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J Gerstoft

Publications and source records attributed to J Gerstoft.

At least 91 records · Page 5Linked to original sources

Quantification of HIV-1 RNA during antiretroviral therapy: association with viral phenotype and development of resistance.

The aim of this study was to analyse the interplay between the treatment responses, as assessed by serum HIV-1 RNA levels and CD4 cell counts, virological phenotype and the development of phenotypic and genotypic resistance. A total of 47 late-stage, HIV-1-infected, antiretroviral-naive patients treated with reverse transcriptase inhibitors (zidovudine or didanosine monotherapy or alternating zidovudine and didanosine) as part of a randomized study and remaining on treatment for a minimum of 1 year were included in the study. Baseline serum HIV-1 RNA levels did not differ between the patients harbouring syncytium-inducing (SI) virus and those harbouring non-syncytium-inducing (NSI) virus (P = 0.66), despite the fact that the group of patients with SI virus had a significantly lower median CD4 cell count (P < 0.00005) and a higher proportion of patients diagnosed with AIDS at study entry (11/19 versus 6/25) than did the group with NSI virus. The patients harbouring SI virus had significantly faster clinical progression than that of the patients harbouring NSI virus (P < 0.001). The patients wit

Anti-HIV Agents↗

Epidemiology of AIDS-related Kaposi's sarcoma in Europe over 10 years. AIDS in Europe Study Group.

OBJECTIVES: To determine the incidence and risk factors associated with Kaposi's sarcoma (KS) occurrence as an AIDS-defining condition or after the diagnosis of AIDS. DESIGN: Multicentre retrospective cohort study of AIDS in Europe database from 52 clinical centres in 17 European countries. METHODS: Patients' charts (n = 6546) were reviewed and collected in the database of the AIDS in Europe Study Group from 1979 to 1989. At the time of AIDS diagnosis 1394 patients had KS, whereas an additional 525 others developed KS after AIDS diagnosis. Univariate analysis and development of multivariate models determined factors associated with KS occurrence. RESULTS: Frequency of KS as an AIDS-defining condition significantly declined over time (P < 0.0001). In our cohort of patients, homo-/bisexual men from central Europe with CD4 cell counts > 150 x 10(6)/l were statistically more likely to develop KS at the time of AIDS diagnosis (P < 0.0001). For patients with an AIDS diagnosis other than KS, the probability of developing KS during the follow-up was 10 and 24% after 12 and 36 months, respectively. Variables significantly associated with a further KS development were transmission group, central European residence, previous herpes simplex infection other than ulcers, and low CD4 cells (< 150 x 10(6)/l). Previous zidovudine therapy had no influence on KS appearance. For patients who developed KS subsequent to AIDS diagnosis, there was no significant decline of the incidence over the 10-year time period. CONCLUSIONS: This large cohort study clearly shows that demographic data such as sex, transmission group and region of Europe have a major influence on KS development. It also suggests that KS as an AIDS-defining disease occurs earlier in the course of the chronic HIV infection than other opportunistic diseases. Reasons for geographical variations and its declining frequency as an initial AIDS diagnosis remain undetermined.

AIDS-Related Opportunistic Infections↗

Changing patterns of Kaposi's sarcoma in Danish acquired immunodeficiency syndrome patients with complete follow-up. The Danish Study Group for HIV Infection (DASHI).

The objective was to study changes in the occurrence of human immunodeficiency virus type 1-related Kaposi's sarcoma and the association with degree of immunodeficiency over time. Danish patients with acquired immunodeficiency syndrome (AIDS) diagnosed between 1979 and 1990 (n = 687) were followed clinically and with consecutive CD4 cell count measurement from time of AIDS-defining illness to date of death or censoring date, whichever came first. The proportion of homo-/bisexual men (n = 520) with Kaposi's sarcoma (n = 100) at AIDS diagnosis declined from 31% before 1985 to 13% in 1990, whereas the proportion of patients who died with Kaposi's sarcoma remained constant over time. Furthermore, the CD4 cell count at time of AIDS for patients diagnosed with Kaposi's sarcoma has declined in recent years. A CD4 cell count < 200 x 106/liter at the time of AIDS diagnosis predicted an increased risk of developing Kaposi's sarcoma after the AIDS diagnosis. Age, antiretroviral therapy, and primary Pneumocystis carinii pneumonia prophylaxis failed to influence the development of Kaposi's sarcoma. Thus, the occurrence of Kaposi's sarcoma remained constant over time but developed later in the course of AIDS and was associated with more severe immunosuppression in recent years.

Acquired Immunodeficiency Syndrome↗

[AIDS in Denmark. 1. Opportunistic infections and malignant diseases. Danish Study Group for HIV infection].

To examine the distribution of AIDS-defining illnesses among Danish AIDS patients, data on 687 AIDS patients diagnosed in the period from 1980 to 1990 (93% of all reported cases in the period) were collected. The most frequent AIDS-defining illness was Pneumocystis carinii pneumonia followed by candida oesophagitis and Kaposis sarcoma. The proportion of homo/bisexual men presenting with Kaposis sarcoma as the initial AIDS-defining illness declined over time. Patients with extrapulmonary tuberculosis had higher CD4 cell counts than patients presenting with other illnesses. Cytomegalovirus chorioretinitis and atypical mycobacteriosis were seen more frequently after the time of the AIDS diagnosis, and a low CD4 cell count at time of the AIDS diagnosis was a significant predictor for the development of these opportunistic infections during follow-up. Danish AIDS patients present with a wide spectrum of HIV-related illnesses, reflecting their exposure to opportunistic microorganisms and the degree of immune deficiency. The pattern of HIV-related illnesses is changing over time, and therefore continuous surveillance is needed to optimize therapeutic and prophylactic regimens.

AIDS-Related Opportunistic Infections↗

[AIDS in Denmark. 2. Survival after the diagnosis of AIDS. Danish Study Group for HIV infection].

The survival pattern was studied for 687 Danish AIDS patients (93% of notified cases in the study period) who were diagnosed with AIDS during the period from 1980 to 1990. The median survival was 17 months. Factors significantly associated with a shortened survival were transfusion-acquired HIV infection, age > 40 years, year of diagnosis before 1987, and the presence of either disseminated infection with Mycobacterium avium-complex, Cytomegalovirus chorioretinitis or malignant lymphoma at time of the AIDS diagnosis. There was also a significant association between survival and CD4 cell count at time of AIDS diagnosis. Patients who had CD4 cell counts above 200 x 10(6)/l had twice as long a survival as patients who had CD4 cell counts less than 50 x 10(6)/l. The prognosis of Danish AIDS patients remains poor. The most important determinant of survival time appears to be the degree of immune deficiency at time of diagnosis.

Acquired Immunodeficiency Syndrome↗

[Controlled, clinical trial of isoprinosine administration to HIV-infected patients. Results of a Danish/Swedish multicenter study. The Scandinavian Isoprinosine Study Group].

The safety and efficacy 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 separately. Of 866 HIV-seropositive individuals randomized, 832 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. Within 48 weeks, 10/412 patients (2.4%) assigned isoprinosine and 27/420 (6.4%) assigned placebo progressed to AIDS (p = 0.005; odds ratio: 2.8, 95% CI: 1.3-6.2). Intention-to-treat analysis showed identical results. No severe adverse reactions or toxicities were observed. We conclude that HIV-infected individuals without AIDS may be safely and effectively treated with isoprinosine.

Acquired Immunodeficiency Syndrome↗

[Antiviral treatment of HIV infection].

During the past six years Zidovudine has been the main antiviral drug directed against HIV. The indications for its use have slowly been extended and a reduced dose has limited the side effects. The therapeutical gain is a survival benefit of three to nine months. Other nucleoside analogues such as didanosin and zalcitabin have shown antiviral efficacy but the side effects are different from those of zidovudine. A number of drugs, including protease inhibitors and non-nucleoside reverse transcriptase inhibitors have shown antiviral effects, and are being tested in clinical trials. As no single drug appears to be able to control HIV for an extended period of time, combination regimens including multiple drugs, often administered early in the course of infection, seem to be a promising approaches, which are being pursued in a number of clinical trials.

Antiviral Agents↗

[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↗