Comparison of two simulators for individual based models in HIV epidemiology in a population with HSV 2 in Yaoundé (Cameroon).

Model comparisons have been widely used to guide intervention strategies to control infectious diseases. Agreement between different models is crucial for providing robust evidence for policy-makers because differences in model properties can influence their predictions. In this study, we compared models implemented by two individual-based model simulators for HIV epidemiology in a heterosexual population with Herpes simplex virus type-2 (HSV-2). For each model simulator, we constructed four models, starting from a simplified basic model and stepwise including more model complexity. For the resulting eight models, the predictions of the impact of behavioural interventions on the HIV epidemic in Yaoundé-Cameroon were compared. The results show that differences in model assumptions and model complexity can influence the size of the predicted impact of the intervention, as well as the predicted qualitative behaviour of the HIV epidemic after the intervention. These differences in predictions of an intervention were also observed for two models that agreed in their predictions of the HIV epidemic in the absence of that intervention. Without additional data, it is impossible to determine which of these two models is the most reliable. These findings highlight the importance of making more data available for the calibration and validation of epidemiological models.

Influence of sexual risk behaviour and STI co-infection dynamics on the evolution of HIV set point viral load in MSM.

HIV viral load (VL) is an important predictor of HIV progression and transmission. Anti-retroviral therapy (ART) has been reported to reduce HIV transmission by lowering VL. However, apart from this beneficial effect, increased levels of population mean set-point viral load (SPVL), an estimator for HIV virulence, have been observed in men who have sex with men (MSM) in the decade following the introduction of ART in The Netherlands. Several studies have been devoted to explain these counter-intuitive trends in SPVL. However, to our knowledge, none of these studies has investigated an explanation in which it arises as the result of a sexually transmitted infection (STI) co-factor in detail. In this study, we adapted an event-based, individual-based model to investigate how STI co-infection and sexual risk behaviour affect the evolution of HIV SPVL in MSM before and after the introduction of ART. The results suggest that sexual risk behaviour has an effect on SPVL and indicate that more data are needed to test the effect of STI co-factors on SPVL. Furthermore, the observed trends in SPVL cannot be explained by sexual risk behaviour and STI co-factors only. We recommend to develop mathematical models including also factors related to viral evolution as reported earlier in the literature. However, this requires more complex models, and the collection of more data for parameter estimation than what is currently available.

Assessing the uncertainty around age-mixing patterns in HIV transmission inferred from phylogenetic trees.

Understanding age-mixing patterns in Human Immunodeficiency Virus (HIV) transmission networks can enhance the design and implementation of HIV prevention strategies in sub-Saharan Africa. Due to ethical consideration, it is less likely possible to conduct a benchmark study to assess which sampling strategy, and sub-optimal sampling coverage which can yield best estimates for these patterns. We conducted a simulation study, using phylogenetic trees to infer estimates of age-mixing patterns in HIV transmission, through the computation of proportions of pairings between men and women, who were phylogenetically linked across different age groups (15-24 years, 25-39 years, and 40-49 years); and the means, and standard deviations of their age difference. We investigated also the uncertainty around these estimates as a function of the sampling coverage in four sampling strategies: when missing sequence data were missing completely at random (MCAR), and missing at random (MAR) with at most 30%-50%-70% of women in different age groups being in the sample. The results suggested that age-mixing patterns in HIV transmission can be unveiled from proportions of phylogenetic pairings between men and women across age groups; and the mean, and standard deviation of their age difference. A 55% sampling coverage was sufficient to provide the best values of estimates of age-mixing patterns in HIV transmission with MCAR scenario. But we should be cautious in interpreting proportions of men phylogenetically linked to women because they may be overestimated or underestimated, even at higher sampling coverage. The findings showed that, MCAR was the best sampling strategy. This means, it is advisable not to use sequence data collected in settings where we can find a systematic imbalance of age and gender to investigate age-mixing in HIV transmission. If not possible, ensure to take into consideration the imbalance in interpreting the results.

Early access to antiretroviral therapy versus standard of care among HIV-positive participants in Eswatini in the public health sector: the MaxART stepped-wedge randomized controlled trial.

INTRODUCTION: The WHO recommends antiretroviral treatment (ART) for all HIV-positive patients regardless of CD4 count or disease stage, referred to as "Early Access to ART for All" (EAAA). The health systems effects of EAAA implementation are unknown. This trial was implemented in a government-managed public health system with the aim to examine the "real world" impact of EAAA on care retention and viral suppression. METHODS: In this stepped-wedge randomized controlled trial, 14 public sector health facilities in Eswatini were paired and randomly assigned to stepwise transition from standard of care (SoC) to EAAA. ART-naïve participants ≥18 years who were not pregnant or breastfeeding were eligible for enrolment. We used Cox proportional hazard models with censoring at clinic transition to estimate the effects of EAAA on retention in care and retention and viral suppression combined. RESULTS: Between September 2014 and August 2017, 3405 participants were enrolled. In SoC and EAAA respectively, 12-month HIV care retention rates were 80% (95% CI: 77 to 83) and 86% (95% CI: 83 to 88). The 12-month combined retention and viral suppression endpoint rates were 44% (95% CI: 40 to 48) under SoC compared to 80% (95% CI: 77 to 83) under EAAA. EAAA increased both retention (HR: 1·60, 95% CI: 1·15 to 2·21, p = 0.005) and retention and viral suppression combined (HR: 4.88, 95% CI: 2.96 to 8.05, p < 0.001). We also identified significant gaps in current health systems ability to provide viral load (VL) monitoring with 80% participants in SoC and 66% in EAAA having a missing VL at last contact. CONCLUSIONS: The observed improvement in retention in care and on the combined retention and viral suppression provides an important co-benefit of EAAA to HIV-positive adults themselves, at least in the short term. Our results from this "real world" health systems trial strongly support EAAA for Eswatini and countries with similar HIV epidemics and health systems. VL monitoring needs to be scaled up for appropriate care management.

Calibration of individual-based models to epidemiological data: A systematic review.

Individual-based models (IBMs) informing public health policy should be calibrated to data and provide estimates of uncertainty. Two main components of model-calibration methods are the parameter-search strategy and the goodness-of-fit (GOF) measure; many options exist for each of these. This review provides an overview of calibration methods used in IBMs modelling infectious disease spread. We identified articles on PubMed employing simulation-based methods to calibrate IBMs informing public health policy in HIV, tuberculosis, and malaria epidemiology published between 1 January 2013 and 31 December 2018. Articles were included if models stored individual-specific information, and calibration involved comparing model output to population-level targets. We extracted information on parameter-search strategies, GOF measures, and model validation. The PubMed search identified 653 candidate articles, of which 84 met the review criteria. Of the included articles, 40 (48%) combined a quantitative GOF measure with an algorithmic parameter-search strategy-either an optimisation algorithm (14/40) or a sampling algorithm (26/40). These 40 articles varied widely in their choices of parameter-search strategies and GOF measures. For the remaining 44 (52%) articles, the parameter-search strategy could either not be identified (32/44) or was described as an informal, non-reproducible method (12/44). Of these 44 articles, the majority (25/44) were unclear about the GOF measure used; of the rest, only five quantitatively evaluated GOF. Only a minority of the included articles, 14 (17%) provided a rationale for their choice of model-calibration method. Model validation was reported in 31 (37%) articles. Reporting on calibration methods is far from optimal in epidemiological modelling studies of HIV, malaria and TB transmission dynamics. The adoption of better documented, algorithmic calibration methods could improve both reproducibility and the quality of inference in model-based epidemiology. There is a need for research comparing the performance of calibration methods to inform decisions about the parameter-search strategies and GOF measures.

SimpactCyan 1.0: An Open-source Simulator for Individual-Based Models in HIV Epidemiology with R and Python Interfaces.

SimpactCyan is an open-source simulator for individual-based models in HIV epidemiology. Its core algorithm is written in C++ for computational efficiency, while the R and Python interfaces aim to make the tool accessible to the fast-growing community of R and Python users. Transmission, treatment and prevention of HIV infections in dynamic sexual networks are simulated by discrete events. A generic "intervention" event allows model parameters to be changed over time, and can be used to model medical and behavioural HIV prevention programmes. First, we describe a more efficient variant of the modified Next Reaction Method that drives our continuous-time simulator. Next, we outline key built-in features and assumptions of individual-based models formulated in SimpactCyan, and provide code snippets for how to formulate, execute and analyse models in SimpactCyan through its R and Python interfaces. Lastly, we give two examples of applications in HIV epidemiology: the first demonstrates how the software can be used to estimate the impact of progressive changes to the eligibility criteria for HIV treatment on HIV incidence. The second example illustrates the use of SimpactCyan as a data-generating tool for assessing the performance of a phylodynamic inference framework.

Drivers of vaccine decision-making in South Africa: A discrete choice experiment.

To increase vaccination coverage, it is essential to understand the vaccine decision-making process. High population coverage is required to obtain herd immunity and to protect vulnerable groups in terms of age (e.g. the very young) or health (e.g. immunodeficiency). Vaccine confidence and coverage in South Africa are relatively low, opening the window for sustained outbreaks of vaccine-preventable diseases in a country facing one of the most severe HIV epidemics in the world. To capture the vaccine-related decision-making process in South Africa, we performed a discrete choice experiment with 1200 participants in December 2017. We asked for their preferences with respect to (1) vaccine effectiveness, (2) vaccine-preventable burden of disease, (3) accessibility of the vaccine in terms of co-payment and prescription requirements, (4) frequency of mild vaccine-related side-effects, (5) population vaccination coverage and (6) local vaccination coverage. We distinguished between decision-making for vaccines administered to the participant, and for vaccines administered to their youngest child. We analyzed the data for each of these groups using a panel mixed logit model and found similar results for decisions to vaccinate oneself or one's child. Vaccine effectiveness was the most important attribute followed by population coverage and burden of disease. Local coverage and accessibility were also important determinants of vaccination behavior, but to a lesser extent. Regarding population and local coverage, we observed a positive effect on vaccine utility indicating the potential of peer influence. As such, social normative influence could be exploited to increase vaccination confidence and coverage. With respect to vaccine-preventable burden of the disease, the marginal utilities showed disease severity to be more important than frequency of disease. Policymakers and health care workers should stress the effectiveness of vaccines together with the severity of vaccine-preventable diseases.

Differential sexual network connectivity offers a parsimonious explanation for population-level variations in the prevalence of bacterial vaginosis: a data-driven, model-supported hypothesis.

BACKGROUND: The prevalence of bacterial vaginosis (BV) and vaginal microbiota types varies dramatically between different populations around the world. Understanding what underpins these differences is important, as high-diversity microbiotas associated with BV are implicated in adverse pregnancy outcomes and enhanced susceptibility to and transmission of sexually transmitted infections. MAIN TEXT: We hypothesize that these variations in the vaginal microbiota can, in part, be explained by variations in the connectivity of sexual networks. We argue: 1) Couple-level data suggest that BV-associated bacteria can be sexually transmitted and hence high sexual network connectivity would be expected to promote the spread of BV-associated bacteria. Epidemiological studies have found positive associations between indicators of network connectivity and the prevalence of BV; 2) The relationship between BV prevalence and STI incidence/prevalence can be parsimoniously explained by differential network connectivity; 3) Studies from other mammals are generally supportive of the association between network connectivity and high-diversity vaginal microbiota. CONCLUSION: To test this hypothesis, we propose a combination of empirical and simulation-based study designs.

Feasibility, acceptability and potential sustainability of a 'diagonal' approach to health services for female sex workers in Mozambique.

BACKGROUND: Female sex workers (FSWs) in many settings have restricted access to sexual and reproductive health (SRH) services. We therefore conducted an implementation study to test a 'diagonal' intervention which combined strengthening of FSW-targeted services (vertical) with making public health facilities more FSW-friendly (horizontal). We piloted it over 18 months and then assessed its performance. METHODS: Applying a convergent parallel mixed-methods design, we triangulated the results of the analysis of process indicators, semi-structured interviews with policy makers and health managers, structured interviews with health care providers and group discussions with peer outreach workers. We then formulated integrated conclusions on the interventions' feasibility, acceptability by providers, managers and policy makers, and potential sustainability. RESULTS: The intervention, as designed, was considered theoretically feasible by all informants, but in practice the expansion of some of the targeted services was hampered by insufficient financial resources, institutional capacity and buy-in from local government and private partners, and could not be fully actualised. In terms of acceptability, there was broad consensus on the need to ensure FSWs have access to SRH services, but not on how this might be achieved. Targeted clinical services were no longer endorsed by national government, which now prefers a strategy of making public services more friendly for key populations. Stakeholders judged that the piloted model was not fully sustainable, nor replicable elsewhere in the country, given its dependency on short-term project-based funding, lack of government endorsement for targeted clinical services, and viewing the provision of community activities as a responsibility of civil society. CONCLUSIONS: In the current Mozambican context, a 'diagonal' approach to ensure adequate access to sexual and reproductive health care for female sex workers is not fully feasible, acceptable or sustainable, because of insufficient resources and lack of endorsement by national policy makers for the targeted, vertical component.

The role of age-mixing patterns in HIV transmission dynamics: Novel hypotheses from a field study in Cape Town, South Africa.

BACKGROUND: Age-disparate relationships are thought to put young women at increased risk of HIV, though current evidence is inconclusive. Studying population-level age-mixing patterns as well as individual-level measures of age difference variation may provide insight into the persistence and magnitude of the epidemic in South Africa. METHODS: We used data from a survey in Cape Town (n = 506) to describe age-mixing dynamics in the four population strata of HIV negative and HIV positive male and female participants. Mixed-effects models were used to calculate the average increase in partner age for each year increase in age of participant, the average partner age for 15 year olds, and the between-subject and the within-subject standard deviation of partner ages. We conducted 2000 bootstrap replications of the models. Using negative binomial models, we also explored whether HIV status was associated with participants having a larger range in partner ages. RESULTS: HIV positive women had large variability in partner ages at the population level, and at the individual level had nearly three times the expected range of partner ages compared to HIV negative women. This pattern may increase the potential for HIV transmission across birth cohorts and may partially explain the persistence of the epidemic in South Africa. Young men, who have been previously absent from the age-disparity discourse, also choose older partners who may be putting them at increased risk of HIV infection due to the high HIV prevalence among older age categories of women.

Impact of a "Diagonal" Intervention on Uptake of Sexual and Reproductive Health Services by Female Sex Workers in Mozambique: A Mixed-Methods Implementation Study.

BACKGROUND: Female sex workers (FSWs) have high risks for adverse sexual and reproductive health (SRH) outcomes, yet low access to services. Within an implementation research project enhancing uptake of SRH services by FSWs, we piloted a "diagonal" intervention, which combined strengthening of FSW-targeted services (vertical) with making public health facilities more FSW-friendly (horizontal), and tested its effect. METHODS: The study applied a convergent parallel mixed-methods design to assess changes in access to SRH services. Results of structured interviews with FSWs pre-intervention (N = 311) and thereafter (N = 404) were compared with the findings of eight post-intervention focus group discussions (FGDs) with FSWs and two with FSW-peer educators (PEs). RESULTS: Marked and statistically significant rises occurred in consistent condom use with all partners (55.3-67.7%), ever use of female condoms (37.9-54.5%), being tested for HIV in the past 6 months (56.0-76.6%), using contraception (84.5-95.4%), ever screened for cervical cancer (0.0-16.9%) and having ≥10 contacts with a PE in the past year (0.5-24.45%). Increases mostly resulted from FSW-targeted outreach, with no rise detected in utilization of public health facilities. FGD participants reported that some facilities had become more FSW-friendly, but barriers such as stock-outs, being asked for bribes and disrespectful treatment persisted. CONCLUSION: The combination of expanding FSW-targeted SRH services with improving access to the public health services resulted in an overall increased uptake of services, but almost exclusively because of the strengthened targeted (vertical) outreach services. Utilization of public SRH services had not yet increased and many barriers to access remained. Our diagonal approach was thus only successful in its vertical component. Improving access to the general health services remains nevertheless important and further research is needed how to reduce barriers. Ideally, the combination approach should be maintained and more successful approaches to increase utilization of public services should be explored.

Effect of a 'diagonal' intervention on uptake of HIV and reproductive health services by female sex workers in three sub-Saharan African cities.

OBJECTIVES: To enhance uptake of sexual and reproductive health (SRH) services by female sex workers (FSWs), we conducted an implementation study in which we piloted and tested context-specific 'diagonal' interventions, combining vertical, targeted interventions with horizontally improved access to the general health services, in three cities in sub-Saharan Africa. METHODS: We collected indicators of SRH service uptake through face-to-face interviews with approximately 400 FSWs, pre- and post-intervention, in Durban, South Africa; Tete, Mozambique; and Mombasa, Kenya, recruited by respondent-driven sampling. Changes in uptake were tested for their statistical significance using multivariate logistic regression models. RESULTS: In all cities, overall uptake of services increased. Having used all services for contraception, STI care, HIV testing, HIV care, cervical cancer screening and sexual violence, if needed, increased from 12.5% to 41.5% in Durban, 25.0% to 40.1% in Tete and 44.9% to 69.1% in Mombasa. Across cities, the effect was greatest in having been tested for HIV in the past six months which increased from 40.9% to 83.2% in Durban, 56.0% to 76.6% in Tete and 70.9% to 87.6% in Mombasa. In Tete and Mombasa, rise in SRH service use was almost entirely due to a greater uptake of targeted services. Only in Durban was there additionally an increase in the utilisation of general health services. CONCLUSION: SRH service utilisation improved in the short-term in three different sub-Saharan African contexts, primarily through vertical, targeted components. The long-term effectiveness of diagonal approaches, in particular on the use of general, horizontal health services, needs further investigation.

Partner age differences and associated sexual risk behaviours among adolescent girls and young women in a cash transfer programme for schooling in Malawi.

BACKGROUND: Age disparities in sexual relationships have been proposed as a key risk factor for HIV transmission in Sub-Saharan Africa, but evidence remains inconclusive. The SIHR study, a cluster randomised trial of a cash transfer programme in Malawi, found that young women in the intervention groups were less likely to have had a sexual partner aged 25 or older, and less likely to test positive for HIV and HSV-2 at follow-up compared to control groups. We examined the hypotheses that girls in the intervention groups had smaller age differences than control groups and that large age differences were associated with relationship-level HIV transmission risk factors: inconsistent condom use, sex frequency, and relationship duration. METHODS: We conducted an analysis of schoolgirls in the Schooling, Income, and Health Risk (SIHR) study aged 13-22 at baseline (n = 2907). We investigated the effects of study arm, trial stage and participant age on age differences in sexual relationships using a linear mixed-effects model. Cumulative-link mixed-effects models were used to estimate the effect of relationship age difference on condom use and sex frequency, and a Cox proportional hazard model was used to estimate the effect of relationship age difference on relationship duration. We controlled for the girl's age, number of partners, study group and study round. RESULTS: Girls receiving cash transfers, on average, had smaller age differences in relationships compared to controls, though the estimated difference was not statistically significant (- 0.43 years; 95% CI: -1.03, 0.17). The older the participant was, the smaller her age differences (- 0.67 per 4-year increase in age; 95% CI: -0.99, - 0.35). Among controls, after the cash transfers had ended the average age difference was 0.82 years larger than during the intervention (95% CI: 0.43, 1.21), suggesting a possible indirect effect of the study on behaviour in the community as a whole. Across treatment groups, larger age differences in relationships were associated with lower levels of condom use, more frequent sex, and longer relationship durations. CONCLUSIONS: Cash-transfer programmes may prevent HIV transmission in part by encouraging young women to form age-similar relationships, which are characterised by increased condom use and reduced sex frequency. The benefits of these programmes may extend to those who are not directly receiving the cash.

It's the network, stupid: a population's sexual network connectivity determines its STI prevalence.

There is little consensus as to why sexually transmitted infections (STIs), including HIV and bacterial vaginosis (BV) are more prevalent in some populations than others. Using a broad definition of sexual network connectivity that includes both structural and conductivity-related factors, we argue that the available evidence suggests that high prevalence of traditional STIs, HIV and BV can be parsimoniously explained by these populations having more connected sexual networks. Positive feedback, whereby BV and various STIs enhance the spread of other STIs, then further accentuates the spread of BV, HIV and other STIs. We review evidence that support this hypothesis and end by suggesting study designs that could further evaluate the hypothesis, as well as implications of this hypothesis for the prevention and management of STIs.

Impact of early initiation versus national standard of care of antiretroviral therapy in Swaziland's public sector health system: study protocol for a stepped-wedge randomized trial.

BACKGROUND: There is robust clinical evidence to support offering early access to antiretroviral treatment (ART) to all HIV-positive individuals, irrespective of disease stage, to both improve patient health outcomes and reduce HIV incidence. However, as the global treatment guidelines shift to meet this evidence, it is still largely unknown if early access to ART for all (also referred to as "treatment as prevention" or "universal test and treat") is a feasible intervention in the resource-limited countries where this approach could have the biggest impact on the course of the HIV epidemics. The MaxART Early Access to ART for All (EAAA) implementation study was designed to determine the feasibility, acceptability, clinical outcomes, affordability, and scalability of offering early antiretroviral treatment to all HIV-positive individuals in Swaziland's public sector health system. METHODS: This is a three-year stepped-wedge randomized design with open enrollment for all adults aged 18 years and older across 14 government-managed health facilities in Swaziland's Hhohho Region. Primary endpoints are retention and viral suppression. Secondary endpoints include ART initiation, adherence, drug resistance, tuberculosis, HIV disease progression, patient satisfaction, and cost per patient per year. Sites are grouped to transition two at a time from the control (standard of care) to intervention (EAAA) stage at each four-month step. This design will result in approximately one half of the total observation time to accrue in the intervention arm and the other half in the control arm. Our estimated enrolment number, which is supported by conservative power calculations, is 4501 patients over the course of the 36-month study period. A multidisciplinary, mixed-methods approach will be adopted to supplement the randomized controlled trial and meet the study aims. Additional study components include implementation science, social science, economic evaluation, and predictive HIV incidence modeling. DISCUSSION: A stepped-wedge randomized design is a causally strong and robust approach to determine if providing antiretroviral treatment for all HIV-positive individuals is a feasible intervention in a resource-limited, public sector health system. We expect our study results to contribute to health policy decisions related to the HIV response in Swaziland and other countries in sub-Saharan Africa. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02909218 . Registered on 10 July 2016.

Sexual and reproductive health services utilization by female sex workers is context-specific: results from a cross-sectional survey in India, Kenya, Mozambique and South Africa.

BACKGROUND: Female sex workers (FSWs) are extremely vulnerable to adverse sexual and reproductive health (SRH) outcomes. To mitigate these risks, they require access to services covering not only HIV prevention but also contraception, cervical cancer screening and sexual violence. To develop context-specific intervention packages to improve uptake, we identified gaps in service utilization in four different cities. METHODS: A cross-sectional survey was conducted, as part of the baseline assessment of an implementation research project. FWSs were recruited in Durban, South Africa (n = 400), Mombasa, Kenya (n = 400), Mysore, India (n = 458) and Tete, Mozambique (n = 308), using respondent-driven sampling (RDS) and starting with 8-16 'seeds' identified by the peer educators. FSWs responded to a standardised interviewer-administered questionnaire about the use of contraceptive methods and services for cervical cancer screening, sexual violence and unwanted pregnancies. RDS-adjusted proportions and surrounding 95% confidence intervals were estimated by non-parametric bootstrapping, and compared across cities using post-hoc pairwise comparison tests with Dunn-Sidák correction. RESULTS: Current use of any modern contraception ranged from 86.2% in Tete to 98.4% in Mombasa (p = 0.001), while non-barrier contraception (hormonal, IUD or sterilisation) varied from 33.4% in Durban to 85.1% in Mysore (p < 0.001). Ever having used emergency contraception ranged from 2.4% in Mysore to 38.1% in Mombasa (p < 0.001), ever having been screened for cervical cancer from 0.0% in Tete to 29.0% in Durban (p < 0.001), and having gone to a health facility for a termination of an unwanted pregnancy from 15.0% in Durban to 93.7% in Mysore (p < 0.001). Having sought medical care after forced sex varied from 34.4% in Mombasa to 51.9% in Mysore (p = 0.860). Many of the differences between cities remained statistically significant after adjusting for variations in FSWs' sociodemographic characteristics. CONCLUSION: The use of SRH commodities and services by FSWs is often low and is highly context-specific. Reasons for variation across cities need to be further explored. The differences are unlikely caused by differences in socio-demographic characteristics and more probably stem from differences in the availability and accessibility of SRH services. Intervention packages to improve use of contraceptives and SRH services should be tailored to the particular gaps in each city.

Age differences between sexual partners, behavioural and demographic correlates, and HIV infection on Likoma Island, Malawi.

Patterns of age differences between sexual partners - "age-mixing" - may partially explain the magnitude of HIV epidemics in Sub-Saharan Africa. However, evidence of age-disparity as a risk factor for HIV remains mixed. We used data from a socio-centric study of sexual behaviour in Malawi to quantify the age-mixing pattern and to find associations between relationship characteristics and age differences for 1,922 participants. Three age difference measures were explored as predictors of prevalent HIV infection. We found that for each year increase in male participant age, the average age difference with their partners increased by 0.26 years, while among women it remained approximately constant around 5 years. Women in the study had larger within-individual variation in partner ages compared to men. Spousal partnerships and never using a condom during sex were associated with larger age differences in relationships of both men and women. Men who were more than five years younger than their partners had 5.39 times higher odds (95% CI: 0.93-31.24) of being HIV-infected than men 0-4 years older. The relationship between HIV-infection and age-asymmetry may be more complex than previously described. The role that women play in HIV transmission should not be under-estimated, particularly in populations with large within-individual variation in partner ages.

Beyond Risk Compensation: Clusters of Antiretroviral Treatment (ART) Users in Sexual Networks Can Modify the Impact of ART on HIV Incidence.

INTRODUCTION: Concerns about risk compensation-increased risk behaviours in response to a perception of reduced HIV transmission risk-after the initiation of ART have largely been dispelled in empirical studies, but other changes in sexual networking patterns may still modify the effects of ART on HIV incidence. METHODS: We developed an exploratory mathematical model of HIV transmission that incorporates the possibility of ART clusters, i.e. subsets of the sexual network in which the density of ART patients is much higher than in the rest of the network. Such clusters may emerge as a result of ART homophily-a tendency for ART patients to preferentially form and maintain relationships with other ART patients. We assessed whether ART clusters may affect the impact of ART on HIV incidence, and how the influence of this effect-modifying variable depends on contextual variables such as HIV prevalence, HIV serosorting, coverage of HIV testing and ART, and adherence to ART. RESULTS: ART homophily can modify the impact of ART on HIV incidence in both directions. In concentrated epidemics and generalized epidemics with moderate HIV prevalence (≈ 10%), ART clusters can enhance the impact of ART on HIV incidence, especially when adherence to ART is poor. In hyperendemic settings (≈ 35% HIV prevalence), ART clusters can reduce the impact of ART on HIV incidence when adherence to ART is high but few people living with HIV (PLWH) have been diagnosed. In all contexts, the effects of ART clusters on HIV epidemic dynamics are distinct from those of HIV serosorting. CONCLUSIONS: Depending on the programmatic and epidemiological context, ART clusters may enhance or reduce the impact of ART on HIV incidence, in contrast to serosorting, which always leads to a lower impact of ART on HIV incidence. ART homophily and the emergence of ART clusters should be measured empirically and incorporated into more refined models used to plan and evaluate ART programmes.

HIV prevention and care-seeking behaviour among female sex workers in four cities in India, Kenya, Mozambique and South Africa.

OBJECTIVE: To identify gaps in the use of HIV prevention and care services and commodities for female sex workers, we conducted a baseline cross-sectional survey in four cities, in the context of an implementation research project aiming to improve use of sexual and reproductive health services. METHODS: Using respondent-driven sampling, 400 sex workers were recruited in Durban, 308 in Tete, 400 in Mombasa and 458 in Mysore and interviewed face-to-face. RDS-adjusted proportions were estimated by nonparametric bootstrapping and compared across cities using post hoc pairwise comparison. RESULTS: Condom use with last client ranged from 88.3% to 96.8%, ever female condom use from 1.6% to 37.9%, HIV testing within the past 6 months from 40.5% to 70.9%, receiving HIV treatment and care from 35.5% to 92.7%, care seeking for last STI from 74.4% to 87.6% and having had at least 10 contacts with a peer educator in the past year from 5.7% to 98.1%. Many of the differences between cities remained statistically significant (P < 0.05) after adjusting for differences in FSWs' socio-demographic characteristics. CONCLUSION: The use of HIV prevention and care by FSWs is often insufficient and differed greatly between cities. Differences could not be explained by variations in socio-demographic sex worker characteristics. Models to improve use of condoms and HIV prevention and care services should be tailored to the specific context of each site. Programmes at each site must focus on improving availability and uptake of those services that are currently least used.