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

Monitoring recently acquired HIV infections in Amsterdam, The Netherlands:The attribution of test locations

Background:  Surveillance of recent HIV infections (RHI) using an avidity assay has been implemented at Dutch sexual health centres (SHC) since 2014, but data on RHI diagnosed at other test locations is lacking. Setting:  Implementation of the avidity assay in HIV treatment clinics for the purpose of studying RHI among HIV patients tested at different test locations. Methods: We retrospectively tested leftover specimens from newly diagnosed HIV patients in care in 2013–2015 in Amsterdam. Avidity Index (AI) values ≤0.80 indicated recent infection (acquired ≤6 months prior to diagnosis), and AI > 0.80 indicated established infection (acquired >6 months prior to diagnosis). An algorithm for RHI was applied to correct for false recency. Recency based on this algorithm was compared with recency based on epidemiological data only. Multivariable logistic regression analysis was used to identify factors associated with RHI among men who have sex with men (MSM).Results: We tested 447 specimens with avidity; 72% from MSM. Proportions of RHI were 20% among MSM and 10% among heterosexuals. SHC showed highest proportions of RHI (27%), followed by GPs (15%), hospitals (5%), and other/unknown locations (11%) (p < 0.001). Test location was the only factor associated with RHI among MSM. A higher proportion of RHI was found based on epidemiological data compared to avidity testing combined with the RHI algorithm. Conclusion:  SHC identify more RHI infections compared to other test locations, as they serve high-risk populations and offer frequent HIV testing. Using avidity-testing for surveillance purposes may help targeting prevention programs, but the assay lacks robustness and its added value may decline with improved, repeat HIV testing and data collection

Single Nucleotide Polymorphism in Gene Encoding Transcription Factor Prep1 Is Associated with HIV-1-Associated Dementia

BACKGROUND: Infection with HIV-1 may result in severe cognitive and motor impairment, referred to as HIV-1-associated dementia (HAD). While its prevalence has dropped significantly in the era of combination antiretroviral therapy, milder neurocognitive disorders persist with a high prevalence. To identify additional therapeutic targets for treating HIV-associated neurocognitive disorders, several candidate gene polymorphisms have been evaluated, but few have been replicated across multiple studies. METHODS: We here tested 7 candidate gene polymorphisms for association with HAD in a case-control study consisting of 86 HAD cases and 246 non-HAD AIDS patients as controls. Since infected monocytes and macrophages are thought to play an important role in the infection of the brain, 5 recently identified single nucleotide polymorphisms (SNPs) affecting HIV-1 replication in macrophages in vitro were also tested. RESULTS: The CCR5 wt/Δ32 genotype was only associated with HAD in individuals who developed AIDS prior to 1991, in agreement with the observed fading effect of this genotype on viral load set point. A significant difference in genotype distribution among all cases and controls irrespective of year of AIDS diagnosis was found only for a SNP in candidate gene PREP1 (p = 1.2 × 10(-5)). Prep1 has recently been identified as a transcription factor preferentially binding the -2,518 G allele in the promoter of the gene encoding MCP-1, a protein with a well established role in the etiology of HAD. CONCLUSION: These results support previous findings suggesting an important role for MCP-1 in the onset of HIV-1-associated neurocognitive disorders

Comparison of the risks of atherosclerotic events versus death from other causes associated with antiretroviral use.

BACKGROUND: Studies considering the risk of atherosclerotic disease (AtD) associated with the use of HAART have reported inconsistent results. METHODS: Data on antiretroviral therapy (ART) use, risk factors for cardiovascular disease (CVD), AtD and death from other causes in 18 603 HIV-infected patients from two established cohorts were evaluated. The relative hazards of AtD and death from other causes were calculated using a proportional hazards competing risks framework. The impact of protease inhibitor (PI)-containing, non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing or PI + NNRTI-containing regimens on these outcomes were compared to nucleoside reverse transcriptase inhibitor (NRTI)-only regimens or stopping therapy, adjusting for known CVD risk factors. RESULTS: In 77 480 person-years of follow-up (median duration 3.49 years) there were 318 AtD events including 92 myocardial infarctions and 2044 deaths. Older age, hypertension, diabetes mellitus, having smoked and HIV disease stage were significantly associated with increased risk of AtD. PI- and NNRTI-containing regimens significantly reduced the joint risk of either AtD or death from other causes compared to NRTI-only or stopping therapy [hazard ratio (HR) for PI-containing ART, 0.76, 95% confidence interval (CI), 0.73-0.78, P< 0.001; NNRTI-containing ART, 0.69, 95% CI, 0.65-0.74; P< 0.001). PI-containing ART was associated with a borderline significant increased risk of myocardial infarction (cause-specific HR for PI-containing ART 1.19, 95% CI, 1.01-1.40, P = 0.04) but not with increased risk of AtD compared to NRTI-only regimens or stopping therapy (cause-specific HR for PI-containing ART, 1.03, 95% CI, 0.95-1.13, P = 0.44). CONCLUSIONS: Overall benefits of PI- and NNRTI-based ART in reducing mortality significantly outweigh any risks of AtD in the "short-term" follow-up of this study. Traditional cardiac risk factors play an important role in determining AtD risk status

Mortality and progression to AIDS after starting highly active antiretroviral therapy.

OBJECTIVES: To examine survival and progression to AIDS among HIV-infected patients after starting highly active antiretroviral therapy (HAART). METHODS: The study population consisted of 3724 patients from the ATHENA observational cohort who initiated HAART. We considered progression to either an AIDS-defining disease or death, distinguishing HIV-related and non-related (including therapy-related) deaths. A time-dependent multivariate hazards model was fitted to the patient data and 5-year survival probabilities under various therapy scenarios estimated. RESULTS: A total of 459 patients developed AIDS and 346 died during 12 503 person-years of follow-up. HIV-related mortality decreased from 3.8 to 0.7 per 100 person-years between 1996 and 2000 whereas non-HIV-related mortality did not change (0.4 and 0.9, respectively, P = 0.25). For asymptomatic and symptomatic therapy naive patients younger than 50 years with CD4 counts above 10 x 10(6) and 150 x 10(6) cells/l, respectively, predicted 5-year survival probabilities were above 90% when HAART was used continuously. This limit was 450 x 10(6) cells/l when HAART was used during 20 weeks in each 24 week-period of follow-up, and 110 x 10(6) cells/l when patients delayed initiation of HAART for 1 year after becoming eligible for treatment. CONCLUSIONS: Survival probabilities were high among HIV-infected patients initiating HAART at an early stage of infection. The best therapy strategy is therefore to start HAART at this stage of infection. However, deferring HAART in patients with high CD4 cell counts may be clinically more appropriate given toxicity and adherence problems. The lack of any change in non-HIV-related mortality suggests that toxicity has not yet become a major risk factor for death

Phylogenetic evidence for underreporting of male-to-male sex among human immunodeficiency virus-infected donors in the Netherlands and Flanders

Separate transmission networks for human immunodeficiency virus (HIV) coexist. Molecular typing of viral genomes can provide insight in HIV transmission routes in donors for whom risk behavior-based donor selection failed.status: publishe

Comparing viral load metrics and evaluating their use for HIV surveillance

OBJECTIVES: To investigate the value of in-care viral load (ICVL) and other viral load (VL) metrics for HIV surveillance by comparing time trends and associations with numbers of new HIV diagnoses. METHODS: Data from 20,740 HIV patients registered in the Dutch ATHENA-cohort between 2002 and 2013 were used. We compared: six ICVL metrics (i.e. mean of the mean/first/last/highest log VL, median of the median log VL, first log VL for newly diagnosed combined with mean log VL for all others), log VL at diagnosis, proportion of patients with transmission risk (>400 copies/ml) or suppressed VL (≤200 copies/ml). Subgroup differences were assessed using Kruskal-Wallis and chi-square tests. Negative binomial regression was used for studying associations between VL metrics and numbers of new diagnoses 1-4 years later. RESULTS: Most ICVL metrics showed similar decreasing trends over time. Differences in covariables were found for all VL metrics. Mean ICVL showed the strongest association with new diagnoses: a decrease of one log unit in mean ICVL was associated with a 21% decrease in new diagnoses two years later. CONCLUSIONS: VL metrics may be of value for enhancing HIV surveillance by identifying subgroup differences in impact of treatment on viral suppression, and by predicting numbers of new diagnoses in subsequent years

Comparing viral load metrics and evaluating their use for HIV surveillance.

To investigate the value of in-care viral load (ICVL) and other viral load (VL) metrics for HIV surveillance by comparing time trends and associations with numbers of new HIV diagnoses

Cardiovascular Disease Prevention Policy in Human Immunodeficiency Virus : Recommendations From a Modeling Study

Background: Cardiovascular disease (CVD) is expected to contribute a large non-communicable disease burden amongst HIV-positive people. We quantify the impact of prevention interventions on annual CVD burden and costs amongst HIV-positive people in The Netherlands. Methods: We constructed an individual-based model of CVD in HIV-positive people using national ATHENA cohort data on 8,791 patients on combination antiretroviral therapy (cART). The model follows patients as they age, develop CVD (by incorporating a CVD risk equation) and start cardiovascular medication. Four prevention interventions were evaluated: (1) increasing the rate of earlier HIV diagnosis and treatment; (2) avoiding use of cART with increased CVD risk; (3) smoking cessation; (4) intensified monitoring and drug treatment of hypertension and dyslipidaemia, quantifying annual number of averted CVDs and costs. Results: The model predicts that annual CVD incidence and costs will increase by 55% and 36% between 2015-2030. Traditional prevention interventions, i.e. smoking cessation and intensified monitoring and treatment of hypertension and dyslipidaemia, will avert the largest number of annual CVD cases (13.1% and 20.0%) compared to HIV-related interventions, i.e. earlier HIV diagnosis and treatment and avoiding cART with increased CVD risk (0.8% and 3.7%, respectively), as well as reduce cumulative CVD-related costs. Targeting high risk patients could avert the majority of events and costs. Conclusions: Traditional CVD prevention interventions can maximize cardiovascular health and defray future costs, particularly if targeting high risk patients. Quantifying additional public health benefits, beyond CVD, is likely to provide further evidence for policy development