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ABSTRACT: Early identification of persons with undiagnosed HIV infection is an important health care issue. We examined associations between diseases diagnosed in hospitals and risk of subsequent HIV diagnosis.
In this population-based case control study, cases were persons with incident HIV infection diagnosed in Denmark between 1 January 1995 and 1 June 2008. Risk-set sampling was used to identify 19 age- and gender-matched population controls for each HIV case, using the HIV diagnosis date as the index date for both cases and controls. Prior hospital diagnoses obtained from Danish medical databases were first categorized into 22 major disease categories (excluding AIDS-defining diseases except tuberculosis) and then subdivided into 161 subcategories, allowing us to examine specific diseases as potential HIV indicators by conditional logistic regression.
The study included 2,036 HIV cases and 35,718 controls. Persons with the following disease categories had a high risk of HIV diagnosis during the subsequent 5-year period: sexually transmitted infections and viral hepatitis (adjusted odds ratio [aOR] = 12.3, 95% CI: 9.60-15.7), hematological diseases (aOR = 4.28, 3.13-5.85), lower respiratory tract infections (aOR = 3.98, 3.14-5.04)), CNS infections (aOR = 3.44, 1.74-6.80), skin infections (aOR = 3.05, 2.47-3.75), other infections (aOR = 4.64, 3.89-5.54), and substance abuse (aOR = 2.60, 2.06-3.29). Several specific diseases were associated with aORs >20 including syphilis, hepatitis A, non "A" viral hepatitis, herpes zoster, candida infection, endocarditis, thrombocytopenia, and opioid abuse.
Targeted testing for HIV in patients diagnosed with diseases associated with HIV may lead to earlier treatment and thereby reduced morbidity, mortality and HIV transmission.
PLoS ONE 01/2012; 7(3):e32538. · 4.09 Impact Factor
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ABSTRACT: We aimed to estimate the impact of comorbidity acquired before HIV diagnosis on mortality in individuals infected with HIV.
This cohort study compared 2 different cohorts. The prospective population-based nationwide observational Danish HIV Cohort Study was used to compare all adults diagnosed with HIV in Denmark from 1997 with a matched general population cohort. Comorbidity history was ascertained from the Danish National Patient Registry and vital statistics obtained from the Danish Civil Registration System. Cox regression was used to estimate the impact of Charlson comorbidity index (CCI) and hepatitis C virus coinfection on mortality, and population attributable risk was used to assess the proportional impact of comorbidity on mortality.
CCI comorbidity was present before HIV diagnosis in 11.3% of 1638 persons with HIV, and in 8.0% of 156,506 persons in the general population. The risk for death in patients with HIV with at least 1 CCI point was 1.84 times higher than in those with no CCI points (adjusted mortality rate ratio, 95% confidence interval: 1.32 to 2.57). The annual risk of dying for patients with HIV vs general population with 0, 1, 2, and 3+ CCI points was 1.70% (1.44 to 2.00) vs 0.27% (0.26 to 0.28), 4.37% (3.01 to 6.32) vs 1.36% (1.26 to 1.47), 8.06% (4.94 to 13.16) vs 2.44% (2.22 to 2.68), and 10.15% (5.08 to 20.30) vs 5.84% (5.19 to 6.58), respectively. Comorbidity acquired before HIV, hepatitis C virus coinfection, and background mortality accounted for 45% of total mortality in the population infected with HIV.
Almost half of deaths in persons diagnosed with HIV in a health care setting with free access to highly active antiretroviral therapy stemmed from factors unrelated to HIV disease.
JAIDS Journal of Acquired Immune Deficiency Syndromes 04/2011; 57(4):334-9. · 4.43 Impact Factor
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ABSTRACT: Persons infected with human immunodeficiency virus (HIV) are often hyporesponsive to immunization, including pneumococcal vaccines. We hypothesized that adding CPG 7909, a toll-like receptor 9 (TLR9) agonist and vaccine adjuvant, to 7-valent pneumococcal conjugate vaccine (7vPnC) would increase its immunogenicity in HIV-infected adults.
We performed a double-blind, placebo-controlled, phase 1b/2a trial randomizing HIV-positive patients to receive double doses of 7vPnC (Prevnar) at 0 and 3 months and 1 dose of 23-valent pneumococcal polysaccharide vaccine (PPV-23; Pneumo Novum) at 9 months, with experimental patients receiving 1 mg of CPG 7909 added to each of their 3 vaccine doses; control patients had phosphate-buffered saline added instead. Immunogenicity and safety were evaluated for up to 10 months. The primary end point was the proportion of vaccine high responders at 9 months, defined as a 2-fold increase in IgG levels to > or = 1 microg/mL for at least 5 of 7 of the 7vPnC serotypes.
Ninety-seven participants were included in the study. The proportion of vaccine high responders was higher in the experimental group (n = 48) than among controls (n = 49; 48.8% vs 25.0%; P = .02) at 9 months. Greater proportions of high responders were also observed at 3 (51.1% vs 39.6%; P = .26), 4 (77.3% vs 56.3%; P = .03), and 10 months (87.8% vs 51.1%; P < .001). Mild systemic and injection site reactions to 7vPnC were more common in the experimental group than the control group (100% vs 81.3%; P = .002). CPG 7909 did not increase non-7vPnC IgG levels after PPV-23 immunization. No adverse effects on CD4(+) cell count or organ functions occurred in either group.
The addition of a TLR9 agonist to 7vPnC significantly enhanced the proportion of vaccine high responders.
ClinicalTrials.gov identifier: NCT00562939 .
Clinical Infectious Diseases 07/2010; 51(1):42-50. · 9.15 Impact Factor
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ABSTRACT: Vaccination responses may be affected by concomitant use of highly active antiretroviral therapy (HAART). We aimed to determine HAART's impact on seven-valent pneumococcal conjugate (7vPnC) vaccine immunization with or without a Toll-like receptor 9 (TLR9) agonist adjuvant.
Observational cohort study.
Adults with HIV were immunized with double doses of 7vPnC +/-1 mg CPG 7909, a TLR9 agonist and vaccine adjuvant, at 0 and 3 months, and 23-valent pneumococcal polysaccharide vaccine at 9 months. We measured IgG levels (ELISA) and opsonophagocytic activity (OPA) at months 0, 3, 4, 9, and 10. Persistent 7vPnC vaccine responders were defined as individuals with two-fold IgG increases to 1 microg/ml or more for at least five of the 7vPnC serotypes at 9 months.
We included 75 participants on HAART and 20 HAART-naive. Forty-one received CPG 7909 and 48 received placebo adjuvant. More persistent 7vPnC vaccine responders were found among HAART-treated than among HAART-naive (42.3 vs. 15.0%, P = 0.03). Mean loss of vaccine-specific IgG from month 4 to 9 was greater among HAART-naive than among HAART-treated (54.8 vs. 38.1%, P = 0.001). Functional activity (OPA) was higher among HAART-treated than among HAART-naive at 4, 9, and 10 months. In a logistic regression analysis (adjusted for baseline CD4 cell count, CPG 7909, smoking status, BMI, AIDS diagnosis, and age), HAART use was significantly associated with being persistent 7vPnC vaccine responder at month 9 [odds ratio = 4.65, 95% confidence interval (CI) 1.07-20.2].
HIV-infected adults on HAART achieved a more durable antibody response of higher functional activity following pneumococcal conjugate vaccination than HAART-naive individuals, independently of baseline CD4 cell count.
AIDS (London, England) 06/2010; 24(9):1315-22. · 4.91 Impact Factor
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ABSTRACT: CD4 T-cell recovery is impeded in some HIVinfected patients despite successful combination antiretroviral therapy (cART) with suppressed HIV RNA. We hypothesized that T-cell dysfunction would be increased in these patients.
In the Danish HIV Cohort Study, we identified HIV-1-infected patients initiating cART with a CD4 cell count <100 cells per microliter, followed by HIV RNA <50 copies per milliliter for 3 years. Patients with a CD4 count <200 cells per microliter after 3 years were identified as cases; 42 patients with a CD4 count > or = 200 cells per microliter were selected as controls. Six-color flow cytometry was performed on whole blood. Cytokine levels in supernatants from whole blood stimulations were assessed.
The case and control groups comprised 18 and 35 patients, respectively. Cases were older than controls (median: 54/46 years). The fraction of CD28+ cells was decreased among cases in the CD4+ and CD8+ T-cell subsets (P = 0.0014/P = 0.0349) and in the corresponding naive subsets (P = 0.0011/P , 0.0001). Cases had higher expression of human leukocyte antigen (HLA)-DR on naive CD4 and CD8 T cells (P = 0.0007/P = 0.0028). The production of interleukin (IL)-10 and IL-2 to phytohemagglutinin was decreased in cases (P < 0.0001/P = 0.019).
Patients with impaired CD4 recovery shared a dysregulated T-cell phenotype with low CD28, high HLA-DR expression, and low IL-2 and IL-10 production.
JAIDS Journal of Acquired Immune Deficiency Syndromes 03/2010; 53(3):303-10. · 4.43 Impact Factor
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ABSTRACT: The purpose of this study is to validate the diagnosis of spontaneous abortion (SA) recorded in the Danish National Registry of Patients (DNRP).
We randomly selected patients registered in the DNRP with a diagnosis of SA between 1980 and 2008 from hospitals in the county of North Jutland and searched for their discharge records in hospital files. We estimated positive predictive value (PPV) of the DNRP diagnosis and stratified the analysis by period (1980-1994 versus 1995-2008), hospital type (regional versus local), and International Classification of Diseases revisions (ICD-8 versus ICD-10).
We could identify hospital files of 117/174 (67%) sampled registration records. Of those, the diagnosis was confirmed in 114 patients, yielding a PPV of 97.4% (95% confidence interval = 92.7%-99.5%). The PPV did not markedly vary by period, hospital type, or ICD revision. Among the three patients with available data who did not fulfill the criteria for SA, one had an induced abortion and two had threatened abortion but did not miscarry.
Registration of SA in the DNRP accurately reflects the diagnoses recorded in medical charts. The DNRP is a suitable source of data on SAs for epidemiologic research.
Clinical Epidemiology 01/2010; 2:247-50.
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ABSTRACT: HIV-infected persons are at increased risk of pneumonia, even with highly active antiretroviral treatment (HAART). We examined the impact of pneumonia on mortality and identified prognostic factors for death among HIV-infected.
In a nationwide, population-based cohort of individuals with HIV, we included persons hospitalized with pneumonia from the Danish National Hospital Registry and obtained mortality data from the Danish Civil Registration System. Comparing individuals with and without pneumonia, we used Poisson regression to estimate relative mortality and logistic regression to examine prognostic factors for death following pneumonia. From January 1, 1995, to July 1, 2008, we observed 699 episodes of first hospitalization for pneumonia among 4,352 HIV patients. Ninety-day mortality after pneumonia decreased from 22.4% (95% confidence interval [CI]: 16.5%-28.9%) in 1995-1996 to 8.4% (95% CI: 6.1%-11.6%) in 2000-2008. Mortality remained elevated for more than a year after hospitalization for pneumonia: adjusted mortality rate ratio 5.38 (95% CI: 4.27-6.78), 1.80 (95% CI: 1.36-2.37), and 1.62 (95% CI: 1.32-2.00) for days 0-90, 91-365, and 366+, respectively. The following variables predicted mortality within 90 days following hospitalization for pneumonia (adjusted Odds Ratios): male sex (3.77, 95% CI: 1.37-10.4), Charlson Comorbidity Index score > or = 2 (3.86, 95% CI: 2.19-6.78); no current HAART (3.58, 95% CI: 1.83-6.99); history of AIDS (2.46, 95% CI: 1.40-4.32); age per 10 year increase (1.43, 95% CI: 1.11-1.85); and CD4+ cell count < or = 200 (2.52, 95% CI: 1.37-4.65).
The first hospitalization for pneumonia among HIV-infected individuals was associated with elevated risk of death up to more than a year later. Use of HAART decreased the risk, independent of current CD4+ cell count. Prognosis following pneumonia improved over calendar time.
PLoS ONE 01/2009; 4(9):e7022. · 4.09 Impact Factor
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ABSTRACT: Newer antiretroviral treatment regimens for HIV carry a lower risk of inducing drug resistance mutations. We estimated changes in incidence rates (IRs) of new mutations in HIV-infected individuals receiving highly active antiretroviral therapy (HAART).
Population-based data were obtained from the Danish HIV Cohort Study and the Danish HIV Sequence Database. We included treatment-naive patients initiating HAART after December 1997 and computed time to first drug resistance mutation, identified as new mutations detected within 1 year after a 60-day period of treatment failure (HIV RNA>1,000 copies/ml). We estimated annual IRs of new resistance mutations towards nucleoside reverse transcriptase inhibitors (NRTIs), non-NRTIs (NNRTIs) and protease inhibitors (PI), and of new specific resistance mutations.
A total of 1,829 individuals were observed for 7,294 person-years at risk (PYR). The IR of NRTI resistance decreased from 13.1 per 1,000 PYR (95% confidence interval [CI] 4.9-35.0) in 1999 to 3.7 (1.9-7.2) in 2004-2005 (test for trend P=0.024). The IR of NNRTI resistance decreased from 15.4 (2.2-109.6) in 1999 to 7.9 (4.6-13.6) in 2004-2005 (P=0.077). The IR of PI resistance decreased from 7.5 (1.4-21.8) in 1999 to 2.9 (0.7-11.4) in 2002-2003 (P=0.148). The IRs were low for specific resistance mutations, except for M184V (IR 5.6 [4.0-7.9]) and K103N (IR 8.2 [5.6-12.0]).
The incidence of acquired drug resistance has decreased among HIV-infected patients treated with HAART in Denmark during 1999-2005.
Antiviral therapy 01/2009; 14(7):995-1000. · 3.16 Impact Factor
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ABSTRACT: Human immunodeficiency virus (HIV)-infected individuals with high CD4(+) cell counts may have increased susceptibility to other infections. We compared incidence rates of pneumonia among individuals with and without HIV infection and explored risk factors for pneumonia in the HIV-infected population.
This was an observational cohort study conducted during 1995-2007. Each member of a Danish population-based nationwide cohort of HIV-infected individuals was matched with up to 99 control individuals from the general population. Data on age, mortality, emigration, and hospital discharge diagnoses from 1977 onward were obtained from nationwide administrative databases. Individuals without previous hospitalization for pneumonia were observed from the date of HIV diagnosis until the first hospitalization to treat pneumonia (excluding pneumonia attributable to Pneumocystis jiroveci). Risk factors were assessed by Poisson regression.
The study included 3516 persons with HIV infection and 328,738 persons without HIV infection, which provided 23,677 person-years and 2,944,760 person-years of observation, respectively. Incidence rates of pneumonia in HIV-infected individuals decreased from 50.6 hospitalizations per 1000 person-years (95% confidence interval [CI], 42.9-59.7 hospitalizations per 1000 person-years) during 1995-1996 to 19.7 hospitalizations per 1000 person-years (95% CI, 16.2-23.8 hospitalizations per 1000 person-years) during 2005-2007. Compared with control individuals, incidence rate ratios were 34.6 (95% CI, 28.4-41.8) during 1995-1996; 6.3 (95% CI, 5.1-7.7) during 2005-2007; and 5.9 (95% CI, 4.2-7.6) during 2005-2007 for the subgroup with a CD4(+) cell count >500 cells/microL. Injection drug use, low current CD4(+) cell count, nadir CD4(+) cell count, increasing age, and no current receipt of highly active antiretroviral therapy increased the risk of pneumonia.
The risk of pneumonia in persons with HIV infection has decreased substantially since the introduction of highly active antiretroviral therapy, but HIV infection remains a strong risk factor for the need for hospitalization to treat pneumonia, even in persons with high CD4(+) cell counts.
Clinical Infectious Diseases 11/2008; 47(10):1345-53. · 9.15 Impact Factor
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Clinical Infectious Diseases 08/2008; 47(2):294-5; author reply 295-6. · 9.15 Impact Factor
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ABSTRACT: A molecular epidemiologic study of HIV-1 in Greenland showed distinct transmission clusters correlated with demographic and behavioral data. Resistance mutations were found in a majority of the pol sequences. The objective of the present study was to estimate prevalence of drug resistance in Greenland and identify transmission chains by comparing resistance data with phylogeny and treatment history. Of 60 untreated patients, 15 (25%) had primary resistance mutations. The most prevalent mutations were T69D/N (15%), K70R (15%), and M184V (10%). Four possible transmission chains were identified based on phylogeny and mutation profiles. The clusters consisted of treated and untreated patients and showed the same mutation profiles in both resistance and nonresistance positions. Prevalence of transmitted drug resistance in Greenland (25%) is higher than in Denmark where only 3% transmission was observed. Suboptimal use of nucleoside reverse transcriptase inhibitor (NRTI) in Greenland was reflected in the high prevalence of NRTI-related resistance in the patients. A combination of phylogeny and genotypic resistance tests enabled us to study the number of transmissions and how the virus was transmitted. Resistance mutations detected in untreated patients were backed up by the treatment history of index patients in the possible transmission chains and indicated that these drug-resistant variants were in fact transmitted and had not emerged due to unregistered drug intake.
AIDS research and human retroviruses 08/2008; 24(8):1073-7. · 2.18 Impact Factor
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Simon Høegh, Nicolai Lohse,
Ann-Brit Eg Hansen,
Jan Gerstoft,
Gitte Kronborg,
Carsten S Larsen,
Court Pedersen,
Gitte Pedersen,
Alex L Laursen,
Birgit Kvinesdal,
Axel Møller,
Niels Obel
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ABSTRACT: The incidence of new HIV diagnoses in Denmark has remained stable since 1991, but it has increased among the subgroup of homosexual men in recent years. This may reflect an actual increase in newly infected, e.g. as a result of increased risk behaviour, or it may reflect increased HIV testing. To clarify the causes of this increase we describe and analyse the development of HIV infection in Denmark in the period 1995-2005 with special emphasis on the route of transmission, immunological status at the time of diagnosis and the prevalence of patients at risk of transmitting HIV.
Observational study based on the Danish HIV Cohort Study, which includes all adults seen at Danish HIV clinics since 1995.
From 2000 to 2004 the number of newly-infected homosexual men increased (from 69 to 123), particularly in persons under 30 years (from 5 to 42). The median CD4 cell count at the time of diagnosis increased in this group (median 19.1 cells/microL per year [95% CI: 3.7-11.3]), while it remained stable among heterosexually infected. The number of newly-diagnosed homosexually infected under 30 years with a CD4 cell count over 400 cells/microL increased from 0 in 2000 to 23 in 2004. The prevalence of patients with high viral load (and thus potentially at risk of transmitting HIV) decreased in all risk groups.
Newly-diagnosed homosexual men present at an earlier stage of disease progression and with a better preserved immune system today than 5-10 years ago, presumably due to a combination of frequent HIV testing and increased risk behaviour among young homosexuals in particular. Increased preventive measures targeting known risk groups are necessary to prevent further spread.
Ugeskrift for laeger 03/2008; 170(9):740-4.
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ABSTRACT: Analyses from the Danish HIV Cohort Study showed that, despite comparable economic means and general education of healthcare personnel, antiretroviral treatment of HIV in Greenland began later and has been implemented at a slower pace with lower therapeutic effectiveness than in Denmark. However, implementation and quality of care improved considerably in recent years.
Emerging infectious diseases 02/2008; 14(1):56-9. · 6.17 Impact Factor
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ABSTRACT: A human immunodeficiency virus (HIV) patient in 2007 has the option to commence an antiretroviral regimen that is extremely efficacious in suppressing the virus and has few side effects. In a recent study, we estimated the median remaining lifetime of a newly diagnosed 25-year-old HIV-infected individual to be 39 years. The prospect of a near-normal life expectancy has implications for the HIV-infected persons as well as for the handling of the disease in the healthcare system. The patients can now on a long-term perspective plan their professional career, join a pension plan and start a family. Further, they may expect to be treated equally with other members of society with respect to access to mortgage, health insurance and life insurance. As the infected population ages, more patients will contract age-related diseases, and the disease burden on some individuals may even come to be dominated by non-HIV-related conditions that may have a worse prognosis and therefore become more important than HIV-related conditions. Despite the improvements in antiretroviral therapy, there is still an excess mortality among HIV patients, which appears to be only partially attributable to immunodeficiency, with lifestyle factors potentially playing a pronounced role. Consequently, an effort to further increase survival must target risk factors for both HIV-related and -unrelated mortality. The continuation of the positive trend may be achieved by increased HIV testing, earlier initiation of antiretroviral therapy, improved drug adherence, prevention and treatment of HIV-unrelated co-morbidity and collaboration with other medical specialists to treat an ageing co-morbidity-acquiring HIV population.
Journal of Antimicrobial Chemotherapy 10/2007; 60(3):461-3. · 5.07 Impact Factor
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ABSTRACT: It has been difficult to measure the median survival of HIV-infected patients by comparing selected HIV samples and control groups. Data from the Danish HIV Cohort Study combined with the Central Registration System has made it possible to accurately compare the survival of HIV-infected persons and uninfected persons. In 2000 to 2005, the median remaining lifetime at age 25 years in the general population was 51 years and 39 years for HIV-infected persons without hepatitis C virus infection. In conclusion, persons with HIV infection have a good, albeit far from normal, life expectancy.
Ugeskrift for laeger 07/2007; 169(26):2529-32.
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ABSTRACT: Introduction of HIV-1 into a population may not always give rise to a subsequent epidemic. Greenland is an isolated and sparsely populated island in The Danish Kingdom. We aimed to estimate the number of introductions of HIV-1 into Greenland, the number of subsequent epidemics, and the countries from which the virus was introduced. Phylogenetic analyses were performed on three regions of HIV-1 (gag, pol, and env) in samples from 70 Greenlandic patients. Furthermore, we included gene sequences from contemporary Danish HIV-1-infected patients and sequences from the Los Alamos HIV Sequence Database. All Greenlandic sequences were subtype B except one sequence found to be a recombinant (probably CRF13). Sequence clusters in the phylogenetic trees indicated that there had been at least nine introductions of HIV-1 into Greenland. One cluster, supported by bootstrap values of 81, 76, and 96% for gag, pol, and env, corresponding to one introduction, contained 53 (76%) of the Greenland patients. The patients in the cluster differed from other Greenlandic patients in epidemiological parameters. Two distinct subgroups within the main cluster were concentrated around the two largest Greenlandic towns. Although HIV-1 has been introduced into Greenland at least nine times, only one introduction gave rise to an epidemic. The phylogeny did not indicate from where the main Greenland cluster had been introduced as no database sequence from outside Greenland was genetically close to this cluster. The large diversity between the main Greenland cluster and the rest of the sequences is most likely due to a founder effect.
AIDS Research and Human Retroviruses 06/2007; 23(5):675-81. · 2.25 Impact Factor
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Ugeskrift for laeger 03/2007; 169(12):1109.
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ABSTRACT: The expected survival of HIV-infected patients is of major public health interest.
To estimate survival time and age-specific mortality rates of an HIV-infected population compared with that of the general population.
Population-based cohort study.
All HIV-infected persons receiving care in Denmark from 1995 to 2005.
Each member of the nationwide Danish HIV Cohort Study was matched with as many as 99 persons from the general population according to sex, date of birth, and municipality of residence.
The authors computed Kaplan-Meier life tables with age as the time scale to estimate survival from age 25 years. Patients with HIV infection and corresponding persons from the general population were observed from the date of the patient's HIV diagnosis until death, emigration, or 1 May 2005.
3990 HIV-infected patients and 379,872 persons from the general population were included in the study, yielding 22,744 (median, 5.8 y/person) and 2,689,287 (median, 8.4 years/person) person-years of observation. Three percent of participants were lost to follow-up. From age 25 years, the median survival was 19.9 years (95% CI, 18.5 to 21.3) among patients with HIV infection and 51.1 years (CI, 50.9 to 51.5) among the general population. For HIV-infected patients, survival increased to 32.5 years (CI, 29.4 to 34.7) during the 2000 to 2005 period. In the subgroup that excluded persons with known hepatitis C coinfection (16%), median survival was 38.9 years (CI, 35.4 to 40.1) during this same period. The relative mortality rates for patients with HIV infection compared with those for the general population decreased with increasing age, whereas the excess mortality rate increased with increasing age.
The observed mortality rates are assumed to apply beyond the current maximum observation time of 10 years.
The estimated median survival is more than 35 years for a young person diagnosed with HIV infection in the late highly active antiretroviral therapy era. However, an ongoing effort is still needed to further reduce mortality rates for these persons compared with the general population.
Annals of internal medicine 02/2007; 146(2):87-95. · 16.73 Impact Factor
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ABSTRACT: 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.
PLoS ONE 02/2007; 2(8):e738. · 4.09 Impact Factor
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ABSTRACT: To examine the prevalence of drug-resistance-associated mutations in HIV patients with triple-drug class virological failure (TCF) and their association with long-term mortality.
Population-based study from the Danish HIV Cohort Study (DHCS).
We included all patients in the DHCS who experienced TCF between January 1995 and November 2004, and we performed genotypic resistance tests for International AIDS Society (IAS)-USA primary mutations on virus from plasma samples taken around the date of TCF. We computed time to all-cause death from date of TCF. The relative risk of death according to the number of mutations and individual mutations was estimated by Cox regression analysis and adjusted for potential confounders.
Resistance tests were done for 133 of the 179 patients who experienced TCF. The median number of resistance mutations was eight (interquartile range 2-10), and 81 (61%) patients had mutations conferring resistance towards all three major drug classes. In a regression model adjusted for CD4+ T-cell count, HIV RNA, year of TCF, age, gender and previous inferior antiretroviral therapy, harbouring > or =9 versus < or =8 mutations was associated with increased mortality (mortality rate ratio [MRR] 2.3 [95% confidence interval (CI) 1.1-4.8]), as were the individual mutations T215Y (MRR 3.4 [95% CI 1.6-7.0]), G190A/S (MRR 3.2 [95% CI 1.6-6.6]) and V82F/A/T/S (MRR 2.5 [95% CI 1.2-5.3]).
In HIV patients with TCF, the total number of genotypic resistance mutations and specific single mutations predicted mortality.
Antiviral therapy 01/2007; 12(6):909-17. · 3.16 Impact Factor
