[Nosocomial HIV transmission at a Danish hospital department].
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Blood-Borne Pathogens↗
Biomedical subjects
T L Katzenstein
Publications and source records attributed to T L Katzenstein.
Nosocomial HIV-transmission in an outpatient clinic detected by epidemiological and phylogenetic analyses.
OBJECTIVE: To determine if a case of HIV-infection in a patient (GP) with common variable immunodeficiency, and with no known risk factors for HIV-infection, could be due to horizontal nosocomial transmission. METHODS: For determination of time of transmission stored serum-samples from GP were analysed for HIV RNA content. Patient records were used to identify patients, who had received intravenous therapy on the same day as GP. Samples from GP and these possible source patients were identified and phylogenetic analyses of the env, gag and RT-encoding region of pol were performed. Furthermore, routines in conjunction with intravenous therapy were examined. RESULTS: We identified a patient (FDL) harbouring virus almost indistinguishable from the virus isolated from GP. The pairwise nucleotide distance between the C2-V3-C3 region of the env and gag sequences from the two patients were 1.9 and 0.9% respectively. In addition, GP harboured HIV RNA with a foscarnet resistance mutation further lending support to virus from the foscarnet-treated FDL being the source of the infection. Interestingly, GP experienced increases in immunoglobulin production after contracting the HIV-infection, and decreases after antiretroviral-induced viral suppression. A clinical procedure which, under stressful conditions, could lead to breaches in infection control measures was identified. The source of the infection was most likely a contaminated multidose vial. CONCLUSION: Through epidemiological and phylogenetic analyses a case of horizontal nosocomial HIV-transmission was disclosed. Identification of multidose vials as possible vehicles for horizontal nosocomial transmission recently led to the recommendation of restriction of the use of multidose vials, a recommendation supported by the present study. The study underlies the importance of a constant survey of infection control precautions.
Ambulatory Care Facilities↗
Combination therapy containing ritonavir plus saquinavir has superior short-term antiretroviral efficacy: a randomized trial.
OBJECTIVES: To compare the efficacy and safety of indinavir 800 mg three times a day, ritonavir 600 mg twice a day, and a combination of ritonavir 400 mg twice a day and saquinavir 400 mg twice a day, when administered with two nucleoside analogues. DESIGN: A randomized, open-labelled, controlled trial. Two hundred and eighty-four patients started randomized treatment. The primary end-point was the proportion of patients with HIV RNA of 200 copies/ml or less (Roche Amplicor) and HIV RNA of 20 copies/ml or less (Roche ultradirect assay) at 6 months. Analysis was performed as intent-to-treat, and missing values were accounted for as failures. RESULTS: As of 1 May 1998, 269 patients should have completed 24 weeks of treatment. The proportion of patients with HIV RNA of 200 copies/ml or less was 71% (indinavir), 67% (ritonavir), and 82% (ritonavir + saquinavir), P = 0.07. In antiretroviral drug-naive patients (n = 119), the corresponding figures were 63, 57, and 89% (P < 0.01), whereas among drug-experienced patients (n = 165) 77, 74, and 77% had HIV RNA of 200 copies/ml or less (P = 0.90). The same pattern was observed in the ultradirect analysis. All three regimens were generally safe, but significantly more patients in the ritonavir group (37%) stopped treatment because of adverse drug reactions compared with the indinavir group (8%) and the ritonavir plus saquinavir group (16%) (P < 0.001). CONCLUSIONS: Treatment with saquinavir plus ritonavir in combination with two nucleoside analogues is generally safe, and has superior short-term antiviral efficacy compared with indinavir and ritonavir also combined with two nucleoside analogues in antiretroviral drug-naive patients. Further follow-up is needed to determine the durability of the viral response.
Adult↗
Changes in use of antiretroviral therapy in regions of Europe over time. EuroSIDA Study Group.
OBJECTIVES: To analyse use of antiretroviral therapy within Europe between 1994 and 1997. DESIGN: From September 1994, the EuroSIDA study (cohorts I-III) has prospectively followed unselected HIV-infected patients from 50 clinical centres in 17 European countries (total, 7230). METHODS: Patients under follow-up at half-year intervals from September 1994 (n=2871) to September 1997 (n=3682) were classified according to number of drugs currently used (none, one, two, three, four or more). Use of antiretroviral therapy was stratified by CD4 cell count (< 200 versus > or = 200 x 10(6)/l) and by region of Europe (south, central, or north). Frequency data were compared by chi2 test and logistic regression modelling. RESULTS: The proportion of patients on antiretroviral monotherapy diminished over time (1994, 42%; 1997, 3%), as did the proportion of patients without therapy (from 37 to 9%). Over time, the proportion of patients on triple (from 2 to 55%) and quadruple (from 0 to 9%) therapy increased, whereas use of dual therapy peaked in 1996 and subsequently fell. In the three regions of Europe, changes in use of antiretroviral therapy differed substantially. However, as of September 1997, only minor differences persisted. The proportion of patients on dual, triple, and quadruple therapy were as follow: south, 33, 52 and 5%, respectively; central, 23, 55 and 14%, respectively; north, 16, 59 and 10%, respectively. In September 1997, odds for use of three or more drugs including at least one protease inhibitor did not differ significantly between regions. CONCLUSIONS: Use of antiretroviral therapy in Europe has changed dramatically towards combination treatment in the last few years. Regional differences in use of antiretroviral therapy have decreased, and by September 1997 only minor differences remained. Antiretroviral therapy with three or more drugs and use of protease inhibitors has become more common in all regions of Europe.
Adult↗
The relative prognostic value of plasma HIV RNA levels and CD4 lymphocyte counts in advanced HIV infection.
OBJECTIVE: It has been suggested that the plasma HIV RNA level is a better predictor of AIDS and death than the CD4 lymphocyte count. We assessed whether the prognostic value of plasma virus levels was different according to the CD4 count. DESIGN: Prospective cohort study of HIV-infected patients followed for a median of 2.91 years (range, 0.02-4.54). SETTING: Department of Infectious Diseases at Rigshospitalet, Copenhagen, Denmark. PARTICIPANTS: A group of 255 HIV-infected individuals with an initial measurement of CD4 lymphocyte count and plasma HIV RNA. MAIN OUTCOME MEASURE: Survival time. RESULTS: The plasma HIV RNA (median 101410 copies/ml; range (range 200-7200000) and the CD4 lymphocyte count (median 250 cells x 10(6)/l; range 1-1247) were negatively correlated (Pearson r = -0.53; P < 0.00001). Of the 255 patients, 110 died during follow-up. Overall, a higher HIV RNA level was associated with increased risk of death, but the association was smaller in patients with lower CD4 lymphocyte counts (test for interaction P < 0.0001). In patients with CD4 count below 50 cells x 10(6)/l the association between HIV RNA and risk of death was not statistically significant (relative hazard per 10-fold higher HIV RNA level was 1.53; P = 0.11; adjusted for age and CD4 count) while that between the CD4 count and risk of death was highly significant (relative hazard per 50% lower CD4 count 1.38; P = 0.005; adjusted for age and HIV RNA level). CONCLUSIONS: Patients were relatively lightly treated with antiretroviral drugs both before and during this study. In this situation, it appears that the HIV RNA level has a relatively weak association with risk of death in patients with advanced HIV infection and that the CD4 lymphocyte count is probably more useful in assessing prognosis.
Adult↗
[Toxoplasma encephalitis with atypical manifestation and normal CT].
A case of cerebral toxoplasmosis in a HIV-positive man with unusual clinical manifestations and a normal computed tomographic (CT) scanning is presented. Even though most patients with cerebral toxoplasmosis have focal neurological deficits on physical examination, the patients can also present with more diffuse symptoms. Neither the lack of antitoxoplasma antibodies nor normal findings at CT scanning exclude the diagnosis of toxoplasma encephalitis. The sensitivity is higher with magnetic resonance than with CT scanning. We present a case story that demonstrate how delusive cerebral toxoplasmosis can be in HIV positive patients. It is recommended that the possibility of cerebral toxoplasmosis be considered in every HIV-positive patient with neurological symptoms and empirical therapy be instituted on wide indications.
AIDS-Related Opportunistic Infections↗
[HIV quantification--how and why].
The principals of four methods for measurements of viral load (HIV endpoint dilution, NASBA, bDNA and Amplicor PCR) are outlined. HIV quantification has increased our knowledge about the natural history of the HIV infection and the influences of exogenous factors on HIV replication. Furthermore measurements of HIV RNA early in the course of the infection have proven to be prognostic for the clinical outcome of the infection. Last but not least, HIV quantification has been shown to be a good marker for the efficacy of antiretroviral treatment and will hence be a valuable tool for the monitoring and management of anti-retroviral treatment.
DNA Probes↗
HIV-infected individuals with the CCR delta32/CCR5 genotype have lower HIV RNA levels and higher CD4 cell counts in the early years of the infection than do patients with the wild type. Copenhagen AIDS Cohort Study Group.
The relations among serum HIV RNA levels, CD4 cell counts, presence of the mutant CCR5-allele in heterozygous form, and clinical outcome was analyzed in 96 patients from the Copenhagen AIDS Cohort. In the early years of the infection, patients with the CCR5 delta32/CCR5 genotype had significantly lower HIV RNA levels (p = 0.005) and higher CD4 cell counts (p < 0.005) than did patients homozygous for the normal allele. The long-term clinical benefit of being heterozygous is small and cannot solely explain the large interpatient variation in progression rates. The beneficial effect of being heterozygous seems to be mediated by events in the early stages of the HIV infection.
CD4 Lymphocyte Count↗
Decreased short-term production of tumor necrosis factor-alpha and interleukin-1beta in human immunodeficiency virus-seropositive subjects.
Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) were measured by ELISA in 4.5-h, lipopolysaccharide-stimulated whole blood cultures of 347 human immunodeficiency virus type 1-infected patients and 107 healthy seronegative controls. The production of TNF-alpha was decreased in both AIDS and non-AIDS patients, whereas the production of IL-1beta was decreased in AIDS patients only. The production of TNF-alpha and IL-1beta was positively affected by the concentrations of CD14+ monocytes and CD8+ lymphocytes; however, in patients, the concentration of CD4+ lymphocytes and the presence of AIDS had a negative effect on cytokine production as determined by multiple linear regression analysis. It is concluded that low whole blood cytokine production is mainly caused by low numbers of cells, but a functional defect may also exist.
Acquired Immunodeficiency Syndrome↗
Pneumococcal vaccination of HIV-infected individuals: safety and efficacy.
The finding of an increased risk of HIV-infected individuals for contracting pneumococcal diseases has led to the recommendation of antipneumococcal vaccination of HIV-infected individuals. However, due to reports of increased viral replication following immune stimulation, the vaccination policy has been called into question. The literature on changes in viral load and CD4 T cells following vaccination and the studies on the clinical efficacy of antipneumococcal vaccination is evaluated. It is concluded that the prevailing data do not lend support to the concern of a lasting effect of vaccination on viral load. Data on the clinical efficacy and serological responses of vaccination are too scanty to support the recommendation of antipneumococcal vaccination to HIV-infected individuals. In addition to the issue of clinical efficacy; many question remain to be addressed; for example, the protective antibody level, optimal timing and vaccination regimen are yet to be determined.
Bacterial Vaccines↗
Longitudinal serum HIV RNA quantification: correlation to viral phenotype at seroconversion and clinical outcome.
OBJECTIVE: To investigate the longitudinal changes in serum HIV RNA, and to clarify whether the viral load early in infection has a predictive value for the clinical outcome; also, to correlate viral phenotype at seroconversion and changes in CD4 cell counts with viral burden. DESIGN: Twenty seroconverters with HIV isolates available at seroconversion had HIV RNA quantified by polymerase chain reaction (PCR) at seroconversion and thereafter every 6 months. Mean follow-up time was 65 months. Patients were classified according to viral phenotype at seroconversion, time to AIDS progression, serum viral load within the first year (less or more than 1.5 x 10(4) copies/ml). RESULTS: High viral load at seroconversion was followed by a significant decline within the first months (P < 0.0005). Decline to < 1.5 x 10(4) copies/ml was correlated with slower progression to AIDS (P < 0.05). A correlation between the rate of CD4 decline and the median viral load during the ensuing viral load plateau phase was also shown (P < 0.05). Subsequent to this phase the viral burden increased. Rapid progressors had higher viral load than slow- or non-progressors; this was particularly pronounced late in infection. Harbouring syncytium-inducing (SI) virus at seroconversion was associated with faster progression to AIDS than non-SI (NSI; P < 0.005). The increased in vitro replication rate of SI over NSI was not translated into significantly higher serum HIV RNA. CONCLUSION: Serum HIV RNA is high around the time of seroconversion. A significant decline within the first months hereafter is followed by a plateau phase, which in turn is followed by an increase in HIV RNA. HIV RNA early in infection has a predictive value for the clinical outcome. The increased virulence of SI over NSI virus did not translate into significantly higher HIV RNA values.
Acquired Immunodeficiency Syndrome↗
Assessments of plasma HIV RNA and CD4 cell counts after combined Pneumovax and tetanus toxoid vaccination: no detectable increase in HIV replication 6 weeks after immunization.
The influence of simultaneous vaccination with Pneumovax and tetanus toxoid on plasma human immunodeficiency virus (HIV) RNA and CD4 cell counts was assessed in patients with HIV infection. Six weeks after immunization plasma HIV RNA did not differ significantly from baseline values. A slight decline in CD4 cell counts after vaccination was detected. There was no correlation between the serological responses to pneumococcal vaccination and baseline CD4 cell counts, changes in HIV RNA or CD4 cell counts. In conclusion, immunization did not induce an increase in viral replication detectable 6 weeks after immunization.
Bacterial Vaccines↗
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↗
[Multiple liver abscesses caused by Fusobacterium necrophorum infection].
A case of multiple liver abscesses caused by Fusobacterium necrophorum infection is presented. In cases with fever of unknown origin and biochemical signs of derangement of hepatic function, it is recommended that an abdominal scan is performed. Before initiating antibiotic treatment relevant specimens should be collected. Finally we describe how the use of resin-containing blood culture medium enhance the possibility of bacterial detection in patients receiving antibiotics.
Diagnosis, Differential↗
[Legionnaires' disease--a multifaceted syndrome].
Multiorgan involvement is often seen in Legionella infections. We report two cases, with classical pneumonia complicated by facial paresis and severe kidney affection demanding haemodialysis. One patient had Legionella infection concomitantly with pneumococcal pneumonia. As the diagnosis often is not verified till weeks after onset of illness, it is concluded that the treatment should be started and maintained on clinical suspicion. Isolation of another respiratory pathogen does not exclude the possibility of Legionella infection.
Acute Kidney Injury↗