Co-infection with hepatitis C in HIV-infected individuals is associated with 3- to 4-fold higher mortality among these patients' siblings, compared with siblings of mono-infected HIV-patients or population controls. This indicates that risk factors shared by family members partially account for the excess mortality of HIV/HCV-co-infected patients. We aimed to explore the causes of death contributing to the excess sibling mortality.
We retrieved causes of death from the Danish National Registry of Deaths and estimated cause-specific excess mortality rates (EMR) for siblings of HIV/HCV-co-infected individuals (n = 436) and siblings of HIV mono-infected individuals (n = 1837) compared with siblings of population controls (n = 281,221). Siblings of HIV/HCV-co-infected individuals had an all-cause EMR of 3.03 (95% CI, 1.56-4.50) per 1,000 person-years, compared with siblings of matched population controls. Substance abuse-related deaths contributed most to the elevated mortality among siblings [EMR = 2.25 (1.09-3.40)] followed by unnatural deaths [EMR = 0.67 (-0.05-1.39)]. No siblings of HIV/HCV co-infected patients had a liver-related diagnosis as underlying cause of death. Siblings of HIV-mono-infected individuals had an all-cause EMR of 0.60 (0.16-1.05) compared with siblings of controls. This modest excess mortality was due to deaths from an unknown cause [EMR = 0.28 (0.07-0.48)], deaths from substance abuse [EMR = 0.19 (-0.04-0.43)], and unnatural deaths [EMR = 0.18 (-0.06-0.42)].
HCV co-infection among HIV-infected patients was a strong marker for family-related mortality due to substance abuse and other unnatural causes. To reduce morbidity and mortality in HIV/HCV-co-infected patients, the advances in antiviral treatment of HCV should be accompanied by continued focus on interventions targeted at substance abuse-related risk factors.
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Cites: J Infect Dis. 2007 Jan 15;195(2):230-517191168
Cites: Am J Psychiatry. 2003 Apr;160(4):687-9512668357
Cites: Lancet. 2003 Nov 22;362(9397):1708-1314643119
Cites: Ugeskr Laeger. 1980 Jan 21;142(4):257-617355510
OBJECTIVES: To analyse the incidence, prevalence, and predictors for development of triple-class antiretroviral drug failure (TCF) in individuals infected with HIV. DESIGN: Population-based observational cohort study from 1 January 1995 to 31 December 2003, focusing on all 2722 recipients of highly active antiretroviral therapy (HAART) in Denmark. METHODS: We used person-years analysis, Kaplan-Meier survival curves and Cox regression analysis. TCF was defined as a minimum of 120 days with viral load > 1000 copies/ml on treatment with each of the three major drug classes. RESULTS: We observed 177 TCFs, yielding a crude incidence rate (IR) of 1.8 per 100 person-years [95% confidence interval (CI), 1.6-2.1]. Seven years after initiation of HAART, 17.2% (95% CI, 14.5-20.5) of antiretroviral (ART)-experienced patients, but only 7.0% (95% CI, 4.3-11.2) of ART-naive patients were estimated to have failed. After an initial rise, the IR from the third to the sixth year of HAART declined significantly for ART-experienced patients [incidence rate ratio (IRR), 0.80 per year (95% CI, 0.66-0.97); P = 0.022], and non-significantly for ART-naive patients [IRR, 0.79 per year (95% CI, 0.53-1.18); P = 0.255]. The IR for all patients being followed each year declined from 1997 to 2003 [IRR, 0.88 (95% CI, 0.81-0.96); P = 0.002]. The prevalence of TCF remained stable at less than 7% after 2000. Predictors of TCF at commencement of HAART were a CD4 cell count below 200, a previous AIDS-defining event, previous antiretroviral exposure, earlier year of HAART initiation, and young age. CONCLUSIONS: The risk of TCF is declining in Denmark and the prevalence remains stable.
The study objective was to describe demographic and clinical characteristics among HIV late presenters in a Danish university hospital.
Patients > 15 years of age were enrolled in this retrospective study. Data from the medical patient records were analyzed in accordance with the CD4 count at the time of HIV diagnosis.
Among 194 HIV patients (138 men and 56 women), 63 (33%) were diagnosed with a CD4 count below 200 cells/microlitre (late presenters). Heterosexuals constituted a larger proportion of patients in the late presenter group than did homosexual men (MSM) (p = 0.02), whereas a higher proportion of MSM than heterosexuals were diagnosed with HIV during primary infection (p
Highly active antiretroviral treatment is compromised by viral resistance mutations. Transmitted drug resistance (TDR) is therefore monitored closely, but follow-up studies of these patients are limited. Virus from 1405 individuals diagnosed with HIV-1 in Denmark between 2001 and 2009 was analyzed for TDR, and molecular-epidemiological links and progression of the infection were described based on data from standardized questionnaires, the prospective Danish HIV Cohort Study, and by phylogenetic analysis. Eighty-five individuals were found to be infected with virus harboring mutations resulting in a prevalence of 6.1%, with no changes over time. The main resistance mutations were nucleoside reverse transcriptase inhibitor (NRTI) mutation 215 revertants, as well as nonnucleoside reverse transcriptase inhibitor (NNRTI) mutation 103N/S and protease inhibitor (PI) mutations 90M and 85V. Phylogenetic analysis confirmed 12 transmission chains involving 37 TDR individuals. Of these 21 were also documented epidemiologically. The virus included in the transmission chain carried similar resistance mutations to the TDR index case, whereas controls chains from index cases without TDR were generally without resistance mutations. We observed no difference in progression of the infection between individuals infected with TDR and individuals infected with wild-type HIV-1. The prevalence of TDR is low in Denmark and transmission of dual-drug-resistant HIV-1 is infrequent. The TDR isolates were shown to originate from local patients failing therapy.
Brain abscess is a potentially fatal disease. This study assesses clinical aspects of brain abscess in a large hospital cohort.
Retrospective review of adult patients with pyogenic brain abscess at Rigshospitalet University Hospital, Denmark between 1994 and 2009. Prognostic factors associated with Glasgow Outcome Score (GOS) (death, severe disability or vegetative state) were assessed by logistic regression.
102 patients were included. On admission, only 20% of patients had a triad of fever, headache and nausea, 39% had no fever, 26% had normal CRP and 49% had no leucocytosis. Median delay from symptom onset to antibiotic treatment was 7 days (range 0-97 days). Source of infection was contiguous in 36%, haematogenous in 28%, surgical or traumatic in 9% and unknown in 27% of cases. Abscess location did not accurately predict the portal of entry. 67% were treated by burr hole aspiration, 20% by craniotomy and 13% by antibiotics alone. Median duration of antibiotic treatment was 62 days. No cases of recurrent abscess were observed. At discharge 23% had GOS =3. The 1-, 3- and 12-month mortality was 11%, 17% and 19%. Adverse outcome was associated with a low GCS at admission, presence of comorbidities and intraventricular rupture of abscess.
The clinical signs of brain abscess are unspecific, many patients presented without clear signs of infection and diagnosis and treatment were often delayed. Decreased GCS, presence of comorbidities and intraventricular rupture of brain abscess were associated with poor outcome. Brain abscess remains associated with considerable morbidity and mortality.
Cites: Medicine (Baltimore). 1986 Nov;65(6):415-313784900
BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) drug resistance is an important threat to the overall success of antiretroviral therapy (ART). Because of the limited sensitivity of commercial assays, transmitted drug resistance (TDR) may be underestimated; thus, the effect that TDR has on treatment outcome needs to be investigated. The objective of this study was to investigate the prevalence of TDR in HIV-infected patients and to evaluate the significance of TDR with respect to treatment outcome by analyzing plasma viral RNA and peripheral blood mononuclear cell proviral DNA for the presence of drug resistance mutations. METHODS: In a prospective study, we investigated the level of TDR in 61 patients by comparing the results of a sensitive multiplex-primer-extension approach (termed HIV-SNaPshot) that is capable of screening for 9 common nucleoside reverse-transcriptase inhibitor and nonnucleotide reverse-transcriptase inhibitor mutations with those of a commercial genotyping kit, ViroSeq (Abbott). RESULTS: Twenty-two patients were found to carry mutations. More patients with TDR were identified by the HIV-SNaPshot assay than by ViroSeq analysis (33% vs 13%; [P=.015). There was no significant difference in the time from initiation of ART to virological suppression between susceptible patients and those carrying low- or high-level resistance mutations (mean +/- standard deviation, 128 +/- 59.1 vs 164.9 +/- 120.4; P=.147). Furthermore, analyses of CD4 cell counts showed no significant difference between these 2 groups 1 year after the initiation of ART (mean, 184 vs 219 cells/microL; P=.267). CONCLUSION: We found the prevalence of TDR in recently infected ART-naive patients to be higher than that estimated by ViroSeq genotyping alone. Follow-up of patients after treatment initiation showed a trend toward there being more clinical complications for patients carrying TDR, although a significant effect on treatment outcome could not be demonstrated. Therefore, the clinical relevance of low-abundance resistant quasispecies in early infection is still in question.