Anne K. Goplen

HIV dementia and apolipoprotein E

The effect of apolipoprotein E genotypes on the occurrence of HIV dementia and HIV encephalitis was studied in a sample of 132 AIDS patients in whom clinical data on dementia was available and full autopsy had been performed. There was no statistically significant correlation between risk of HIV dementia or HIV encephalitis in relation to apolipoprotein E genotypes, even after correction for length of survival with AIDS and antiretroviral treatment.

Changing incidence of HIV-induced brain lesions in Oslo, 1983-1994 : effects of zidovudine treatment

ObjectiveTo investigate the relation between HIV-induced brain lesions, zidovudine (ZDV) treatment and survival length in a well-defined population of HIV-positive patients. Methods and patientsUllevål Hospital has the responsibility for treating all AIDS patients from the city of Oslo except haemophiliac patients. The patient population in this autopsy study comprised all adult AIDS patients in Oslo who were treated at our hospital and died during 1983–1994 (n = 171). This represents 86% of all adult AIDS patients from Oslo who died during the same period. Full autopsy, including neuropathological examination of the brain and spinal cord, was performed on 128 (75%) of those who died. ResultsNo significant differences were found between autopsy and non-autopsy cases with regard to sex, age, risk groups, survival length or ZDV treatment. In the autopsy material, multinucleated giant cells (MGC) in brain tissue were found in 29 cases and diffuse damage of white matter in 52 cases. Analysis shows that ZDV (600 mg per day) reduced the incidence of these brain lesions, but only if continued until death. A second finding was an increased incidence of HIV-induced brain lesions for those with long-term survival. Together these observations may explain a substantial part of the time-trend in the incidence of MGC in Oslo. MGC were frequent (40%) during the first years of the epidemic, although survival length was short in this period. The incidence fell markedly around the time ZDV was introduced and later remained low in those using ZDV until death. The incidence of MGC has, however, increased during the later years, the new cases mainly occurring in patients who had discontinued ZDV use. ConclusionIf continued until death, ZDV can reduce the incidence of HIV-induced brain lesions in AIDS patients. When ZDV treatment is terminated a rapid increase occurs in the incidence of HIV encephalitis.

AIDS-related primary central nervous system lymphoma: a Norwegian national survey 1989–2003

BackgroundPrimary central nervous system lymphoma (PCNSL) is a frequent complication in acquired immunodeficiency syndrome (AIDS). The objective of this survey was to investigate incidence, clinical features, radiological findings, histologic diagnosis, treatment and outcome for all patients with histologically verified AIDS-related PCNSL diagnosed in Norway in 1989–2003.MethodsWe identified the patients by chart review of all cases recorded as PCNSL in The Norwegian Cancer Registry (by law recording all cases of cancer in Norway) and all cases recorded as AIDS-related PCNSL in the autopsy registry at a hospital having 67% autopsy rate and treating 59% of AIDS patients in Norway, from 1989 to 2003. Histologic material and radiological images were reviewed. We used person-time techniques to calculate incidence rates of PCNSL among AIDS patients based on recordings on AIDS at the Norwegian Surveillance System for Communicable Diseases (by law recording all cases of AIDS in Norway).ResultsTwenty-nine patients had histologically confirmed, newly diagnosed AIDS-related PCNSL in Norway from 1989–2003. Only 2 patients had this diagnosis established while alive. AIDS patients had 5.5% lifetime risk of PCNSL. Their absolute incidence rate of PCNSL per 100 person-years was 1.7 (95%CI: 1.1–2.4) and decreased during the consecutive 5-year periods from 3.6, to 2.5, and to 0.4 (p < 0.001). Median survival from initial symptom of PCNSL was 2.3 months, but one patient was still alive 4 years after completed radiotherapy.ConclusionThis is the first national survey to confirm decreasing incidence of AIDS-related PCNSL. Despite dismal survival in most patients, the possibility of long term survival should prompt more aggressive diagnostics in suspected PCNSL.

The impact of primary central nervous system lymphoma in AIDS patients : A population-based autopsy study from Oslo

This study comprises the 255 adult AIDS patients treated at Ullevål hospital 1983-1995. These patients, fulfilling the Centers of Disease Control (CDC) clinical criteria for AIDS, correspond to 91% of all adult AIDS cases in Oslo. By the end of the study period, 44 patients were alive and 211 had died. Full autopsy was performed on 153 (73%) of the deceased. Supplementary analyses were carried out on the 344 patients (225 deceased) fulfilling the U.S. definition of AIDS, which includes CD4 cell counts below 200 cells/mm3. In the autopsy group, histologically verified non-Hodgkin B-cell lymphoma was found in 29 cases (19%). Nineteen of these (12%) had primary central nervous system (PCNS) lymphoma. Survival curves indicate that PCNS lymphoma constitutes a small risk early in the AIDS stage, but it has a serious impact on long-term survival. For patients not contracting other fatal diseases, one fourth are estimated to die of PCNS lymphoma within about 3 years. Comparison of clinical diagnoses and autopsy results show that PCNS lymphoma has been difficult to separate from other CNS disorders, which probably has caused marked underestimation of the incidence in previous assessments. We conclude that PCNS lymphoma is a major threat to long-term survival in AIDS victims.

CMV Disease in AIDS Patients: Incidence of CMV Disease and Relation to Survival in a Population-based Study from Oslo

CMV disease is an important cause of morbidity and mortality in patients with AIDS. The purpose of this study was to investigate the incidence of CMV disease in a well-defined population of AIDS patients with a high rate of autopsy. No such study has previously been published from Scandinavia. A total of 248 patients who developed clinical AIDS in Oslo during the period 1 January, 1983 to 31 December, 1995 were included. Autopsy was performed in 152 of 213 deaths (71.3%). CMV disease was diagnosed in 95 patients. In the autopsy group, 73 patients (48%) had CMV disease, and in 52 of these patients CMV disease was first detected at autopsy. Retinitis was the most frequent manifestation, followed by adrenalitis, pneumonitis, encephalitis and gastrointestinal disease. No intravenous drug users (IVDUs) were diagnosed alive with CMV disease. All patients diagnosed with CMV disease before death had evidence of CMV disease at autopsy despite anti-CMV treatment. CMV disease was associated with increased risk of death. We conclude that CMV disease was frequent in patients with AIDS during the study period, was associated with increased mortality and was often diagnosed too late for the administration of appropriate therapy.

Early psychomotor slowing predicts the development of HIV dementia and autopsy‐verified HIV encephalitis

Objectives– To ask if slowed motor speed predicts later human immunodeficiency virus (HIV) dementia and HIV encephalitis. Methods– In 100 deceased acquired immunodeficiency syndrome (AIDS) patients prior results from repeated testing of the movement reaction time test were correlated with later clinical signs of HIV dementia and with neuropathological signs of HIV encephalitis. Autopsy was performed in 72 patients. Results– Movement reaction time 1–2 years prior to death, or at the time of clinical AIDS diagnosis predicted both development of HIV dementia (P < 0.05) and HIV encephalitis at autopsy (P < 0.01). Conclusion– Testing for early psychomotor slowing may be used to identify patients at risk of HIV dementia and HIV encephalitis.

CMV quantitative PCR in the diagnosis of CMV disease in patients with HIV-infection – a retrospective autopsy based study

BackgroundPatients with advanced HIV infection at the time of diagnosis and patients not responding to antiretroviral therapy are at risk of cytomegalovirus (CMV) disease. Earlier studies of patients with HIV infection have demonstrated that the diagnosis is often first made post-mortem. In recent years new molecular biological tests have become available for diagnosis of CMV disease. Although clinical evaluation of tests for diagnosis of CMV disease in HIV-infected individuals is suboptimal without autopsy, no results from such studies have been published. The aim of this study was to explore the diagnostic utility of CMV quantitative polymerase chain reaction (PCR) in plasma from HIV and CMV seropositive patients who died during the period 1991–2002 and in whom autopsy was performed.MethodsAutopsy was performed in all cases, as part of routine evaluation of HIV-infected cases followed at Ullevaal University Hospital. Of 125 patients included, 53 had CMV disease, 37 of whom were first diagnosed at autopsy. CMV disease was diagnosed either by ophthalmoscopic findings typical of CMV retinitis, biopsy or autopsy. One or two plasma samples taken prior to the first diagnosis of CMV disease (alive or at autopsy) or death without CMV disease were analysed by CMV quantitative PCR. Sensitivity, specificity, positive and negative predictive values were calculated for different CMV viral load cut-offs and according to detection of viraemia in one versus two samples.ResultsTwenty-seven of 53 patients with CMV disease (51%) and 10 of 72 patients without CMV disease (14%) had detectable viraemia in at least one sample. Sensitivity and negative predictive value (NPV) of the test, maximised with a cut-off at the tests limit of detection of CMV viraemia (400 copies/mL), were 47% and 70%, respectively. With cut-off at 10 000 copies/mL, specificity and positive predictive value (PPV) were 100%. With a requirement for CMV viraemia in two samples, specificity and PPV were 100% in patients with CMV viraemia above the limit of detection.ConclusionOur results indicate that quantitative CMV PCR is best used to rule in, rather than to rule out CMV disease in HIV-infected individuals at high risk.

Risk of toxoplasmic encephalitis in AIDS patients : Indications for prophylaxis

To establish the indications for primary prophylaxis against toxoplasmic encephalitis in the Norwegian HIV-positive population, we estimated the incidence of toxoplasmic encephalitis, and related the degree of immunodeficiency and the presence of IgG antibodies against Toxoplasma gondii (T. gondii) to the development of toxoplasmic encephalitis. This retrospective study includes all HIV-positive patients at our hospital from April 1983 to October 1994 (n = 705). A total of 238 patients had AIDS, which represents almost 90% of all AIDS patients in Oslo. Autopsy was done in over 70% of the patients who died during this period; 19 patients developed toxoplasmic encephalitis (8.0%). The median CD4 cell count was 75 x 10(6) cell/I (range 0-280) at the time of diagnosis of toxoplasmic encephalitis. T. gondii serology was studied in 698 (99.0%) of the patients, and was found positive for 17.8%. Of the patients with toxoplasmic encephalitis 18/19 had IgG antibodies against T. gondii and of the 40 AIDS patients who had anti-T. gondii IgG, 18 (45%) developed toxoplasmic encephalitis. We conclude that there is indication for prophylactic treatment of HIV positive patients who have IgG antibodies against T. gondii and who have fewer than 200 x 10(6) CD4 cells/I.

Dementia in AIDS patients in Oslo; the role of HIV encephalitis and CMV encephalitis.

In a well-defined population of adult AIDS patients from Oslo, we studied the correlation between clinical dementia and autopsy results. The study included 91% of all adult AIDS patients from Oslo who died between 1983 and 1996. The autopsy rate was 73% (167/229). Twenty-three percent of patients had definite dementia and 24% possible dementia. In more than half of the patients with definite dementia multinucleated giant cells were present in the brain tissue, suggesting that the dementia was due to HIV encephalitis. Diffuse damage of white matter also showed a significant association with clinical dementia. When found alone it tended to occur in symptomatic patients with a short survival time from onset of dementia until death. This indicates that diffuse damage of white matter may be an early stage of HIV encephalitis. CMV encephalitis was found in 28 cases (17%). Of these, 20 were classified as definitely or possibly demented. In 14 of these 20 cases we detected no multinucleated giant cells, suggesting that CMV caused or contributed to the dementia. Multiple logistic regression supported an association between CMV and conditions clinically classified as HIV dementia. We conclude that HIV encephalitis is the major cause of dementia in AIDS patients, but that CMV encephalitis as a cause of dementia has been underestimated.

High incidence and aggressive growth of non‐AIDS‐defining cancers among AIDS patients in Oslo

The spectrum of cancers advanced by AIDS is disputed. To supplement the register‐based investigations, we have studied the occurrence of non‐AIDS‐defining malignancies in a closely followed population of AIDS patients. The population comprises 255 patients fulfilling CDCs clinical AIDS definition, representing 91% of all adult AIDS patients from Oslo 1983–1995. Full autopsy was performed on 73% of the 211 fatal cases. Adding patients with CD4 cell counts below 200 cells/mm3 to match the US AIDS definition, the population increases to 344, including 225 deceased. The expected number of cancer cases was calculated from age‐ and sex‐specific cancer incidence rates for Oslo 1988–1992. The number of non‐AIDS‐defining cancers was six (clinical CDC criteria) or eight (US AIDS definition), compared to expected numbers of 0.54 and 1.0, respectively. At autopsy, four of eight cases showed extensive tumor dissemination with involvement of the heart. These observations suggest that (at least some) non‐AIDS‐defining cancers occur at increased rates and show aggressive growth pattern in AIDS.