Production of CD8+ T cell nonlytic suppressive factors by CD28, CD38, and HLA-DR subpopulations.

HIV infection may be modified by CD8(+) T cells by the production of nonlytic antiviral factors. To determine subpopulations that mediate nonlytic, antiviral activity, we examined the production of beta chemokines and of CD8 antiviral factor (CAF) by different subsets, using CD8(+) cells derived from 24 HIV-1-infected and 25 uninfected individuals. Subjects with CD8(+) cell counts greater than 200/microl produced increased levels of MIP-1alpha by CD8(+)CD28(+), CD8(+)CD38(-), and CD8(+)HLA-DR(+) subsets as compared with uninfected controls.

Selection of lymphocyte gating protocol has an impact on the level of reliability of T-cell subsets in aging specimens.

Background: In the past decade, human immunodeficiency virus (HIV) lymphocyte immunophenotyping has evolved significantly. New fluorochromes, new multicolor reagents, enhanced instruments, and the capacity to provide absolute cell counts using the single-platform technique have all contributed to the reliability of T-cell subset measurements. In this study, four gating protocols were evaluated to select the most robust method for T-cell subset enumeration.

Interleukin-7 receptor expression on CD8(+) T cells is reduced in HIV infection and partially restored with effective antiretroviral therapy.

Interleukin (IL)-7 enhances CD8 T-cell proliferation and cytolytic activity. The expression of its receptor, CD127 (IL-7R alpha), may therefore be important in the immunopathogenesis of HIV disease. CD127 expression on CD8(+) T cells from HIV seronegative controls, untreated HIV-seropositive patients, and HIV-positive patients receiving antiretroviral therapy with sustained viral suppression was analyzed by flow cytometry in a cross-sectional study.

Induction of cell death in human immunodeficiency virus-infected macrophages and resting memory CD4 T cells by TRAIL/Apo2l.

Because the persistence of human immunodeficiency virus (HIV) in cellular reservoirs presents an obstacle to viral eradication, we evaluated whether tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L) induces apoptosis in such reservoirs. Lymphocytes and monocyte-derived macrophages (MDM) from uninfected donors do not die following treatment with either leucine zipper human TRAIL (LZhuTRAIL) or agonistic anti-TRAIL receptor antibodies. By contrast, such treatment induces apoptosis of in vitro HIV-infected MDM as well as peripheral blood lymphocytes from HIV-infected patients, including CD4(+) CD45RO(+) HLA-DR(-) lymphocytes.

Modulation of HIV transcription by CD8(+) cells is mediated via multiple elements of the long terminal repeat.

HIV replication and LTR-mediated gene expression can be modulated by CD8(+) cells in a cell type-dependent manner. We have previously shown that supernatant fluids of activated CD8(+) cells of HIV-infected individuals suppress long terminal repeat (LTR)-mediated transcription of HIV in T cells while enhancing transcription in monocytic cells. Here, we have examined the effect of culture of T cells and monocytic cells with CD8(+) supernatant fluids, and subsequent binding of transcription factors to the HIV-1 LTR.

Effect of cessation of highly active antiretroviral therapy during a discordant response: implications for scheduled therapeutic interruptions.

Although treatment with combination antiretroviral therapy leads to a reduction in the level of plasma viremia and an improvement in CD4 T cell count for most patients, for a minority of patients, an improvement in CD4 T cell count occurs despite the failure of treatment to suppress viral replication. Recent reports suggest that these discordant improvements in CD4 T cell count may last for months to years and are associated with improved clinical outcomes. In a retrospective observational study, we evaluated the effect of therapy cessation on 8 patients with discordant immunologic responses to therapy and found that improved CD4 T cell responses are dependent upon ongoing drug pressure.

Decreased HIV-associated T cell apoptosis by HIV protease inhibitors.

Antiretroviral treatment of patients infected with HIV results in improvements in CD4+ T cell number. Emerging evidence suggests that some of the improvements in CD4+ T cell number that occur in response to protease inhibitor (PI) therapy may not be accounted for solely by enhanced viral suppression, implying that PI may directly affect T cell survival. Since HIV T cell depletion is associated with enhanced apoptosis, we analyzed the effect of PIs on T cell apoptosis.

Cerebrospinal fluid HIV RNA and drug levels with combination ritonavir and saquinavir.

Unlabelled: Combination antiretroviral therapy with ritonavir and saquinavir has established potent and durable activity on plasma viremia. CNS HIV infection may be sequestered from drug therapy that does not penetrate the blood-brain barrier. Penetration of these protease inhibitors into the cerebrospinal fluid (CSF) and CSF HIV RNA levels on such therapy has not been well described.

Amplicor HIV monitor, NASBA HIV-1 RNA QT and quantiplex HIV RNA version 2.0 viral load assays: a Canadian evaluation.

Background: HIV-1 viral load quantitation is now recognized as a useful tool to monitor the efficiency of antiviral treatment and a powerful predictor of disease outcome. Three HIV-1 viral load quantitation methods have been currently available as commercial kits in Canada since 1996.

Objective: To evaluate the ability to quantify HIV-1 RNA in plasma of the Amplicor HIV Monitor Test, the NASBA HIV-1 RNA QT Assay and the Quantiplex HIV RNA Assay, version 2.

Effect of antiretroviral therapy and viral load on the perceived risk of HIV transmission and the need for safer sexual practices.

Background: Dramatic reductions in plasma HIV RNA levels are possible with current antiretroviral regimens; the effect of potent therapies and "undetectable" viral load on the perceived risk of HIV transmission and need for safer practices remains unknown.

Methods: A questionnaire was developed to examine perceptions of HIV transmission risk and need for safer practices with unprotected anal, vaginal, and oral sex and intravenous drug use with needle sharing for HIV-discordant couples in which the HIV-infected partner was receiving no therapy, was receiving reverse transcriptase inhibitor therapy, and protease inhibitor (PI)-based therapy with viral load "undetectable". This was applied anonymously to 147 unselected HIV-infected individuals attending a university-based HIV clinic.

Causes of death of HIV-infected persons in Ottawa, Ontario, 1984-1995.

Background: Acquired immunodeficiency syndrome (AIDS) has become a leading cause of death of young men in the United States. With the introduction of prophylaxes and antiretrovirals for opportunistic infection, there have been significant changes in the clinical history of human immunodeficiency virus (HIV) infection.

Objective: To determine the cause of death of the patients followed up by our clinic from 1984 to 1995.

Impact of Mycobacterium avium complex prophylaxis on the incidence of mycobacterial infections and transfusion-requiring anemia in an HIV-positive population.

Disseminated Mycobacterium avium complex (MAC) infection is common in persons with advanced HIV infection and can be prevented by prophylactic use of rifabutin; however, routine prophylaxis is costly and incompletely effective. Chronic anemia is a common manifestation of MAC infection. We conducted a retrospective population study of the annual incidence of MAC bacteremia and blood transfusion for anemia in a regional HIV-positive population before and after the introduction of rifabutin to determine the effect of MAC prophylaxis on the incidence of transfusion-requiring anemia.

A phase I evaluation of concomitant rifabutin and didanosine in symptomatic HIV-infected patients.

It has been suggested that didanosine (ddI) may undergo hepatic metabolism. Rifabutin is an inducer of drug metabolism. Fifteen human immunodeficiency virus-infected patients whose conditions were stabilized on twice-daily doses of ddI participated in a Phase I, open-label, pharmacokinetic and safety drug interaction study between rifabutin and ddI.

Cations in the didanosine tablet reduce ciprofloxacin bioavailability.

The effect of the magnesium-aluminum cations contained in didanosine chewable tablets on ciprofloxacin pharmacokinetics was evaluated in 12 healthy volunteers. The study was designed as a randomized, balanced, open, two-period, two-treatment crossover trial with a 7-day washout period between treatments. In one phase, subjects received a single 750 mg ciprofloxacin tablet alone.

Evaluation of the in vivo effect of naproxen on zidovudine pharmacokinetics in patients infected with human immunodeficiency virus.

Objective: To determine if therapeutic doses of naproxen affect the in vivo disposition of zidovudine.

Methods: This was designed as a randomized, two-period, two-treatment, crossover study. The patients were 12 men infected with human immunodeficiency virus who had acquired immunodeficiency syndrome (AIDS) or AIDS-related complex.

The effect of a protein meal on zidovudine pharmacokinetics in HIV-infected patients.

Eleven HIV-infected men participated in a randomized, two-treatment, two-period crossover study to determine the effect of a 25 g protein meal on zidovudine pharmacokinetics. On two separate occasions, 1 week apart, each patient received 200 mg zidovudine in a fasting state or immediately following the protein meal. A protein meal significantly decreased Cmax [532 (228 s.

The use of ozone-treated blood in the therapy of HIV infection and immune disease: a pilot study of safety and efficacy.

The use of ozone therapy is reported to be effective in a variety of viral illnesses, including HIV disease. We performed a phase I study of ozone blood treatments in 10 patients in whom no significant toxicity was observed. Three patients with moderate immunodeficiency showed improvement in surrogate markers of HIV-associated immune disease.