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J Gerstoft

Publications and source records attributed to J Gerstoft.

At least 109 records · Page 6Linked to original sources

[Survival of patients with zidovudine resistant HIV].

The survival of 35 patients with AIDS or advanced HIV infection on zidovudine treatment was related to the viral sensitivity to the drug and to the CD4+ cell count. Fourteen patients died, the survivors were followed up for an average of 804 days. In a univariate Cox model, survival was strongly related to log IC90 (p = 0.0003) and to the CD4+ count (p = 0.0002). In a bivariate model, log IC90 and the CD4+ count contributed to the prediction of survival (p = 0.12 and 0.06, respectively). Large studies of combination or alternation therapy with several anti-HIV-drugs should be given high priority.

Acquired Immunodeficiency Syndrome↗

Biological properties of HIV isolates in primary HIV infection: consequences for the subsequent course of infection.

OBJECTIVE: To characterize the biological properties of HIV isolates obtained at the time of primary infection, and relate this to the subsequent course of the infection. METHODS: Syncytium-inducing (SI) capacity, tropism for cell lines (MT4 and H9) and replication rate were determined in 49 HIV isolates obtained from 17 HIV seroconverters. Thirteen of the 17 patients had a symptomatic primary HIV infection. Correlation between biological phenotype and clinical progression was analysed. RESULTS: SI isolates were recovered in six patients from the first sample taken during primary infection, non-SI (NSI) isolates only were identified in 10 of the patients and isolation culture was negative in one patient. For all patients from whom SI virus was initially isolated, this phenotype persisted during the follow-up period (range, 17-219 weeks). The duration of fever during primary infection was longer for patients with SI isolates than for patients with NSI isolates (P = 0.05). Both types of isolates were associated with a significant fall in CD4 lymphocytes during follow-up (P < 0.05). Patients with SI isolates developed HIV-related immune deficiency more rapidly than patients with NSI isolates (P < 0.05). CONCLUSIONS: The biological phenotype of HIV strains isolated during the time of seroconversion may be an important determinant of the subsequent course of the infection.

CD4-Positive T-Lymphocytes↗

Development of resistance to zidovudine in HIV strains isolated from CD4+ lymphocytes and plasma during therapy.

An assay based on production of HIV antigen in cultures of CD4+ lymphocytes infected 'in vitro' with cell-free virus was established. Using this assay it was possible to isolate, propagate and reliably determine the zidovudine susceptibility of HIV isolates from all patients despite differences in cellular tropism and syncytium inducing capacity. Using this assay, differences in zidovudine susceptibility of 52 serial isolates obtained from 16 patients before and after initiation of therapy were examined. HIV with a 10- to 100-fold reduced susceptibility to zidovudine were isolated from 13 patients as early as 4 months after initiation of therapy. Number of months of zidovudine treatment was strongly associated with development of viral resistance, and high CD4 cell counts tended to be associated with lower rates of development of resistance. That patients can harbor mixtures of virus strains with different susceptibility to zidovudine was confirmed by the differences in susceptibility between isolates obtained simultaneously from CD4+ lymphocyte and plasma, and by the differences in susceptibility between virus strains isolated from clones of CD4+ lymphocytes.

Acquired Immunodeficiency Syndrome↗

Prognosis in glomerulonephritis. III. A longitudinal analysis of changes in serum creatinine and proteinuria during the course of disease: effect of immunosuppressive treatment. Report from Copenhagen Study Group of Renal Diseases.

A total of 395 consecutive patients with biopsy-proven glomerulonephritis were followed up for 14 years. At the time of entry to the study the patients were classified as having one of nine states of kidney disease according to serum creatinine levels and proteinuria. The transitions of the patients between the nine states were analysed. The influence of 14 independent variables including treatment with cytostatic drugs and prednisolone was estimated by the Cox proportional hazard model. Treatment with immunosuppressive drugs had an influence that emerged within the first month and continued for the next 2 months. Subsequent treatment with cytostatic drugs in combination with prednisolone delayed further improvement. Treatment with prednisolone or cytostatic drugs as single therapy for up to 6 months increased the risk of improvement of the disease, and had no significant effect on deterioration. The beneficial effect of the treatment persisted after withdrawal of the immunosuppressive drugs. The analysis revealed only a slight influence of the histological character of the glomerular changes. Post-streptococcal glomerulonephritis carried an increased tendency for improvement. Arterial hypertension affected the process in several states of kidney disease. Heavy proteinuria increased the risk of increasing serum creatinine levels.

Azathioprine↗

One-year follow-up on the safety and efficacy of isoprinosine for human immunodeficiency virus infection. Scandinavian Isoprinosine Study Group.

The safety and clinical impact of isoprinosine in HIV-infected individuals were assessed in a multicentre, randomized, double-blind, 24-week study phase, followed by an optional 24-week open treatment phase. The results of the double-blind phase have been reported. Of 866 HIV-seropositive patients randomized, 832 subjects were eligible for efficacy analysis. On completion of the double-blind phase, 596 patients started open treatment. All patients were evaluated with regard to progression to AIDS and/or death. Within 48 weeks, 10/412 (2.4%) patients assigned isoprinosine and 27/420 (6.4%) patients assigned placebo progressed to AIDS (P = 0.005). Intention-to-treat analysis showed identical results. Viewing the open treatment phase in isolation revealed no difference in progression rates between those treated and those not receiving the drug, perhaps reflecting the higher proportion of patients receiving zidovudine or PCP prophylaxis in the latter group. No severe adverse reactions or toxicities were observed. We conclude that HIV-seropositive patients without AIDS may be safely and effectively treated with isoprinosine.

Acquired Immunodeficiency Syndrome↗

Molluscum contagiosum in HIV-infected patients.

The clinical presentation of molluscum contagiosum is described in detail in 16 HIV-infected patients. Atypical facial lesions with either multiple small papules or giant nodular tumors prevailed in patients with AIDS or AIDS-related complex. A theoretical basis for the atypical localization of the disease is lacking.

AIDS-Related Complex↗

Trend towards decreased survival in patients infected with HIV resistant to zidovudine.

The survival of 35 patients with AIDS or advanced HIV infection on treatment with zidovudine was related to the viral sensitivity to the drug and to the CD4+ cell count. 14 patients died, the survivors were followed up for an average of 804 days. In a univariate Cox model, survival was strongly related to log IC90 (p = 0.0003) and to the CD4+ count (p = 0.0002). In a bivariate model, log IC90 and the CD4+ count contributed to the prediction of survival (p = 0.12 and 0.06, respectively). Large studies of combination or alternation therapy with several anti-HIV drugs should be given high priority.

Acquired Immunodeficiency Syndrome↗

Adjunctive corticosteroid therapy for Pneumocystis carinii pneumonia in AIDS: a randomized European multicenter open label study.

Fifty-nine human immunodeficiency virus type-1-infected patients with a microscopically proven first episode of moderate to severe Pneumocystis carinii pneumonia (PCP) were enrolled into a randomized European multicenter study. The effect of adjunctive corticosteroid (CS) therapy was assessed on (a) survival to discharge, (b) need for mechanical ventilation, and (c) survival at day 90. CS was given within 24 h of standard therapy as intravenous methylprednisolone 2 mg/kg body weight daily for 10 days. All patients received cotrimoxazole as standard treatment. Inclusion criteria were a PaO2 less than 9.0 kPa (67.5 mm Hg) and/or a PaCO2 less than 4.0 kPa (30.0 mm Hg) while breathing room air. During the acute episode of PCP, 9 (31%) of the 29 control patients died versus 3 (10%) of the 30 CS patients; p = 0.01. Mechanical ventilation was necessary in 15 patients; 12 (41%) in the control group and 3 (10%) in the CS group; p = 0.01. The 90-day survival was 69% in controls versus 87% in CS patients; p = 0.07. Based on these data we conclude that adjunctive CS therapy for moderate to severe PCP in AIDS patients reduces the acute mortality and the need for mechanical ventilation.

Acquired Immunodeficiency Syndrome↗

HIV-associated lymphoma: histopathology and association with Epstein-Barr virus genome related to clinical, immunological and prognostic features.

All 51 cases of HIV-related malignant lymphoma in Denmark diagnosed from 1983 to 1989 were reviewed. There were 12 Burkitt-type lymphomas, 30 immunoblast-rich lymphomas and 9 other lymphomas. Patients with immunoblast-rich lymphomas had significantly lower CD4 cell counts (median 60 vs. 188 x 10(6)/l, P less than 0.05), and more often a history of previous AIDS-defining illnesses (50% vs. 0%, P less than 0.005), compared with patients with Burkitt-type lymphomas. Epstein-Barr virus (EBV) DNA was demonstrated in 14 of 19 immunoblast-rich tumours, and in 2 of 7 Burkitt-type lymphomas (P = 0.10). Compared with EBV DNA-negative tumours EBV DNA-positive tumours were associated with lower CD4 cell counts (median 39 vs. 188 x 10(6)/l, P = 0.01). It is concluded that two main types of HIV-related malignant lymphoma exist. One is associated with severe immunosuppression, is often of immunoblast-rich morphology, and may be linked to EBV, whereas the other may occur in the absence of immunosuppression, is often of Burkitt-type morphology, and is probably not linked to EBV. In addition to these two main types, other non-Hodgkin lymphomas and Hodgkin's disease do occur.

Adult↗

Cellular profiles in bronchoalveolar lavage fluid of HIV-infected patients with pulmonary symptoms: relation to diagnosis and prognosis.

Bronchoalveolar lavage (BAL) cell differentials and T-lymphocyte subpopulations were analysed in 95 HIV-infected patients with pulmonary symptoms to determine whether the type of cellular inflammatory response could be useful in diagnosis or as a prognostic marker. Patients with Pneumocystis carinii pneumonia (PCP) had more BAL fluid lymphocytes, mainly comprising CD8+ cells, and patients with bacterial infection had more neutrophils than other patients. Neither of these changes were mirrored in peripheral blood. Seven patients who died after their acute episode of PCP had significantly higher BAL fluid neutrophils than 53 patients with PCP who survived (P = 0.002). There seems to be correlation between BAL fluid neutrophilia, PCP and concomitant bacterial infection since four out of seven patients with a fatal outcome had coinfection with bacteria, whereas only one patient with PCP and bacterial coinfection survived (P = 0.0007).

Acquired Immunodeficiency Syndrome↗

The prognosis in HIV-infected patients with pneumonia. Relation to microbiological diagnoses.

Ninety consecutive first-time fiberoptic bronchoscopies (FB) were performed on HIV-infected patients with pulmonary symptoms and radiographic evidence of active pneumonitis. Microbiological data were analysed for acute and long-term prognostic significance. 56/90 (63%) patients had one type of microbiological agent recovered from FB, 22/90 (24%) patients had more types recovered, and 12/90 (13%) patients had no types recovered. Nine patients (10%) died during the acute episode of pneumonia. A prognostic factor of a fatal outcome of the acute episode of pneumonia was concurrent multiple pulmonary infections (p = 0.002), mainly ascribed to patients with Pneumocystis carinii pneumonia (PCP) and concomitant bacterial pneumonia (p = 0.003). Specific microbiological findings at FB did not influence long-term survival of patients, and, when omitting patients who died during the acute episode of pneumonia (n = 9), no difference in survival was observed between patients with a) no agent, b) one type of agent or c) more types of agents recovered from FB. Only non-pulmonary parameters such as CD4-count, haemoglobin and age were found to be prognostic parameters. Thus, increased attention should be paid to co-pathogens presenting in HIV-infected patients with pulmonary infection and appropriate therapy instituted.

Acquired Immunodeficiency Syndrome↗

[HIV infected women in Copenhagen. Risk factors and sex behavior].

A total of 115 women were found to be HIV-antibody positive during the period January 1985 to September 1988 in the three large hospitals in Copenhagen. Thirty-five women (31%) had been infected heterosexually, 63 (55%) were intravenous drug addicts, 12 (10%) had been infected by transfusion and in five (4%) the mode of transmission was unknown. In 1988, 73% of the women who were found to be HIV-positive were infected heterosexually while only 14% were infected in this manner in 1985. Out of the heterosexually HIV-infected women, 25 (71%) had probably been infected by a man from a risk group while nine further women were infected by a known HIV-positive man with-out connection to any risk group. Eleven women (31%) stated that they practised "safe sex" prior to the HIV test while 22 (74%) did so after the positive HIV-test, which represents a considerable improvement. Out of the drug addicted women, six (10%) stated that they had always practiced "safe sex" prior to the test while 13 (28%) did so after the HIV-test. Approximately 1/3 of these women periodically shared syringes and needles with others. It is concluded that heterosexual contact among HIV-infected women in Copenhagen is a route of transmission of significance. Women infected heterosexually appear to alter their sexual behavior when they are made aware of the positive HIV-test.

Denmark↗

The efficacy of inosine pranobex in preventing the acquired immunodeficiency syndrome in patients with human immunodeficiency virus infection. The Scandinavian Isoprinosine Study Group.

We performed a randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of inosine pranobex (Isoprinosine) [corrected] in the treatment of patients with human immunodeficiency virus (HIV) infection but without manifest acquired immunodeficiency syndrome (AIDS). A total of 866 patients were enrolled in 21 centers in Denmark and Sweden. The patients were stratified in three groups according to their CD4+ cell count and randomly assigned to receive either inosine pranobex (1 g three times a day) (n = 429) or matching placebo (n = 437) for 24 weeks. Of the 831 patients who could be evaluated, AIDS developed in 17 in the placebo group as compared with 2 in the inosine pranobex group (P less than 0.001; odds ratio, 8.6 [95 percent confidence limits, 2.2 and 52.6]). There were no significant differences between the groups with respect to changes in CD4+ cell count or the development of other HIV-related conditions, with the exception of thrush, which developed in fewer patients in the inosine pranobex group (P = 0.05). No serious side effects were observed. We conclude that treatment with inosine pranobex delays progression to AIDS in patients with HIV infection. The duration of this beneficial effect, the optimal dose, and the mode of action of inosine pranobex remain to be clarified.

Acquired Immunodeficiency Syndrome↗

Opportunistic infections and malignancies in 231 Danish AIDS patients.

We analysed cumulative disease frequencies in the first 231 adult Danish AIDS patients with life tables. There was a certain hierarchical pattern in the occurrence of complicating diseases. Herpes zoster, Kaposi's sarcoma and Pneumocystis carinii pneumonia were early manifestations, whereas diseases caused by cytomegalovirus and atypical mycobacteria tended to occur later in the course of AIDS. Compared with all other AIDS patients, homosexual men were more likely to develop Kaposi's sarcoma, cytomegalovirus chorioretinitis and mucocutaneous herpes simplex virus infection. The proportion of patients who developed particular diseases changed with calendar time. Most striking was a three to fourfold decrease in diseases caused by cytomegalovirus. In conclusion, the study showed that disease frequencies in patients with AIDS may vary with the patients risk behaviour and duration of AIDS, and that the frequencies of particular diseases may change with calendar time.

Acquired Immunodeficiency Syndrome↗

Trends in survival of Danish AIDS patients from 1981 to 1989.

Length of survival was analysed in relation to year of diagnosis, AIDS-indicative disease, age, risk behaviour, zidovudine therapy, and CD4 cell count and serum immunoglobulin (Ig) levels at the time of diagnosis in a group of 231 consecutive adult Danish AIDS patients reported before 1 January 1988. The cumulative survival rate was 53% (95% confidence interval 47-59%) at 1 year, 29% (22-36%) at 2 years and 18% (10-26%) at 3 years. Length of survival increased significantly (P less than 0.001) over time for patients who were initially diagnosed with Pneumocystis carinii pneumonia (PCP), 17% (3-31%) at 2 years prior to 1986, 32% (16-49%) in 1986 and 52% (34-69%) in 1987, whereas survival remained stable for patients with other AIDS-indicative diseases. Survival was similar for patients who were diagnosed with Kaposi's sarcoma alone and PCP alone. Independent predictors of a shortened survival were a CD4 cell count less than 200 x 10(6)/l, a serum IgA level greater than 4 g/l, and an initial diagnosis with opportunistic infections other than PCP. In addition, the multivariate analysis suggested an improved survival in recent years for patients diagnosed with PCP, independent of other factors examined. We conclude that length of survival in AIDS patients is highly variable. Determinants of progression include CD4 cell count, serum IgA level, and presenting disease. Survival has increased markedly for patients with PCP and median survival now exceeds 24 months.

Acquired Immunodeficiency Syndrome↗

Effects of isoprinosine treatment of HIV-positive patients on blood mononuclear cell subsets, NK- and T-cell function, tumour necrosis factor, and interleukins 1, 2, and 6.

The immunomodulatory drug isoprinosine has been found to delay the occurrence of opportunistic infections in HIV-infected individuals. To elucidate the mechanism of action, eight HIV-positive, healthy patients were treated with isoprinosine, 3 g/day for 28 days; six patients received no treatment but were examined in parallel, and two patients were withdrawn. All patients had blood collected just before the start as well as on days 14 and 28 of isoprinosine treatment. Isoprinosine significantly enhanced the lymphoproliferative response after stimulation with phytohaemagglutinin (PHA) and purified derivative of tuberculin (PPD), while isoprinosine had no effect on the following immune parameters: the expression of surface markers on blood mononuclear cells including CD2, CD3, CD4, CD8, CD14, CD19, CD20, CD25, leu-8, and HLA-DR. Furthermore isoprinosine did not influence the ability of interleukin 2 (IL-2) to stimulate the proliferation of lymphocytes or the natural killer (NK) cell activity either unstimulated or stimulated in vitro with alpha interferon (IFN-alpha), IL-2, or indomethacin. Neither did isoprinosine affect the in vitro production of (IL-1) alpha or beta, IL-2, IL-6, or tumour necrosis factor (TNF).

Adult↗

Heterosexually acquired human immunodeficiency virus infection in women in Copenhagen: sexual behavior and other risk factors.

In order to describe the risk pattern including sexual behaviour among HIV-infected women in Copenhagen we studied the charts of all women tested seropositive between January 1985 and August 1988 in the three main hospitals handling HIV/AIDS. One hundred and fifteen women were positive for HIV antibodies: 35 (31%) were infected by heterosexual contact and 63 (55%) were intravenous drug users. Among the heterosexually transmitted cases 25 (71%) had intercourse with a man from a high risk group and nine women had intercourse with a known HIV antibody positive man without known risk factors. Use of condoms was claimed by 31% of the heterosexually-transmitted women before the HIV test, and by 74% (P = 0.002) after the test. In 1988 73% of the women tested HIV positive were infected by heterosexual contact, in 1985 only 14%. We conclude that among HIV infected women in Copenhagen heterosexual transmission is a problem. These women seem to change sexual behaviour when informed about HIV positivity.

Contraceptive Devices, Male↗