The role of raltegravir in the treatment of HIV-2 infections: evidence from a case series.

We describe five patients with HIV-2 infection (four antiretroviral-experienced and one antiretroviral-naive) treated with a regimen containing raltegravir. All responded to treatment as demonstrated by viral load and CD4(+) T-cell count monitoring. Our series confirms the clinical effectiveness of raltegravir in HIV-2-infected patients when given with other antiretrovirals to which the virus is susceptible.

Short communication: no evidence of HTLV-3 and HTLV-4 infection in New York State subjects at risk for retroviral infection.

The primate T-cell lymphoma viruses (PTLV) are divided into six distinct species. The biology and epidemiology of PTLV-1 and PTLV-2 are very well understood. However, that of PTLV-3, 4, 5, and 6 are not.

Evidence of dysregulation of dendritic cells in primary HIV infection.

Myeloid and plasmacytoid dendritic cells (DCs) are important mediators of both innate and adaptive immunity against pathogens such as HIV. During the course of HIV infection, blood DC numbers fall substantially. In the present study, we sought to determine how early in HIV infection the reduction occurs and whether the remaining DC subsets maintain functional capacity.

DEC-205 receptor on dendritic cells mediates presentation of HIV gag protein to CD8+ T cells in a spectrum of human MHC I haplotypes.

Optimal HIV vaccines should elicit CD8+ T cells specific for HIV proteins presented on MHC class I products, because these T cells contribute to host resistance to viruses. We had previously found that the targeting of antigen to dendritic cells (DCs) in mice efficiently induces CD8+ T cell responses. To extend this finding to humans, we introduced the HIV p24 gag protein into a mAb that targets DEC-205/CD205, an endocytic receptor of DCs.

Dendritic cell numbers in the blood of HIV-1 infected patients before and after changes in antiretroviral therapy.

Antigen presenting dendritic cells (DCs) can serve as sites for HIV replication and as vehicles for transmission of the virus to T cells. It is known that the numbers of DCs in blood is reduced during HIV-1 infection. Here we monitored the two major subsets of blood DCs in 12 individuals undergoing a change, primarily initiation, of highly active antiretroviral therapy.

CD8+ T cells from most HIV-1-infected patients, even when challenged with mature dendritic cells, lack functional recall memory to HIV gag but not other viruses.

Chronically HIV-1-infected patients fail to contain their viremia despite high frequencies of HIV-1-specific, IFN-gamma-producing CD8(+) T cells. However, these cells are known to exhibit both phenotypic and functional defects. We tested if mature dendritic cells (DC) could correct defective HIV-1 gag-specific T cell responses and if responses to other viral antigens were comparably affected.

HIV-1-infected monocyte-derived dendritic cells do not undergo maturation but can elicit IL-10 production and T cell regulation.

Dendritic cells (DCs) undergo maturation during virus infection and thereby become potent stimulators of cell-mediated immunity. HIV-1 replicates in immature DCs, but we now find that infection is not accompanied by many components of maturation in either infected cells or uninfected bystanders. The infected cultures do not develop potent stimulating activity for the mixed leukocyte reaction (MLR), and the DCs producing HIV-1 gag p24 do not express CD83 and DC-lysosome-associated membrane protein maturation markers.

Interferon-producing plasmacytoid dendritic cells and the pathogenesis of AIDS.

Interferon-alpha (IFN-alpha) generation by peripheral blood mononuclear cells (PBMC) responding in vitro to HSV was first found to be deficient in patients with severe ulcerative herpes simplex virus (HSV) infections early in the AIDS epidemic. Such deficits were soon found to be associated with all opportunistic infections (OI). Further studies during the natural history of HIV infection indicated that OI did not occur so long as IFN generation remained relatively intact.

Circulating human plasmacytoid dendritic cells are highly sensitive to corticosteroid administration.

Plasmacytoid dendritic cells (pDC), the major interferon-producing cell type found in human blood, have been implicated in the pathogenesis of systemic lupus erythematosus (SLE). Previous studies in SLE have shown substantial deviations from normal in this minor but immunologically important leukocyte population. Many of the lupus patients studied were receiving corticosteroids.

Circulating, interferon-producing plasmacytoid dendritic cells decline during human ageing.

Increased frequency and severity of infections in the elderly have been taken as indicative of declining immune function. Dendritic cells (DCs), the most important antigen-presenting cells, play a central role in initiating and modulating immune responses. One type, DC2, arises from precursor plasmacytoid DCs (pDCs), a rare population of circulating blood cells, whose hallmark function is rapid and copious production of interferon-alpha (IFN-alpha) upon microbial challenge.

Immunologic profile of highly exposed yet HIV type 1-seronegative men.

The host immune factors that determine susceptibility to HIV-1 infection are poorly understood. We compared multiple immunologic parameters in three groups of HIV-1-seronegative men: 14 highly exposed (HR10), 7 previously reported possibly to have sustained transient infection (PTI), and a control group of 14 low risk blood bank donors (BB). Virus-specific cellular immune assays were performed for CD4(+) T helper cell responses, CD8(+) cytotoxic T lymphocyte activity, CD8(+) cell chemokine release, and CD8(+) cell-derived antiviral soluble factor activity.

Interferon-alpha generation and immune reconstitution during antiretroviral therapy for human immunodeficiency virus infection.

Objectives: To quantify the effect of HIV infection and HIV-suppressive therapy on interferon-alpha (IFN-alpha) production by human blood mononuclear cells; to compare, in parallel, effects on CD4+ T-cell numbers; and to ascertain the relationship of these interferon and CD4 parameters to resistance to opportunistic infections.

Design: Serial studies of 294 unselected patients with HIV infection during therapy, with outcomes analysis.

Methods: Determination of IFN generation by blood mononuclear cells via bioassay, and T-lymphocyte subset analysis via flow cytometry; serial studies of individual patients; linear regression and chi2 contingency table analysis.

Corticosteroids depress IFN-alpha-producing plasmacytoid dendritic cells in human blood.

Glucocorticoids are strongly immunosuppressive and are associated with reactivation of some intracellular infections. The plasmacytoid dendritic cell is a rare blood mononuclear cell detected through its production of IFN-alpha in response to herpes simplex virus and by surface immunophenotyping. We here report that steroid administration results in a decrease of IFN-alpha generation of approximately 25-fold, accompanied by reduction in circulating plasmacytoid dendritic cell numbers.

Prevalence of HTLV-I-associated T-cell lymphoma.

In order to assess the prevalence rate of HTLV-1-associated T-cell lymphomas and human retrovirus infection in general, approximately 21,000 individuals representing various patient populations, retroviral risk groups, and blood donors were examined for HTLV-I, HTLV-II, HIV-1, or HIV-2 infection using serologic and PCR assays. The prevalence rates among volunteer blood donors were 0.02% and 0% for HTLV and HIV, respectively.

The nature of the principal type 1 interferon-producing cells in human blood.

Interferons (IFNs) are the most important cytokines in antiviral immune responses. "Natural IFN-producing cells" (IPCs) in human blood express CD4 and major histocompatibility complex class II proteins, but have not been isolated and further characterized because of their rarity, rapid apoptosis, and lack of lineage markers. Purified IPCs are here shown to be the CD4(+)CD11c- type 2 dendritic cell precursors (pDC2s), which produce 200 to 1000 times more IFN than other blood cells after microbial challenge.

Absence of age-related increase in systolic blood pressure in ambulatory patients with HIV infection.

Background: Systolic blood pressure is well known to increase significantly with age and is strongly correlated with stroke and coronary artery disease. We and other investigators have reported a low prevalence of hypertension in subgroups of patients with HIV infection. In the present study, we examined an ambulatory population of patients with HIV infection to determine whether in the outpatient setting they may lack an age-related increase in systolic blood pressure.

AIDS-associated membranous nephropathy with advanced renal failure: response to prednisone.

We report the case of a patient with acquired immunodeficiency syndrome (AIDS) who developed nephrotic syndrome and progressive renal failure mimicking human immunodeficiency virus (HIV)-associated focal segmental glomerulosclerosis (FSGS) who required initiation of hemodialysis and was found on renal biopsy to have membranous nephropathy. Hepatitis B and C serologies were negative. Although she required hemodialysis, she was treated with prednisone and experienced a progressive decline in her serum creatinine from 10.

Early clinical markers and CD4 percentage in subjects with human immunodeficiency virus infection.

In a clinical trial involving asymptomatic, HIV-seropositive subjects treated with either the HIV-1 immunogen (an inactivated, gp120-depleted HIV-1 virus in incomplete Freund's adjuvant) or an adjuvant control, we examined the relationship between changes in the percentage of CD4 cells over time and early clinical markers of HIV disease progression. Subjects who had an early clinical event were more likely to have a greater decline in the percentage of CD4 cells than those subjects who did not have a clinical event (p = 0.054).

Rifabutin prophylaxis for Mycobacterium avium complex infection in patients with AIDS.

Rifabutin, a macrophage-penetrating lipophilic rifamycin, has a long half-life and activity in vitro against Mycobacterium avium complex (MAC). Preliminary studies of patients with AIDS and those with AIDS-related complex defined dose-limiting toxic effects (arthralgia/arthritis and uveitis) and suggested that rifabutin alone might reduce the incidence of MAC infections. Two double-blind, randomized, placebo-controlled trials involving 1,100 subjects confirmed the safety and efficacy of low doses of rifabutin; this therapy halved the rate of MAC bacteremia and significantly reduced symptoms associated with disseminated MAC infections.

Apoptotic depletion of CD4+ T cells in idiopathic CD4+ T lymphocytopenia.

Progressive loss of CD4+ T lymphocytes, accompanied by opportunistic infections characteristic of the acquired immune deficiency syndrome, ahs been reported in the absence of any known etiology. The pathogenesis of this syndrome, a subset of idiopathic CD4+ T lymphocytopenia (ICL), is uncertain. We report that CD4+ T cells from seven of eight ICL patients underwent accelerated programmed cell death, a process facilitated by T cell receptor cross-linking.