The Potential Impact of Long-Acting Cabotegravir for HIV Prevention in South Africa: A Mathematical Modeling Study.

BACKGROUND: Although effective, some oral pre-exposure prophylaxis (PrEP) users face barriers to adherence using daily pills, which could be reduced by long-acting formulations. Long-acting cabotegravir (CAB LA) is a potential new injectable formulation for human immunodeficiency virus (HIV) PrEP being tested in phase III trials. METHODS: We use a mathematical model of the HIV epidemic in South Africa to simulate CAB LA uptake by population groups with different levels of HIV risk. We compare the trajectory of the HIV epidemic until 2050 with and without CAB LA to estimate the impact of the intervention. RESULTS: Delivering CAB LA to 10% of the adult population could avert more than 15% of new infections from 2023 to 2050. The impact would be lower but more efficient if delivered to populations at higher HIV risk: 127 person-years of CAB LA use would be required to avert one HIV infection within 5 years if used by all adults and 47 person-years if used only by the highest risk women. CONCLUSIONS: If efficacious, a CAB LA intervention could have a substantial impact on the course of the HIV epidemic in South Africa. Uptake by those at the highest risk of infection, particularly young women, could improve the efficiency of any intervention.

Risk pathways for gonorrhea acquisition in sex workers: can we distinguish confounding from an exposure effect using a priori hypotheses?

The population distribution of sexually transmitted infections (STIs) varies broadly across settings. Although there have been many studies aiming to define subgroups at risk of infection that should be a target for prevention interventions by identifying risk factors, questions remain about how these risk factors interact, how their effects jointly influence the risk of acquisition, and their differential importance across populations. Theoretical frameworks describing the interrelationships among risk determinants are useful in directing both the design and analysis of research studies and interventions. In this article, we developed such a framework from a review looking at determinants of risk for STI acquisition, using gonorrhea as an index infection. We also propose an analysis strategy to interpret the associations found to be significant in uniform analyses of observational data. The framework and the hierarchical analysis strategy are of particular relevance in the understanding of risk formation and might prove useful in identifying determinants that are part of the causal pathway and therefore amenable to prevention strategies across populations.

Trends in concurrency, polygyny, and multiple sex partnerships during a decade of declining HIV prevalence in eastern Zimbabwe.

BACKGROUND: Observed declines in the prevalence of human immunodeficiency virus (HIV) infection in Zimbabwe have been attributed to population-level reductions in sexual partnership numbers. However, it remains unknown whether certain types of sex partnerships were more important to this decline. Particular debate surrounds the epidemiologic importance of polygyny (the practice of having multiple wives). METHODS: We analyze changes in reported multiple partnerships, nonmarital concurrency, and polygyny in eastern Zimbabwe during a period of declining HIV prevalence, from 1998 to 2011. Trends are reported for adult men (age, 17-54 years) and women (age, 15-49 years) from 5 survey rounds of the Manicaland HIV/STD Prevention Project, a general-population open cohort study. RESULTS: At baseline, 34.2% of men reported multiple partnerships, 11.9% reported nonmarital concurrency, and 4.6% reported polygyny. Among women, 4.6% and 1.8% reported multiple partnerships and concurrency, respectively. All 3 partnership indicators declined by similar relative amounts (around 60%-70%) over the period. Polygyny accounted for around 25% of male concurrency. Compared with monogamously married men, polygynous men reported higher levels of subsequent divorce/separation (adjusted relative risk [RR], 2.92; 95% confidence interval [CI], 1.87-4.55) and casual sex partnerships (adjusted RR, 1.63; 95% CI, 1.41-1.88). CONCLUSIONS: No indicator clearly dominated declines in partnerships. Polygyny was surprisingly unstable and, in this population, should not be considered a safe form of concurrency.

Effects of unconditional and conditional cash transfers on child health and development in Zimbabwe: a cluster-randomised trial.

BACKGROUND: Cash-transfer programmes can improve the wellbeing of vulnerable children, but few studies have rigorously assessed their effectiveness in sub-Saharan Africa. We investigated the effects of unconditional cash transfers (UCTs) and conditional cash transfers (CCTs) on birth registration, vaccination uptake, and school attendance in children in Zimbabwe. METHODS: We did a matched, cluster-randomised controlled trial in ten sites in Manicaland, Zimbabwe. We divided each study site into three clusters. After a baseline survey between July, and September, 2009, clusters in each site were randomly assigned to UCT, CCT, or control, by drawing of lots from a hat. Eligible households contained children younger than 18 years and satisfied at least one other criteria: head of household was younger than 18 years; household cared for at least one orphan younger than 18 years, a disabled person, or an individual who was chronically ill; or household was in poorest wealth quintile. Between January, 2010, and January, 2011, households in UCT clusters collected payments every 2 months. Households in CCT clusters could receive the same amount but were monitored for compliance with several conditions related to child wellbeing. Eligible households in all clusters, including control clusters, had access to parenting skills classes and received maize seed and fertiliser in December, 2009, and August, 2010. Households and individuals delivering the intervention were not masked, but data analysts were. The primary endpoints were proportion of children younger than 5 years with a birth certificate, proportion younger than 5 years with up-to-date vaccinations, and proportion aged 6-12 years attending school at least 80% of the time. This trial is registered with ClinicalTrials.gov, number NCT00966849. FINDINGS: 1199 eligible households were allocated to the control group, 1525 to the UCT group, and 1319 to the CCT group. Compared with control clusters, the proportion of children aged 0-4 years with birth certificates had increased by 1·5% (95% CI -7·1 to 10·1) in the UCT group and by 16·4% (7·8-25·0) in the CCT group by the end of the intervention period. The proportions of children aged 0-4 years with complete vaccination records was 3·1% (-3·8 to 9·9) greater in the UCT group and 1·8% (-5·0 to 8·7) greater in the CCT group than in the control group. The proportions of children aged 6-12 years who attended school at least 80% of the time was 7·2% (0·8-13·7) higher in the UCT group and 7·6% (1·2-14·1) in the CCT group than in the control group. INTERPRETATION: Our results support strategies to integrate cash transfers into social welfare programming in sub-Saharan Africa, but further evidence is needed for the comparative effectiveness of UCT and CCT programmes in this region. FUNDING: Wellcome Trust, the World Bank through the Partnership for Child Development, and the Programme of Support for the Zimbabwe National Action Plan for Orphans and Vulnerable Children.

Mathematical models in the evaluation of health programmes.

Modelling is valuable in the planning and evaluation of interventions, especially when a controlled trial is ethically or logistically impossible. Models are often used to calculate the expected course of events in the absence of more formal assessments. They are also used to derive estimates of rare or future events from recorded intermediate points. When developing models, decisions are needed about the appropriate level of complexity to be represented and about model structure and assumptions. The degree of rigor in model development and assessment can vary greatly, and there is a danger that existing beliefs inappropriately influence judgments about model assumptions and results.

Effect of concurrent sexual partnerships on rate of new HIV infections in a high-prevalence, rural South African population: a cohort study.

BACKGROUND: Concurrent sexual partnerships are widely believed to be one of the main drivers of the HIV epidemic in sub-Saharan Africa. This view is supported by theoretical models predicting that increases in prevalence of concurrent partnerships could substantially increase the rate of spread of the disease. However, the effect of concurrent partnerships on HIV incidence has not been appropriately tested in a sub-Saharan African setting. METHODS: For this population-based cohort study, we used data from the Africa Centre demographic surveillance site in KwaZulu-Natal, South Africa, to try to find support for the concurrency hypothesis. We used a moving-window approach to construct estimates of the geographical variation in reported concurrent and lifetime partners in sexually active men aged 15-55 years (n=2153) across the study area. We then followed up 7284 HIV-negative women (≥15 years of age) in the population and quantified the effect of the sexual behaviour profiles of men in the surrounding local community on a woman's hazard of HIV acquisition. FINDINGS: During 5 years' follow-up, 693 new female HIV infections occurred (incidence 3.60 cases per 100 person-years). We identified substantial intercommunity heterogeneity in the estimated point-prevalence of partnership concurrency (range 4.0-76.3%; mean 31.5%) and mean number of lifetime sexual partners (3.4-12.9; mean 6.3) in sexually active men in this population. After adjustment for individual-level sexual behaviour and demographic, socioeconomic, and environmental factors associated with HIV acquisition, mean lifetime number of partners of men in the immediate local community was predictive of hazard of HIV acquisition in women (adjusted hazard ratio [HR] 1.08, 95% CI 1.03-1.14, p=0.004), whereas a high prevalence of partnership concurrency in the same local community was not associated with any increase in risk of HIV acquisition (adjusted HR 1.02, 95% CI 0.95-1.09, p=0.556). INTERPRETATION: We find no evidence to suggest that concurrent partnerships are an important driver of HIV incidence in this typical high-prevalence rural African population. Our findings suggest that in similar hyperendemic sub-Saharan African settings, there is a need for straightforward, unambiguous messages aimed at the reduction of multiple partnerships, irrespective of whether those partnerships overlap in time. FUNDING: US National Institute of Child Health and Human Development; Wellcome Trust.

Understanding the modes of transmission model of new HIV infection and its use in prevention planning.

The modes of transmission model has been widely used to help decision-makers target measures for preventing human immunodeficiency virus (HIV) infection. The model estimates the number of new HIV infections that will be acquired over the ensuing year by individuals in identified risk groups in a given population using data on the size of the groups, the aggregate risk behaviour in each group, the current prevalence of HIV infection among the sexual or injecting drug partners of individuals in each group, and the probability of HIV transmission associated with different risk behaviours. The strength of the model is its simplicity, which enables data from a variety of sources to be synthesized, resulting in better characterization of HIV epidemics in some settings. However, concerns have been raised about the assumptions underlying the model structure, about limitations in the data available for deriving input parameters and about interpretation and communication of the model results. The aim of this review was to improve the use of the model by reassessing its paradigm, structure and data requirements. We identified key questions to be asked when conducting an analysis and when interpreting the model results and make recommendations for strengthening the model's application in the future.

Patterns of uptake of HIV testing in sub-Saharan Africa in the pre-treatment era.

OBJECTIVES: To compare nationally representative trends in self-reported uptake of HIV testing and receipt of results in selected countries prior to treatment scale-up. METHODS: Demographic and Health Survey (DHS) data from 13 countries in sub-Saharan Africa were used to describe the pattern of uptake of testing for HIV among sexually active participants. Univariate and multivariate logistic regression were used to analyse the associations between socio-demographic and behavioural characteristics and the uptake of testing. RESULTS: Knowledge of serostatus ranged from 2.2% among women in Guinea (2005) to 27.4% among women in Rwanda (2005). Despite varied levels of testing, univariate analysis showed the profile of testers to be remarkably similar across countries, with respect to socio-demographic characteristics such as area of residence and socio-economic status. HIV-positive participants were more likely to have tested and received their results than HIV-negative participants, with the exception of women in Senegal and men in Guinea. Adjusted analyses indicate that a secondary or higher level of education was a key determinant of testing, and awareness that treatment exists was independently positively associated with testing, once other characteristics were taken into account. CONCLUSION: This work provides a baseline for monitoring trends in testing and exploring changes in the profile of those who get tested after the introduction and scale-up of treatment.

Optimal uses of antiretrovirals for prevention in HIV-1 serodiscordant heterosexual couples in South Africa: a modelling study.

BACKGROUND: Antiretrovirals have substantial promise for HIV-1 prevention, either as antiretroviral treatment (ART) for HIV-1-infected persons to reduce infectiousness, or as pre-exposure prophylaxis (PrEP) for HIV-1-uninfected persons to reduce the possibility of infection with HIV-1. HIV-1 serodiscordant couples in long-term partnerships (one member is infected and the other is uninfected) are a priority for prevention interventions. Earlier ART and PrEP might both reduce HIV-1 transmission in this group, but the merits and synergies of these different approaches have not been analyzed. METHODS AND FINDINGS: We constructed a mathematical model to examine the impact and cost-effectiveness of different strategies, including earlier initiation of ART and/or PrEP, for HIV-1 prevention for serodiscordant couples. Although the cost of PrEP is high, the cost per infection averted is significantly offset by future savings in lifelong treatment, especially among couples with multiple partners, low condom use, and a high risk of transmission. In some situations, highly effective PrEP could be cost-saving overall. To keep couples alive and without a new infection, providing PrEP to the uninfected partner could be at least as cost-effective as initiating ART earlier in the infected partner, if the annual cost of PrEP is <40% of the annual cost of ART and PrEP is >70% effective. CONCLUSIONS: Strategic use of PrEP and ART could substantially and cost-effectively reduce HIV-1 transmission in HIV-1 serodiscordant couples. New and forthcoming data on the efficacy of PrEP, the cost of delivery of ART and PrEP, and couples behaviours and preferences will be critical for optimizing the use of antiretrovirals for HIV-1 prevention. Please see later in the article for the Editors' Summary.

Condom use by female sex workers and their clients in Mexico: who decides and does it matter?

OBJECTIVES: To explore the effect of different patterns of condom use by clients and female sex workers (FSW) on HIV transmission in Mexico. METHODS: Data from 2401 face-to-face interviews among FSW from Morelos and Michoacán in Mexico were used to build and parameterise a deterministic model of HIV transmission between FSW, their stable partners and clients. RESULTS: For the observed patterns of condom use among FSW, a range of patterns of use among clients would be consistent. Two extreme patterns were explored: either clients conformed to FSW decision, or they had a strict preference for bought sex with or without condoms. HIV prevalence in the model is greater in the first of these scenarios. CONCLUSIONS: Patterns of condom use between sex workers and clients are an important, but hidden, determinant of epidemic spread. More detailed information on condom use negotiation and behavioural patterns of clients is needed to understand the potential for transmission in these populations and in order to direct intervention efforts more effectively.

Did national HIV prevention programs contribute to HIV decline in Eastern Zimbabwe? Evidence from a prospective community survey.

OBJECTIVE: To add to the evidence on the impact of national HIV prevention programs in reducing HIV risk in sub-Saharan African countries. METHODS: Statistical analysis of prospective data on exposure to HIV prevention programs, relatives with AIDS and unemployment, and sexual behavior change and HIV incidence, in a population cohort of 4047 adults, collected over a period (1998-2003) when HIV prevalence and risk-behavior declined in eastern Zimbabwe. RESULTS: Exposure to HIV prevention programs and relatives with AIDS-but not unemployment-increased from 1998 to 2003. Men and women exposed to media campaigns and HIV/AIDS meetings had greater knowledge and self-efficacy, attributes that were concomitantly protective against HIV infection. Women attending community HIV/AIDS meetings before recruitment were more likely than other women to adopt lower-risk behavior (96.4% vs. 90.8%; adjusted odds ratio, 3.09; 95% confidence interval [CI], 1.27-7.49) and had lower HIV incidence (0.9% vs. 1.8%; adjusted incidence rate ratio, 0.63; 95% CI, 0.32-1.24) during the intersurvey period. Prior exposure to relatives with AIDS was not associated with differences in behavior change. More newly unemployed men as compared with employed men adopted lower-risk behavior (84.2% vs. 76.0%; adjusted odds ratio, 2.13; 95% CI, 0.98-4.59). CONCLUSIONS: Community-based HIV/AIDS meetings reduced risk-behavior amongst women who attended them, contributing to HIV decline in eastern Zimbabwe.

Concurrent sexual partnerships and primary HIV infection: a critical interaction.

The combination of long-term concurrent sexual partnerships and high infectiousness early in HIV infection has been suggested as a key driver of the extensive spread of HIV in general populations in sub-Saharan Africa, but this has never been scientifically investigated. We use a mathematical model to simulate HIV spreading on sexual networks with different amounts of concurrency. The models show that if HIV infectiousness is constant over the duration of infection, the amount of concurrency has much less influence on HIV spread compared to when infectiousness varies over three stages of infection with high infectiousness in the first months. The proportion of transmissions during primary infection is sensitive to the amount of concurrency and, in this model, is estimated to be between 16 and 28% in spreading epidemics with increasing concurrency. The sensitivity of epidemic spread to the amount of concurrency is greater than predicted by models that do not include primary HIV infection.

Host immunity and synchronized epidemics of syphilis across the United States.

A central question in population ecology is the role of 'exogenous' environmental factors versus density-dependent 'endogenous' biological factors in driving changes in population numbers. This question is also central to infectious disease epidemiology, where changes in disease incidence due to behavioural or environmental change must be distinguished from the nonlinear dynamics of the parasite population. Repeated epidemics of primary and secondary syphilis infection in the United States over the past 50 yr have previously been attributed to social and behavioural changes. Here, we show that these epidemics represent a rare example of unforced, endogenous oscillations in disease incidence, with an 8-11-yr period that is predicted by the natural dynamics of syphilis infection, to which there is partially protective immunity. This conclusion is supported by the absence of oscillations in gonorrhoea cases, where a protective immune response is absent. We further demonstrate increased synchrony of syphilis oscillations across cities over time, providing empirical evidence for an increasingly connected sexual network in the United States.

Studying complex interactions among determinants of healthcare-seeking behaviours: self-medication for sexually transmitted infection symptoms in female sex workers.

OBJECTIVES: To describe the frequency and determinants of self-medication for symptoms of sexually transmitted infections (STI) in a female sex worker (FSW) population. To present a methodology exploring the best predictors as well as the interactions between determinants of self-medication. METHODS: A cross-sectional survey of 4153 FSW carried out in Peru. The prevalence of self-medication was estimated from the subsample of participants who had experienced symptoms of STI in the past 12 months (n=1601), and used successive logistic regression models to explore the determinants. RESULTS: Self-medication prevalence for a reported symptomatic episode during the past 12 months was 32.1% (95% CI 29.8 to 34.6). It was negatively correlated with work in brothels (adjusted odds ratio (OR) 0.51, 95% CI 0.28 to 0.93; p=0.028) and awareness of STI services available for FSW (adjusted OR 0.49, 95% CI 0.29 to 0.81; p=0.006). Other determinants were organised at different levels of proximity to the outcome creating pathways leading to self-medication. CONCLUSIONS: The importance of the staggered analysis presented in this study resides in its potential to improve the understanding of associations between determinants and, consequently, the targeting of interventions. The awareness of STI services available for FSW increases access to health care, which in turn decreases self-medication. In addition, the sharing of information that takes place between brothel-based FSW was also related to a diminishing prevalence of self-medication. These two main predictors provide an opportunity for prevention programmes, in particular those designed to be led by peers.

Measuring and correcting biased child mortality statistics in countries with generalized epidemics of HIV infection.

OBJECTIVE: Under Millennium Development Goal 4, countries are required to reduce child mortality by two-thirds between 1990 and 2015. In countries with generalized epidemics of human immunodeficiency virus (HIV) infection, standard statistics based on fertility history may misrepresent progress towards this target owing to the correlation between deaths among mothers and early childhood deaths from acquired immunodeficiency syndrome. METHODS: To empirically estimate this bias, child mortality data and fertility history, including births to deceased women, were collected through prospective household surveys in eastern Zimbabwe during 1998-2005. A mathematical model was then used to investigate the determinants and temporal dynamics of the bias, first in Zimbabwe and then in other countries with different background mortality rates and HIV-related epidemic profiles. FINDINGS: According to the empirical data, standard cross-sectional survey statistics underestimated true infant and under-5 mortality by 6.7% and 9.8%, respectively. These estimates were in agreement with the output from the model, in which the bias varied according to the magnitude and stage of the epidemic of HIV infection and background mortality rates. The bias was greater the longer the period elapsed before the survey and in later stages of the epidemic. Bias could substantially distort the measured effect of interventions to reduce non-HIV-related mortality and of programmes to prevent mother-to-child transmission, especially when trends are based on data from a single survey. CONCLUSION: The correlation between the HIV-related deaths of mothers and their children can bias survey estimates of early child mortality. A mathematical model with a user-friendly interface is available to correct for this bias when measuring progress towards Millennium Development Goal 4 in countries with generalized epidemics of HIV infection.

Patterns of self-reported behaviour change associated with receiving voluntary counselling and testing in a longitudinal study from Manicaland, Zimbabwe.

Voluntary counselling and testing (VCT) is promoted as a potential HIV prevention measure. We describe trends in uptake of VCT for HIV, and patterns of subsequent behaviour change associated with receiving VCT in a population-based open cohort in Manicaland, Zimbabwe. The relationship between receipt of VCT and subsequent reported behaviour was analysed using generalized linear models with random effects. At the third survey, 8.6% of participants (1,079/12,533), had previously received VCT. Women who received VCT, both those positive and negative, reduced their reported number of new partners. Among those testing positive, this risk reduction was enhanced with time since testing. Among men, no behavioural risk reduction associated with VCT was observed. Significant increases in consistent condom use, with regular or non-regular partners, following VCT, were not observed. This study suggests that, among women, particularly those who are infected, behavioural risk reduction does occur following VCT.

A tale of two cascades: promoting a standardized tool for monitoring progress in HIV prevention.

INTRODUCTION: To achieve significant progress in global HIV prevention from 2020 onward, it is essential to ensure that appropriate programmes are being delivered with high quality and sufficient intensity and scale and then taken up by the people who most need and want them in order to have both individual and public health impact. Yet, currently, there is no standard way of assessing this. Available HIV prevention indicators do not provide a logical set of measures that combine to show reduction in HIV incidence and allow for comparison of success (or failure) of HIV prevention programmes and for monitoring progress in meeting global targets. To redress this, attention increasingly has turned to the prospects of devising an HIV prevention cascade, similar to the now-standard HIV treatment cascade; but this has proven to be a controversial enterprise, chiefly due to the complexity of primary prevention. DISCUSSION: We address a number of core issues attendant with devising prevention cascades, including: determining the population of interest and accounting for the variability and fluidity of HIV-related risk within it; the fact that there are multiple HIV prevention methods, and many people are exposed to a package of them, rather than a single method; and choosing the final step (outcome) in the cascade. We propose two unifying models of prevention cascades-one more appropriate for programme managers and monitors and the other for researchers and programme developers-and note their relationship. We also provide some considerations related to cascade data quality and improvement. CONCLUSIONS: The HIV prevention field has been grappling for years with the idea of developing a standardised way to regularly assess progress and to monitor and improve programmes accordingly. The cascade provides the potential to do this, but it is complicated and highly nuanced. We believe the two models proposed here reflect emerging consensus among the range of stakeholders who have been engaging in this discussion and who are dedicated to achieving global HIV prevention goals by ensuring the most appropriate and effective programmes and methods are supported.

The effect of 90-90-90 on HIV-1 incidence and mortality in eSwatini: a mathematical modelling study.

BACKGROUND: The rapid scale-up of antiretroviral therapy (ART) towards the UNAIDS 90-90-90 goals over the last decade has sparked considerable debate as to whether universal test and treat can end the HIV-1 epidemic in sub-Saharan Africa. We aimed to develop a network transmission model, calibrated to capture age-specific and sex-specific gaps in the scale-up of ART, to estimate the historical and future effect of attaining and surpassing the UNAIDS 90-90-90 treatment targets on HIV-1 incidence and mortality, and to assess whether these interventions will be enough to achieve epidemic control (incidence of 1 infection per 1000 person-years) by 2030. METHODS: We used eSwatini (formerly Swaziland) as a case study to develop our model. We used data on HIV prevalence by 5-year age bins, sex, and year from the 2007 Swaziland Demographic Health Survey (SDHS), the 2011 Swaziland HIV Incidence Measurement Survey, and the 2016 Swaziland Population Health Impact Assessment (PHIA) survey. We estimated the point prevalence of ART coverage among all HIV-infected individuals by age, sex, and year. Age-specific data on the prevalence of male circumcision from the SDHS and PHIA surveys were used as model inputs for traditional male circumcision and scale-up of voluntary medical male circumcision (VMMC). We calibrated our model using publicly available data on demographics; HIV prevalence by 5-year age bins, sex, and year; and ART coverage by age, sex, and year. We modelled the effects of five scenarios (historical scale-up of ART and VMMC [status quo], no ART or VMMC, no ART, age-targeted 90-90-90, and 100% ART initiation) to quantify the contribution of ART scale-up to declines in HIV incidence and mortality in individuals aged 15-49 by 2016, 2030, and 2050. FINDINGS: Between 2010 and 2016, status-quo ART scale-up among adults (aged 15-49 years) in eSwatini (from 34·0% in 2010 to 74·1% in 2016) reduced HIV incidence by 43·57% (95% credible interval 39·71 to 46·36) and HIV mortality by 56·17% (54·06 to 58·92) among individuals aged 15-49 years, with larger reductions in incidence among men and mortality among women. Holding 2016 ART coverage levels by age and sex into the future, by 2030 adult HIV incidence would fall to 1·09 (0·87 to 1·29) per 100 person-years, 1·42 (1·13 to 1·71) per 100 person-years among women and 0·79 (0·63 to 0·94) per 100 person-years among men. Achieving the 90-90-90 targets evenly by age and sex would further reduce incidence beyond status-quo ART, primarily among individuals aged 15-24 years (an additional 17·37% [7·33 to 26·12] reduction between 2016 and 2030), with only modest additional incidence reductions in adults aged 35-49 years (1·99% [-5·09 to 7·74]). Achieving 100% ART initiation among all people living with HIV within an average of 6 months from infection-an upper bound of plausible treatment effect-would reduce adult HIV incidence to 0·73 infections (0·55 to 0·92) per 100 person-years by 2030 and 0·46 (0·33 to 0·59) per 100 person-years by 2050. INTERPRETATION: Scale-up of ART over the last decade has already contributed to substantial reductions in HIV-1 incidence and mortality in eSwatini. Focused ART targeting would further reduce incidence, especially in younger individuals, but even the most aggressive treatment campaigns would be insufficient to end the epidemic in high-burden settings without a renewed focus on expanding preventive measures. FUNDING: Global Good Fund and the Bill & Melinda Gates Foundation.

Self-medication prevalence for sexually transmitted diseases: meta-analysis and meta-regression of population level determinants.

BACKGROUND: Estimated prevalence of self-medication for sexually transmitted diseases (STDs) in observational studies differs between studies and it may vary according to population characteristics. METHODS: We investigated the extent of self-medication use for STD and explored population and study level factors correlated to the variability observed between populations. Medical databases were systematically searched for published studies. Crude prevalence data were extracted. Pooled estimates were calculated using random effects models. Univariate and multivariate meta-regression models with categorical population level covariates were constructed. RESULTS: Of the 35 studies that met the inclusion criteria for all self-medication use, 20 were also included in the analysis of antibiotic only use. There was significant heterogeneity present across prevalence estimates for all self-medication, Q = 3954.82, P <0.001; and among antibiotic only self-medication, Q = 3797.94, P <0.001. In meta-regression analyses, publication year seemed to explain 22.5% of variation among studies of self-medication with antibiotic only. No other significant associations with population or study characteristics were found. CONCLUSIONS: No population level factors leading to high levels of self-medication use for STD were identified. Publications before year 2000 seem to present a higher prevalence of antibiotic use for self-medication. Greater risk awareness of antibiotic misuse and improved control of antibiotic availability at population level might explain this result. An analysis of individual level characteristics should indicate which are influential and whether their local prevalence can explain the observed heterogeneity better.