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

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

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

The roles of the general practitioner and sexual health centre in HIV testing:comparative insights and impact on HIV incidence rates in the Rotterdam area, the Netherlands - a cross-sectional population-based study

Background: Access to HIV testing is crucial for detection, linkage to treatment, and prevention. In less urbanised areas, reliance on general practitioners (GPs) for HIV testing is probable, as sexual health centres (SHC) are mostly located within urbanised areas. Limited insight into individuals undergoing HIV testing stems from sparse standard registration of demographics at GPs. This cross-sectional study aims (1) to assess and compare HIV testing at the GP and SHC, and (2) to assess population- and provider-specific HIV incidence. Methods: Individual HIV testing data of GPs and SHC were linked to population register data (aged ≥ 15 years, Rotterdam area, 2015–2019). We reported the proportion HIV tested, and compared GP and SHC testing rates with negative binomial generalised additive models. Data on new HIV diagnoses (2015–2019) from the Dutch HIV Monitoring Foundation relative to the population were used to assess HIV incidence. Results: The overall proportion HIV tested was 1.14% for all residents, ranging from 0.41% for ≥ 40-year-olds to 4.70% for Antilleans. The GP testing rate was generally higher than the SHC testing rate with an overall rate ratio (RR) of 1.61 (95% CI: 1.56–1.65), but not for 15-24-year-olds (RR: 0.81, 95% CI: 0.74–0.88). Large differences in HIV testing rate (1.36 to 39.47 per 1,000 residents) and GP-SHC ratio (RR: 0.23 to 7.24) by geographical area were observed. The GPs’ contribution in HIV testing was greater for GP in areas further away from the SHC. In general, population groups that are relatively often tested are also the groups with most diagnoses and highest incidence (e.g., men who have sex with men, non-western). The overall incidence was 10.55 per 100,000 residents, varying from 3.09 for heterosexual men/women to 24.04 for 25–29-year-olds. Conclusions: GPs have a pivotal role in HIV testing in less urbanised areas further away from the SHC, and among some population groups. A relatively high incidence often follows relatively high testing rates. Opportunities to improve HIV testing have been found for migrants, lower-educated individuals, in areas less urbanised areas and further away from GP/SHC. Strategies include additional targeted testing, via for example SHC branch locations and outreach activities.</p

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

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

Testing and healthcare seeking behavior preceding HIV diagnosis among migrant and non-migrant individuals living in the Netherlands: Directions for early-case finding

OBJECTIVES: To assess differences in socio-demographics, HIV testing and healthcare seeking behavior between individuals diagnosed late and those diagnosed early after HIV-acquisition. DESIGN: Cross-sectional study among recently HIV-diagnosed migrant and non-migrant individuals living in the Netherlands. METHODS: Participants self-completed a questionnaire on socio-demographics, HIV-testing and healthcare seeking behavior preceding HIV diagnosis between 2013-2015. Using multivariable logistic regression, socio-demographic determinants of late diagnosis were explored. Variables on HIV-infection, testing and access to care preceding HIV diagnosis were compared between those diagnosed early and those diagnosed late using descriptive statistics. RESULTS: We included 143 individuals with early and 101 with late diagnosis, of whom respectively 59/143 (41%) and 54/101 (53%) were migrants. Late diagnosis was significantly associated with older age and being heterosexual. Before HIV diagnosis, 89% of those with early and 62% of those with late diagnosis had ever been tested for HIV-infection (p<0.001), and respectively 99% and 97% reported healthcare usage in the Netherlands in the two years preceding HIV diagnosis (p = 0.79). Individuals diagnosed late most frequently visited a general practitioner (72%) or dentist (62%), and 20% had been hospitalized preceding diagnosis. In these settings, only in respectively 20%, 2%, and 6% HIV-testing was discussed. CONCLUSION: A large proportion of people diagnosed late had previously tested for HIV and had high levels of healthcare usage. For earlier-case finding of HIV it therefore seems feasible to successfully roll out interventions within the existing healthcare system. Simultaneously, efforts should be made to encourage future repeated or routine HIV testing among individuals whenever they undergo an HIV test

Estimating HIV incidence and number of undiagnosed individuals living with HIV in the European Union/European Economic Area, 2015

Helena Cortes Martins, Departamento de Doenças Infeciosas do Instituto Nacional de Saúde Doutor Ricardo Jorge, IPSince 2011, human immunodeficiency virus (HIV) incidence appears unchanged in the European Union/European Economic Area with between 29,000 and 33,000 new cases reported annually up to 2015. Despite evidence that HIV diagnosis is occurring earlier post-infection, the estimated number of people living with HIV (PLHIV) who were unaware of being infected in 2015 was 122,000, or 15% of all PLHIV (n=810,000). This is concerning as such individuals cannot benefit from highly effective treatment and may unknowingly sustain transmission.Members of the ECDC HIV/AIDS Surveillance and Dublin Declaration Monitoring Networks: Portugal: Kamal Mansinho, Helena Cortes Martins, Teresa Melo.info:eu-repo/semantics/publishedVersio

Bayesian mixture models for phylogenetic source attribution from consensus sequences and time since infection estimates

In stopping the spread of infectious diseases, pathogen genomic data can be used to reconstruct transmission events and characterize population-level sources of infection. Most approaches for identifying transmission pairs do not account for the time that passed since divergence of pathogen variants in individuals, which is problematic in viruses with high within-host evolutionary rates. This is prompting us to consider possible transmission pairs in terms of phylogenetic data and additional estimates of time since infection derived from clinical biomarkers. We develop Bayesian mixture models with an evolutionary clock as signal component and additional mixed effects or covariate random functions describing the mixing weights to classify potential pairs into likely and unlikely transmission pairs. We demonstrate that although sources cannot be identified at the individual level with certainty, even with the additional data on time elapsed, inferences into the population-level sources of transmission are possible, and more accurate than using only phylogenetic data without time since infection estimates. We apply the approach to estimate age-specific sources of HIV infection in Amsterdam MSM transmission networks between 2010-2021. This study demonstrates that infection time estimates provide informative data to characterize transmission sources, and shows how phylogenetic source attribution can then be done with multi-dimensional mixture models

Immunovirological Response to Triple Nucleotide Reverse-Transcriptase Inhibitors and Ritonavir-Boosted Protease Inhibitors in Treatment-Naive HIV-2-Infected Patients: The ACHIEV2E Collaboration Study Group

This European inter-cohort collaboration shows poorer immunological and virological responses with triple NRTI compared to PI/r-containing cART in treatment-naïve HIV-2-infected patients, regardless of baseline CD4 cell count. PI/r-containing cART should be recommended as first-line antiretroviral regimens in HIV-2 infectio