http://repub.eur.nl/res/aut/5733/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/33992/ 2011-12-01T00:00:00Z Mobility is associated with HIV due to more risky sexual behaviour of mobile groups such as travellers and migrants. Limited participation of such groups may reduce the effectiveness of HIV interventions disproportionally. The established STDSIM model, which simulates transmission and control of HIV and STD, was extended to simulate mobility patterns based on data from Tanzania. We explored the impact of non-participation of mobile groups (travellers and recent migrants) on the effectiveness of two interventions: condom promotion and health education aiming at partner reduction. If mobile groups do not participate, the effectiveness of both interventions could be reduced by 40%. The impact of targeting travellers with a combined HIV campaign is close to that of a general population intervention. In conclusion, it is important to account for possible non-participation of migrants and travellers. If non-participation is substantial, impact of interventions can be greatly improved by actively approaching these people. http://repub.eur.nl/res/pub/34344/ 2011-11-01T00:00:00Z Background Descriptions of the effects of moderate alcohol consumption during pregnancy on adverse pregnancy outcomes have been inconsistent. Objective To review systematically and perform meta-analyses on the effect of maternal alcohol exposure on the risk of low birthweight, preterm birth and small for gestational age (SGA). Search strategy Using Medical Subject Headings, a literature search of MEDLINE, EMBASE, CINAHL, CABS, WHOlist, SIGLE, ETOH, and Web of Science between 1 January 1980 and 1 August 2009 was performed followed by manual searches. Selection criteria Case-control or cohort studies were assessed for quality (STROBE), 36 available studies were included. Data collection and analysis Two reviewers independently extracted the information on low birthweight, preterm birth and SGA using a standardised protocol. Meta-analyses on dose-response relationships were performed using linear as well as first-order and second-order fractional polynomial regressions to estimate best fitting curves to the data. Main results Compared with abstainers, the overall dose-response relationships for low birthweight and SGA showed no effect up to 10 g pure alcohol/day (an average of about 1 drink/day) and preterm birth showed no effect up to 18 g pure alcohol/day (an average of 1.5 drinks/day); thereafter, the relationship showed a monotonically increasing risk for increasing maternal alcohol consumption. Moderate consumption during pre-pregnancy was associated with reduced risks for all outcomes. Conclusions Dose-response relationship indicates that heavy alcohol consumption during pregnancy increases the risks of all three outcomes whereas light to moderate alcohol consumption shows no effect. Preventive measures during antenatal consultations should be initiated. © 2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology http://repub.eur.nl/res/pub/31130/ 2011-08-24T00:00:00Z We used an established microsimulation model, quantified to a rural South African setting with a well developed antiretroviral treatment programme, to predict the impact of antiretroviral therapy on the HIV epidemic in the population aged over 50 years. We show that the HIV prevalence in patients aged over 50 years will nearly double in the next 30 years, whereas the fraction of HIV-infected patients aged over 50 years will triple in the same period. This ageing epidemic has important consequences for the South African healthcare system, as older HIV patients require specialized care. http://repub.eur.nl/res/pub/31228/ 2011-08-18T00:00:00Z Background: The only successful HIV vaccine trial to date is the RV144 trial of the ALVAC/AIDSVAX vaccine in Thailand, which showed an overall incidence reduction of 31%. Most cases were prevented in the first year, suggesting a rapidly waning efficacy. Here, we predict the population level impact and cost-effectiveness of practical implementation of such a vaccine in a setting of a generalised epidemic with high HIV prevalence and incidence. Methods: We used STDSIM, an established individual-based microsimulation model, tailored to a rural South African area with a well-functioning HIV treatment and care programme. We estimated the impact of a single round of mass vaccination for everybody aged 15-49, as well as 5-year and 2-year re-vaccination strategies for young adults (aged 15-29). We calculated proportion of new infections prevented, cost-effectiveness indicators, and budget impact estimates of combined ART and vaccination programmes. Results: A single round of mass vaccination with a RV144-like vaccine will have a limited impact, preventing only 9% or 5% of new infections after 10 years at 60% and 30% coverage levels, respectively. Revaccination strategies are highly cost-effective if vaccine prices can be kept below 150 US/vaccine for 2-year revaccination strategies, and below 200 US/vaccine for 5-year revaccination strategies. Net cost-savings through reduced need for HIV treatment and care occur when vaccine prices are kept below 75 US/vaccine. These results are sensitive to alternative assumptions on the underlying sexual network, background prevention interventions, and individual's propensity and consistency to participate in the vaccination campaign. Discussion: A modestly effective vaccine can be a cost-effective intervention in highly endemic settings. To predict the impact of vaccination strategies in other endemic situations, sufficient knowledge of the underlying sexual network, prevention and treatment interventions, and individual propensity and consistency to participate, is key. These issues are all best addressed in an individual-based microsimulation model. http://repub.eur.nl/res/pub/34665/ 2011-07-26T00:00:00Z Background: Since November 2009, WHO recommends that adults infected with HIV should initiate antiretroviral therapy (ART) at CD4+ cell counts of ≤350 cells/μl rather than ≤200 cells/μl. South Africa decided to adopt this strategy for pregnant and TB co-infected patients only. We estimated the impact of fully adopting the new WHO guidelines on HIV epidemic dynamics and associated costs. Methods and Finding: We used an established model of the transmission and control of HIV in specified sexual networks and healthcare settings. We quantified the model to represent Hlabisa subdistrict, KwaZulu-Natal, South Africa. We predicted the HIV epidemic dynamics, number on ART and program costs under the new guidelines relative to treating patients at ≤200 cells/μl for the next 30 years. During the first five years, the new WHO treatment guidelines require about 7% extra annual investments, whereas 28% more patients receive treatment. Furthermore, there will be a more profound impact on HIV incidence, leading to relatively less annual costs after seven years. The resulting cumulative net costs reach a break-even point after on average 16 years. Conclusions: Our study strengthens the WHO recommendation of starting ART at ≤350 cells/μl for all HIV-infected patients. Apart from the benefits associated with many life-years saved, a modest frontloading appears to lead to net savings within a limited time-horizon. This finding is robust to alternative assumptions and foreseeable changes in ART prices and effectiveness. Therefore, South Africa should aim at rapidly expanding its healthcare infrastructure to fully embrace the new WHO guidelines. http://repub.eur.nl/res/pub/28384/ 2010-12-01T00:00:00Z Objective: To compare the effects of polygyny (only men can form concurrent partnerships) and gender-symmetric concurrency (both genders can form concurrent partnerships) on prevalence of long-duration sexually transmitted infections (STIs) using a dynamic stochastic network model. Methods: We modelled two pairs of scenarios: polygyny and gender symmetry at higher and lower levels of network concurrency (measured by the average number of concurrent partnerships per partnership). The same level of sexual activity was modelled in all scenarios (measured by mean per capita partnership incidence and per capita number of sex acts). Partnership duration and network concurrency were constant within each of the polygyny/symmetry pairs. Infections that mimicked characteristics of herpes simplex virus type 2 (HSV2) and HIV were introduced onto the networks separately. The mean prevalence 100 years after introduction for the HSV2-like infection and 30 years after introduction for the HIV-like infection were calculated over 1000 model iterations. Results: Prevalence of both simulated STIs was significantly lower in the polygyny scenarios than in the symmetry scenarios. At lower concurrency, polygyny resulted in a relative reduction in HSV2-like infection prevalence of 19% (95% CI 15 to 23) compared to gender symmetry. At higher concurrency polygyny led to a relative reduction of 20% (16 to 23). The relative reduction in prevalence of the HIV-like infection after 30 years was 14% (10 to 17) at lower concurrency and 8% (5 to 11) at higher concurrency. Conclusions: Polygyny can result in lower STI prevalence compared to populations where both genders practise concurrency. Further work is required to explore whether this reduction is observed when modelling more realistic populations and infection characteristics. http://repub.eur.nl/res/pub/24519/ 2009-02-05T00:00:00Z Herpes simplex virus type-2 (HSV2) infection increases HIV transmission. We explore the impact of a potential prophylactic HSV2 vaccination on HIV incidence in Africa using STDSIM an individual-based model. A campaign that achieved 70% coverage over 5 years with a vaccine that reduced susceptibility to HSV2 acquisition and HSV2 reactivation by 75% for 10 years, reduced HIV incidence by 30-40% after 20 years (range 4-66%). Over 20 years, in most scenarios fewer than 100 vaccinations were required to avert one HIV infection. HSV2 vaccines could have a substantial impact on HIV incidence. Intensified efforts are needed to develop an effective HSV2 vaccine. http://repub.eur.nl/res/pub/30291/ 2008-10-01T00:00:00Z Background: Herpes simplex virus type 2 (HSV-2) infection increases acquisition and transmission of HIV, but the results of trials measuring the impact of HSV-2 therapy on HIV genital shedding and HIV acquisition are mixed, and the potential impact of HSV-2 therapy on the incidence of HIV at the population level is unknown. Methods: The effects of episodic and suppressive HSV-2 therapy were simulated using the individual-level model STDSIM fitted to data from Cotonou, Benin (relatively low HIV prevalence) and Kisumu, Kenya (high HIV prevalence). Clinician- and patient-initiated episodic therapy, started when symptomatic, were assumed to reduce ulcer duration. Suppressive therapy, given regardless of symptoms, was also assumed to reduce ulcer frequency and HSV-2 infectiousness. Results: Clinician-initiated episodic therapy in the general population had almost no effect on the incidence of HIV. The impact of patient-initiated therapy was higher because of earlier treatment initiation, but still low (<5%) unless symptom recognition and treatment-seeking behaviour were very high. Suppressive therapy given to female sex workers (FSW) in Kisumu had little effect on population HIV incidence. In Cotonou, suppressive therapy in FSW with high coverage and long duration reduced population HIV incidence by >20% in the long term. Impact was increased in both cities by also treating a proportion of their clients. Long-term suppressive therapy with high coverage in the general population could reduce HIV incidence by more than 30%. Conclusions: These results show that HSV-2 therapy could potentially have a population-level impact on the incidence of HIV, especially in more concentrated epidemics. However, a substantial impact requires high coverage and long duration therapy, or very high symptom recognition and treatment-seeking behaviour. http://repub.eur.nl/res/pub/29539/ 2008-09-12T00:00:00Z BACKGROUND AND OBJECTIVE: Male circumcision (circumcision) reduces HIV incidence in men by 50-60%. The United Nations Joint Programme on HIV/AIDS (UNAIDS) recommends the provision of safe circumcision services in countries with high HIV and low circumcision prevalence, prioritizing 12-30 years old HIV-uninfected men. We explore how the population-level impact of circumcision varies by target age group, coverage, time-to-scale-up, level of risk compensation and circumcision of HIV-infected men. DESIGN AND METHODS: An individual-based model was fitted to the characteristics of a typical high-HIV-prevalence population in sub-Saharan Africa and three scenarios of individual-level impact corresponding to the central and the 95% confidence level estimates from the Kenyan circumcision trial. The simulated intervention increased the prevalence of circumcision from 25 to 75% over 5 years in targeted age groups. The impact and cost-effectiveness of the intervention were calculated over 2-50 years. Future costs and effects were discounted and compared with the present value of lifetime HIV treatment costs (US$ 4043). RESULTS: Initially, targeting men older than the United Nations Joint Programme on HIV/AIDS recommended age group may be the most cost-effective strategy, but targeting any adult age group will be cost-saving. Substantial risk compensation could negate impact, particularly if already circumcised men compensate. If circumcision prevalence in HIV-uninfected men increases less because HIV-infected men are also circumcised, this will reduce impact in men but would have little effect on population-level impact in women. CONCLUSION: Circumcision is a cost-saving intervention in a wide range of scenarios of HIV and initial circumcision prevalence but the United Nations Joint Programme on HIV/AIDS/WHO recommended target age group should be widened to include older HIV-uninfected men and counselling should be targeted at both newly and already circumcised men to minimize risk compensation. To maximize infections-averted, circumcision must be scaled up rapidly while maintaining quality. http://repub.eur.nl/res/pub/32369/ 2008-04-01T00:00:00Z The aim of this study was to determine whether a temporary rise in sexual risk behaviour during war in Guinea - Bissau could explain the observed trends in HIV-1 and HIV-2 prevalence, and to explore the possible contribution of competitive elimination of HIV-2 by HIV-1. A simulation model of the heterosexual transmission of sexually transmitted infections was parameterized using demographic, behavioural and epidemiological data from rural Guinea - Bissau, and fitted to the observed HIV-1 and HIV-2 trends with and without a historic rise in risk behaviour. The observed trends could only be simulated by assuming a temporary rise in risk behaviour. Around 30% of the projected decline in HIV-2 prevalence from a peak of 8.7% to 4.3% in 2010 was due to competitive elimination by HIV-1. Importantly for public health, HIV-1 prevalence was predicted to continue increasing and to become the dominant HIV type by 2010. Data collection is required to validate this prediction. http://repub.eur.nl/res/pub/30466/ 2008-03-01T00:00:00Z BACKGROUND: Evidence regarding the effectiveness of sexually transmitted infection (STI) treatment for HIV prevention in Africa is equivocal, leading some policy makers to question whether it should continue to be promoted for HIV control. We explore whether treating curable STIs remains a cost-effective HIV control strategy in Africa. METHODS: The model STDSIM was fitted to the characteristics of 4 populations in East and West Africa. Over the simulated HIV epidemics, the population-attributable fractions (PAFs) of incident HIV attributable to STIs, the impact of syndromic STI management on HIV incidence, and the cost per HIV infection averted were evaluated and compared with an estimate of lifetime HIV treatment costs (US $3500). RESULTS: Throughout the HIV epidemics in all cities, the total PAF for all STIs remained high, with ≥50% of HIV transmission attributed to STIs. The PAF for herpes simplex virus type 2 increased during the epidemics, whereas the PAF for curable STIs and the relative impact of syndromic management decreased. The models showed that the absolute impact of syndromic management remains high in generalized epidemics, and it remained cost-saving in 3 of the 4 populations in which the cost per HIV infection averted ranged between US $321 and $1665. CONCLUSION: Curable STI interventions may remain cost-saving in populations with generalized HIV epidemics, particularly in populations with high-risk behaviors or low male circumcision rates. http://repub.eur.nl/res/pub/14623/ 2007-10-01T00:00:00Z http://repub.eur.nl/res/pub/36781/ 2007-08-01T00:00:00Z Objective: To understand the changing impact of herpes simplex 2 (HSV-2) and other sexually transmitted infections (STIs) on HIV incidence over time in four sub-Saharan African cities, using simulation models. Methods: An individual-based stochastic model was fitted to demographic, behavioural and epidemiological data from cross-sectional population-based surveys in four African cities (Kisumu, Kenya; Ndola, Zambia; Yaoundé, Cameroon; and Cotonou, Benin) in 1997. To estimate the proportion of new HIV infections attributable to HSV-2 and other STIs over time, HIV incidence in the fitted model was compared with that in model scenarios in which the cofactor effect of the STIs on HIV susceptibility and infectivity were removed 5, 10, 15, 20 and 25 years into the simulated HIV epidemics. Results: The proportion of incident HIV attributable to HSV-2 infection (the model estimated population attributable fraction (PAFM)) increased with maturity of the HIV epidemic. In the different cities, the PAFMwas 8-31% 5 years into the epidemic, but rose to 35-48% 15 years after the introduction of HIV. In contrast, the proportion of incident HIV attributable to chancroid decreased over time with strongest effects five years after HIV introduction, falling to no effect 15 years after. Sensitivity analyses showed that, in the model, recurrent HSV-2 ulcers had more of an impact on HIV incidence than did primary HSV-2 ulcers, and that the effect of HSV-2 on HIV infectivity may be more important for HIV spread than the effect on HIV susceptibility, assuming that HSV-2 has similar cofactor effects on HIV susceptibility and infectivity. The overall impact of other curable STIs on HIV spread (syphilis, gonorrhoea and chlamydia) remained relatively constant over time. Conclusions: Although HSV-2 appears to have a limited impact on HIV incidence in the early stages of sub-Saharan African HIV epidemics when the epidemic is concentrated in core groups, it has an increasingly large impact as the epidemic progresses. In generalised HIV epidemics where control programmes for curable STIs are already in place, interventions against HSV-2 may have a key role in HIV prevention. http://repub.eur.nl/res/pub/9927/ 2002-01-01T00:00:00Z An assessment was made of how the HIV epidemic may have influenced sexually transmitted disease (STD) epidemiology in Uganda, and how HIV would affect the effectiveness of syndromic STD treatment programmes during different stages of the epidemic. The dynamic transmission model STDSIM was used to simulate the spread of HIV and four bacterial and one viral STD. Model parameters were quantified using demographic, behavioural, and epidemiological data from rural Rakai and other Ugandan populations. The findings suggest that severe HIV epidemics can markedly alter STD epidemiology, especially if accompanied by a behavioural response. Likely declines in bacterial causes of genital ulcers should be considered in defining policies on syndromic STD management in severe HIV epidemics.