Mortality in patients with successful initial response to highly active antiretroviral therapy is still higher than in non-HIV-infected individuals.

Mortality in HIV-infected patients has decreased dramatically since the introduction of highly active antiretroviral therapy (HAART). We analyzed progression to death in a population of 3678 antiretroviral treatment-naive patients from the ATHENA national observational cohort from 24 weeks after the start of HAART. Mortality was compared with that in the general population in the Netherlands matched by age and gender. Only log-transformed CD4 cell count (hazard ratio [HR] = 0.50, 95% confidence interval [CI]: 0.40 to 0.61 per unit increase) and plasma viral load (HR = 0.30, 95% CI: 0.15 to 0.60, HIV RNA level or = 100,000 copies/mL) measured at 24 weeks and infection via intravenous drug use (IDU) (HR = 0.16, 95% CI: 0.10 to 0.26, non-IDU vs. IDU) were significantly associated with progression to death. For non-IDU patients with 600 x 10 CD4 cells/L and an HIV RNA level <100,000 copies/mL at 24 weeks, mortality was predicted to be 5.3 (95% CI: 3.5 to 8.4) and 10.4 (95% CI: 6.4 to 17.4) times higher than in the general population for 25-year-old men and women, respectively, and 1.15 (95% CI: 1.08 to 1.25) and 1.29 (95% CI: 1.16 to 1.50) times higher for 65-year-old men and women, respectively. Hence, mortality in HIV-infected patients with a good initial response to HAART is still higher than in the general population

Resurgence of HIV infection among men who have sex with men in Switzerland : mathematical modelling study

New HIV infections in men who have sex with men (MSM) have increased in Switzerland since 2000 despite combination antiretroviral therapy (cART). The objectives of this mathematical modelling study were: to describe the dynamics of the HIV epidemic in MSM in Switzerland using national data; to explore the effects of hypothetical prevention scenarios; and to conduct a multivariate sensitivity analysis. METHODOLOGY/PRINCIPAL FINDINGS: The model describes HIV transmission, progression and the effects of cART using differential equations. The model was fitted to Swiss HIV and AIDS surveillance data and twelve unknown parameters were estimated. Predicted numbers of diagnosed HIV infections and AIDS cases fitted the observed data well. By the end of 2010, an estimated 13.5% (95% CI 12.5, 14.6%) of all HIV-infected MSM were undiagnosed and accounted for 81.8% (95% CI 81.1, 82.4%) of new HIV infections. The transmission rate was at its lowest from 1995-1999, with a nadir of 46 incident HIV infections in 1999, but increased from 2000. The estimated number of new infections continued to increase to more than 250 in 2010, although the reproduction number was still below the epidemic threshold. Prevention scenarios included temporary reductions in risk behaviour, annual test and treat, and reduction in risk behaviour to levels observed earlier in the epidemic. These led to predicted reductions in new infections from 2 to 26% by 2020. Parameters related to disease progression and relative infectiousness at different HIV stages had the greatest influence on estimates of the net transmission rate. CONCLUSIONS/SIGNIFICANCE: The model outputs suggest that the increase in HIV transmission amongst MSM in Switzerland is the result of continuing risky sexual behaviour, particularly by those unaware of their infection status. Long term reductions in the incidence of HIV infection in MSM in Switzerland will require increased and sustained uptake of effective interventions

Elimination prospects of the Dutch HIV epidemic among men who have sex with men in the era of preexposure prophylaxis.

OBJECTIVE: Preexposure prophylaxis (PrEP) is a promising intervention to help end the HIV epidemic among men who have sex with men (MSM) in the Netherlands. We aimed to assess the impact of PrEP on HIV prevalence in this population and to determine the levels of PrEP coverage necessary for HIV elimination. DESIGN AND METHODS: We developed a mathematical model of HIV transmission in a population stratified by sexual risk behavior with universal antiretroviral treatment (ART) and daily PrEP use depending on an individual's risk behavior. We computed the effective reproduction number, HIV prevalence, ART and PrEP coverage for increasing ART and PrEP uptake levels, and examined how these were affected by PrEP effectiveness and duration of PrEP use. RESULTS: At current levels of ART coverage of 80%, PrEP effectiveness of 86% and PrEP duration of 5 years, HIV elimination required 82% PrEP coverage in the highest risk group (12 000 MSM with more than 18 partners per year). If ART coverage increased by 9%, the elimination threshold was at 70% PrEP coverage. For shorter PrEP duration and lower effectiveness elimination prospects were less favorable. For the same number of PrEP users distributed among two groups with highest risk behavior, prevalence dropped from the current 8 to 4.6%. CONCLUSION: PrEP for HIV prevention among MSM could, in principle, eliminate HIV from this population in the Netherlands. The highest impact of PrEP on prevalence was predicted when ART and PrEP coverage increased simultaneously and PrEP was used by the highest risk individuals

Seksueel overdraagbare aandoeningen, waaronder HIV, in Nederland in 2007

Net als in 2006 was chlamydia in 2007 de meest gediagnosticeerde bacterikle geslachtsziekte in de soacentra, vooral bij jongeren. Het percentage positieve chlamydiatesten nder heteroseksuele mannen en vrouwen daalde enigszins, voor het eerst sinds vier jaar (van 10,6% naar 10,1%). In 2006 stabiliseerde dit percentage bij mannen die seks hebben met mannen (MSM), en die trend zette door in 2007. Het percentage positieve gonorroe-, syfilis- en hivtesten nam net als voorgaande jaren af in 2007 (respectievelijk 2,4%, 0,9% en ,5%). Deze infecties werden het meest gediagnosticeerd bij MSM. In 2007 zijn er 306 nieuwe hivdiagnoses gesteld in de soacentra, ongeveer een derde van de 864 hivpositieven die dat jaar landelijk in de hivcentra zijn gemeld. Eind 2007 waren in totaal 14.019 personen in Nederland met hiv geregistreerd. Het aandeel van MSM onder de nieuw hivinfecties nam in 2007 verder toe. Net als eerdere jaren werd in de soacentra bij MSM die bekend zijn met hun positieve hivstatus vaak nog een andere geslachtsziekte gevonden (45%). In deze groep is sinds 2004 regelmatig LGV, een agressieve variant van chlamydia, en sinds 2007 hepatitis C gediagnosticeerd. Versterkte surveillance en innovatieve interventies zijn nodig om verdere verspreiding onder MSM en naar andere groepen te voorkomen. Onder bepaalde migrantengroepen in Nederland (onder andere afkomstig uit Suriname, de Nederlandse Antillen en Aruba) komen hiv, chlamydia, gonorroe en syfilis relatief vaker voor dan onder autochtone Nederlanders. Ook deze constatering vraagt om vernieuwende maatregelen die op de bevolkingsgroepen zijn toegespitst. De soacentra bieden soazorg aan hoogrisicogroepen. In 2007 hebben ruim 78.000 personen zich daar laten testen, een toename van 13% ten opzichte van 2006. Net als in 2006 was chlamydia in 2007 de meest gediagnosticeerde bacterikle geslachtsziekte in de soacentra, vooral bij jongeren. Het percentage positieve chlamydiatesten onder heteroseksuele mannen en vrouwen daalde enigszins, voor het eerst sinds vier jaar (van 10,6% naar 10,1%). In 2006 stabiliseerde dit percentage bij mannen die seks hebben met mannen (MSM), en die trend zette door in 2007. Het percentage positieve gonorroe-, syfilis- en hivtesten nam net als voorgaande jaren af in 2007 (respectievelijk 2,4%, 0,9% en 0,5%). Deze infecties werden het meest gediagnosticeerd bij MSM.In 2007, chlamydia was the most common bacterial sexually transmitted infection (STI) diagnosed in Dutch STI centres. Similar to previous years, infections were reported especially in young heterosexuals. The proportion of positive chlamydia tests among heterosexual men and women decreased slightly for the first time in four years (from 10.6% to 10.1%). In 2006, this proportion had stabilized in men who have sex with men (MSM) with the trend continuing in 2007. The positivity rate for gonorrhoea (2.4%), syphilis (0.9%) and HIV (0.5%) continued to decrease in 2007. These infections were most frequently diagnosed in MSM. In 2007, 306 new positive HIV cases were diagnosed in STI centres in the Netherlands. This number amounts to about one third of the total number of 864 positive HIV cases registered nationally. At the end of 2007, a total of 14,019 HIV cases in care were registered in the Netherlands. The proportion of MSM among new HIV cases rose further in 2007. In line with previous years, concurrent STIs were diagnosed very frequently among MSM visiting STI centres (45%) who had known HIV positive status. In this group of men, Lymphogranuloma Venereum (LGV) an aggressive type of chlamydia, has been reported frequently since 2004; this has also been the case for hepatitis C since 2007. In this group of men, strengthened surveillance and innovative interventions are warranted in order to prevent further transmission both among MSM and to other population groups. In some specific migrant groups in the Dutch population -- for example, people from Surinam, the Netherlands Antilles and Aruba -- HIV, chlamydia, gonorrhoea and syphilis are more common than in the autochthonous Dutch population. This indicates the need for targeted intervention by risk profile. The specialised STI centres in the Netherlands offer STI testing and care targeted at high risk groups. In 2007, approximately 78,000 people used this service amounting to a rise of 13% compared to 2006

3+1 dimensional Yang-Mills theory as a local theory of evolution of metrics on 3 manifolds

An explicit canonical transformation is constructed to relate the physical subspace of Yang-Mills theory to the phase space of the ADM variables of general relativity. This maps 3+1 dimensional Yang-Mills theory to local evolution of metrics on 3 manifolds.Comment: 7 pages, revte

Towards standardized definitions for monitoring the continuum of HIV care in Europe

International audienceThe continuum of HIV care is a simple conceptual framework for monitoring HIV programmes, comprising a series of stages that people living with HIV (PLHIV) pass through to access antiretroviral treatment (ART) and achieve viral suppression [1,2]. Individual benefits of suppression include reduced risk of morbidity and mortality. At the population level, viral suppression reduces the risk of onward transmission and enables epidemic containment [3]. Transmission risk may be further reduced by lowering the number of undiagnosed PLHIV [4,5]. Complete continua are, therefore, constructed beginning with the total number of PLHIV in a given population and ending with the number virally suppressed. Intervening stages have included the numbers diagnosed, linked to HIV care, retained in care, eligible for ART, on ART and adhering to ART. Although people can move between stages, the continuum is typically conceptualized as a ‘snapshot’ at one time-point

Changing patterns of undiagnosed HIV infection in the Netherlands: Who benefits most from intensified HIV test and treat policies?

Objectives: To estimate HIV prevalence, the number of people living with HIV/AIDS (PLWHA) and the undiagnosed proportion in the Netherlands for 2012, and to compare these with published 2007 estimates. Design: Synthesis of all available data sources. Methods: Multi-Parameter Evidence Synthesis (MPES) was used to obtain estimates in mutually exclusive key populations at higher risk in three geographical regions (Amsterdam, Rotterdam, rest of the Netherlands). Data sources included HIV prevalence surveys, diagnoses at STI clinics, and registered cases in HIV care. Group specific estimates were reported as Bayesian posterior medians and 95% credible intervals (CrI). Results: The 2012 model estimated 24,350 PLWHA (95% CrI 20,420-31,280) aged 15-70 years; 2,906 (+14%) more than in 2007. The estimated population HIV prevalence was 0.20% (95% CrI 0.17-0.26%). The overall proportion of undiagnosed HIV was lower in 2012 (34%, 95% CrI 22-49%) compared to 2007 (40%, 95% CrI 25-55%). After MSM, migrants from sub-Saharan Africa and the Caribbean formed the largest groups of PLWHA, but proportions of undiagnosed HIV remained high in these groups, 48% and 44% respectively. Amsterdam had lowest proportions undiagnosed for most key populations at higher risk, including MSM and migrants. Conclusions: In 2012, the number of PLWHA was higher compared to 2007, while the proportion of undiagnosed HIV was lower, especially among MSM. Higher HIV testing rates, earlier treatment, and an improved life expectancy may explain these differences. HIV interventions need to be expanded in all key populations at higher risk, with special focus on migrants and key populationsliving outside of Amsterdam. Copyright