- [Show abstract] [Hide abstract] 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.
- [Show abstract] [Hide abstract] 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.
- [Show abstract] [Hide abstract] ABSTRACT: Objective: 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. Design: Population-based study from the Danish HIV Cohort Study (DHCS). Methods: 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. Results: 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 ≥9 versus ≤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]). Conclusions: In HIV patients with TCF, the total number of genotypic resistance mutations and specific single mutations predicted mortality.
- [Show abstract] [Hide abstract] ABSTRACT: We discuss the diagnosis, treatment and prognosis of a Danish male with disseminated coccidioidomycosis. He presented with headaches and slight fever. Examination showed pulmonary, cutaneous and cerebral and cerebellar granulomas, a rare complication. He was treated with intravenously and subsequently orally administered fluconazole. Symptoms and clinical findings regressed during treatment.
- [Show abstract] [Hide abstract] ABSTRACT: Malaria may be misdiagnosed in non-endemic countries when the necessary experience for rapid expert microscopy is lacking. Rapid diagnostic tests may improve the diagnosis and may play a role as a bedside diagnostic tool. In a multicentre study we recruited patients suspected of malaria over a period of 14 months. The Binax Now Malaria rapid test was used at the bedside and in the clinical microbiology laboratory. The training of clinical staff was monitored and their experience with the use of the test was recorded. 542 patients were included, 80 of whom had malaria diagnosed by microscopy. The rapid test used at the bedside had a sensitivity of 88% for the detection of P. falciparum compared to 95% when the test was performed in the microbiology laboratory. The risk of technical problems and invalid tests was highest when the test was used at the bedside. The rapid diagnostic test may be useful for the diagnosis of P. falciparum malaria when used by routine laboratory staff, but could lead to misdiagnoses when used at the bedside. Microscopy is still essential in order to identify the few missed diagnoses, to determine the degree of parasitaemia, and to ensure species diagnosis, including mixed infections.
- [Show abstract] [Hide abstract] ABSTRACT: Transmission of drug-resistant HIV is a potential threat to the substantial clinical benefit of highly active antiretroviral therapy (HAART). To explore the background for the low rates of drug resistance transmission (2.5%) in our population, we estimated acquisition of HIV drug resistance and examined temporal trends in the prevalence of patients at risk of transmitting drug-resistant HIV. The study population included all 4,025 patients from The Danish HIV Cohort Study seen during the period 1995-2004. Virological failure to a given drug class was defined as a viral load (VL) > 1,000 copies/ml for 120 days while on a HAART regimen including that drug class. In addition, receiving nucleoside reverse transcriptase inhibitors (NRTIs) for 180 days before HAART counted as NRTI failure irrespective of VL. Having experienced failure was considered a proxy for harbouring drug-resistant virus in subsequent observation time. Patients with a current VL > 1,000 copies/ml were considered at risk of transmitting HIV. We found a decrease from 1997 to 2004 in the prevalence of potential transmitters of drug-resistant HIV. The number of these patients with previous NRTI failure decreased from 429 (24% of all patients) in 1998 to 213 (8.0% of all patients) in 2004. Previous protease inhibitor (PI) failure peaked at 279 (14%) in 1999, declining to 142 (5.3%) in 2004. Previous NNRTI failure peaked at 121 patients (4.7%) in 2002, and occurred in 113 patients (4.2%) in 2004. Of all 686 potential transmitters in 2004, 31% had previously experienced NRTI failure, 21% PI failure, and 16% non-NRTI failure. In the population of HIV-infected individuals in Denmark with complete follow-up, the number at risk of transmitting drug-resistant virus declined over time.
- [Show abstract] [Hide abstract] ABSTRACT: To analyse the incidence, prevalence, and predictors for development of triple-class antiretroviral drug failure (TCF) in individuals infected with HIV. 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. 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. 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. The risk of TCF is declining in Denmark and the prevalence remains stable.
- [Show abstract] [Hide abstract] ABSTRACT: We used a population-based cohort study design to describe the demographic characteristics of the HIV-infected population in Denmark and their variation over time. HIV treatment in Denmark is restricted to 9 centres, and all 3941 HIV-1 infected patients more than 15 y old seen at these centres in 1995-2003 were included. We found an estimated HIV prevalence of 70 per 100,000, and a mean annual incidence rate of 5.1 per 100,000 persons. The number of newly infected individuals was stable with a median of 231 per y (period 1995-2002), whereas the number of deaths decreased from 166 in 1995 to 50 in 2000 (p=0.000) and remained stable thereafter. Of the enrolled patients, 75% were males, 80% were Caucasian, 13% were black African, and the primary risk behaviour was male-to-male sexual contact (44%), heterosexual contact (36%), and injection drug use (11%). During the y 1995-2003 we found an increase in age at diagnosis (p=0.000), and no major changes in gender, race, mode of infection, or baseline CD4+ cell count and viral load, neither overall not within subgroups of patients. In this period 14.5% had AIDS at the time of HIV diagnosis. Our data do not confirm concerns about unmonitored evolution in the HIV epidemic in Denmark.
- [Show abstract] [Hide abstract] ABSTRACT: commercial HIV-1 qualitative DNA PCR tests have the potential to detect virus in patients in whom antibody tests may be ineffective, such as patients with primary HIV infection and infants born to HIV seropositive mothers. However, the genetic diversity of HIV-1 raises concern about the ability of the PCR tests to detect all current subtypes. to asses the sensitivity of the Amplicor HIV-1 test on 126 whole-blood samples representing seven different subtypes and to investigate the sensitivity when the standard assay was modified by including the primer pair SK145 and SKCC1B. of the 126 HIV-1 infected persons, 113 were tested positive and 13 were DNA PCR negative. On the basis of these results, the standard Amplicor HIV-1 test had a sensitivity of 90% in our cohort. In addition, 9% of the positive samples showed a low reactivity but above the cut-off of the assay. The standard assay yielded sensitivities of 100% for subtype B (n=16), D (n=9) and G (n=1), but only 83% for subtype A (n=41), 98% for subtype C (n=43), 79% for subtype E (n=14) and 0% for subtype F (n=2). All samples with low reactivity were non-B subtype. Eight of the DNA PCR negative samples, four subtype A, one C and three E were amplified with the modified Amplicor HIV-1 test with addition of SK145/SKCC1B primers. Using this modified protocol, six samples out of eight became positive. However, two samples (one A and one C) remained DNA PCR negative. this study confirms that the Amplicor HIV-1 test does not detect all subtypes with equivalent sensitivity and 10% of the samples, tested negative. Thus, it is preferable to add the SK145/SKCC1B primers to the standard test, where infection with non-B subtype is suspected.
Article: HIV-1 subtypes in Denmark[Show abstract] [Hide abstract] ABSTRACT: The objective of this study was to investigate the presence of non-subtype B HIV-1 in Denmark. The C2-V3-C3 region of the env gene from proviral DNA obtained from patients suspected of being infected with non-subtype B virus was PCR-amplified and directly sequenced. The DNA sequences were aligned with full-length HIV-1 reference strains from each subtype and analysed using the phylogenetic package PHYLIP 3.1. The neighbour-joining method was used with 100 bootstraps. Of the 144 patients included in this study C2-V3-C3 sequences were obtained from 129 patients (90%). The phylogenetic analyses showed that virus from 49 patients (38%) was subtype A, 39 (30%) subtype C, 9 (7%) subtype D, 14 (11%) subtype CRF01_AE, 16 (12%) subtype B, 1 (1%) subtype F and 1 (1%) subtype J. This study demonstrates that almost all subtypes can be detected in Denmark; all non-subtype B infections could be traced to countries with a high prevalence of non-subtype B virus.
- [Show abstract] [Hide abstract] ABSTRACT: Pneumococcal infections are frequently observed in patients with human immunodeficiency virus (HIV) infection and active immunization has been recommended as prophylaxis in this patient group. We studied 103 out-patients with asymptomatic or mildly symptomatic HIV infection with respect to specific IgG and IgG2 pneumococcal antibodies before and after vaccination with a 23-valent pneumococcal polysaccharide vaccine. A significant increase ( > 2-fold) in IgG and IgG2 antibody levels was observed after 1 month in 69/103 patients (67%) with no correlation with the CD4 cell count at the time of vaccination. The response rate was not influenced by concurrent treatment with anti-retroviral monotherapy, or by age or gender. After immunization a strong correlation between IgG and IgG2 anti-pneumococcal antibodies was demonstrated. Nevertheless, 12 months after vaccination the specific antibody titres were not significantly different from pre-vaccination values. In conclusion, antibodies induced by pneumococcal vaccination in patients with HIV infection have a short duration. This raises the question as to whether vaccination will have any impact on clinical end-point in this group of patients.