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

The Fading of the Mpox Outbreak Among Men Who Have Sex With Men: A Mathematical Modelling Study

BACKGROUND: In the Netherlands, the number of mpox cases started declining before mpox vaccination was initiated. Most cases were men who have sex with men (MSM). We investigated whether the decline in mpox could be attributed to infection-induced immunity or behavioural adaptations. METHODS: We developed a transmission model and accounted for possible behavioural adaptations: less casual partners and shorter time until MSM with mpox refrain from sexual contacts. RESULTS: Without behavioural adaptations, the peak in modelled cases matched observations, but the decline was less steep than observed. With behavioural adaptations in the model, we found a decline of 16-18% in numbers of casual partners in June and 13-22% in July 2022. Model results showed a halving of the time before refraining from sex. When mpox vaccination started, 57% of MSM with very high sexual activity in the model had been infected. Model scenarios revealed that the outbreak could have waned by November 2022 even without vaccination. CONCLUSIONS: The limited duration of the mpox outbreak in the Netherlands can be ascribed primarily to infection-induced immunity among MSM with high sexual activity levels. The decline was accelerated by behavioural adaptations. Immunity among those most sexually active is essential to impede mpox resurgence

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

‘Living a life less ordinary’: exploring the experiences of Australian men who have acquired HIV overseas

Background: Increasing international mobility has led to a growth of cross-border HIV transmission around the world. In Australia, increasing rates of HIV infections acquired overseas have been reported, particularly among men. This qualitative study explored experiences and risk perceptions of 14 Australian men who acquired HIV while living or travelling overseas from the year 2000. Methods: Symbolic interaction provided the study’s theoretical perspective and analytical framework. Australian men living with HIV who were aged 18 years and older, believed they had acquired their infection while working or travelling overseas during or after the year 2000, and were diagnosed from 2003 onwards were eligible to participate. A semistructured interview schedule was developed and tested for content validity with the study reference group. Analysis was conducted using an adapted form of grounded theory to form the basis for the development of the experiences domains. Results: Analysis produced four domains of experience: (1) a fantasy realised, (2) escaping and finding a new self or life, (3) living a life less ordinary and (4) living local but still an outsider. The description of the four experience domains highlights how risk generally, particularly sexual risk, did or did not feature in these men’s understanding of their experiences. Conclusion: Perceptions and experiences of long-term travel played a decisive role for men who acquired HIV when travelling overseas. Appealing to desired experiences such as connection to local culture or sustaining a new or adventurous life may provide important implications for guiding health promotion programs and policy

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

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

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

Measuring and modelling concurrency

This article explores three critical topics discussed in the recent debate over concurrency (overlapping sexual partnerships): measurement of the prevalence of concurrency, mathematical modelling of concurrency and HIV epidemic dynamics, and measuring the correlation between HIV and concurrency. The focus of the article is the concurrency hypothesis – the proposition that presumed high prevalence of concurrency explains sub-Saharan Africa's exceptionally high HIV prevalence. Recent surveys using improved questionnaire design show reported concurrency ranging from 0.8% to 7.6% in the region. Even after adjusting for plausible levels of reporting errors, appropriately parameterized sexual network models of HIV epidemics do not generate sustainable epidemic trajectories (avoid epidemic extinction) at levels of concurrency found in recent surveys in sub-Saharan Africa. Efforts to support the concurrency hypothesis with a statistical correlation between HIV incidence and concurrency prevalence are not yet successful. Two decades of efforts to find evidence in support of the concurrency hypothesis have failed to build a convincing case