Showing papers by "David A. Cooper published in 1995"
TL;DR: In this short-term study, ritonavir was well tolerated and had potent activity against HIV-1, but its clinical benefits remain to be established.
Abstract: Background Reverse-transcriptase inhibitors have only moderate clinical efficacy against the human immunodeficiency virus type 1 (HIV-1). Ritonavir is an inhibitor of HIV-1 protease with potent in vitro anti-HIV properties and good oral bioavailability. Methods We evaluated the antiviral activity and safety of ritonavir in a double-blind, randomized, placebo-controlled phase 1 and 2 study of 84 HIV-positive patients with 50 or more CD4+ lymphocytes per cubic millimeter. The patients were randomly assigned to one of four regimens of ritonavir therapy, or to placebo for four weeks and then (by random assignment) to one of the ritonavir regimens. Results During the first 4 weeks, increases in CD4+ lymphocyte counts and reductions in the log number of copies of HIV-1 RNA per milliliter of plasma were similar among the four dosage groups, but in the three lower-dosage groups there was a return to base-line levels by 16 weeks. After 32 weeks, in the seven patients in the highest-dosage group (600 mg of ritonavi...
543 citations
TL;DR: Antiretroviral therapy administered during primary HIV infection may improve the subsequent clinical course and increase the CD4 cell count.
Abstract: Background It is possible that antiretroviral treatment given early during primary infection with the human immunodeficiency virus (HIV) may reduce acute symptoms, help preserve immune function, and improve the long-term prognosis. Methods To assess the effect of early antiviral treatment, we conducted a multicenter, double-blind, placebo-controlled trial in which 77 patients with primary HIV infection were randomly assigned to receive either zidovudine (250 mg twice daily; n = 39) or placebo (n = 38) for six months. Results The mean time from the onset of symptoms until enrollment in the study was 25.1 days. Among the 43 patients who were still symptomatic at the time of enrollment, there was no appreciable difference in the mean (±SE) duration of the retroviral syndrome between the zidovudine group (15.0±4.1 days) and the placebo group (15.8±3.6 days). During a mean follow-up period of 15 months, minor opportunistic infections developed in eight patients: oral candidiasis in four, herpes zoster in two, ...
316 citations
TL;DR: Primary HIV infection is characterized by a depletion of CD4+ lymphocytes, especially of the CD45RA+ phenotype, and by an increase in CD8+ lymphocyte with an activated phenotype; the latter was also seen in patients with infectious mononucleosis but not in HIV non-converters or HIV-seronegative patients.
Abstract: Objective : To analyse changes in T-lymphocyte subsets in patients with primary HIV infection and to determine their specificity (and therefore their diagnostic utility) by comparing these changes with those seen in other acute illnesses as well as in HlV-uninfected patients. Methods : T-lymphocyte subsets were analysed by two- and three-colour flow cytometry, and compared between HIV seroconverters (n = 16), HIV-infected (n = 18) and uninfected (n = 33) controls, patients with infectious mononucleosis (n = 7), and patients suspected clinically of having primary HIV infection but who were later found to be uninfected (referred to as HIV non-converters ; n =17). Results : CD4+ lymphocyte counts were significantly lower in HIV seroconverters (mean, 444x10 6 /l) than in the HIV non-converters (793x10 6 /l ; P=0.003), HIV-seronegative controls (888x10 6 /l ; P 0.2). Conclusions : Primary HIV infection is characterized by a depletion of CD4+ lymphocytes, especially of the CD45RA+ phenotype, and by an increase in CD8+ lymphocytes with an activated phenotype ; the latter was also seen in patients with infectious mononucleosis but not in HIV non-converters or HlV-seronegative patients. Patients suspected clinically of having primary HIV infection but with normal T-cell phenotype are less likely to have primary HIV infection. These phenotypic changes, as well as an inverted CD4 : CDB ratio, can readily distinguish patients with primary HIV infection from HlV-uninfected patients except those with infectious mononucleosis. Therefore, T-cell-subset enumeration may be useful in the diagnosis of primary HIV infection.
75 citations
TL;DR: Initial AIDS-defining illness, as well as age at diagnosis, year of diagnosis, HIV exposure and CD4+ cell count at diagnosis), plays an important role in survival following AIDS in Australia.
Abstract: Objective : To examine the role of initial AIDS-defining illness in survival following AIDS and survival trends over time. Design : States and Territory Health Departments notified new diagnoses of AIDS to the National AIDS Registry. Information on vital status and date of last medical contact was sought annually. Methods : Survival was calculated for all adult and adolescent AIDS cases (n = 3204) in Australia diagnosed until 1 November 1991 and reported to the National AIDS Registry by 31 March 1994. The Cox regression method was used to identify independent predictors for survival. Results : Age <50 years, a CD4+ cell count ≥100x10 6 /l and an initial diagnosis of Kaposi's sarcoma were independently associated with longer survival (P<0.05). Acquisition of HIV through blood transfusion and the AIDS-defining illness non-Hodgkin's lymphoma were significantly associated with shorter survival. Survival improved substantially from 1986 to 1987, but did not improve further thereafter. A further study of initial AIDS-defining illnesses in a subgroup of individuals, i.e., men aged <50 years at diagnosis who acquired HIV infection through homosexual or bisexual contact and diagnosed after 1987, showed that Kaposi's sarcoma, Pneumocystis carinii pneumonia, oesophageal candidiasis and herpes simplex virus as initial AIDS-defining illnesses had a relatively better prognosis than other single illnesses. Furthermore, patients with multiple illnesses did not have a worse prognosis than patients with a single illness, provided all illnesses were those with a better prognosis. Conclusions : Initial AIDS-defining illness, as well as age at diagnosis, year of diagnosis, HIV exposure and CD4+ cell count at diagnosis, plays an important role in survival following AIDS in Australia.
57 citations
TL;DR: It is found that macrophages infected with macrophage tropic isolates of HIV-1 led to QUIN production while lymphocytes did not produce QUIN.
Abstract: We sought to determine whether the neurotoxin quinolinic acid (QUIN) was produced by macrophages or lymphocytes infected with isolates of HIV-1 with varying degrees of macrophage tropism derived fr...
53 citations
TL;DR: The results confirm that non‐CD4 expressing cells, such as endothelial cells and certain colon epithelial cells, serve as targets and reservoirs for HIV and the production of IL‐6 by HIV‐infected endothelial Cells may be a contributing factor to the aberrant immunoregulation associated with HIV infection in vivo.
Abstract: Productive in vitro infection of human umbilical vein endothelial cells and three colon carcinoma cell lines with HIV-1
35 citations
01 Jan 1995
31 citations
TL;DR: The study shows the importance of naturally occurring mutations in the V3 loop in controlling the biologic properties of HIV-1.
Abstract: V3 loop sequences were compared from 5 human immunodeficiency virus type 1 (HIV-1)-infected patients over time. Three patients remained asymptomatic and 2 became symptomatic with large decrease in CD4 cell counts. The patient isolates were previously evaluated for phenotypic and antigenic properties and had different sensitivities to serum neutralization and changes in phenotype. This study showed a number of amino acid changes for the 2 symptomatic patients, each of whom progressed to AIDS during the study. The only amino acid substitution consistently associated with reduced CD4 cell counts, cytopathic effect, and progression to AIDS was Arg at position 11. Specific amino acid changes could not be correlated with increasing serum neutralization resistance or cytotropism changes. Increased loop charge was associated with a switch from macrophage to T cell tropism and a decrease in the number of CD4 cells. The study shows the importance of naturally occurring mutations in the V3 loop in controlling the biologic properties of HIV-1.
10 citations
10 citations
TL;DR: To the Editor: Of the more than 40 million patients hospitalized in the United States yearly, approximately 2 million acquire nosocomial infections and patients with infections frequently remain in hospital for at least a year after diagnosis.
Abstract: To the Editor: Of the more than 40 million patients hospitalized in the United States yearly, approximately 2 million acquire nosocomial infections.1 Patients with infections frequently remain in t...
9 citations
TL;DR: Kit‐based methods of measuring HIV‐1 virus load are on the horizon and are likely to improve the quality and efficiency of existing and new approaches to HIV diagnosis and treatment.
Abstract: Kit‐based methods of measuring HIV‐1 virus load are on the horizon
TL;DR: New research is reaping benefits for developing countries by using nanofiltration membranes for the recovery of phosphorous with a second type of technology, called a “silicon-like substance” by scientists at the University of California, Berkeley.
Abstract: New research is reaping benefits for developing countries