Faculty Bibliography

PURPOSE/OBJECTIVE:This study was designed to measure response rates and survival in patients with acquired immunodeficiency syndrome (AIDS) and suspected Toxoplasma encephalitis treated empirically and in AIDS patients treated for biopsy-proven toxoplasmosis. PATIENTS AND METHODS/METHODS:AIDS patients identified at Bellevue Hospital between August 1985 and May 1986, who had abnormal computed tomographic scans of the brain and who received empiric treatment for toxoplasmosis, constitute the empirically treated cohort. A cohort with biopsy-proven toxoplasmosis was identified from Bellevue Hospital neuropathology records spanning 1981 through 1986. Patient records were reviewed with a standardized data form, and tomograms were evaluated by neuroradiologists unaware of the identity of the scans. Survival analysis was performed by the product limit method. RESULTS:Of 38 empirically treated patients, 26 responded clinically and radiographically within four weeks of initiation of therapy. Four of nine patients who underwent biopsy responded to treatment. There was no difference in these response rates (68% versus 44%, p = 0.24). The median survival of the empirically treated responders, from first diagnosis of AIDS to last follow-up, was 422 days. Among the 30 responders, five patients discontinued therapy and four of them had relapses. No relapses occurred in the 25 patients who continued full-dose therapy indefinitely (p = 0.0004). Sixteen of 30 patients (53%) receiving continuous therapy developed toxicity, which required a change in medication. There was no difference in the survival of patients who continued to receive sulfadiazine and pyrimethamine compared with those in whom clindamycin was substituted for sulfadiazine (median, 311 days versus 422 days, p = 0.25). CONCLUSION/CONCLUSIONS:A policy of empiric treatment of suspected Toxoplasma encephalitis is satisfactory, and patients who respond to such therapy and continue to take full therapeutic doses of anti-Toxoplasma drugs have relatively long survivals.

Liver biopsy specimens from 168 patients who underwent a total of 364 biopsies were examined. Of 83 patients receiving biopsies before methotrexate treatment, 14 had one or more risk factors predictive of liver abnormality but they had normal pretreatment biopsy specimens. Among 17 patients with abnormal biopsy specimens before methotrexate treatment, only 1 had an identifiable risk factor and 5 had abnormal results of liver function tests. The probability of a normal biopsy specimen after methotrexate treatment dropped below 50% at a cumulative methotrexate dose of 3115 mg for the 31 patients with biopsy specimens from before and after methotrexate treatment and 5776 mg for those who had biopsies only after methotrexate treatment; this difference was statistically significant and is thought to be related to the fact that the patients who had biopsies before and after methotrexate treatment had received most of their medication by the parenteral rather than the oral route. A significant association existed between biopsy grade after methotrexate treatment and obesity. Other risk factors were not correlated with biopsy grade. Blood chemistry tests were not predictive of histopathologic findings. Eight of 11 patients with fibrosis or cirrhosis showed meaningful improvement in liver histologic findings after methotrexate treatment had been withdrawn for 6 months or more; none had progression of abnormalities

Human immunodeficiency virus type 1 (HIV-1) core antigen was assayed in the plasma of children at risk for infection with HIV to determine its usefulness in the diagnosis of infection and to correlate it with the clinical stage of disease. Antigen was detected in the plasma of all children less than 15 months of age with acquired immunodeficiency syndrome (AIDS). Two thirds of children with AIDS-related illnesses and half of children with asymptomatic infection had antigen. Although 53% of plasma specimens originating from HIV-infected children younger than 6 months of age contained antigen, only 25% of plasma specimens from children younger than 6 months who had no symptoms and none of the 10 specimens from HIV-infected newborn infants contained antigen. Half of the specimens containing core antigen also contained anticore antibody. Quantitative mean antigen levels were more likely to be elevated in children with AIDS (516 pg/ml) than in children with AIDS-related illnesses (295 pg/ml) or in those who had no symptoms (70 pg/ml). Antigen levels tended to increase over time in children with advancing clinical illness, but they tended to decrease over time after a diagnosis of AIDS was made. Antigen was detected in the plasma of 4 of 14 children without symptoms who subsequently reverted to an HIV seronegative state. We conclude that the detection of core antigen occurs with high frequency in children, even young infants, with symptomatic HIV infection. Plasma core antigen was less frequent in children without symptoms and was not detected in 10 infected children when they were tested at birth

Eight patients being treated for tuberculosis prior to starting azidothymidine therapy (study group) were compared with 56 patients who were treated with azidothymidine but not with antimycobacterial agents (control group). Toxicity was assessed 12 wk after the initiation of treatment with azidothymidine. Study group patients were more likely than control subjects to be either black or Hispanic (75% versus 30%, p = 0.02). There were no other statistically significant demographic differences. Seven study patients, and 20 control subjects experienced a fall in leukocyte count greater than 10% (88% versus 36%, p = 0.01). Within each group, patients with acquired immune deficiency syndrome (AIDS) were more likely to experience this degree of hematologic toxicity than were patients with AIDS-related complex (p = 0.03). However, analysis of covariance showed no significant differences between the groups after 12 wk of azidothymidine with regard to mean leukocyte or platelet counts, hemoglobin levels, or values for tests of liver function. The groups were similar in transfusion requirements and frequency of changes in azidothymidine dosage. Although this study was limited in power by the number of patients and the nonrandomized, retrospective design, the data suggest that patients can tolerate concurrent therapy with azidothymidine and antimycobacterial agents without unacceptable toxicity

The prognosis of 111 children and adolescents (from 2.5 months to 19.5 years of age) infected with human immunodeficiency virus (HIV) was assessed by survival analysis based on risk factors and clinical status. Risk factors included: maternal HIV infection 93; transfusion 12; both maternal HIV infection and transfusion 2; sexual abuse 1; and intravenous drug use and/or sexual activity 3. Children with perinatal infection survived from 2.5 months to 10.25 years (median, 1.87 years) and had inapparent infection from 6 weeks to 7.3 years (median, 0.75 years). Children who acquired HIV infection via transfusion had inapparent infection from 4 months to 5.7 years (median, 3.6 years). Actuarial survival following infection was not significantly different from maternally and transfusion-acquired infection; however, survival from infection was longer for children infected by transfusion beyond 2 years of age (mean, 7.5 years) than for children infected perinatally (mean, 5.6 years). The case-fatality ratio was 32%, with 25% of subjects succumbing within 1 year of developing an HIV-associated illness. Opportunistic infection was the most common acquired immunodeficiency syndrome-defining illness and the cause of death in 22 of the 35 children who died. Pneumocystis carinii and fungal pneumonias had the worst prognosis. Cryptosporidiosis and other opportunistic infections had a better prognosis. Because of difficulties in case finding, diagnosis of infection and variable survival of HIV-infected children, arge longitudinal studies and pooling of data among centers will be necessary to have an accurate understanding of the prognosis of individual clinical syndromes.(ABSTRACT TRUNCATED AT 250 WORDS)

We examined the incidence of zoster in 346 children with underlying acute lymphoblastic leukemia who were immunized with live attenuated varicella vaccine while in remission. We also compared a subset of 84 of these children with a matched group of 84 children with leukemia who had had natural infection with varicella. Of the 346 vaccinated children, 5 (1.45 percent) became infected with zoster after 10,878 months of observation, for an incidence of 0.552 case per 100 person-years. Among the matched pairs of subjects, zoster occurred in 3 (3.6 percent) of the 84 vaccinated subjects during 2936 months of observation--an incidence of 1.23 cases per 100 person-years--and in 11 (13.1 percent) of the subjects with natural infection during 4245 months--an incidence of 3.11 cases of zoster per 100 person-years. Although the incidence of zoster was more than twice as high in the control children as in the vaccinated children (3.11 vs. 1.23 cases per 100 person-years), a Kaplan-Meier product-limit analysis revealed no significant differences in incidence between the two groups. Children from both groups in whom leukemia recurred were more likely to contract zoster than those who did not have a recurrence (7 of 35 vs. 7 of 133, P less than 0.025). Zoster was not a marker for impending relapse. No case of zoster was severe or disseminated. We conclude that the incidence of zoster following immunization with live attenuated varicella vaccine is no greater than that following natural varicella infection

Blood specimens from 165 intravenous drug users who were seropositive for the human immunodeficiency virus (HIV), from 158 seropositive homosexual men with lymphadenopathy, and from 77 patients with acquired immunodeficiency syndrome (AIDS) were assessed immunologically. Immunologic parameters were analyzed by the Guttman scalogram technique to determine if immunologic abnormalities occurred in a nonrandom pattern. The following four patterns emerged: (i) seropositivity for HIV with no immunologic abnormalities; (ii) seropositivity for HIV with a depressed T4/T8 cell ratio; (iii) seropositivity with a depressed T4/T8 cell ratio and T4-cell depletion; and (iv) seropositivity with a depressed T4/T8 cell ratio, T4-cell depletion, and lymphopenia. Ninety-two to 100% of subjects in each of the three groups of patients were found \'to scale\' because the abnormalities occurred in the cumulative, ordered fashion described. This nonrandom occurrence of abnormalities indicates an ordered progression of immunologic abnormalities in individuals infected with HIV, a finding useful in the staging of both symptomatic and asymptomatic HIV-seropositive subjects.

A group of 44 homosexual patients with immune thrombocytopenia and serologic evidence of infection with the human immunodeficiency virus (HIV) was observed for a total of 844 person-months. The risk of developing the acquired immunodeficiency syndrome (AIDS), an actuarial incidence of 36.5% in 37 months, was no different than that reported for seropositive homosexual men from New York who are nonthrombocytopenic and asymptomatic. A statistical analysis comparing the hazard function with a constant-risk model showed that the hazard of developing AIDS was not constant but increased with duration of seropositivity