Attempts to isolate human immunodeficiency virus (HIV) from blood plasma using inoculation of pellets from ultracentrifuged samples into cultures of peripheral blood mononuclear cells (PBMC) resulted in a high overall recovery rate (75%) of the virus from 76 patients in various stages of HIV infection. The recovery rate was dependent on the stage of infection; in patients with acquired immunodeficiency syndrome (AIDS) it was 100%, in AIDS-related complex (ARC) 86%, in persistent generalized lymphadenopathy (PGL) 64%, and in asymptomatic patients 54%. The HIV isolation rates compared favorably with those obtained after cocultivation of patient and target PBMC (overall recovery rate 67%). HIV was isolated from plasma but not from PBMC in 8 cases, whereas the reverse was true in 3 of 71 simultaneously tested cases. Isolation from plasma was found to be superior to detection of serum p24 antigen for the demonstration of HIV (positivity rates 75% and 30%, respectively). The time to appearance of p24 antigen in cultures inoculated with HIV-containing plasma samples was inversely related to the presence of detectable p24 antigen in serum. There was a significantly shorter time to culture positivity of plasma samples from AIDS and ARC patients than from PGL and asymptomatic patients. These results suggested that there is a progressive increase in the concentrations of infectious HIV in plasma from the asymptomatic to the AIDS stage. HIV isolation from plasma samples is a reliable means of demonstrating HIV viremia and has obvious advantages over the more commonly used cocultivation procedures. The frequent occurrence of cell-free, infectious HIV in plasma suggests that the majority of HIV-infected patients have a relative lack of functional neutralizing antibodies against the virus, at least during the late stages of disease.
To investigate the pharmacokinetics and effects of intravenous foscarnet, 13 relatively healthy male patients with human immunodeficiency virus infection and a mean CD4+ lymphocyte value of 0.45 x 10-9 cells per liter were given a continuous intravenous infusion of foscarnet (0.14 to 0.19 mg/kg per min) for 8 to 21 days. Blood and urine samples were taken during and after drug administration to monitor foscarnet concentrations. Lumbar puncture was performed during the infusion in five patients. The concentrations in plasma showed large variations both within and between patients. The disposition of foscarnet could be explained by a triexponential equation (tl2,1, 0.40 to 2.52 h; t112X, 3.20 to 16.7 h; tl/2J3, 36 to 196 h). Renal clearance accounted for most of the plasma clearance, the dilerence probably reflecting the passage of foscarnet into bone. Up to 20% of the cumulative dose may have been deposited in bone 7 days postinfusion. Foscarnet was distributed to the cerebrospinal fluid in a concentration varying from 13 to 68% of the simultaneous concentration in plasma. Polyuria and polydipsia were recorded in all patients. There appears to be an association between the degree of malaise, including symptoms such as nausea, vomiting, fatigue, and headache, and concentrations in plasma above 350 ,umol/liter.
In recent years evidence has emerged that most post-transfusion hepatitis is caused by one or more previously unknown agents named non-A, non-B. A prospective investigation was made of 74 patients who underwent open-heart surgery. Only volunteer blood was used for transfusions. Transfusion-associated hepatitis appeared in 15 (20%) of the patients 4-12 weeks after the operation. In no case was the hepatitis found to be caused by hepatitis B, A or Epstein-Barr virus. One patient had a cytomegalovirus infection; the other 14 cases (19%) were classified by definition as non-A, non-B hepatitis. Although most of the patients were asymptomatic and all were anicteric, the course of the hepatitis was protracted in many cases. Thus, 6/12 observed patients still had pathologic transferase values more than a year after the onset of hepatitis. Liver biopsy was performed in 3 cases and showed histologic signs of chronic active hepatitis in all of them.
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