Is modelling complexity always needed? Insights from modelling PrEP introduction in South Africa.

BACKGROUND: Mathematical models can be powerful policymaking tools. Simple, static models are user-friendly for policymakers. More complex, dynamic models account for time-dependent changes but are complicated to understand and produce. Under which conditions are static models adequate? We compare static and dynamic model predictions of whether behavioural disinhibition could undermine the impact of HIV pre-exposure prophylaxis (PrEP) provision to female sex workers in South Africa. METHODS: A static model of HIV risk was developed and adapted into a dynamic model. Both models were used to estimate the possible reduction in condom use, following PrEP introduction, without increasing HIV risk. The results were compared over a 20-year time horizon, in two contexts: at epidemic equilibrium and during an increasing epidemic. RESULTS: Over time horizons of up to 5 years, the models are consistent. Over longer timeframes, the static model overstates the tolerated reduction in condom use where initial condom use is reasonably high ($\ge$50%) and/or PrEP effectiveness is low ($\le$45%), especially during an increasing epidemic. CONCLUSIONS: Static models can provide useful deductions to guide policymaking around the introduction of a new HIV intervention over short-medium time horizons of up to 5 years. Over longer timeframes, static models may not sufficiently emphasise situations of programmatic importance, especially where underlying epidemics are still increasing.

Projected early spread of COVID-19 in Africa through 1 June 2020.

For 45 African countries/territories already reporting COVID-19 cases before 23 March 2020, we estimate the dates of reporting 1,000 and 10,000 cases. Assuming early epidemic trends without interventions, all 45 were likely to exceed 1,000 confirmed cases by the end of April 2020, with most exceeding 10,000 a few weeks later.

Cost-effectiveness of tenofovir gel in urban South Africa: model projections of HIV impact and threshold product prices.

BACKGROUND: There is urgent need for effective HIV prevention methods that women can initiate. The CAPRISA 004 trial showed that a tenofovir-based vaginal microbicide had significant impact on HIV incidence among women. This study uses the trial findings to estimate the population-level impact of the gel on HIV and HSV-2 transmission, and price thresholds at which widespread product introduction would be as cost-effective as male circumcision in urban South Africa. METHODS: The estimated 'per sex-act' HIV and HSV-2 efficacies were imputed from CAPRISA 004. A dynamic HIV/STI transmission model, parameterised and fitted to Gauteng (HIV prevalence of 16.9% in 2008), South Africa, was used to estimate the impact of gel use over 15 years. Uptake was assumed to increase linearly to 30% over 10 years, with gel use in 72% of sex-acts. Full economic programme and averted HIV treatment costs were modelled. Cost per DALY averted is estimated and a microbicide price that equalises its cost-effectiveness to that of male circumcision is estimated. RESULTS: Using plausible assumptions about product introduction, we predict that tenofovir gel use could lead to a 12.5% and 4.9% reduction in HIV and HSV-2 incidence respectively, by year 15. Microbicide introduction is predicted to be highly cost-effective (under $300 per DALY averted), though the dose price would need to be just $0.12 to be equally cost-effective as male circumcision. A single dose or highly effective (83% HIV efficacy per sex-act) regimen would allow for more realistic threshold prices ($0.25 and $0.33 per dose, respectively). CONCLUSIONS: These findings show that an effective coitally-dependent microbicide could reduce HIV incidence by 12.5% in this setting, if current condom use is maintained. For microbicides to be in the range of the most cost-effective HIV prevention interventions, product costs will need to decrease substantially.

Relationship between exposure to the Avahan intervention and levels of reported condom use among men who have sex with men in southern India.

BACKGROUND: The Avahan intervention promotes consistent (100%) condom use amongst men who have sex with men in southern India. We assessed how condom use varies with intervention exposure for men who have sex with men in Bangalore. METHODS: Self-reported condom use and intervention exposure data were derived from a cross-sectional survey. Consistent condom use and condom use at last sex act with all, main, and casual male sex partners were assessed. Binary and continuous variables reflecting intervention exposure (including contact(s) with intervention staff, receiving condoms and seeing condom demonstrations) were used. Multivariable logistic regression was employed to assess the relationship between condom use with each type of partner and each exposure variable independently, controlling for socio-demographic and behavioural factors associated with condom use or intervention exposure. RESULTS: Condom use with all partners was higher among those who had ever been contacted by, received condoms from, or seen a condom demonstration by intervention staff (adjusted odds ratio >2, p < 0.02 for all). Consistent condom use with all types of partner increased with the number of condom demonstrations seen in the last month (adjusted odds ratio = 2.1 per demonstration, p < 0.025), while condom use at last sex act with a casual (but not main) partner increased with the number of condoms received from the intervention (adjusted odds ratio = 1.4 per condom, p = 0.04). CONCLUSIONS: Direct contact with Avahan program staff is associated with increased reported condom use among men who have sex with men in Bangalore. Reported consistent condom use and condom use at last sex act are associated with contacts involving demonstrations of correct condom use, and with receiving condoms, respectively.

Uncertainty in environmental health impact assessment: quantitative methods and perspectives.

Environmental health impact assessment models are subjected to great uncertainty due to the complex associations between environmental exposures and health. Quantifying the impact of uncertainty is important if the models are used to support health policy decisions. We conducted a systematic review to identify and appraise current methods used to quantify the uncertainty in environmental health impact assessment. In the 19 studies meeting the inclusion criteria, several methods were identified. These were grouped into random sampling methods, second-order probability methods, Bayesian methods, fuzzy sets, and deterministic sensitivity analysis methods. All 19 studies addressed the uncertainty in the parameter values but only 5 of the studies also addressed the uncertainty in the structure of the models. None of the articles reviewed considered conceptual sources of uncertainty associated with the framing assumptions or the conceptualisation of the model. Future research should attempt to broaden the way uncertainty is taken into account in environmental health impact assessments.

Supply-side factors influencing demand for facility-based delivery in Tanzania: a multilevel analysis.

BACKGROUND: Improving access to facility-based delivery care has the potential to reduce maternal and newborn deaths across settings. Yet, the access to a health facility for childbirth remains low especially in low-income settings. To inform evidence-based interventions, more evidence is needed especially accounting for demand- and supply-side factors influencing access to facility-based delivery care. We aimed to fill this knowledge gap using data from Tanzania. METHODS: We used data from a cross-sectional survey (conducted in January 2012) of 150 health facilities, 1494 patients and 2846 households with women who had given births in the last 12 months before the survey across 11 districts in three regions in Tanzania. The main outcome was the place of delivery (giving birth in a health facility or otherwise), while explanatory variables were measured at the individual woman and facility level. Given the hierarchical structure of the data and variance in demand across facilities, we used a multilevel mixed-effect logistic regression to explore the determinants of facility-based delivery care. RESULTS: Eighty-six percent of 2846 women gave birth in a health facility. Demand for facility-based delivery care was influenced more by demand-side factors (76%) than supply-side factors (24%). On demand-side factors, facility births were more common among women who were educated, Muslim, wealthier, with their first childbirth, and those who had at least four antenatal care visits. On supply-side factors, facility births were more common in facilities offering outreach services, longer consultation times and higher interpersonal quality. In contrast, facilities with longer average waiting times, longer travel times and higher chances of charging delivery fees had few facility births. CONCLUSIONS: Policy responses should aim for strategies to improve demand like health education to raise awareness towards care seeking among less educated groups and those with higher parity, reduce financial barriers to access (including time costs to reach and access care), and policy interventions to enhance interpersonal quality in service provision.

A systematic review of the cost-effectiveness of interventions to increase cervical cancer screening among underserved women in Europe.

BACKGROUND: This study aimed to conduct a systematic review of the cost-effectiveness studies of interventions to increase cervical cancer screening uptake rates in underserved women in Europe. METHODS: A search of Embase, Medline, Global Health, PsychINFO, and NHS Economic Evaluation Database was conducted for studies published between January 2000 and September 2022. Studies were eligible if they analysed the cost-effectiveness of any interventions to improve participation in cervical cancer screening among underserved women of any age eligible to participate in cervical cancer screening in European countries, in any language. Study characteristics and cost-effectiveness results were summarised. Study quality was assessed using the Drummond Checklist, and methodological choices were further compared. RESULTS: The searches yielded 962 unique studies, with 17 of these (from twelve European countries) meeting the eligibility criteria for data extraction. All studies focused on underscreened women as an overarching group, with no identified studies focusing on specific subgroups of underserved women. Generally, self-HPV testing and reminder interventions were shown to be cost-effective to increase the uptake rates. There was also research showing that addressing access issues and adopting different screening modalities could be economically attractive in some settings, but the current evidence is insufficient due to the limited number of studies. CONCLUSION: This systematic review has revealed a gap in the literature on the cost-effectiveness of interventions to improve uptake rates of cervical cancer screening through tailored provision for specific groups of underserved women.

Cervical cancer screening among HIV-infected women: an economic evaluation in a middle-income country.

Due to the recent widespread availability of highly active antiretroviral therapy (HAART) in middle-income countries, there has been an increase in life expectancy for women on HAART, but no corresponding decrease in cervical cancer incidence. This study evaluates the optimal cervical cancer screening strategy for HIV-infected women in a middle-income country. We developed a mathematical model, which simulates the natural history of the HPV infection, as well as the HIV-mediated immunosupression among women in Brazil. Our model was calibrated using data from the IPEC/FIOCRUZ Women's HIV-infected cohort. The model compares the lifetime effects, costs and cost-effectiveness of strategies combining cytology, HPV DNA test and colposcopy at different screening intervals for different CD4 count strata (27 strategies in total). We found that the strategy with the best cost-effectiveness profile (cost-effectiveness ratio-U$4,911/year of life saved [YLS] and probability of being cost-effective-86%) was HPV testing followed by cytology triage every year for all HIV infected women, considering a very cost-effective threshold given by Brazil's GDP per capita (US$8,625/YLS). The results were robust to changes in the input parameters as demonstrated in one-way, scenario, threshold and probabilistic sensitivity analysis. Our study indicates that annual HPV testing followed by cytology triage for all HIV-infected women is likely to be very cost-effective in a middle-income country like Brazil. The results reflect the synergic effect of using a highly sensitive screening test (HPV DNA test) in sequence with a highly specific test (cytology).

Viewing the global health system as a complex adaptive system - implications for research and practice.

The global health system (GHS) is ill-equipped to deal with the increasing number of transnational challenges. The GHS needs reform to enhance global resilience to future risks to health. In this article we argue that the starting point for any reform must be conceptualizing and studying the GHS as a complex adaptive system (CAS) with a large and escalating number of interconnected global health actors that learn and adapt their behaviours in response to each other and changes in their environment. The GHS can be viewed as a multi-scalar, nested health system comprising all national health systems together with the global health architecture, in which behaviours are influenced by cross-scale interactions. However, current methods cannot adequately capture the dynamism or complexity of the GHS or quantify the effects of challenges or potential reform options. We provide an overview of a selection of systems thinking and complexity science methods available to researchers and highlight the numerous policy insights their application could yield.   We also discuss the challenges for researchers of applying these methods and for policy makers of digesting and acting upon them. We encourage application of a CAS approach to GHS research and policy making to help bolster resilience to future risks that transcend national boundaries and system scales.

Attaining realistic and substantial reductions in HIV incidence: model projections of combining microbicide and male circumcision interventions in rural Uganda.

OBJECTIVES: This study simulates the potential impact of male circumcision and female microbicide interventions, singularly and in combination, in rural Uganda. METHODS: A dynamic model was parameterised and fitted to setting-specific data, and used to estimate the impact on HIV transmission of a microbicide and/or male circumcision intervention over 15 years. The proportion of circumcised men or women using microbicides was assumed to increase linearly from 0.18 (male circumcision) or 0.00 (microbicide use) to the final proportion 10 years later, then remain constant for 5 years. Women using microbicides were assumed to use the product in 80% of penile-vaginal sex acts. Male circumcision or microbicide use was assumed to reduce the per-act probability of HIV acquisition in men or women, respectively, by 60%. RESULTS: Independently, to obtain a 30% relative reduction in HIV incidence at 15 years, the model suggests that the final proportion of women using microbicides would need to be 0.91 (95% CI 0.75 to 1.00) or the proportion of circumcised men would need to be 0.96 (0.83 to impact not possible). The same impact could be achieved by combining the interventions, eg, if the proportion of women using microbicides was 0.49 (0.39 to 0.56) and the proportion of circumcised men was 0.67 (0.57 to 0.74). CONCLUSIONS: Under these assumptions, as separate interventions it is unlikely that increases in either the proportion of men circumcised or of women using microbicides could reduce HIV incidence by 30% or more at 15 years. A combination-prevention strategy using complementary interventions may be a more feasible approach to achieve substantial reductions in incidence.

Modelling the interactions between herpes simplex virus type 2 and HIV: implications for the HIV epidemic in southern India.

BACKGROUND: The role of herpes simplex virus type 2 (HSV-2) in the HIV epidemic and the potential impact of HSV-2 suppressive therapy have previously been explored only within the context of sub-Saharan Africa. In this analysis, modelling is used to estimate the contribution of HSV-2 to HIV transmission from clients to female sex workers (FSW) in a southern Indian setting and the maximum potential impact of 'perfect' HSV-2 suppressive therapy on HIV incidence. METHODS: A dynamic HSV-2/HIV model was developed, parameterised and fitted to Mysore data. The model estimated the attributable fractions of HIV infections due to HSV-2. Multivariate sensitivity analyses and regression analyses were conducted. RESULTS: The model suggests that 36% (95% CI 22% to 62%) of FSW HIV infections were due to HSV-2, mostly through HSV-2 asymptomatic shedding. Even if HSV-2 suppressive therapy could eliminate the effect of HSV-2 on HIV infectivity among all co-infected clients, only 15% (95% CI 3% to 41%) of HIV infections among FSW would have been averted. 36% (95% CI 18% to 61%) of HIV infections among HSV-2-infected FSW could have been averted if suppressive therapy reduced their risk of HIV acquisition to that of HSV-2-uninfected FSW. CONCLUSIONS: HSV-2 contributes substantially to HIV in this southern Indian context. However, even in the best case scenario, HSV-2 suppressive therapy is unlikely to reduce HIV transmission or acquisition by more than 50% (as aimed for in recent trials), because of the limited strength of the interaction effect between HSV-2 and HIV.

The cost-effectiveness of herpes simplex virus-2 suppressive therapy with daily aciclovir for delaying HIV disease progression among HIV-1-infected women in South Africa.

BACKGROUND: The Partners in Prevention HSV/HIV transmission trial (Partners HSV/HIV Transmission Study) showed that herpes simplex virus-2 (HSV-2) suppressive therapy with daily aciclovir could decrease HIV disease progression amongst HIV-1/HSV-2 coinfected individuals. The cost-effectiveness of daily aciclovir for delaying HIV-1 disease progression in women not eligible for antiretroviral therapy (ART) is estimated. METHODS: Resource use/cost data for delivering daily aciclovir at a primary health care HIV clinic were collected in Johannesburg. Effectiveness estimates were obtained from the Partners HSV/HIV Transmission Study trial and epidemiologic data from South Africa. A Markov model simulated the cost-effectiveness of daily aciclovir on HIV-1 disease progression in ART-naive women. Therapy was given to all HIV-1-infected women. Cost-effectiveness was compared against cost per life-year gained (∼US $1200 per LYG) of ART provision in South Africa. RESULTS: For an ART eligibility criteria of CD4 count <200 cells/µL and the cheapest internationally available aciclovir (US $0.026 per day for 2 × 400 mg aciclovir), the median cost per LYG is US $1023 (95% confidence interval [CI]: 537-2842), whereas it decreases to US $737 (95% CI: 373-2489) if the ART eligibility criteria is CD4 count <350 cells/µL. Both these projections compare favorably with the estimated cost-effectiveness of ART in South Africa (∼US $1200 per LYG). The cost per LYG increases dramatically for the current aciclovir cost in South Africa (US $0.14 per day), if salary costs are higher and if HSV-2 prevalence amongst HIV-1-infected women are lower. Projections suggest HSV-2 suppressive therapy could dramatically increase the proportion of women initiating ART. CONCLUSIONS: HSV-2 suppressive therapy could be an affordable strategy for reducing HIV-1 disease progression and retaining women in care before ART initiation, but cheaply available aciclovir is needed.

A comparative analysis of cervical cancer prevention between Nigeria and Nordic countries that have experienced a decline in cervical cancer incidence.

BACKGROUND: A modelling analysis carried out in 2014 suggested that, without cervical cancer screening programmes, the incidence of cervical cancer in Denmark, Finland, Norway and Sweden would have been as high as that in some low- and middle-income countries. We compare programme strategies between Nigeria and these Nordic countries and develop translatable recommendations. METHODS: A literature review using a systematic approach through Medline, Popline, Global Health, CINAHL PLUS, Cochrane Library, EMBASE, Google Scholar, Africa Wide and WHO databases was conducted. RESULTS: Fifteen journal articles and two grey literature reports met our criteria. Six descriptive studies from Nigeria noted that services in Nigeria were mainly provided in urban secondary/tertiary facilities and that uptake was low even where screening was free. Trials in Nigeria and Sweden noted that subsidies and free programmes alone did not improve uptake; a Danish trial demonstrated that reminders and invitations issued by general practitioners improved participation. CONCLUSION: Free screening programmes are important but should also consider incentivisation of treatment when needed and demand creation among health workers. Additionally, effective monitoring and evaluation of programme data are key to improving and maintaining quality. More broadly, we suggest that Nigeria can build success through stakeholder-led implementation of well-defined policies with national consensus to ensure coordination and sustainability.

Remodelling core group theory: the role of sustaining populations in HIV transmission.

BACKGROUND AND OBJECTIVES: Core group theory describes the central role of groups with high rates of sexual partner change in HIV transmission. Research illustrates the heterogeneous and dynamic nature of commercial sex, and that some men involved in the organisation or policing of sex work regularly have sex with sex workers. These findings are used to explore gaps in core group theory. METHODS: Evidence from developing countries on the duration that women sell and men buy sex was reviewed. Simple compartmental dynamic models were used to derive analytical expressions for the relative HIV equilibrium levels among sex workers and partners, incorporating partner change rates and duration in commercial sex settings. Simulations explored the degree to which HIV infection can be attributable to men with low partner change rates who remain in sex work settings for long periods, and their influence on the impact of HIV intervention. RESULTS: Partner change rates and duration of time in a setting determine equilibrium HIV levels. Modelling projections suggest that men with low mobility can substantially contribute to HIV prevalence among sex workers, especially in settings with prevalences <50%. This effect may reduce the impact of sex-worker interventions on HIV incidence in certain scenarios by one-third. Reductions in impact diminish at higher sex-worker prevalences. CONCLUSION: In commercial sex settings, patterns of HIV risk and transmission are influenced by both partner change rates and duration in a setting. The latter is not reflected in classic core group theory. Men who control the sex industry and regular clients may form an important 'sustaining population' that increases infection and undermines the impact of intervention. Intervention activities should include these groups, and examine the social organisation of sex work that underpins many of these relationships.

Sexual violence and conflict in Africa: prevalence and potential impact on HIV incidence.

BACKGROUND AND AIMS: Sexual violence (SV) is common during conflict. Despite reports of rape-related incidents of HIV infection, ecological analyses have found no association between SV and HIV at a population level. This has led to debate in the humanitarian, security and public health arenas about whether SV is an important HIV risk factor in conflict-affected settings. This paper uses published evidence on sexual violence in Africa and modelling to explore when SV may increase individual HIV risk and community HIV incidence. METHODS: Publications on sexual violence in conflict settings were reviewed and a mathematical model describing the probability of HIV acquisition was adapted to include the potential effect of genital injury and used to estimate the relative risk of HIV acquisition in 'conflict' versus 'non-conflict' situations. An analytical equation was developed to estimate the impact of SV on HIV incidence. RESULTS: A rape survivor's individual HIV risk is determined by potentially compounding effects of genital injury, penetration by multiple perpetrators and the increased likelihood that SV perpetrators are HIV infected. Modelling analysis suggests risk ratios of between 2.4 and 27.1 for the scenarios considered. SV could increase HIV incidence by 10% if rape is widespread (>40%); genital injury increases HIV transmission (threefold or more); at least 10% of perpetrators are HIV infected and underlying HIV incidence is low (<0.5%). CONCLUSION: The analysis illustrates that SV is likely to be an important HIV risk factor in some conflict-affected settings. More generally, it indicates the limitations of using broad aggregate analysis to derive epidemiological conclusions. Conflict-related initiatives offer important opportunities to assist survivors and prevent future abuses through collaborative programming on reconstruction, HIV and sexual violence.

Interim modelling analysis to validate reported increases in condom use and assess HIV infections averted among female sex workers and clients in southern India following a targeted HIV prevention programme.

OBJECTIVES: This study assesses whether the observed declines in HIV prevalence since the beginning of the 'Avahan' India HIV/AIDS prevention initiative are consistent with self-reported increases in condom use by female sex workers (FSWs) in two districts of southern India, and provides estimates of the fraction of new infections averted among FSWs and clients due to increases in condom use in commercial sex after 2004. METHODS: A deterministic compartmental model of HIV/sexually transmitted infection (STI) transmission incorporating heterogeneous sexual behaviour was developed, parameterised and fitted using data from two districts in Karnataka, India. Three hypotheses of condom use among FSWs were tested: (H(0)), that condom use increased in line with reported FSW survey data prior to the Avahan initiative but remained constant afterwards; (H(1)) that condom use increased following the Avahan initiative, in accordance with survey data; (H(2)) that condom use increased according to estimates derived from condom distribution data. The proportion of fits to HIV/STI prevalence data was examined to determine which hypothesis was most consistent. RESULTS: For Mysore 0/36/82.7 fits were identified per million parameter sets explored under hypothesis H(0)/H(1)/H(2), respectively, while for Belgaum 9.7/8.3/0 fits were identified. The HIV epidemics in Belgaum and Mysore are both declining. In Mysore, increases in condom use during commercial sex between 2004 and 2009 may have averted 31.2% to 47.4% of new HIV infections in FSWs, while in Belgaum it may have averted 24.8% to 43.2%, if there was an increase in condom use. DISCUSSION: Increased condom use following the Avahan intervention is likely to have played a role in curbing the HIV epidemic in Mysore. In Belgaum, given the limitations in available data, this method cannot be used alone to decide if there has been an increase in condom use.

Catastrophic Health Impacts of Spiraling Climate Change: How Certain Can We Be About Their Magnitudes?

Recently, there has been a strong interest in the climate emergency and the human health impacts of climate change. Although estimates have been quoted, the modeling methods used have either been simplistic or opaque, making it difficult for policy makers to have confidence in these estimates. Providing central estimates of health impacts, without any quantification of their uncertainty, is deficient because such an approach does not acknowledge the inherent uncertainty in extreme environmental exposures associated with spiraling climate change and related health impacts. Furthermore, presenting only the uncertainty bounds around central estimates, without information on how the uncertainty in each of the model parameters and assumptions contribute to the total uncertainty, is insufficient because this approach hides those parameters and assumptions which contribute most to the total uncertainty. We propose a framework for calculating the catastrophic human health impacts of spiraling climate change and the associated uncertainties. Our framework comprises three building blocks: (A) a climate model to simulate the environmental exposure extremes of spiraling climate change; (B) a health impact model which estimates the health burdens of the extremes of environmental exposures; and (C) an analytical mathematical method which characterizes the uncertainty in (A) and (B), propagates the uncertainty in-between and through these models, and attributes the proportion of uncertainty in the health outcomes to model assumptions and parameter values. Once applied, our framework can be of significant value to policy makers because it handles uncertainty transparently while taking into account the complex interactions between climate and human health.

Using data from 'visible' populations to estimate the size and importance of 'hidden' populations in an epidemic: A modelling technique.

We used reported behavioural data from cisgender men who have sex with men and transgender women (MSM/TGW) in Bangalore, mainly collected from 'hot-spot' locations that attract MSM/TGW, to illustrate a technique to deal with potential issues with the representativeness of this sample. A deterministic dynamic model of HIV transmission was developed, incorporating three subgroups of MSM/TGW, grouped according to their reported predominant sexual role (insertive, receptive or versatile). Using mathematical modelling and data triangulation for 'balancing' numbers of partners and role preferences, we compared three different approaches to determine if our technique could be useful for inferring characteristics of a more 'hidden' insertive MSM subpopulation, and explored their potential importance for the HIV epidemic. Projections for 2009 across all three approaches suggest that HIV prevalence among insertive MSM was likely to be less than half that recorded in the surveys (4.5-6.5% versus 13.1%), but that the relative size of this subgroup was over four times larger (61-69% of all MSM/TGW versus 15%). We infer that the insertive MSM accounted for 10-20% of all prevalent HIV infections among urban males aged 15-49. Mathematical modelling can be used with data on 'visible' MSM/TGW to provide insights into the characteristics of 'hidden' MSM. A greater understanding of the sexual behaviour of all MSM/TGW is important for effective HIV programming. More broadly, a hidden subgroup with a lower infectious disease prevalence than more visible subgroups, has the potential to contain more infections, if the hidden subgroup is considerably larger in size.

Dynamic modeling of herpes simplex virus type-2 (HSV-2) transmission: issues in structural uncertainty.

The sexually transmitted infection (STI) Herpes simplex virus type-2 (HSV-2) is of public health concern because it is a very common frequently unrecognized lifelong infection, which may facilitate HIV transmission. Within HIV/STI modeling, structural uncertainty has received less attention than parametric uncertainty. By merging the compartments of a "complex" model, a "simple" HSV-2 model is developed. Sexual interactions between female sex workers (FSWs) and clients are modeled using data from India. Latin Hypercube Sampling selects from parameter distributions and both models are run for each of the 10,000 parameter sets generated. Outputs are compared (except for 2,450 unrealistic simulations). The simple model is a good approximation to the complex model once the HSV-2 epidemic has reached 60% of the equilibrium prevalence (95% of the 7,550 runs produced <10% relative error). The simple model is a reduced version of the complex model that retains details implicitly. For late-stage epidemics, the simple model gives similar prevalence trends to the complex model. As HSV-2 epidemics in many populations are advanced, the simple model is accurate in most instances, although the complex model may be preferable for early epidemics. The analysis highlights the issue of structural uncertainty and the value of reducing complexity.