Biomedical subjects

J Spritzler

Publications and source records attributed to J Spritzler.

24 records · Page 2Linked to original sources

PubMed1999

Characterization of viral dynamics in human immunodeficiency virus type 1-infected patients treated with combination antiretroviral therapy: relationships to host factors, cellular restoration, and virologic end points.

Biphasic plasma viral decays were modeled in 48 patients treated with ritonavir, zidovudine, and lamivudine. Estimated first- and second-phase decay rates were d1 as 0.47/day and d2 as 0.04/day. Interpatient differences in both decay rates were significant. The d1 was directly correlated with baseline CD4+, CD4+CD28+, and CD8+CD28+ T lymphocyte counts (P<.05) and inversely correlated with baseline virus load (P=.044) and the magnitude of CD4+ and CD8+ T lymphocyte recovery (P<.01). The d2 was directly correlated with baseline percentage of CD8+ T lymphocytes (P=.023), the CD8+CD38+ cell number (P=.024), and the level of IgG that binds to human immunodeficiency virus (HIV) type 1 gp120 (P=.02). Viral decay rates were not predictive of treatment failure or durability of viral suppression. These exploratory findings are consistent with a model in which immunologic factors contribute to elimination of HIV-infected cells and suggest a dynamic interplay between regulation of HIV expression and lymphocyte activation and recovery.

ADP-ribosyl Cyclase↗

PubMed1999

Thalidomide for the treatment of esophageal aphthous ulcers in patients with human immunodeficiency virus infection. National Institute of Allergy and Infectious Disease AIDS Clinical Trials Group.

A multicenter, double-blind, randomized, placebo-controlled clinical trial was conducted to determine the safety and efficacy of thalidomide for treating esophageal aphthous ulceration in persons infected with human immunodeficiency virus (HIV). Twenty-four HIV-infected patients with biopsy-confirmed aphthous ulceration of the esophagus were randomly assigned to receive either oral thalidomide, 200 mg/day, or oral placebo daily for 4 weeks. Eight (73%) of 11 patients randomized to receive thalidomide had complete healing of aphthous ulcers at the 4-week endoscopic evaluation, compared with 3 (23%) of 13 placebo-randomized patients (odds ratio, 13.82; 95% confidence interval, 1.16-823.75; P=.033). Odynophagia and impaired eating ability caused by esophageal aphthae were improved markedly by thalidomide treatment. Adverse events among patients receiving thalidomide included somnolence (4 patients), rash (2 patients), and peripheral sensory neuropathy (3 patients). Thalidomide is effective in healing aphthous ulceration of the esophagus in patients infected with HIV.

Acquired Immunodeficiency Syndrome↗

PubMed1998

Immunologic responses associated with 12 weeks of combination antiretroviral therapy consisting of zidovudine, lamivudine, and ritonavir: results of AIDS Clinical Trials Group Protocol 315.

Human immunodeficiency virus (HIV)-1 infection is associated with progressive cell-mediated immune deficiency and abnormal immune activation. Although highly active antiretroviral therapy regimens can increase circulating CD4 T lymphocyte counts and decrease the risk of opportunistic complications, the effects of these treatments on immune reconstitution are not well understood. In 44 persons with moderately advanced HIV-1 infection, after 12 weeks of treatment with zidovudine, lamivudine, and ritonavir, plasma HIV-1 RNA fell a median of 2.3 logs (P < .0001). Circulating numbers of naive and memory CD4 T lymphocytes (P < .001), naive CD8 T lymphocytes (P < .004), and B lymphocytes (P < .001) increased. Improved lymphocyte proliferation to certain antigens and a tendency to improvement in delayed-type hypersensitivity also were seen. Dysregulated immune activation was partially corrected by this regimen; however, the perturbed expression of T cell receptor V regions in the CD4 and CD8 T lymphocyte populations was not significantly affected. Ongoing studies will ascertain if longer durations of virus suppression will permit more complete immune restoration.

Adult↗

PubMed1998

Measurement of induced cytokines in AIDS clinical trials using whole blood: a preliminary report. ACTG Inducible Cytokines Focus Group. AIDS Clinical Trials Group.

Measures of immune function have become increasingly important as endpoints in AIDS clinical trials, with respect to both modulation and reconstitution of immunity by experimental therapies. Measurement of immune function in this setting requires the development of robust analytic approaches suitable for the clinical laboratory. Experiments were performed to evaluate the suitability of using cultured heparinized ("whole") blood for induction of tumor necrosis factor alpha (TNF-alpha) and gamma interferon (IFN-gamma), two cytokines critical in AIDS pathogenesis. TNF-alpha expression ranged from 229 to 769 pg/ml in lipopolysaccharide (LPS)-stimulated cultures and was not detected in unstimulated cultures. IFN-gamma expression ranged from 0 to 112,000 pg/ml in phytohemagglutinin A (PHA)-stimulated cultures and from 0 to 789 pg/ml in antigen-stimulated cultures. The mean coefficient of variation observed in three weekly determinations was 0.47 for TNF-alpha and ranged from 0.12 to 1.73 for IFN-gamma. These values indicate that sample sizes of 8, 24, and 29 subjects would be sufficient to detect twofold changes in LPS-induced TNF-alpha and in PHA- and antigen-induced IFN-gamma respectively, if two baseline and two treatment determinations were obtained, and if the interpatient variability of changes in true levels from baseline to follow-up is negligible compared to the variability in the three weekly measurements. Measurement of LPS-induced TNF-alpha and mitogen- or antigen-induced IFN-gamma can be performed simply and reproducibly in human immunodeficiency virus-infected persons by the whole-blood culture method. Further studies are warranted to determine the effect of overnight shipping on assay reproducibility and to determine the extent to which responses can be reliably detected in subjects with low CD4 cell numbers.

Acquired Immunodeficiency Syndrome↗

PubMed1997

Thalidomide for the treatment of oral aphthous ulcers in patients with human immunodeficiency virus infection. National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group.

BACKGROUND: In patients with advanced human immunodeficiency virus (HIV) infection, aphthous ulceration of the mouth and oropharynx can become extensive and debilitating. Preliminary reports suggest that thalidomide may promote the healing of oral aphthous ulcers. METHODS: We performed a double-blind, randomized, placebo-controlled study of thalidomide as therapy for oral aphthous ulcers in HIV-infected patients. The patients received a four-week course of either 200 mg of thalidomide or placebo orally once per day. They were evaluated weekly for the condition of the ulcers, their quality of life, and evidence of toxicity. Assays were performed for plasma tumor necrosis factor alpha (TNF-alpha), soluble TNF-alpha receptors, and HIV RNA. RESULTS: Sixteen of 29 patients in the thalidomide group (55 percent) had complete healing of their aphthous ulcers after four weeks, as compared with only 2 of 28 patients in the placebo group (7 percent; odds ratio, 15; 95 percent confidence interval after adjustment for group sequential testing, 1.8 to 499; unadjusted P<0.001). Pain diminished and ability to eat improved with thalidomide treatment. The adverse effects noted with thalidomide included somnolence and rash (7 patients each), and 6 of the 29 patients discontinued treatment because of toxicity. Thalidomide treatment increased HIV RNA levels (median increase, 0.42 log10 copies per milliliter; increase with placebo, 0.05; P=0.04). With thalidomide treatment there were unexpected increases in the plasma concentrations of TNF-alpha and soluble TNF-alpha receptors. CONCLUSIONS: Thalidomide is an effective treatment for aphthous ulceration of the mouth and oropharynx in patients with HIV infection.

Acquired Immunodeficiency Syndrome↗

PubMed1996

Human immunodeficiency virus type 1 activation after blood transfusion.

BACKGROUND: Anemia and transfusion are predictors of disease progression in AIDS patients. This study was designed to examine the effects of blood transfusion on human immunodeficiency virus type 1 (HIV-1) expression. STUDY DESIGN AND METHODS: Assays of plasma viral load were performed before and after transfusion in nine HIV-1-infected patients who required blood transfusion for refractory anemia. RESULTS: There was a modest rise in plasma HIV-1 p24 antigen and plasma HIV-1 RNA beginning 1 to 2 weeks after the blood transfusion. The mean change in plasma p24 antigen for all patients was 9.3 +/- 5.1 (mean +/- SE) pg per mL at Week 2 after transfusion and 18 +/- 11.1 pg per mL at Week 4. Plasma HIV-1 RNA levels were unchanged immediately after transfusion and exceeded pretransfusion levels with a mean rise of 84 +/- 40 percent (SE) at Week 1, 70 +/- 27 percent at Week 2, and 67 +/- 38 percent at Week 4 (p = 0.006, exact permutation test). There was no increase in spontaneous or interleukin 2-induced lymphocyte proliferation or p24 antigen production by patients' lymphocytes that were examined immediately after blood transfusion. CONCLUSION: The transfusion of blood to persons with advanced HIV-1 infection modestly increases plasma levels of HIV-1. The activation of HIV-1 expression by transfusion may help to explain the accelerated course of HIV-1 disease in recipients of blood transfusion.

Anemia↗