Robust Reconstitution of Tuberculosis-Specific Polyfunctional CD4+ T-Cell Responses and Rising Systemic Interleukin 6 in Paradoxical Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome.

Background: The immunopathogenesis of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) remains unclear. We determined the association between pathogen-specific T-cell responses and development of paradoxical TB-IRIS on antiretroviral therapy (ART).

Methods: This study was nested within a prospective cohort study of HIV-infected patients with active pulmonary tuberculosis and baseline CD4 counts ≤125 cells/µL initiating ART.

Immunological profiling of tuberculosis-associated immune reconstitution inflammatory syndrome and non-immune reconstitution inflammatory syndrome death in HIV-infected adults with pulmonary tuberculosis starting antiretroviral therapy: a prospective observational cohort study.

Background: Patients co-infected with advanced HIV and tuberculosis are at risk of tuberculosis-associated immune reconstitution inflammatory syndrome (IRIS) and death soon after initiation of antiretroviral therapy (ART). Tuberculosis-associated IRIS has been associated with quicker recovery of cellular immune responses after ART initiation and early mortality with slower recovery of these responses. We aimed to assess whether patients who have these outcomes have distinct immunological profiles before and after ART initiation.

Early immunologic failure is associated with early mortality among advanced HIV-infected adults initiating antiretroviral therapy with active tuberculosis.

Background: The relationship between antiretroviral therapy (ART) response and early mortality after ART initiation is unknown. We hypothesized that early mortality is associated with decreased early immunologic response to ART.

Methods: We prospectively determined the association between changes in plasma human immunodeficiency virus type 1 (HIV-1) RNA and CD4(+) T-cell counts (CD4 count) after 4 weeks of ART and early mortality in adults with pulmonary tuberculosis and pre-ART CD4 counts ≤ 125 cells/µL.

Isoniazid-resistant tuberculous meningitis, United States, 1993-2005.

To determine patient characteristics associated with isoniazid resistance in cases of tuberculous meningitis, we conducted a cross-sectional study by using data from the US National Tuberculosis Surveillance System during 1993-2005. Foreign-born patients were more likely to be infected with an isoniazid-resistant strain.

Isoniazid resistance and death in patients with tuberculous meningitis: retrospective cohort study.

Objective: To determine whether initial isoniazid resistance is associated with death during the treatment of tuberculous meningitis.

Design: Retrospective cohort study.

Setting: National Tuberculosis Surveillance System at the Centers for Disease Control in the United States.

Safety and immunogenicity of a live attenuated varicella vaccine in VZV-seropositive HIV-infected adults.

Background: Herpes-zoster is common in HIV-infected patients in spite of antiretroviral therapy. We evaluated the safety and immunogenicity of a live attenuated varicella-zoster virus (VZV) vaccine as a candidate for protecting HIV-infected adults against herpes-zoster.

Results: Sixty-seven HIV-infected and 15 uninfected subjects, 18 to 65 years old, were enrolled.

Tuberculous meningitis in HIV-infected individuals.

HIV-infected individuals are at increased risk for all forms of extrapulmonary tuberculosis, including tuberculous meningitis. This risk is increased at more advanced levels of immunosuppression. The time interval between onset of symptoms and presentation to medical care may vary widely, and consequently individuals may present with acute or chronic meningitis.

Cryptococcus and lymphocytic meningitis in Botswana.

We retrospectively reviewed microbiological data from a tertiary care hospital in Botswana, and found that Cryptococcus neoformans was cultured from 15% (193/1307) of all cerebrospinal fluid (CSF) specimens submitted for analysis, making it the most common diagnosed cause of meningitis in this population. Moreover, almost 70% of CSF samples with significant lymphocytosis did not yield a pathogen, suggesting that many causes of lymphocytic meningitis go undiagnosed.

Serological evidence of HIV-associated infection among HIV-1-infected adults in Botswana.

In industrialized countries, it is recommended that adults with human immunodeficiency virus type 1 (HIV-1) infection undergo baseline screening for pathogens that might cause latent or active infections, such as syphilis, hepatitis B, hepatitis C, infection due to Toxoplasma gondii, and cytomegalovirus infection. A paucity of data exist from sub-Saharan Africa describing the prevalence of these pathogens. We report data for HIV-1-infected adults referred for initiation of highly active antiretroviral therapy in Botswana.

Gene transfer in humans using a conditionally replicating lentiviral vector.

We report findings from a clinical evaluation of lentiviral vectors in a phase I open-label nonrandomized clinical trial for HIV. This trial evaluated the safety of a conditionally replicating HIV-1-derived vector expressing an antisense gene against the HIV envelope. Five subjects with chronic HIV infection who had failed to respond to at least two antiviral regimens were enrolled.

Management of potential neurocysticercosis in patients with HIV infection.

In patients with human immunodeficiency virus, the diagnosis of neurocysticercosis can be complex, and the current diagnostic criteria may not apply. We report 3 cases and suggest including the CD4+ T lymphocyte count as an important factor in the proper diagnosis and treatment of patients with human immunodeficiency virus and potential neurocysticercosis.

IL-13 acutely augments HIV-specific and recall responses from HIV-1-infected subjects in vitro by modulating monocytes.

We show in this study that acute exposure of PBMCs derived from HIV-infected subjects to IL-13 results in increased recall T cell lymphoproliferative responses against HIV-1 p24 (n = 30, p < 0.0001) and other recall Ags (influenza, n = 43, p < 0.0001; purified protein derivative tuberculin, n = 6, p = 0.

Clinical, microbiological, and immunological characteristics in HIV-infected subjects at risk for disseminated Mycobacterium avium complex disease: an AACTG study.

The clinical, microbiologic, and immunologic parameters in HIV-infected subjects first presenting with disseminated Mycobacterium avium complex (DMAC) were determined. Four HIV-positive groups not yet on DMAC treatment were enrolled: 19 subjects with CD4 lymphocyte counts < or =50/microl thought to have DMAC on clinical grounds; 18 subjects newly found to have a positive blood culture for MAC; 25 asymptomatic controls (CD4 cell counts < or =50); and 25 asymptomatic controls (CD4 counts 100-250/microl). Outcome measures include comparisons between groups for clinical characteristics; results of cultures from blood, marrow, and gastrointestinal and respiratory tracts; immunological markers from staining of marrow and flow cytometry of circulating lymphocytes; and cytokine production of PBMCs.

A tale of 2 epidemics: the intersection between obesity and HIV infection in Philadelphia.

Background: Obesity and HIV infection are ongoing epidemics in the United States. Obesity predisposes to diabetes and cardiovascular disease, which are complications also associated with HIV and/or its treatment.

Objective: To determine the prevalence and risk factors for overweight and obesity in HIV-infected individuals.

Stavudine entry into cerebrospinal fluid after single and multiple doses in patients infected with human immunodeficiency virus.

Study Objective: To establish the pharmacokinetics of stavudine within the cerebrospinal fluid (CSF) of patients infected with human immunodeficiency virus (HIV).

Design: Pharmacokinetic study.

Setting: General clinical research center.

Plasmid vaccination of stable HIV-positive subjects on antiviral treatment results in enhanced CD8 T-cell immunity and increased control of viral "blips".

Antiviral therapy prolongs suppression of viral replication and allows for significant immune reconstitution but has not been effective in eradicating reservoirs of virus, which produce resurgent viremia when highly active antiretroviral therapy (HAART) is discontinued. Immune-based therapy may provide an additional antiviral effect. We vaccinated stable HIV-positive patients on HAART with an HIV plasmid vaccine to determine safety, immunogenicity, and therapeutic potential.

Regulatory considerations for novel gene therapy products: a review of the process leading to the first clinical lentiviral vector.

This review is intended to exemplify the roles and responsibilities of the two agencies under the Department of Health and Human Services, the National Institutes of Health and the Food and Drug Administration, that have oversight for human gene transfer clinical protocols, as seen through our experience of bringing a first-in-its-class lentiviral vector to clinical trials. In response to the changing circumstances in gene therapy research between 1999 and 2002, the concerns of these agencies regarding gene therapy have been evolving. This review provides an overview of the major safety concerns regarding insertional oncogenesis, the generation of a replication- competent lentivirus (RCL), and vector mobilization thought to be related to lentiviral vectors, which had to be addressed during the regulatory review process before initiating the clinical trial.

Differential virulence of Mycobacterium avium strains isolated from HIV-infected patients with disseminated M. avium complex disease.

The role that colonization with Mycobacterium avium plays in the development of disseminated disease is unclear. In this study, we determined whether all M. avium strains isolated from the portals of M.

Identifying the vector of Lyme disease.

Lyme disease is the most common vector-borne illness in the United States. It is caused by the spirochete Borrelia burgdorferi, which is transmitted by the deer tick. Deer ticks have a four-stage life cycle (egg, larva, nymph, and adult), and nymphal ticks transmit B.

A prospective, randomized trial examining the efficacy and safety of clarithromycin in combination with ethambutol, rifabutin, or both for the treatment of disseminated Mycobacterium avium complex disease in persons with acquired immunodeficiency syndrome.

This multicenter, randomized, open-label phase 3 clinical trial compared the safety and efficacy of 3 clarithromycin-containing combination regimens for the treatment of disseminated Mycobacterium avium complex (MAC) disease in persons with acquired immunodeficiency syndrome. A total of 160 eligible patients with bacteremic MAC disease were randomized to receive clarithromycin with either ethambutol (C+E), rifabutin (C+R), or both (C+E+R) for 48 weeks. After 12 weeks of treatment, the proportion of subjects with a complete microbiologic response was not statistically significantly different among treatment arms: the proportion was 40% in the C+E group, 42% in the C+R group, and 51% in the C+E+R group (P=.

A study of discontinuing maintenance therapy in human immunodeficiency virus-infected subjects with disseminated Mycobacterium avium complex: AIDS Clinical Trial Group 393 Study Team.

The present nonrandomized prospective study evaluated whether antimycobacterial therapy for disseminated Mycobacterium avium complex (MAC) could be withdrawn from human immunodeficiency virus-infected subjects who experienced immunologic recovery while receiving highly active antiretroviral therapy (HAART). Eligible subjects had received macrolide-based therapy for least 12 months, were asymptomatic for MAC, had received HAART for at least 16 weeks, and had CD4+ T cell counts >100 cells/microL. Forty-eight subjects were enrolled, with a median CD4+ T cell count of 240 cells/microL at the time of discontinuation of MAC therapy.

Endemic babesiosis in another eastern state: New Jersey.

In the United States, most reported cases of babesiosis have been caused by Babesia microti and acquired in the northeast. Although three cases of babesiosis acquired in New Jersey were recently described by others, babesiosis has not been widely known to be endemic in New Jersey. We describe a case of babesiosis acquired in New Jersey in 1999 in an otherwise healthy 53-year-old woman who developed life-threatening disease.

T-cell responses induced in normal volunteers immunized with a DNA-based vaccine containing HIV-1 env and rev.

Objective: An effective HIV-1 vaccine will likely need to induce strong cell-mediated immunity in humans. Therefore, we examined the ability of a DNA HIV-1 vaccine to induce a T-cell response in HIV-1 seronegative humans.

Design: Individuals were enrolled in a phase I clinical trial of safety and immune responses to an env/rev-containing plasmid at doses of 100, 300 or 1000 microg.