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.

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.

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.

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.

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.

Can mother-to-child transmission of HIV be eliminated without addressing the issue of stigma? Modeling the case for a setting in South Africa.

BACKGROUND: Stigma and discrimination ontinue to undermine the effectiveness of the HIV response. Despite a growing body of evidence of the negative relationship between stigma and HIV outcomes, there is a paucity of data available on the prevalence of stigma and its impact. We present a probabilistic cascade model to estimate the magnitude of impact stigma has on mother-to-child-transmission (MTCT). METHODS: The model was parameterized using 2010 data from Johannesburg, South Africa, from which loss-to-care at each stage of the antenatal cascade were available. Three scenarios were compared to assess the individual contributions of stigma, non-stigma related barriers, and drug ineffectiveness on the overall number of infant infections. Uncertainty analysis was used to estimate plausible ranges. The model follows the guidelines in place in 2010 when the data were extracted (WHO Option A), and compares this with model results had Option B+ been implemented at the time. RESULTS: The model estimated under Option A, 35% of infant infections being attributed to stigma. This compares to 51% of total infections had Option B+ been implemented in 2010. Under Option B+, the model estimated fewer infections than Option A, due to the availability of more effective drugs. Only 8% (Option A) and 9% (Option B+) of infant infections were attributed to drug ineffectiveness, with the trade-off in the proportion of infections being between stigma and non-stigma-related barriers. CONCLUSIONS: The model demonstrates that while the effect of stigma on retention of women at any given stage along the cascade can be relatively small, the cumulative effect can be large. Reducing stigma may be critical in reaching MTCT elimination targets, because as countries improve supply-side factors, the relative impact of stigma becomes greater. The cumulative nature of the PMTCT cascade results in stigma having a large effect, this feature may be harnessed for efficiency in investment by prioritizing interventions that can affect multiple stages of the cascade simultaneously.

Potential impact of pre-exposure prophylaxis for female sex workers and men who have sex with men in Bangalore, India: a mathematical modelling study.

INTRODUCTION: In Bangalore, new HIV infections of female sex workers and men who have sex with men continue to occur, despite high condom use. Pre-exposure prophylaxis (PrEP) has high anti-HIV efficacy for men who have sex with men. PrEP demonstration projects are underway amongst Indian female sex workers. We estimated the impact and efficiency of prioritizing PrEP to female sex workers and/or men who have sex with men in Bangalore. METHODS: A mathematical model of HIV transmission and treatment for female sex workers, clients, men who have sex with men and low-risk groups was parameterized and fitted to Bangalore data. The proportion of transmission attributable (population attributable fraction) to commercial sex and sex between men was calculated. PrEP impact (infections averted, life-years gained) and efficiency (life-years gained/infections averted per 100 person-years on PrEP) were estimated for different levels of PrEP adherence, coverage and prioritization strategies (female sex workers, high-risk men who have sex with men, both female sex workers and high-risk men who have sex with men, or female sex workers with lower condom use), under current conditions and in a scenario with lower baseline condom use amongst key populations. RESULTS: Population attributable fractions for commercial sex and sex between men have declined over time, and they are predicted to account for 19% of all new infections between 2016 and 2025. PrEP could prevent a substantial proportion of infections amongst female sex workers and men who have sex with men in this setting (23%/27% over 5/10 years, with 60% coverage and 50% adherence), which could avert 2.9%/4.3% of infections over 5/10 years in the whole Bangalore population. Impact and efficiency in the whole population was greater if female sex workers were prioritized. Efficiency increased, but impact decreased, if only female sex workers with lower condom use were given PrEP. Greater impact and efficiency was predicted for the scenario with lower condom use. CONCLUSIONS: PrEP could be beneficial for female sex workers and men who have sex with men in Bangalore, and give some benefits in the general population, especially in similar settings with lower condom use levels.

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.

International scientific collaboration in HIV and HPV: a network analysis.

Research endeavours require the collaborative effort of an increasing number of individuals. International scientific collaborations are particularly important for HIV and HPV co-infection studies, since the burden of disease is rising in developing countries, but most experts and research funds are found in developed countries, where the prevalence of HIV is low. The objective of our study was to investigate patterns of international scientific collaboration in HIV and HPV research using social network analysis. Through a systematic review of the literature, we obtained epidemiological data, as well as data on countries and authors involved in co-infection studies. The collaboration network was analysed in respect to the following: centrality, density, modularity, connected components, distance, clustering and spectral clustering. We observed that for many low- and middle-income countries there were no epidemiological estimates of HPV infection of the cervix among HIV-infected individuals. Most studies found only involved researchers from the same country (64%). Studies derived from international collaborations including high-income countries and either low- or middle-income countries had on average three times larger sample sizes than those including only high-income countries or low-income countries. The high global clustering coefficient (0.9) coupled with a short average distance between researchers (4.34) suggests a "small-world phenomenon." Researchers from high-income countries seem to have higher degree centrality and tend to cluster together in densely connected communities. We found a large well-connected community, which encompasses 70% of researchers, and 49 other small isolated communities. Our findings suggest that in the field of HIV and HPV, there seems to be both room and incentives for researchers to engage in collaborations between countries of different income-level. Through international collaboration resources available to researchers in high-income countries can be efficiently used to enroll more participants in low- and middle-income countries.

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.

Quantifying uncertainty in health impact assessment: a case-study example on indoor housing ventilation.

Quantitative health impact assessment (HIA) is increasingly being used to assess the health impacts attributable to an environmental policy or intervention. As a consequence, there is a need to assess uncertainties in the assessments because of the uncertainty in the HIA models. In this paper, a framework is developed to quantify the uncertainty in the health impacts of environmental interventions and is applied to evaluate the impacts of poor housing ventilation. The paper describes the development of the framework through three steps: (i) selecting the relevant exposure metric and quantifying the evidence of potential health effects of the exposure; (ii) estimating the size of the population affected by the exposure and selecting the associated outcome measure; (iii) quantifying the health impact and its uncertainty. The framework introduces a novel application for the propagation of uncertainty in HIA, based on fuzzy set theory. Fuzzy sets are used to propagate parametric uncertainty in a non-probabilistic space and are applied to calculate the uncertainty in the morbidity burdens associated with three indoor ventilation exposure scenarios: poor, fair and adequate. The case-study example demonstrates how the framework can be used in practice, to quantify the uncertainty in health impact assessment where there is insufficient information to carry out a probabilistic uncertainty analysis.

Can the UNAIDS modes of transmission model be improved? A comparison of the original and revised model projections using data from a setting in west Africa.

OBJECTIVE: The UNAIDS modes of transmission model (MoT) is a user-friendly model, developed to predict the distribution of new HIV infections among different subgroups. The model has been used in 29 countries to guide interventions. However, there is the risk that the simplifications inherent in the MoT produce misleading findings. Using input data from Nigeria, we compare projections from the MoT with those from a revised model that incorporates additional heterogeneity. METHODS: We revised the MoT to explicitly incorporate brothel and street-based sex-work, transactional sex, and HIV-discordant couples. Both models were parameterized using behavioural and epidemiological data from Cross River State, Nigeria. Model projections were compared, and the robustness of the revised model projections to different model assumptions, was investigated. RESULTS: The original MoT predicts 21% of new infections occur in most-at-risk-populations (MARPs), compared with 45% (40-75%, 95% Crl) once additional heterogeneity and updated parameterization is incorporated. Discordant couples, a subgroup previously not explicitly modelled, are predicted to contribute a third of new HIV infections. In addition, the new findings suggest that women engaging in transactional sex may be an important but previously less recognized risk group, with 16% of infections occurring in this subgroup. CONCLUSION: The MoT is an accessible model that can inform intervention priorities. However, the current model may be potentially misleading, with our comparisons in Nigeria suggesting that the model lacks resolution, making it challenging for the user to correctly interpret the nature of the epidemic. Our findings highlight the need for a formal review of the MoT.

Assessing framing assumptions in quantitative health impact assessments: a housing intervention example.

Health impact assessment (HIA) is often used to determine ex ante the health impact of an environmental policy or an environmental intervention. Underpinning any HIA is the framing assumption, which defines the causal pathways mapping environmental exposures to health outcomes. The sensitivity of the HIA to the framing assumptions is often ignored. A novel method based on fuzzy cognitive map (FCM) is developed to quantify the framing assumptions in the assessment stage of a HIA, and is then applied to a housing intervention (tightening insulation) as a case-study. Framing assumptions of the case-study were identified through a literature search of Ovid Medline (1948-2011). The FCM approach was used to identify the key variables that have the most influence in a HIA. Changes in air-tightness, ventilation, indoor air quality and mould/humidity have been identified as having the most influence on health. The FCM approach is widely applicable and can be used to inform the formulation of the framing assumptions in any quantitative HIA of environmental interventions. We argue that it is necessary to explore and quantify framing assumptions prior to conducting a detailed quantitative HIA during the assessment stage.

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.

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.

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.

Calibrating models in economic evaluation: a seven-step approach.

In economic evaluation, mathematical models have a central role as a way of integrating all the relevant information about a disease and health interventions, in order to estimate costs and consequences over an extended time horizon. Models are based on scientific knowledge of disease (which is likely to change over time), simplifying assumptions and input parameters with different levels of uncertainty; therefore, it is sensible to explore the consistency of model predictions with observational data. Calibration is a useful tool for estimating uncertain parameters, as well as more accurately defining model uncertainty (particularly with respect to the representation of correlations between parameters). Calibration involves the comparison of model outputs (e.g. disease prevalence rates) with empirical data, leading to the identification of model parameter values that achieve a good fit. This article provides guidance on the theoretical underpinnings of different calibration methods. The calibration process is divided into seven steps and different potential methods at each step are discussed, focusing on the particular features of disease models in economic evaluation. The seven steps are (i) Which parameters should be varied in the calibration process? (ii) Which calibration targets should be used? (iii) What measure of goodness of fit should be used? (iv) What parameter search strategy should be used? (v) What determines acceptable goodness-of-fit parameter sets (convergence criteria)? (vi) What determines the termination of the calibration process (stopping rule)? (vii) How should the model calibration results and economic parameters be integrated? The lack of standards in calibrating disease models in economic evaluation can undermine the credibility of calibration methods. In order to avoid the scepticism regarding calibration, we ought to unify the way we approach the problems and report the methods used, and continue to investigate different methods.

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.

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.