Rapid elimination of cervical cancer while maintaining the harms and benefits ratio of cervical cancer screening: a modelling study.

BACKGROUND: Human papillomavirus (HPV) vaccination and intensifying screening expedite cervical cancer (CC) elimination, yet also deteriorate the balance between harms and benefits of screening. We aimed to find screening strategies that eliminate CC rapidly but maintain an acceptable harms-benefits ratio of screening. METHODS: Two microsimulation models (STDSIM and MISCAN) were applied to simulate HPV transmission and CC screening for the Dutch female population between 2022 and 2100. We estimated the CC elimination year and harms-benefits ratios of screening for 228 unique scenarios varying in vaccination (coverage and vaccine type) and screening (coverage and number of lifetime invitations in vaccinated cohorts). The acceptable harms-benefits ratio was defined as the number of women needed to refer (NNR) to prevent one CC death under the current programme for unvaccinated cohorts (82.17). RESULTS: Under current vaccination conditions (bivalent vaccine, 55% coverage in girls, 27.5% coverage in boys), maintaining current screening conditions is projected to eliminate CC by 2042, but increases the present NNR with 41%. Reducing the number of lifetime screens from presently five to three and increasing screening coverage (61% to 70%) would prevent an increase in harms and only delay elimination by 1 year. Scaling vaccination coverage to 90% in boys and girls with the nonavalent vaccine is estimated to eliminate CC by 2040 under current screening conditions, but exceeds the acceptable NNR with 23%. Here, changing from five to two lifetime screens would keep the NNR acceptable without delaying CC elimination. CONCLUSIONS: De-intensifying CC screening in vaccinated cohorts leads to little or no delay in CC elimination while it substantially reduces the harms of screening. Therefore, de-intensifying CC screening in vaccinated cohorts should be considered to ensure acceptable harms-benefits ratios on the road to CC elimination.

No increased HIV risk in general population near sex work sites: A nationally representative cross-sectional study in Zimbabwe.

OBJECTIVES: Sex work sites have been hypothesised to be at the root of the observed heterogeneity in HIV prevalence in sub-Saharan Africa. We determined if proximity to sex work sites is associated with HIV prevalence among the general population in Zimbabwe, a country with one of the highest HIV prevalence in the world. METHODS: In this cross-sectional study we use a unique combination of nationally representative geolocated individual-level data from 16,121 adults (age 15-49 years) from 400 sample locations and the locations of 55 sex work sites throughout Zimbabwe; covering an estimated 95% of all female sex workers (FSWs). We calculated the shortest distance by road from each survey sample location to the nearest sex work site, for all sites and by type of sex work site, and conducted univariate and multivariate multilevel logistic regressions to determine the association between distance to sex work sites and HIV seropositivity, controlling for age, sex, male circumcision status, number of lifetime sex partners, being a FSW client or being a stable partner of an FSW client. RESULTS: We found no significant association between HIV seroprevalence and proximity to the nearest sex work site among the general population in Zimbabwe, regardless of which type of site is closest (city site adjusted odds ratio [aOR] 1.010 [95% confidence interval {CI} 0.992-1.028]; economic growth point site aOR 0.982 [95% CI 0.962-1.002]; international site aOR 0.995 [95% CI 0.979-1.012]; seasonal site aOR 0.987 [95% CI 0.968-1.006] and transport site aOR 1.007 [95% CI 0.987-1.028]). Individual-level indicators of sex work were significantly associated with HIV seropositivity: being an FSW client (aOR 1.445 [95% CI 1.188-1.745]); nine or more partners versus having one to three lifetime partners (aOR 2.072 [95% CI 1.654-2.596]). CONCLUSIONS: Sex work sites do not seem to directly affect HIV prevalence among the general population in surrounding areas. Prevention and control interventions for HIV at these locations should primarily focus on sex workers and their clients, with special emphasis on including and retaining mobile sex workers and clients into services.

Evidence-based policymaking when evidence is incomplete: The case of HIV programme integration.

Jan Hontelez and co-authors discuss the use of different types of evidence to inform HIV program integration.

Integrating HIV services and other health services: A systematic review and meta-analysis.

BACKGROUND: Integration of HIV services with other health services has been proposed as an important strategy to boost the sustainability of the global HIV response. We conducted a systematic and comprehensive synthesis of the existing scientific evidence on the impact of service integration on the HIV care cascade, health outcomes, and cost-effectiveness. METHODS AND FINDINGS: We reviewed the global quantitative empirical evidence on integration published between 1 January 2010 and 10 September 2021. We included experimental and observational studies that featured both an integration intervention and a comparator in our review. Of the 7,118 unique peer-reviewed English-language studies that our search algorithm identified, 114 met all of our selection criteria for data extraction. Most of the studies (90) were conducted in sub-Saharan Africa, primarily in East Africa (55) and Southern Africa (24). The most common forms of integration were (i) HIV testing and counselling added to non-HIV services and (ii) non-HIV services added to antiretroviral therapy (ART). The most commonly integrated non-HIV services were maternal and child healthcare, tuberculosis testing and treatment, primary healthcare, family planning, and sexual and reproductive health services. Values for HIV care cascade outcomes tended to be better in integrated services: uptake of HIV testing and counselling (pooled risk ratio [RR] across 37 studies: 1.67 [95% CI 1.41-1.99], p < 0.001), ART initiation coverage (pooled RR across 19 studies: 1.42 [95% CI 1.16-1.75], p = 0.002), time until ART initiation (pooled RR across 5 studies: 0.45 [95% CI 0.20-1.00], p = 0.050), retention in HIV care (pooled RR across 19 studies: 1.68 [95% CI 1.05-2.69], p = 0.031), and viral suppression (pooled RR across 9 studies: 1.19 [95% CI 1.03-1.37], p = 0.025). Also, treatment success for non-HIV-related diseases and conditions and the uptake of non-HIV services were commonly higher in integrated services. We did not find any significant differences for the following outcomes in our meta-analyses: HIV testing yield, ART adherence, HIV-free survival among infants, and HIV and non-HIV mortality. We could not conduct meta-analyses for several outcomes (HIV infections averted, costs, and cost-effectiveness), because our systematic review did not identify sufficient poolable studies. Study limitations included possible publication bias of studies with significant or favourable findings and comparatively weak evidence from some world regions and on integration of services for key populations in the HIV response. CONCLUSIONS: Integration of HIV services and other health services tends to improve health and health systems outcomes. Despite some scientific limitations, the global evidence shows that service integration can be a valuable strategy to boost the sustainability of the HIV response and contribute to the goal of 'ending AIDS by 2030', while simultaneously supporting progress towards universal health coverage.

Comparative genomics of the nonlegume Parasponia reveals insights into evolution of nitrogen-fixing rhizobium symbioses.

Nodules harboring nitrogen-fixing rhizobia are a well-known trait of legumes, but nodules also occur in other plant lineages, with rhizobia or the actinomycete Frankia as microsymbiont. It is generally assumed that nodulation evolved independently multiple times. However, molecular-genetic support for this hypothesis is lacking, as the genetic changes underlying nodule evolution remain elusive. We conducted genetic and comparative genomics studies by using Parasponia species (Cannabaceae), the only nonlegumes that can establish nitrogen-fixing nodules with rhizobium. Intergeneric crosses between Parasponia andersonii and its nonnodulating relative Trema tomentosa demonstrated that nodule organogenesis, but not intracellular infection, is a dominant genetic trait. Comparative transcriptomics of P. andersonii and the legume Medicago truncatula revealed utilization of at least 290 orthologous symbiosis genes in nodules. Among these are key genes that, in legumes, are essential for nodulation, including NODULE INCEPTION (NIN) and RHIZOBIUM-DIRECTED POLAR GROWTH (RPG). Comparative analysis of genomes from three Parasponia species and related nonnodulating plant species show evidence of parallel loss in nonnodulating species of putative orthologs of NIN, RPG, and NOD FACTOR PERCEPTION Parallel loss of these symbiosis genes indicates that these nonnodulating lineages lost the potential to nodulate. Taken together, our results challenge the view that nodulation evolved in parallel and raises the possibility that nodulation originated ∼100 Mya in a common ancestor of all nodulating plant species, but was subsequently lost in many descendant lineages. This will have profound implications for translational approaches aimed at engineering nitrogen-fixing nodules in crop plants.

Mapping and characterising areas with high levels of HIV transmission in sub-Saharan Africa: A geospatial analysis of national survey data.

BACKGROUND: In the generalised epidemics of sub-Saharan Africa (SSA), human immunodeficiency virus (HIV) prevalence shows patterns of clustered micro-epidemics. We mapped and characterised these high-prevalence areas for young adults (15-29 years of age), as a proxy for areas with high levels of transmission, for 7 countries in Eastern and Southern Africa: Kenya, Malawi, Mozambique, Tanzania, Uganda, Zambia, and Zimbabwe. METHODS AND FINDINGS: We used geolocated survey data from the most recent United States Agency for International Development (USAID) demographic and health surveys (DHSs) and AIDS indicator surveys (AISs) (collected between 2008-2009 and 2015-2016), which included about 113,000 adults-of which there were about 53,000 young adults (27,000 women, 28,000 men)-from over 3,500 sample locations. First, ordinary kriging was applied to predict HIV prevalence at unmeasured locations. Second, we explored to what extent behavioural, socioeconomic, and environmental factors explain HIV prevalence at the individual- and sample-location level, by developing a series of multilevel multivariable logistic regression models and geospatially visualising unexplained model heterogeneity. National-level HIV prevalence for young adults ranged from 2.2% in Tanzania to 7.7% in Mozambique. However, at the subnational level, we found areas with prevalence among young adults as high as 11% or 15% alternating with areas with prevalence between 0% and 2%, suggesting the existence of areas with high levels of transmission Overall, 15.6% of heterogeneity could be explained by an interplay of known behavioural, socioeconomic, and environmental factors. Maps of the interpolated random effect estimates show that environmental variables, representing indicators of economic activity, were most powerful in explaining high-prevalence areas. Main study limitations were the inability to infer causality due to the cross-sectional nature of the surveys and the likely under-sampling of key populations in the surveys. CONCLUSIONS: We found that, among young adults, micro-epidemics of relatively high HIV prevalence alternate with areas of very low prevalence, clearly illustrating the existence of areas with high levels of transmission. These areas are partially characterised by high economic activity, relatively high socioeconomic status, and risky sexual behaviour. Localised HIV prevention interventions specifically tailored to the populations at risk will be essential to curb transmission. More fine-scale geospatial mapping of key populations,-such as sex workers and migrant populations-could help us further understand the drivers of these areas with high levels of transmission and help us determine how they fuel the generalised epidemics in SSA.

Host- and stage-dependent secretome of the arbuscular mycorrhizal fungus Rhizophagus irregularis.

Arbuscular mycorrhizal fungi form the most wide-spread endosymbiosis with plants. There is very little host specificity in this interaction, however host preferences as well as varying symbiotic efficiencies have been observed. We hypothesize that secreted proteins (SPs) may act as fungal effectors to control symbiotic efficiency in a host-dependent manner. Therefore, we studied whether arbuscular mycorrhizal (AM) fungi adjust their secretome in a host- and stage-dependent manner to contribute to their extremely wide host range. We investigated the expression of SP-encoding genes of Rhizophagus irregularis in three evolutionary distantly related plant species, Medicago truncatula, Nicotiana benthamiana and Allium schoenoprasum. In addition we used laser microdissection in combination with RNA-seq to study SP expression at different stages of the interaction in Medicago. Our data indicate that most expressed SPs show roughly equal expression levels in the interaction with all three host plants. In addition, a subset shows significant differential expression depending on the host plant. Furthermore, SP expression is controlled locally in the hyphal network in response to host-dependent cues. Overall, this study presents a comprehensive analysis of the R. irregularis secretome, which now offers a solid basis to direct functional studies on the role of fungal SPs in AM symbiosis.

Which delivery model innovations can support sustainable HIV treatment?

The rapid scale-up of antiretroviral treatment (ART) for HIV since the mid-2000s, mostly through disease-specific or "vertical" programmes, has been a highly successful undertaking, which averted millions of deaths and prevented many new infections. However, the dynamics of the HIV epidemic and changing political and financial commitment to fight the disease will likely require new models for the delivery of ART over the coming decades if the promises of universal treatment are to be met. Delivery model innovations for ART are intended to improve both the effectiveness and efficiency of the HIV treatment cascade, reaching new people who require ART and providing ART to more people without an increase in resources. We describe twelve models for ART delivery, which could be achieved through five categories of delivery innovations: integrating ART ("vertical ART plus", "partially-integrated ART" and "fully-integrated ART"); modifying steps in the ART value chain ("professional task-shifted ART", "people task-shifted ART" and "technology-supported ART"); eliminating steps in the ART value chain ("immediate ART" and "less frequent ART pick-up"); changing ART locations ("private-sector ART", "traditional-sector ART" and "ART outside the health sector"); and keeping the status quo ("vertical ART"). The different delivery model innovations are not mutually exclusive and several could be combined, such as "vertical ART plus" with "task-shifted ART". Suitability of the models will highly depend on local and national contexts, including existing health systems resources, available funding, and type of HIV epidemic. Future implementation research needs to identify which models are the best fit for different contexts.

Translating international HIV treatment guidelines into local priorities in Indonesia.

OBJECTIVE: International guidelines recommend countries to expand antiretroviral therapy (ART) to all HIV-infected individuals and establish local-level priorities in relation to other treatment, prevention and mitigation interventions through fair processes. However, no practical guidance is provided for such priority-setting processes. Evidence-informed deliberative processes (EDPs) fill this gap and combine stakeholder deliberation to incorporate relevant social values with rational decision-making informed by evidence on these values. This study reports on the first-time implementation and evaluation of an EDP in HIV control, organised to support the AIDS Commission in West Java province, Indonesia, in the development of its strategic plan for 2014-2018. METHODS: Under the responsibility of the provincial AIDS Commission, an EDP was implemented to select priority interventions using six steps: (i) situational analysis; (ii) formation of a multistakeholder Consultation Panel; (iii) selection of criteria; (iv) identification and assessment of interventions' performance; (v) deliberation; and (vi) selection of funding and implementing institutions. An independent researcher conducted in-depth interviews (n = 21) with panel members to evaluate the process. RESULTS: The Consultation Panel included 23 stakeholders. They identified 50 interventions and these were evaluated against four criteria: impact on the epidemic, stigma reduction, cost-effectiveness and universal coverage. After a deliberative discussion, the Consultation Panel prioritised a combination of several treatment, prevention and mitigation interventions. CONCLUSION: The EDP improved both stakeholder involvement and the evidence base for the strategic planning process. EDPs fill an important gap which international guidelines and current tools for strategic planning in HIV control leave unaddressed.

Evidence for scaling up HIV treatment in sub-Saharan Africa: A call for incorporating health system constraints.

Jan Hontelez and colleagues argue that the cost-effectiveness studies of HIV treatment scale-up need to include health system constraints to be more informative.

Behavioural disinhibition in the general population during the antiretroviral therapy roll-out in Sub-Saharan Africa: systematic review and meta-analysis.

OBJECTIVES: Improved life expectancy and reduced transmission probabilities due to ART may result in behavioural disinhibition - that is an increase in sexual risk behaviour in response to a perceived lower risk of HIV. We examined trends in sexual risk behaviour in the general population of sub-Saharan African countries 1999-2015. METHODS: We systematically reviewed scientific literature of sexual behaviour and reviewed trends in Demographic and Health Surveys. A meta-analysis on four indicators of sexual risk behaviour was performed: unprotected sex, multiple sexual partners, commercial sex and prevalence of sexually transmitted infections. RESULTS: Only two peer-reviewed studies met our inclusion criteria, while our review of DHS data spanned 18 countries and 16 years (1999-2015). We found conflicting trends in sexual risk behaviour. Reported unprotected sex decreased consistently across the 18 countries, for both sexes. In contrast, reporting multiple partners was decreasing over the period 1999 to the mid-2000s, yet has been consistently increasing thereafter. Similar trends were found for reported sexually transmitted infections and commercial sex (men only). CONCLUSIONS: In conclusion, we found no clear evidence of behavioural disinhibition due to expanded access to ART in sub-Saharan Africa. Substantial increases in condom use coincided with increases in reported multiple partners, commercial sex and sexually transmitted infections, especially during the period of ART scale-up. Further research is needed into how these changes might affect HIV transmission.

Public Health Benefits of Routine Human Papillomavirus Vaccination for Adults in the Netherlands: A Mathematical Modeling Study.

BACKGROUND: Expanding routine human papillomavirus (HPV) vaccination to adults could be an effective strategy to improve prevention of HPV infection and cervical cancer. METHODS: We evaluated the following adult vaccination strategies for women only and for both women and men in addition to the current girls-only vaccination program in the Netherlands, using the established STDSIM microsimulation model: one-time mass campaign, vaccination at the first cervical cancer screening visit, vaccination at sexual health clinics, and combinations of these strategies. RESULTS: The estimated impact of expanding routine vaccination to adult women is modest, with the largest incremental reductions in the incidence of HPV infection occurring when offering vaccination both at the cervical cancer screening visit and during sexually transmitted infection (STI) consultations (about 20% lower after 50 years for both HPV-16 and HPV-18). Adding male vaccination during STI consultations leads to more-substantial incidence reductions: 63% for HPV-16 and 84% for HPV-18. The incremental number needed to vaccinate among women is 5.48, compared with 0.90 for the current vaccination program. CONCLUSIONS: Offering vaccination to adults, especially at cervical cancer screening visits (for women) and during STI consultations (for both sexes), would substantially reduce HPV incidence and would be an efficient policy option to improve HPV prevention and subsequently avert cervical and possibly male HPV-related cancers.

A symbiosis-dedicated SYNTAXIN OF PLANTS 13II isoform controls the formation of a stable host-microbe interface in symbiosis.

Arbuscular mycorrhizal (AM) fungi and rhizobium bacteria are accommodated in specialized membrane compartments that form a host-microbe interface. To better understand how these interfaces are made, we studied the regulation of exocytosis during interface formation. We used a phylogenetic approach to identify target soluble N-ethylmaleimide-sensitive factor-attachment protein receptors (t-SNAREs) that are dedicated to symbiosis and used cell-specific expression analysis together with protein localization to identify t-SNAREs that are present on the host-microbe interface in Medicago truncatula. We investigated the role of these t-SNAREs during the formation of a host-microbe interface. We showed that multiple syntaxins are present on the peri-arbuscular membrane. From these, we identified SYNTAXIN OF PLANTS 13II (SYP13II) as a t-SNARE that is essential for the formation of a stable symbiotic interface in both AM and rhizobium symbiosis. In most dicot plants, the SYP13II transcript is alternatively spliced, resulting in two isoforms, SYP13IIα and SYP13IIß. These splice-forms differentially mark functional and degrading arbuscule branches. Our results show that vesicle traffic to the symbiotic interface is specialized and required for its maintenance. Alternative splicing of SYP13II allows plants to replace a t-SNARE involved in traffic to the plasma membrane with a t-SNARE that is more stringent in its localization to functional arbuscules.

Equity in utilization of antiretroviral therapy for HIV-infected people in South Africa: a systematic review.

INTRODUCTION: About half a million people in South Africa are deprived of antiretroviral therapy (ART), and there is little systematic knowledge on who they are - e.g. by severity of disease, sex, or socio-economic status (SES). We performed a systematic review to determine the current quantitative evidence-base on equity in utilization of ART among HIV-infected people in South Africa. METHOD: We conducted a literature search based on the Cochrane guidelines. A study was included if it compared for different groups of HIV infected people (by sex, age, severity of disease, area of living, SES, marital status, ethnicity, religion and/or sexual orientation (i.e. equity criteria)) the number initiating/adhering to ART with the number who did not. We considered ART utilization inequitable for a certain criterion (e.g. sex) if between groups (e.g. men versus women) significant differences were reported in ART initiation/adherence. RESULTS: Twelve studies met the inclusion criteria. For sex, 2 out of 10 studies that investigated this criterion found that men are less likely than women to utilize ART, while the other 8 found no differences. For age, 4 out of 8 studies found inequities and reported less utilization for younger people. For area of living, 3 out of 4 studies showed that those living in rural areas or certain provinces have less access and 2 out of 6 studies looking at SES found that people with lower SES have less access. One study which looked at the marital status found that those who are married are less likely to utilize ART. For severity of disease, 5 out of 6 studies used more than one outcome measure for disease stage and reported within their study contradicting results. One of the studies reported inconclusive findings for ethnicity and no study had looked at religion and sexual orientation. CONCLUSION: It seems that men, young people, those living in certain provinces or rural areas, people who are unemployed or with a low educational level, and those being unmarried have less access to ART. As studies stem from different contexts and use different methods conclusions should be taken with caution.

Elimination of HIV in South Africa through expanded access to antiretroviral therapy: a model comparison study.

BACKGROUND: Expanded access to antiretroviral therapy (ART) using universal test and treat (UTT) has been suggested as a strategy to eliminate HIV in South Africa within 7 y based on an influential mathematical modeling study. However, the underlying deterministic model was criticized widely, and other modeling studies did not always confirm the study's finding. The objective of our study is to better understand the implications of different model structures and assumptions, so as to arrive at the best possible predictions of the long-term impact of UTT and the possibility of elimination of HIV. METHODS AND FINDINGS: We developed nine structurally different mathematical models of the South African HIV epidemic in a stepwise approach of increasing complexity and realism. The simplest model resembles the initial deterministic model, while the most comprehensive model is the stochastic microsimulation model STDSIM, which includes sexual networks and HIV stages with different degrees of infectiousness. We defined UTT as annual screening and immediate ART for all HIV-infected adults, starting at 13% in January 2012 and scaled up to 90% coverage by January 2019. All models predict elimination, yet those that capture more processes underlying the HIV transmission dynamics predict elimination at a later point in time, after 20 to 25 y. Importantly, the most comprehensive model predicts that the current strategy of ART at CD4 count ≤350 cells/µl will also lead to elimination, albeit 10 y later compared to UTT. Still, UTT remains cost-effective, as many additional life-years would be saved. The study's major limitations are that elimination was defined as incidence below 1/1,000 person-years rather than 0% prevalence, and drug resistance was not modeled. CONCLUSIONS: Our results confirm previous predictions that the HIV epidemic in South Africa can be eliminated through universal testing and immediate treatment at 90% coverage. However, more realistic models show that elimination is likely to occur at a much later point in time than the initial model suggested. Also, UTT is a cost-effective intervention, but less cost-effective than previously predicted because the current South African ART treatment policy alone could already drive HIV into elimination. Please see later in the article for the Editors' Summary.

Balancing efficiency, equity and feasibility of HIV treatment in South Africa - development of programmatic guidance.

South Africa, the country with the largest HIV epidemic worldwide, has been scaling up treatment since 2003 and is rapidly expanding its eligibility criteria. The HIV treatment programme has achieved significant results, and had 1.8 million people on treatment per 2011. Despite these achievements, it is now facing major concerns regarding (i) efficiency: alternative treatment policies may save more lives for the same budget; (ii) equity: there are large inequalities in who receives treatment; (iii) feasibility: still only 52% of the eligible population receives treatment.Hence, decisions on the design of the present HIV treatment programme in South Africa can be considered suboptimal. We argue there are two fundamental reasons to this. First, while there is a rapidly growing evidence-base to guide priority setting decisions on HIV treatment, its included studies typically consider only one criterion at a time and thus fail to capture the broad range of values that stakeholders have. Second, priority setting on HIV treatment is a highly political process but it seems no adequate participatory processes are in place to incorporate stakeholders' views and evidences of all sorts.We propose an alternative approach that provides a better evidence base and outlines a fair policy process to improve priority setting in HIV treatment. The approach integrates two increasingly important frameworks on health care priority setting: accountability for reasonableness (A4R) to foster procedural fairness, and multi-criteria decision analysis (MCDA) to construct an evidence-base on the feasibility, efficiency, and equity of programme options including trade-offs. The approach provides programmatic guidance on the choice of treatment strategies at various decisions levels based on a sound conceptual framework, and holds large potential to improve HIV priority setting in South Africa.

Changes in context, typology and programme outcomes between early and recent periods of sex work among young female sex workers in Mombasa, Kenya: A cross-sectional study.

INTRODUCTION: The sex work context and typology change continuously and influence HIV related risk and vulnerability for young female sex workers (YFSW). We sought to describe changes in the context and typology of sex work between the first (early) and past month (recent) of sex work among YFSW to inform HIV prevention programming for sex workers. METHODS: We used data from a cross-sectional survey (April-November 2015), administered using physical location-based sampling to 408 cis-women, aged 14-24 years, who self-identified as sex workers, in Mombasa, Kenya. We collected self-reported data on the early and recent month of sex work. The analysis focused on changes in a) sex work context and typology (defined by setting where sex workers practice sex work) where YFSW operated, b) primary typology of sex work, and c) HIV programme outcomes among YFSW who changed primary typology, within the early and recent month of sex work. We analysed the data using a) SPSS27.0 and excel; b) bivariate analysis and χ2 test; and c) bivariate logistic regression models. RESULTS: Overall, the median age of respondents was 20 years and median duration in sex work was 2 years. Higher proportion of respondents in the recent period managed their clients on their own (98.0% vs. 91.2%), had sex with >5 clients per week (39.3% vs.16.5%); were able to meet > 50% of living expenses through sex work income (46.8% vs. 18.8%); and experienced police violence in the past month (16.4% vs. 6.5%). YFSW reported multiple sex work typology in early and recent periods. Overall, 37.2% reported changing their primary typology. A higher proportion among those who used street/ bus stop typology, experienced police violence, or initiated sex work after 19 years of age in the early period reported a change. There was no difference in HIV programme outcomes among YFSW who changed typology vs. those who did not. CONCLUSIONS: The sex work context changes even in a short duration of two years. Hence, understanding these changes in the early period of sex work can allow for development of tailored strategies that are responsive to the specific needs and vulnerabilities of YFSW.

HIV prevalence, risk behaviour, and treatment and prevention cascade outcomes among cisgender men, transgender women, and transgender men who sell sex in Zimbabwe: a cross-sectional analysis of programme data.

BACKGROUND: There is a paucity of evidence on HIV vulnerabilities and service engagements among people who sell sex in sub-Saharan Africa and identify as cisgender men, transgender women, or transgender men. We aimed to describe sexual risk behaviours, HIV prevalence, and access to HIV services among cisgender men, transgender women, and transgender men who sell sex in Zimbabwe. METHODS: We did a cross-sectional analysis of routine programme data that were collected between July 1, 2018, and June 30, 2020, from cisgender men who sell sex, transgender women who sell sex, and transgender men who sell sex, as part of accessing sexual and reproductive health and HIV services provided through the Sisters with a Voice programme, at 31 sites across Zimbabwe. All people who sell sex reached by the programme had routine data collected, including routine HIV testing, and were referred using a network of peer educators. Sexual risk behaviours, HIV prevalence, and HIV services uptake during the period from July, 2018, to June, 2020, were analysed through descriptive statistics by gender group. FINDINGS: A total of 1003 people who sell sex were included in our analysis: 423 (42·2%) cisgender men, 343 (34·2%) transgender women, and 237 (23·6%) transgender men. Age-standardised HIV prevalence estimates were 26·2% (95% CI 22·0-30·7) among cisgender men, 39·4% (34·1-44·9) among transgender women, and 38·4% (32·1-45·0) among transgender men. Among people living with HIV, 66·0% (95% CI 55·7-75·3) of cisgender men, 74·8% (65·8-82·4) of transgender women, and 70·2% (59·3-79·7) of transgender men knew their HIV status, and 15·5% (8·9-24·2), 15·7% (9·5-23·6), and 11·9% (5·9-20·8) were on antiretroviral therapy, respectively. Self-reported condom use was consistently low across gender groups, ranging from 26% (95% CI 22-32) for anal sex among transgender women to 32% (27-37) for vaginal sex among cisgender men. INTERPRETATION: These unique data show that people who sell sex and identify as cisgender men, transgender women, or transgender men in sub-Saharan Africa have high HIV prevalences and risk of infection, with alarmingly low access to HIV prevention, testing, and treatment services. There is an urgent need for people-centred HIV interventions for these high-risk groups and for more inclusive HIV policies and research to ensure we truly attain universal access for all. FUNDING: Aidsfonds Netherlands.

HIV treatment as prevention: systematic comparison of mathematical models of the potential impact of antiretroviral therapy on HIV incidence in South Africa.

BACKGROUND: Many mathematical models have investigated the impact of expanding access to antiretroviral therapy (ART) on new HIV infections. Comparing results and conclusions across models is challenging because models have addressed slightly different questions and have reported different outcome metrics. This study compares the predictions of several mathematical models simulating the same ART intervention programmes to determine the extent to which models agree about the epidemiological impact of expanded ART. METHODS AND FINDINGS: Twelve independent mathematical models evaluated a set of standardised ART intervention scenarios in South Africa and reported a common set of outputs. Intervention scenarios systematically varied the CD4 count threshold for treatment eligibility, access to treatment, and programme retention. For a scenario in which 80% of HIV-infected individuals start treatment on average 1 y after their CD4 count drops below 350 cells/µl and 85% remain on treatment after 3 y, the models projected that HIV incidence would be 35% to 54% lower 8 y after the introduction of ART, compared to a counterfactual scenario in which there is no ART. More variation existed in the estimated long-term (38 y) reductions in incidence. The impact of optimistic interventions including immediate ART initiation varied widely across models, maintaining substantial uncertainty about the theoretical prospect for elimination of HIV from the population using ART alone over the next four decades. The number of person-years of ART per infection averted over 8 y ranged between 5.8 and 18.7. Considering the actual scale-up of ART in South Africa, seven models estimated that current HIV incidence is 17% to 32% lower than it would have been in the absence of ART. Differences between model assumptions about CD4 decline and HIV transmissibility over the course of infection explained only a modest amount of the variation in model results. CONCLUSIONS: Mathematical models evaluating the impact of ART vary substantially in structure, complexity, and parameter choices, but all suggest that ART, at high levels of access and with high adherence, has the potential to substantially reduce new HIV infections. There was broad agreement regarding the short-term epidemiologic impact of ambitious treatment scale-up, but more variation in longer term projections and in the efficiency with which treatment can reduce new infections. Differences between model predictions could not be explained by differences in model structure or parameterization that were hypothesized to affect intervention impact.