Oona Dunlop

Prevalence of Hypertension in HIV-Positive Patients on Highly Active Retroviral Therapy (HAART) Compared with HAART-Naïve and HIV-Negative Controls: Results from a Norwegian Study of 721 Patients

Abstract Highly active antiretroviral therapy (HAART) may induce dyslipidemia, insulin resistance and body fat distribution similar to that seen in the metabolic syndrome. Hypertension is often a part of the classic metabolic syndrome, but few studies are published about hypertension in HIV-positive patients on HAART. The aim of this study was to compare the prevalence of hypertension in HIV-positive patients on HAART with that in HIV-positive/HAART-naïve patients and HIV-negative controls. The cross-sectional study included 283 unselected HIV-positive ambulatory patients, 219 who were on HAART and 64 who were HAART-naïve. Age- and gender-matched controls (n=438) were randomly selected from a simultaneous health survey of the general population. The prevalence of hypertension was 21% in patients on HAART, 13% in HAART-naïve patients (P=0.20), and 24% in HIV-negative controls (P=0.28). Among several possible risk factors for hypertension, only body mass index (BMI) was found to be a confounder. BMI was similar in HAART-treated and HAART-naïve patients but elevated in controls compared to HAART-treated patients. After adjustment for BMI, the prevalence of hypertension in HIV-negative controls was slightly lower than that in patients on HAART (P=0.29). The results demonstrated a prevalence of hypertension in patients on HAART similar to that in HIV-negative controls. The prevalence of hypertension was somewhat higher in patients on HAART compared to HAART-naïve patients, but the difference was not statistically significant. Considering the marked drop in mortality following antiretroviral therapy, we conclude that the possible influence of HAART on the prevalence of hypertension appears to be a minor problem.

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.

Age-related differences in symptoms, diagnosis and prognosis of bacteremia.

BackgroundElderly patients are at particular risk for bacteremia and sepsis. Atypicalpresentation may complicate the diagnosis. We studied patients withbacteremia, in order to assess possible age-related effects on the clinicalpresentation and course of severe infections.MethodsWe reviewed the records of 680 patients hospitalized between 1994 and 2004.All patients were diagnosed with bacteremia, 450 caused by Escherichiacoli and 230 by Streptococcus pneumoniae. Descriptiveanalyses were performed for three age groups (< 65 years,65–84 years, ≥ 85 years). In multivariate analyses age wasdichotomized (< 65, ≥ 65 years). Symptoms werecategorized into atypical or typical. Prognostic sensitivity of CRP and SIRSin identifying early organ failure was studied at different cut-off values.Outcome variables were organ failure within one day after admission andin-hospital mortality.ResultsThe higher age-groups more often presented atypical symptoms (p <0.001),decline in general health (p=0.029), and higher in-hospital mortality(p<0.001). The prognostic sensitivity of CRP did not differ between agegroups, but in those ≥ 85 years the prognostic sensitivity oftwo SIRS criteria was lower than that of three criteria. Classical symptomswere protective for early organ failure (OR 0.67, 95% CI 0.45-0.99), andrisk factors included; age ≥ 65 years (OR 1.65, 95% CI1.09-2.49), comorbid illnesses (OR 1.19, 95% CI 1.02-1.40 per diagnosis),decline in general health (OR 2.28, 95% CI 1.58-3.27), tachycardia (OR 1.50,95% CI 1.02-2.20), tachypnea (OR 3.86, 95% CI 2.64-5.66), and leukopenia (OR4.16, 95% CI 1.59-10.91). Fever was protective for in-hospital mortality (OR0.46, 95% CI 0.24-0.89), and risk factors included; age ≥ 65years (OR 15.02, 95% CI 3.68-61.29), ≥ 1 comorbid illness (OR2.61, 95% CI 1.11-6.14), bacteremia caused by S.pneumoniae (OR 2.79, 95% CI 1.43-5.46), leukopenia (OR 4.62,95% CI 1.88-11.37), and number of early failing organs (OR 3.06, 95% CI2.20-4.27 per failing organ).ConclusionsElderly patients with bacteremia more often present with atypical symptomsand reduced general health. The SIRS-criteria have poorer sensitivity foridentifying organ failure in these patients. Advanced age, comorbidity,decline in general health, pneumococcal infection, and absence of classicalsymptoms are markers of a poor prognosis.

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.

Five different tests of reaction time evaluated in HIV seropositive men

In an attempt to develop a short neuropsychological test battery five different tests of reaction time were assessed according to their ability to discriminate between HIV seropositive men and healthy controls. In all tests a patient group with clinical symptoms was slower than the control group. In the complex reaction time test, which has a large cognitive aspect, even a clinically “asymptomatic” group was slower than the control group. The movement test, a new test with a large motor component, identified most slow responders, defining approximately half of the patients with clinical symptoms and one third of the “asymptomatic” patients as such. A test battery consisting of three tests is suggested for serial assessment and screening.

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.

Calprotectin in Cerebrospinal Fluid of the HIV Infected: A Diagnostic Marker of Opportunistic Central Nervous System Infection?

The calprotectin level in the cerebrospinal fluid (CSF) of 15 HIV positive patients with symptoms from the central nervous system (CNS) was measured. All 5 patients with opportunistic infections had levels above the reference range and all 10 patients with HIV associated encephalopathy had levels within the reference range. Thus, the calprotectin level in CSF can be of diagnostic value in differentiating between HIV associated encephalopathy and opportunistic infection in the HIV positive patient with symptoms from the CNS.

Infectious encephalitis: a description of a Norwegian cohort.

Abstract Background: Prompt recognition and rapid initiation of adequate treatment are important for the outcome of encephalitis. Despite extensive diagnostic testing, the causative agent often remains unknown. The aim of this study was to investigate in how many patients the causative agent was found. Methods: Adults (≥ 18 y) diagnosed with ICD codes indicating encephalitis between 2000 and 2009 at Oslo University Hospital, Ullevål were retrospectively studied. Causative agents, clinical presentation, and demographic characteristics were registered. Those with an identified causative agent were compared to those for whom no agent could be found. Results: Of 136 registered patients, 70 were included in the study. Sixty-six did not fulfil our inclusion criteria or were diagnosed with other, more probable conditions. The causative agent was found in 30/70 (43%) patients; herpes simplex type 1 (10/70, 14%) and varicella zoster virus (6/70, 9%) were the most frequently identified agents. A bacterial cause was found in 6/70 (9%). Patients with an identified agent were more often men and had been ill longer than those for whom no agent could be found. Computed tomography and magnetic resonance imaging were more likely to be abnormal in those patients where a causative agent was found. Five of the 70 (7%) patients died of the infection. The identification rate did not increase during the study period. Conclusions: The diagnosis of encephalitis remains a challenge, and in many patients no causative agent is found. Clinically, immune-mediated encephalitis cannot be differentiated from infectious encephalitis and represents an important differential diagnosis. More knowledge is needed to improve our diagnostic skills.