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Biomedical subjects

D A Cooper

Publications and source records attributed to D A Cooper.

At least 145 records · Page 8Linked to original sources
PubMed1996

Primary infection with zidovudine-resistant human immunodeficiency virus type 1 does not adversely affect outcome at 1 year. Sydney Primary HIV Infection Study Group.

Human immunodeficiency virus type 1 (HIV-1) variants with reduced in vitro sensitivity to zidovudine, conferred by specific mutations in the viral reverse transcriptase, emerge during prolonged therapy. Late-stage disease and declining CD4 cell count are associated with more rapid emergence of these resistant variants. Isolates of HIV-1 from seroconverters were screened for the zidovudine-resistance marker mutation at codon 215. HIV-1 with the altered genotype was detected in 5 (8.2%) of 61 patients soon after onset of symptomatic primary illness and from the sex partner of 1 patient. These transmitted resistant viruses were either replaced by strains susceptible to zidovudine within a few months of infection or persisted for up to 1 year in the absence of prolonged zidovudine therapy. The resistant genotype persisted in 3 of 5 seroconverters but in 2 patients had reverted to wild type at 48 and 52 weeks. Primary infection with zidovudine-resistant variants of HIV-1 was not associated with a more severe symptomatic primary illness or more rapid CD4 cell decline at 1 year after infection.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Nosocomial outbreak of tuberculosis in an outpatient HIV treatment room.

OBJECTIVE: To investigate a possible outbreak of tuberculosis in an outpatient HIV treatment facility in Sydney, Australia. DESIGN: Following the diagnosis of pulmonary tuberculosis in an attendee, a prospective screening program was instituted to investigate the potential outbreak. METHODS: Screening of 89 potentially exposed patients included chest radiographs (n = 89), and sputum examination (n = 37) over a period of 23 weeks. RESULTS: No cases of tuberculosis were detected by the screening program. However, three (3.4%) of this cohort developed pulmonary tuberculosis between 8 and 10 weeks following diagnosis of the index case. The incidence of active tuberculosis during the following-up period (median, 7.4 months) was 5.3 per 100 person years and represents the lower limit of possible tuberculous infection, as both latent infection, and undiagnosed tuberculosis among those who died could not be excluded. Mycobacterium tuberculosis strains isolated from the index case and three subsequent cases were found to be identical by DNA typing. CONCLUSION: Nosocomial transmission of tuberculosis in an outpatient treatment setting has been demonstrated. The risk of nosocomial transmission of tuberculosis is significant in institutions caring for HIV-infected patients even in countries with a low prevalence of tuberculosis infection, and highlights the importance of adherence to tuberculosis control guidelines.

AIDS-Related Opportunistic Infections↗
PubMed1996

A controlled trial of nevirapine plus zidovudine versus zidovudine alone in p24 antigenaemic HIV-infected patients. The Dutch-Italian-Australian Nevirapine Study Group.

OBJECTIVES: Nevirapine is a non-nucleoside reverse transcriptase inhibitor of HIV-1 which exhibits synergy in vitro with zidovudine (ZDV) and also is active against ZDV-resistant HIV. We evaluated the activity and safety of nevirapine in combination with ZDV in patients receiving long-term ZDV therapy. METHODS: We conducted a randomized, open-label, controlled 28-week study of nevirapine (200 mg daily for 2 weeks followed by 200 mg twice daily for 26 weeks) and continued ZDV (500-600 mg daily) versus continued ZDV alone in 49 HIV-1 p24 antigenaemic patients with CD4+ lymphocyte counts < 500 x 10(6)/l and who had been treated with ZDV for at least 6 months. RESULTS: Addition of nevirapine to ZDV resulted in a significant and rapid reduction in circulating RNA load (mean, 0.65), a mean CD4+ lymphocyte rise of 34 x 10(6)/l, a reduction in serum beta 2-microglobulin and a median fall in immune complex dissociated p24 antigen levels of 69%. These changes remained statistically significant for 4, 4, 12 and at least 28 weeks, respectively. The principal adverse event due to nevirapine was a hypersensitivity reaction comprising rash with or without fever and mucositis in eight (32%) patients, which was dose-limiting in seven patients. CONCLUSION: Nevirapine exhibits significant although transient anti-HIV activity in ZDV-pretreated patients but its use is frequently associated with a hypersensitivity reaction.

Adult↗
PubMed1996

Declining incidence and later occurrence of Kaposi's sarcoma among persons with AIDS in Australia: the Australian AIDS cohort.

OBJECTIVE: To explore trends in cumulative incidence of Kaposi's sarcoma (KS) and the level of immunodeficiency at KS diagnosis among people with AIDS in Australia. SETTING: Three hospital-based HIV units. STUDY POPULATION: Retrospective cohort of 2580 people diagnosed with AIDS over the period 1983-1994, representing 45% of cases of AIDS in Australia over this period. METHODS: Data including date and CD4 T-lymphocyte count of KS diagnosis was abstracted from medical records. KS occurring as both an initial and subsequent AIDS illness was included. Three subcohorts were defined based on interval of AIDS diagnosis: 1983-1987, 1988-1990, 1991-1994. Cumulative risk estimates for KS development were calculated by the Kaplan-Meier method. RESULTS: KS was diagnosed in 716 people (27.8%), and in 451 (63%) of these as the initial AIDS illness. There was a decline over time in cumulative incidence of KS (P < 0.0005); the cumulative risk of KS at 1 year after AIDS diagnosis declined from 35% for those diagnosed with AIDS during 1983-1987 to 25% for 1991-1994. This decline was not due to a decline in homosexual HIV exposure category, and was independent of CD4 T-lymphocyte count at AIDS. In multivariate analysis independent risk factors for KS development were year of AIDS diagnosis (P = 0.003), male homosexuality (P = 0.003), and CD4 T-lymphocyte count at AIDS greater than 150 x 10(6)/l (P = 0.02). A decline in median CD4 T-lymphocyte count at KS diagnosis was seen, from 67 x 10(6)/l in 1984-1987 to 20 x 10(6)/l for 1991-1994 (P < 0.0005). CONCLUSION: The decline in incidence and later occurrence of KS suggest several hypotheses, including declining prevalence or reduced virulence of a KS cofactor.

AIDS-Related Opportunistic Infections↗
PubMed1996

Bile acid malabsorption in HIV infected patients with chronic diarrhoea.

AIMS: To look for the presence of bile acid malabsorption in HIV infected patients with chronic diarrhoea and determine whether bile sequestering agents may have a role in palliating this common problem. METHODS: Nineteen HIV infected patients with chronic diarrhoea (duration > one month) poorly controlled on conventional treatment were investigated using the seven day retention of 75seleno-23-homocholic acid taurine (SeHCAT) as a measure of bile acid loss from the enterohepatic circulation. Patients with evidence of bile acid malabsorption were offered cholestyramine. RESULTS: Sixteen (84%) had evidence of bile acid malabsorption (< 15% retention at seven days). Ten of the 16 patients with bile acid malabsorption had terminal ileal biopsies-six had ileitis and four normal histology, suggesting that malabsorption is not always related to terminal ileitis. Thirteen patients with bile acid malabsorption have been treated with cholestyramine and 11 have reported a symptomatic response. CONCLUSIONS: Bile acid malabsorption can be demonstrated in some cases of HIV associated chronic diarrhoea and we suggest a therapeutic trial of a bile sequestering agent in patients whose symptoms are not well controlled using conventional anti-diarrhoeal agents.

Adult↗
PubMed1996

Genetic characterization of human immunodeficiency virus type 1 in blood and genital secretions: evidence for viral compartmentalization and selection during sexual transmission.

To explore the mechanism of sexual transmission of human immunodeficiency virus type 1 (HIV-1), we compared HIV-1 gp120 sequences in longitudinal samples from five acute seroconvertors with those from their corresponding sexual partners (transmitters). We used a quantitative homoduplex tracking assay to compare the overall genetic composition of HIV-1 quasispecies in each transmission pair and to track the transmitted viruses during the acute and asymptomatic stages of HIV-1 infection. In the chronically infected transmitters, HIV-1 variants in genital secretions differed from those in blood and variants in cells differed from those in cell-free plasma, indicating remarkable sequence heterogeneity in these subjects as well as compartmentalization of the virus in different bodily sites. Conversely, two of five seroconvertors had only a few related variants and three of five harbored only one viral population, indicating that in these subjects the transmitted viruses were typically homogeneous. Transmitted viruses were evident in the donor's seminal plasma (one of five cases) and even more so in their seminal cells (three of five cases), suggesting that both cell-associated and cell-free viruses can be transmitted. In every pair studied, the transmitted variant(s) represents only a minor population in the semen of the corresponding transmitter, thereby providing evidence that HIV-1 selection indeed occurs during sexual transmission.

Amino Acid Sequence↗
PubMed1995

A controlled trial of zidovudine in primary human immunodeficiency virus infection.

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, and oral hairy leukoplakia in two. Disease progression was significantly less frequent in the zidovudine group (one opportunistic infection) than in the placebo group (seven opportunistic infections; P = 0.009 by the log-rank test). After adjustment for the base-line CD4 cell count, the patients treated with zidovudine had an average gain of 8.9 CD4 cells per cubic millimeter per month (95 percent confidence interval, -1.4 to 19.1) during the first six months of the study, whereas those receiving placebo had an average loss of 12.0 CD4 cells per cubic millimeter per month (95 percent confidence interval, 5.2 to 18.7), for a between-group difference of 20.9 CD4 cells per cubic millimeter per month (95 percent confidence interval, 8.5 to 33.2; P = 0.001). CONCLUSIONS: Antiretroviral therapy administered during primary HIV infection may improve the subsequent clinical course and increase the CD4 cell count.

AIDS-Related Opportunistic Infections↗
PubMed1995

Productive in vitro infection of human umbilical vein endothelial cells and three colon carcinoma cell lines with HIV-1.

The objective of this study was to assess the ability of HIV-1 to establish an in vitro infection of primary human umbilical vein endothelial cells (HUVEC). The HUVEC and colon carcinoma cell lines were inoculated with different isolates of HIV-1 (HIV-1SF2, HIV-1Mck and HIV-1LAI) and productive viral infection was assessed by both the detection of p24 core antigen in the culture supernatants and the presence of specific spliced HIV mRNA. The infection which was detected in the inoculated HUVEC and all the colon carcinoma cell lines could not be blocked using an antibody targeted against the CD4 receptor. Furthermore, the HIV-inoculated HUVEC secreted elevated levels of IL-6 and this increase was found to be proportional to the size of the viral inoculum. No changes in the production of IL-1 beta, TNF-alpha, IFN-alpha and IFN-gamma were detected following HIV infection. The colon carcinoma cells, however, did not secrete increased levels of these cytokines following HIV-1 inoculation. These results confirm that non-CD4 expressing cells, such as endothelial cells and certain colon epithelial cells, serve as targets and reservoirs for HIV. Moreover, 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.

Base Sequence↗
PubMed1995

Estimations of real-world N2O emissions from road vehicles by means of measurements in a traffic tunnel.

Ambient air measurements of N2O, NOx, CO, and HC based on grab sampling were conducted in a major traffic tunnel in Sweden, that carries up to 4,000 vehicles per hour, in order to estimate real-world emissions of N2O for road traffic. Two different methods--relative and mass balance-were used to calculate a N2O emission factor for the mixed vehicle fleet, which gave an average emission factor, at average speeds of 30-70 km/h, of approximately 25 mg N2O/ km, with a range of 7-56 mg/km.

Air Pollutants↗
PubMed1995

Primary structure of the V3 region of gp120 from sequential human immunodeficiency virus type 1 isolates obtained from patients from the time of seroconversion.

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.

Acquired Immunodeficiency Syndrome↗
PubMed1995

The role of initial AIDS-defining illness in survival following AIDS.

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 > or = 100 x 10(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.

AIDS Dementia Complex↗