treatments for chronic hepatitis B (interferon [IFN]-alpha and lamivudine [3TC]) have limited long-term utility because of side effects or of the development of resistance. Tenofovir disoproxil fumarate (TDF) is a nucleotide analog with excellent activity in vitro against HBV, which is also active against 3TC-resistant HBV variants. In this 24-week pilot study, the anti-HBV activity of TDF was prospectively evaluated in a cohort of 6 HIV coinfected subjects for whom 3TC and IFN therapy had previously failed. At baseline, all patients were taking 3TC or FTC and were hepatitis B surface antigen and hepatitis B e antigen positive; 4 had cirrhosis. Baseline HBV load was 7.95 log(10) copies/mL. By weeks 12 and 24, HBV load had decreased by 3.1 log(10) copies/mL and 4.3 log(10) copies/mL, respectively. There was a transient increase of transaminases after the initiation of treatment. No patient developed HBe antibodies. TDF is a very promising drug for the treatment of chronic hepatitis B in HIV-infected individuals. Copyright © 2002 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

Opportunities for leadership in the specialty of infectious diseases (ID) have markedly increased over the last decade, including in newly recognized areas. Commensurate with the expansion of opportunities in ID, pathways to leadership positions within the Infectious Diseases Society of America (IDSA) are expanding as the Society seeks to advance the field for IDSA members. Acknowledging both the importance of diverse leaders to organizational success and shortfalls in diverse representation within IDSA leadership led to concentrated efforts to enhance transparency and opportunities for members to participate broadly in the work of IDSA. Herein, IDSA leaders reflect on their paths to IDSA leadership, hoping to help guide members seeking to partner with the Society. Features identified as important to individual success include mentorship, networking, participation in ID and IDSA volunteer experiences, passion for ID, and working with IDSA staff to advance the programs and initiatives of IDSA on behalf of members., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

The Infectious Diseases Society of America (IDSA) has grown and evolved considerably since its foundation in 1963 as an academic professional society. It currently has >11 000 members, both domestic and international, drawn from the breadth of infectious diseases practice, from basic research to public health. Governance of the Society has not evolved as rapidly, and, in the last few years, it was increasingly evident to many members that the IDSA leadership was less representative of the membership than it ought to be. As a result of a rigorous review of its governance structure, the Society has committed to a policy of inclusion, diversity, access, and equity. It has also reformed the methods by which future IDSA leaders are identified and given roles. These changes should increase the opportunities for all members of the Society to participate in its volunteer leadership., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: We wished to determine the safety and anti-human immunodeficiency virus (HIV) type 1 activity of single doses of TNX-355, a humanized IgG4 anti-CD4 monoclonal antibody with potent activity against HIV-1 in vitro, in HIV-infected subjects., Methods: Sequential cohorts of 6 HIV-1-infected subjects each received infusions of TNX-355. Data included plasma HIV-1 RNA level, CD4+ T cell count, TNX-355 coating of CD4+ T cells, and serum TNX-355 levels., Results: Dose-related reductions in plasma HIV-1 RNA loads correlated with complete CD4+ T cell coating by TNX-355. Peak median decreases in plasma HIV-1 RNA loads were 0.56, 1.33, and 1.11 log10 copies/mL and occurred on days 4-7, 14, and 21 for the 3.0, 10, and 25 mg/kg doses, respectively. Dose-dependent increases in CD4+ T cell count occurred within 24 h of dosing., Conclusions: Single doses of TNX-355 reduced plasma HIV-1 RNA loads and increased CD4+ T cell counts in HIV-infected subjects. The further assessment of therapeutic potential awaits data from longer-duration trials.

This study evaluates the change in CD4(+) T cell counts among patients who achieved complete viral suppression and subsequently discontinued highly active antiretroviral therapy (HAART). We included 72 human immunodeficiency virus (HIV)-1-infected patients with plasma HIV RNA loads of <500 copies/mL for at least 3 months who then discontinued therapy for at least 12 weeks. The median CD4(+) T decay while off HAART was 16 cells/mm(3)/month (interquartile range, -6 to -34 cells/month). The mean follow-up after therapy ended was 45 weeks. The slope of the CD4(+) T cell decay was inversely correlated with the increase of CD4(+) T cells while receiving HAART, baseline virus load, CD4(+) T cell count at the time therapy was discontinued, age, and duration HIV RNA levels were undetectable. In a multiple regression analysis model, the increase of CD4(+) T cells while receiving therapy and age were independently associated with the rate of CD4(+) T cell loss.

The efficacy and safety of clarithromycin and rifabutin alone and in combination for prevention of Mycobacterium avium complex (MAC) disease were compared in 1178 patients with AIDS who had < or =100 CD4 T cells/microL in a randomized, double-blind, placebo-controlled trial. MAC disease occurred in 9%, 15%, and 7% of those randomized to clarithromycin or rifabutin alone or in combination, respectively; time-adjusted event rates per 100 patient-years (95% confidence interval [CI]) were 6.3 (4.2-8.3), 10.5 (7.8-13.2), and 4. 7 (2.9-6.5). Risk of MAC disease was reduced by 44% with clarithromycin (risk ratio [RR], 0.56; 95% CI, 0.37-0.84; P=.005) and by 57% with combination therapy (RR, 0.43; 95% CI, 0.27-0.69; P=. 0003), versus rifabutin. Combination therapy was not more effective than clarithromycin (RR, 0.79; 95% CI, 0.48-1.31; P=.36). Of those in whom clarithromycin or combination therapy failed, 29% and 27% of MAC isolates, respectively, were resistant to clarithromycin. There were no survival differences. Clarithromycin and combination therapy were more effective than rifabutin for prevention of MAC disease, but combination therapy was associated with more adverse effects (31%; P<.001).

The objective of this study was to correlate cytomegalovirus (CMV) DNA levels in the cerebrospinal fluid (CSF) of subjects with AIDS with clinical and pathologic findings attributable to CMV infection of the central nervous system (CNS). CMV polymerase chain reaction (PCR) was done on serial dilutions of CSF samples from 24 AIDS patients with autopsy-proven CNS disorders. CMV DNA was detected in CSF from 12 of 13 subjects with evidence of CMV infection of the brain or spinal cord but in none of 11 subjects without autopsy evidence of CMV CNS infection. Subjects whose CSF contained > 10(3) CMV DNA molecules/8 microL of CSF had severe CMV CNS disease (e.g., ventriculoencephalitis). PCR appears to be more useful than clinical and neuroradiologic findings for documenting CMV infection of the CNS in patients with AIDS. Quantitation of CMV DNA in CSF shows promise for evaluation of the extent of involvement.

The causative strains in 22 patients with recurrent oral candidiasis were examined using two DNA probes (a Histoplasma capsulatum DNA probe that cross-hybridizes with Candida albicans and a C. albicans strain-specific probe derived from repetitive sequence DNA). C. albicans was the causative organism in all 22 initial episodes of infection and was also obtained from 17 patients with recurrent oral disease. Molecular analysis showed that in 11 cases, the same isolate was identified in each episode. Six patients had a clearly different isolate of C. albicans causing a later episode of candidiasis. Five patients had different Candida species causing recurrent disease: 4, Torulopsis glabrata; 1, Candida parapsilosis. Patients with a new isolate (either new species or a new C. albicans strain) were more immunosuppressed and were significantly more likely (P < .001) than patients with the same recurrent strain to have received suppressive azole antifungal agents. These data indicate that the epidemiology of recurrent candidiasis in individual patients seropositive for the human immunodeficiency virus is complex and that both failure of eradication of Candida from the oral cavity and new infection occur.

In an effort to prevent cytomegalovirus (CMV) pneumonitis, seven consecutive CMV-seronegative lung transplant recipients of organs from seropositive donors (D+/R-) were given ganciclovir, 2.5-5 mg/kg intravenously twice daily for the first 10-21 days after transplantation, and commercial polyvalent immune globulin, 200-400 mg/kg every 7-14 days intravenously, for the first 2-3 weeks after transplantation. This regimen was followed by oral acyclovir. Six patients developed CMV viremia and all developed CMV pneumonitis. Viremia occurred later in these patients compared with D+/R- patients who received alternative forms of CMV prophylaxis or CMV-seropositive recipients who received no specific prophylaxis (P = .023 and P = .021, respectively). There was no statistical difference in incidence or time to onset of CMV pneumonitis. When given as described, prophylactic ganciclovir and immune globulin followed by oral acyclovir may have delayed CMV viremia but did not prevent it or pneumonitis in high-risk lung transplant recipients.

Two friends, one with AIDS, developed severe pulmonary blastomycosis but differed markedly in clinical course. The human immunodeficiency virus-negative patient responded completely to ketoconazole; the patient with AIDS died of progressive disseminated infection despite treatment with fluconazole and amphotericin B. Epidemiologic investigation suggested a common source of infection, but serologic evaluation and environmental cultures were unrevealing. EcoRI digestion of the Blastomyces dermatitidis isolates showed identical restriction fragment patterns that differed from patterns obtained from other clinical isolates. Analysis using a Histoplasma capsulatum ribosomal DNA probe that cross-hybridizes with B. dermatitidis showed that the isolates from the two patients were identical and different from others. Thus, the patients were probably infected with the same strain, possibly from a common source. These data indicate the critical role of cellular immunity in patients with blastomycosis, show that there are multiple genotypes of B. dermatitidis, and suggest that DNA restriction analysis is a useful epidemiologic tool.