Modeling of the HIV infection epidemic in the Netherlands: A multi-parameter evidence synthesis approach

Multi-parameter evidence synthesis (MPES) is receiving growing attention from the epidemiological community as a coherent and flexible analytical framework to accommodate a disparate body of evidence available to inform disease incidence and prevalence estimation. MPES is the statistical methodology adopted by the Health Protection Agency in the UK for its annual national assessment of the HIV epidemic, and is acknowledged by the World Health Organization and UNAIDS as a valuable technique for the estimation of adult HIV prevalence from surveillance data. This paper describes the results of utilizing a Bayesian MPES approach to model HIV prevalence in the Netherlands at the end of 2007, using an array of field data from different study designs on various population risk subgroups and with a varying degree of regional coverage. Auxiliary data and expert opinion were additionally incorporated to resolve issues arising from biased, insufficient or inconsistent evidence. This case study offers a demonstration of the ability of MPES to naturally integrate and critically reconcile disparate and heterogeneous sources of evidence, while producing reliable estimates of HIV prevalence used to support public health decision-making.Comment: Published in at http://dx.doi.org/10.1214/11-AOAS488 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

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

How Hepatitis D Virus Can Hinder the Control of Hepatitis B Virus

BACKGROUND: Hepatitis D (or hepatitis delta) virus is a defective virus that relies on hepatitis B virus (HBV) for transmission; infection with hepatitis D can occur only as coinfection with HBV or superinfection of an existing HBV infection. Because of the bond between the two viruses, control measures for HBV may have also affected the spread of hepatitis D, as evidenced by the decline of hepatitis D in recent years. Since the presence of hepatitis D is associated with suppressed HBV replication and possibly infectivity, it is reasonable to speculate that hepatitis D may facilitate the control of HBV. METHODOLOGY AND PRINCIPAL FINDINGS: We introduced a mathematical model for the transmission of HBV and hepatitis D, where individuals with dual HBV and hepatitis D infection transmit both viruses. We calculated the reproduction numbers of single HBV infections and dual HBV and hepatitis D infections and examined the endemic prevalences of the two viruses. The results show that hepatitis D virus modulates not only the severity of the HBV epidemic, but also the impact of interventions for HBV. Surprisingly we find that the presence of hepatitis D virus may hamper the eradication of HBV. Interventions that aim to reduce the basic reproduction number of HBV below one may not be sufficient to eradicate the virus, as control of HBV depends also on the reproduction numbers of dual infections. CONCLUSIONS AND SIGNIFICANCE: For populations where hepatitis D is endemic, plans for control programs ignoring the presence of hepatitis D may underestimate the HBV epidemic and produce overoptimistic results. The current HBV surveillance should be augmented with monitoring of hepatitis D, in order to improve accuracy of the monitoring and the efficacy of control measures

Increased Genetic Diversity of HIV-1 Circulating in Hong Kong

HIV-1 group M strains are characterized into 9 pure subtypes and 48 circulating recombinant forms (CRFs). Recent studies have identified the presence of new HIV-1 recombinants in Hong Kong and their complexity continues to increase. This study aims to characterize the HIV-1 genetic diversity in Hong Kong. Phylogenetic analyses were performed by using HIV-1 pol sequences including protease and partial reverse transcriptase isolated from 1045 local patients in Hong Kong from 2003 to 2008. For the pol sequences with unassigned genotype, the evidence of recombination was determined by using sliding-window based bootscan plots and their env C2V3 region were also sequenced. Epidemiological background of these patients was further collected. The pol phylogenetic analyses highlighted the extent of HIV-1 genetic diversity in Hong Kong. Subtype B (450/1045; 43.1%) and CRF01_AE (469/1045; 44.9%) variants were clearly predominant. Other genotypes (126/1045; 12.1%) including 3 defined subtypes, 10 CRFs, 1 unassigned subtype and 33 recombinants with 11 different mosaic patterns were observed. Recombinants of subtype B and CRF01_AE were mainly found among local Chinese MSM throughout 2004 to 2008, while the CRF02_AG and subtype G recombinants were circulating among non-Chinese Asian population in Hong Kong through heterosexual transmission starting from 2008. Our study demonstrated the complex recombination of HIV-1 in Hong Kong and the need in developing surveillance system for tracking the distribution of new HIV-1 genetic variants

Untangling the Interplay between Epidemic Spread and Transmission Network Dynamics

The epidemic spread of infectious diseases is ubiquitous and often has a considerable impact on public health and economic wealth. The large variability in the spatio-temporal patterns of epidemics prohibits simple interventions and requires a detailed analysis of each epidemic with respect to its infectious agent and the corresponding routes of transmission. To facilitate this analysis, we introduce a mathematical framework which links epidemic patterns to the topology and dynamics of the underlying transmission network. The evolution, both in disease prevalence and transmission network topology, is derived from a closed set of partial differential equations for infections without allowing for recovery. The predictions are in excellent agreement with complementarily conducted agent-based simulations. The capacity of this new method is demonstrated in several case studies on HIV epidemics in synthetic populations: it allows us to monitor the evolution of contact behavior among healthy and infected individuals and the contributions of different disease stages to the spreading of the epidemic. This gives both direction to and a test bed for targeted intervention strategies for epidemic control. In conclusion, this mathematical framework provides a capable toolbox for the analysis of epidemics from first principles. This allows for fast, in silico modeling - and manipulation - of epidemics and is especially powerful if complemented with adequate empirical data for parameterization

Development of Mathematical Models for the Analysis of Hepatitis Delta Virus Viral Dynamics

BACKGROUND: Mathematical models have shown to be extremely helpful in understanding the dynamics of different virus diseases, including hepatitis B. Hepatitis D virus (HDV) is a satellite virus of the hepatitis B virus (HBV). In the liver, production of new HDV virions depends on the presence of HBV. There are two ways in which HDV can occur in an individual: co-infection and super-infection. Co-infection occurs when an individual is simultaneously infected by HBV and HDV, while super-infection occurs in persons with an existing chronic HBV infection. METHODOLOGY/PRINCIPAL FINDINGS: In this work a mathematical model based on differential equations is proposed for the viral dynamics of the hepatitis D virus (HDV) across different scenarios. This model takes into consideration the knowledge of the biology of the virus and its interaction with the host. In this work we will present the results of a simulation study where two scenarios were considered, co-infection and super-infection, together with different antiviral therapies. Although, in general the predicted course of HDV infection is similar to that observed for HBV, we observe a faster increase in the number of HBV infected cells and viral load. In most tested scenarios, the number of HDV infected cells and viral load values remain below corresponding predicted values for HBV. CONCLUSIONS/SIGNIFICANCE: The simulation study shows that, under the most commonly used and generally accepted therapy approaches for HDV infection, such as lamivudine (LMV) or ribavirine, peggylated alpha-interferon (IFN) or a combination of both, LMV monotherapy and combination therapy of LMV and IFN were predicted to more effectively reduce the HBV and HDV viral loads in the case of super-infection scenarios when compared with the co-infection. In contrast, IFN monotherapy was found to reduce the HDV viral load more efficiently in the case of super-infection while the effect on the HBV viral load was more pronounced during co-infection. The results suggest that there is a need for development of high efficacy therapeutic approaches towards the specific inhibition of HDV replication. These approaches may additionally be directed to the reduction of the half-life of infected cells and life-span of newly produced circulating virions

Effects of a short individually tailored counselling session for HIV prevention in gay and bisexual men receiving Hepatitis B vaccination

Background. There is currently a trend towards unsafe unprotected anal intercourse (UAI) among men who have sex with men. We evaluated a short individual counselling session on reducing UAI among gay and bisexual men. Methods. A quasi-experimental design was used to evaluate the counselling session. This session was conducted during consulting hours at four municipal health clinics during a Hepatitis B vaccination campaign. These clinics offered free vaccination to high-risk groups, such as gay and bisexual men. All gay and bisexual men attending health clinics in four cities in the Netherlands were asked to participate. Each participant in the intervention group received a fifteen-minute individual counselling based on the Theory of Planned Behaviour and Motivational Interviewing. Changes in UAI were measured over a 5-months period, using self-administered questionnaires. UAI was measured separately for receptive and insertive intercourse in steady and casual partners. These measures were combined in an index-score (range 0-8). Results. While UAI in the counselling group remained stable, it increased in the controls by 66% from 0.41 to 0.68. The results show that the intervention had a protective effect on sexual behaviour with steady partners. Intervention effects were strongest within steady relationships, especially for men whose steady-relationship status changed during the study. The intervention was well accepted among the target group. Conclusion. The fifteen-minute individually tailored counselling session was not only well accepted but also had a protective effect on risk behaviour after a follow-up of six months

Sex-Specific Immunization for Sexually Transmitted Infections Such as Human Papillomavirus: Insights from Mathematical Models

Johannes Bogaards and colleagues use mathematical models to investigate whether vaccinating females only, males only, or both sexes is the best way to achieve the most effective reduction in the population prevalence of sexually-transmitted infection

Recent HIV-1 Infection Contributes to the Viral Diffusion over the French Territory with a Recent Increasing Frequency

To analyse the contribution of primary human immunodeficiency virus type 1 (HIV-1) infection (PHI) to the French viral epidemic. sequences included 987 PHI from the French ANRS PRIMO cohort between 1999 and 2010 and were analysed using a population-based phylogenetic approach. Clinical features, risk factors, sexual behaviour and drug resistance for clustered and nonclustered transmission events were ascertained.Viruses from 125 (12.7%) of PHI cosegregated into 56 transmission chains, with increasing frequency during the last years (10.2% before 2006 versus 15.2% of clusters in 2006–2010, p = 0.02). The mean number of patients per cluster was 2.44. Compared to unique PHI, clusters involved more often men, infected through homosexual intercourse, of young age, with a high number of casual sexual partnerships and frequent previous HIV serological tests. Resistant strains were found in 16.0% and 11.1% of clusters and unique PHI, respectively (p = 0.11). Overall, 34% (n = 19) clusters included patients followed in French regions far apart, involving 13 clusters with at least one Parisian patient.PHIs are a significant source of onward transmission, especially in the MSM population. Recently infected people contribute to the spread of the viral epidemic throughout the French territory. Survey of transmitted drug resistance and behavioural characteristics of patients involved into clustered PHI may help to guide prevention and treatment interventions