Does less frequent routine monitoring of patients on a stable, fully suppressed cART regimen lead to an increased risk of treatment failure?

OBJECTIVE: To investigate whether HIV-infected patients on a stable and fully suppressive combination antiretroviral therapy (cART) regimen could safely be monitored less often than the current recommendations of every 3 months. DESIGN: Two thousand two hundred and forty patients from the EuroSIDA study who maintained a stable and fully suppressed cART regimen for 1 year were included in the analysis. METHODS: Risk of treatment failure, defined by viral rebound, fall in CD4 cell count, development of new AIDS-defining illness, serious opportunistic infection or death, in the 12 months following a year of a stable and fully suppressed regimen was assessed. RESULTS: One hundred thirty-one (6%) patients experienced treatment failure in the 12 months following a year of stable therapy, viral rebound occurred in 99 (4.6%) patients. After 3, 6 and 12 months, patients had a 0.3% [95% confidence interval (CI) 0.1-0.5], 2.2% (95% CI 1.6-2.8) and 6.0% (95% CI 5.0-7.0) risk of treatment failure, respectively. Patients who spent more than 80% of their time on cART with fully suppressed viraemia prior to baseline had a 38% reduced risk of treatment failure, hazard ratio 0.62 (95% CI 0.42-0.90, P = 0.01). CONCLUSION: Patients who have responded well to cART and are on a well tolerated and durably fully suppressive cART regimen have a low chance of experiencing treatment failure in the next 3-6 months. Therefore, in this subgroup of otherwise healthy patients, it maybe reasonable to extend visit intervals to 6 months, with cost and time savings to both the treating clinics and the patients.

Fungal infection as a risk factor for HIV disease progression among patients with a CD4 count above 200/microl in the era of cART.

The identification of clinical risk factors for AIDS in patients with preserved immune function is of significant interest. We examined whether patients with fungal infection (FI) and CD4 cell count >or=200/microl were at higher risk of disease progression in the era of cART. 11,009 EuroSIDA patients were followed from their first CD4 cell count >or=200/microl after 1 January 1997 until progression to any non-azoles/amphotericin B susceptible (AAS) AIDS disease, last visit or death. Initiation of antimycotic therapy (AMT) was used as a marker of FI and was modelled as a time-updated covariate using Poisson regression. After adjustment for current CD4 cell count, HIV-RNA, starting cART and diagnosis of AAS-AIDS, AMT was significantly associated with an increased incidence of non-AAS-AIDS (IRR=1.55, 95% CI 1.17-2.06, p=0.0024). Despite low incidence of AIDS in the cART era, FI in patients with a CD4 cell count >or=200/microl is associated with a 55% higher risk of non-AAS-AIDS (95% confidence interval 1.17-2.06, p=0.0024). These data suggest that patients with FI are more immune compromized than would be expected from their CD4 cell count alone. FI can be used as a clinical marker for disease progression and indirect indicator for initiation/changing cART in settings where laboratory facilities are limited.

Influence of HLA-C expression level on HIV control.

A variant upstream of human leukocyte antigen C (HLA-C) shows the most significant genome-wide effect on HIV control in European Americans and is also associated with the level of HLA-C expression. We characterized the differential cell surface expression levels of all common HLA-C allotypes and tested directly for effects of HLA-C expression on outcomes of HIV infection in 5243 individuals. Increasing HLA-C expression was associated with protection against multiple outcomes independently of individual HLA allelic effects in both African and European Americans, regardless of their distinct HLA-C frequencies and linkage relationships with HLA-B and HLA-A. Higher HLA-C expression was correlated with increased likelihood of cytotoxic T lymphocyte responses and frequency of viral escape mutation. In contrast, high HLA-C expression had a deleterious effect in Crohn's disease, suggesting a broader influence of HLA expression levels in human disease.

Forensic science culture

Heretofore the issue of quality in forensic science is approached through a quality management policy whose tenets are ruled by market forces. Despite some obvious advantages of standardization of methods allowing interlaboratory comparisons and implementation of databases, this approach suffers from a serious lack of consideration for forensic science as a science. A critical study of its principles and foundations, which constitutes its culture, enables to consider the matter of scientific quality through a new dimension. A better understanding of what pertains to forensic science ensures a better application and improves elementary actions within the investigative and intelligence processes as well as the judicial process. This leads to focus the attention on the core of the subject matter: the physical remnants of the criminal activity, namely, the traces that produce information in understanding this activity. Adapting practices to the detection and recognition of relevant traces relies on the apprehension of the processes underlying forensic science tenets (Locard, Kirk, relevancy issue) and a structured management of circumstantial information (directindirect information). This is influenced by forensic science education and training. However, the lack of homogeneity with regard to the scientific nature and culture of the discipline within forensic science practitioners and partners represents a real challenge. A sound and critical reconsideration of the forensic science practitioner's roles (investigator, evaluator, intelligence provider) and objectives (prevention, strategies, evidence provider) within the criminal justice system is a means to strengthen the understanding and the application of forensic science. Indeed, the whole philosophy is aimed at ensuring a high degree of excellence, namely, a dedicated scientific quality.

Le principe de Locard est-il scientifique ? Ou analyse de la scientificité des principes fondamentaux de la criminalistique

Constatant que la jurisprudence américaine impose de questionner non plus seulement la méthodologie mais les principes mêmes qui gouvernent un corps de connaissance qualifié de scientifique, la criminalistique peut-elle prétendre à ce statut supérieur devant les tribunaux, ou doit-elle être considérée comme métaphysique sur la base de ses posits fondamentaux de Locard (principe d'échange de traces) et de Kirk (principe d'individualité) ? Une analyse historique et philosophique apprécie la pertinence des épistémologies logiques à reconnaître une science, et propose une démarche néo-expérimentaliste innovante pour le principe de Locard. L'analyse des résultats de quatre brigades de recherches départementales françaises (BRD), du Groupe des techniciens en investigations criminelles (GTIC) et du service d'identité judiciaire vaudois (SIJ VD) permettent de constater la potentialité du principe d'échange de traces, et d'en proposer des voies de maximalisation, préalable à un questionnement pertinent sur la nature scientifique de ce principe par la réfutation poppérienne.

Increased risk of cardiovascular disease (CVD) with age in HIV-positive men : a comparison of the D:A:D CVD risk equation and general population CVD risk equations

OBJECTIVES: The aim of the study was to statistically model the relative increased risk of cardiovascular disease (CVD) per year older in Data collection on Adverse events of anti-HIV Drugs (D:A:D) and to compare this with the relative increased risk of CVD per year older in general population risk equations. METHODS: We analysed three endpoints: myocardial infarction (MI), coronary heart disease (CHD: MI or invasive coronary procedure) and CVD (CHD or stroke). We fitted a number of parametric age effects, adjusting for known risk factors and antiretroviral therapy (ART) use. The best-fitting age effect was determined using the Akaike information criterion. We compared the ageing effect from D:A:D with that from the general population risk equations: the Framingham Heart Study, CUORE and ASSIGN risk scores. RESULTS: A total of 24 323 men were included in analyses. Crude MI, CHD and CVD event rates per 1000 person-years increased from 2.29, 3.11 and 3.65 in those aged 40-45 years to 6.53, 11.91 and 15.89 in those aged 60-65 years, respectively. The best-fitting models included inverse age for MI and age + age(2) for CHD and CVD. In D:A:D there was a slowly accelerating increased risk of CHD and CVD per year older, which appeared to be only modest yet was consistently raised compared with the risk in the general population. The relative risk of MI with age was not different between D:A:D and the general population. CONCLUSIONS: We found only limited evidence of accelerating increased risk of CVD with age in D:A:D compared with the general population. The absolute risk of CVD associated with HIV infection remains uncertain.