Pulmonary intravascular lymphoma.

Intravascular lymphoma (IVL) is a rare form of non-Hodgkin lymphoma characterized by proliferation of malignant lymphoid cells limited to the lumen of small vessels. Clinical manifestations are nonspecific and result from vascular obliteration and hypoxia. The disease affects primarily the skin and central nervous system, often associated with rapid systemic dissemination and aggressive clinical course if appropriate therapy is not initiated early.

Pulmonary hyalinizing granuloma in HIV/AIDS.

A 55-year-old man who was recently diagnosed with HIV/AIDS developed multiple bilateral pulmonary nodules after starting highly active antiretroviral therapy. Workup confirmed the diagnosis of pulmonary hyalinizing granuloma. This is the first described case of pulmonary hyalinizing granuloma in HIV/AIDS, and may represent a rare form of immune reconstitution inflammatory syndrome.

Treatment of CMV retinitis with intravitral ganciclovir in the HAART era.

Objective: To describe the course and outcome of cytomegalovirus (CMV) retinitis among AIDS patients treated with intravitreal ganciclovir and systemic highly active antiretroviral therapy (HAART). The secondary objective was to compare the course of CMV retinitis between patients receiving HAART and those not receiving this treatment.

Design: A retrospective cohort design consisting of 21 eyes from 16 patients with AIDS and CMV retinitis consecutively enrolled between January 1996 and August 1999.

Pneumocystis jiroveci pneumonia prophylaxis is not required with a CD4+ T-cell count < 200 cells/microl when viral replication is suppressed.

Objective: To determine the safety of discontinuing Pneumocystis jiroveci pneumonia (PCP) prophylaxis, in patients on effective antiretroviral therapy with CD4+ T-cell counts that have plateaued at < 200 cells/microl.

Methods: We prospectively evaluated a cohort of HIV infected patients at a multidisciplinary HIV clinic with sustained HIV RNA levels < 50 copies/ml and CD4+ T-cell counts that have plateaued at < 200 cells/microl and who have discontinued PCP prophylaxis.

Results: Nineteen patients fulfilled the above criteria.

Delays in the administration of antibiotics are associated with mortality from adult acute bacterial meningitis.

Background: Bacterial meningitis continues to cause high mortality. Few studies address the possible association between this mortality and antibiotic administration delays.

Aim: To determine whether delays in antibiotic administration are associated with mortality from bacterial meningitis, and to identify inappropriate diagnostic-treatment sequences leading to such delays.

Update on HIV lipodystrophy.

When prescribed appropriately and taken adherently, antiretroviral therapy can consistently and durably suppress HIV replication, potentially translating into years of near normal health for HIV-infected persons. However, presently available antiretrovirals are associated with a cluster of physical and metabolic symptoms termed HIV lipodystrophy. This article reviews the state of knowledge about the pathogenesis and treatment of the various manifestations of these adverse effects.

Virological evaluation of the 'Ottawa case' indicates no evidence for HIV-1 superinfection.

An HIV-1 infected man who experienced rapid disease progression and poor response to therapy after starting a new sexual relationship with an infected partner is known as the 'Ottawa superinfection case'. Subsequent analysis of viral sequences of protease, reverse transcriptase, Gag p17, and Env V3 provided no evidence for the acquisition of genetically divergent viruses before disease progression or drug resistance during virological failure of combination therapy. Whether HIV-1 superinfection contributes to disease progression or the spread of drug-resistant HIV-1 remains unknown.

Normalization of natural killer cell function and phenotype with effective anti-HIV therapy and the role of IL-10.

Objectives: Natural killer (NK) cell function is likely to be important in controlling HIV infection and opportunistic pathogens. We therefore evaluated NK function and phenotype over the course of antiretroviral therapy (ART) and examined the potential mechanisms of altered NK activity in HIV infection.

Methods: We measured NK cell percentage, NK cytolytic activity (both by flow cytometry) and plasma IL-10 concentrations (by enzyme-linked immunosorbent assay) in 10 HIV-seropositive patients before and over one year of effective ART.

Comparative CD4 T-cell responses of reverse transcriptase inhibitor therapy with or without nelfinavir matched for viral exposure.

Background: Therapy of HIV infection with protease inhibitors (PIs) may be associated with improvements in CD4 T-cell number via a mechanism that is independent of effects on plasma viral load (VL).

Purpose: To compare CD4 responses of patients who receive reverse transcriptase inhibitor (RTI) therapies with or without a PI, matched for viral exposure.

Methods: Patient data were analyzed from two prospective randomized trials of antiviral therapy with or without nelfinavir.

HIV lipodystrophy: a review.

The dramatic clinical benefit of highly active antiretroviral therapy has been offset, to an extent, by the development of unforeseen long-term toxicities. Of these, the HIV lipodystrophy syndrome is most prominent. The array of related but possibly separate manifestations includes fat deposition and atrophy and metabolic complications such as hyperlipidemias and diabetes mellitus.

Pharmacology and clinical experience with saquinavir.

Saquinavir is a peptidomimetic inhibitor of HIV protease. Initially marketed as Invirasetrade mark, the effectiveness of saquinavir was greatly hindered by its nearly complete first pass metabolism by cytochrome P450 3A4. A new formulation, Fortovasetrade mark, appears to yield some six times the drug exposure and has been demonstrated to yield virological and immunological results similar to those of other protease inhibitors (PIs) when used in conjunction with two nucleoside reverse transcriptase inhibitors (nRTIs).

Effect of ketoconazole on ritonavir and saquinavir concentrations in plasma and cerebrospinal fluid from patients infected with human immunodeficiency virus.

Aim: Our aim was to evaluate the effect of ketoconazole on ritonavir and saquinavir plasma and cerebrospinal fluid (CSF) concentrations.

Methods: Twelve patients who were human immunodeficiency virus-seropositive and who were receiving 400 mg of ritonavir and 400 mg of saquinavir twice daily completed a nonfasted, two-period, two-group, longitudinal pharmacokinetic study. Blood samples were collected over the daytime 12-hour dosing interval of the protease inhibitors at baseline (period 1, day 0) and after 10 days of coadministration of 200 mg (n = 6) or 400 mg (n = 6) of ketoconazole once daily (period 2, day 10).

Progressive human immunodeficiency virus-specific immune recovery with prolonged viral suppression.

The degree of immune recovery achievable with anti-human immunodeficiency virus (HIV) therapy remains to be established. The effects of potent antiretroviral therapy, including ritonavir and saquinavir, on immune function were studied for a prolonged period in 41 patients. After 96 weeks, 88% of patients had plasma HIV RNA levels below the limit of quantitation.

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.

Dynamic correlation of apoptosis and immune activation during treatment of HIV infection.

T cells from HIV infected patients undergo spontaneous apoptosis at a faster rate than those from uninfected patients, are abnormally susceptible to activation induced cell death (AICD), and undergo increased apoptosis in response to Fas receptor ligation. These observations have led to the hypothesis CD4 T cell apoptosis may be a mechanism of CD4 T cell depletion and the pathogenesis of AIDS. Successful treatment of HIV infected patients is accompanied by quantitative and qualitative improvements in immune function reflecting at least partial reversibility of the underlying pathogenesis of HIV.

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.

Development of cervical fat pads following therapy with human immunodeficiency virus type 1 protease inhibitors.

Eight patients with infection due to human immunodeficiency virus type 1 developed fat pads at the bases of their necks a median of 22 weeks (range, 4-61 weeks) after initiation of protease inhibitor therapy. This finding was seen in association with the use of each of the available protease inhibitors. The patients had no other cushingoid features or histories of corticosteroid use, and all had normal 24-hour urine cortisol levels.

Randomised placebo-controlled trial of ritonavir in advanced HIV-1 disease. The Advanced HIV Disease Ritonavir Study Group.

Background: Ritonavir is a potent, orally bioavailable inhibitor of HIV-1 protease. We undertook an international, multicentre, randomised, double-blind, placebo-controlled trial of ritonavir in patients with HIV-1 infection and CD4-lymphocyte counts of 100 cells/microL or less, who had previously been treated with antiretroviral drugs.

Methods: 1090 patients were randomly assigned twice-daily liquid oral ritonavir 600 mg (n = 543) or placebo (n = 547) while continuing treatment with up to two licensed nucleoside agents.

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.