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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., Author(s): Caroline A. Bulstra 1,2,*, Jan A. C. Hontelez 1,2, Moritz Otto 1, Anna Stepanova 1, Erik Lamontagne 3,4, Anna Yakusik 3, Wafaa M. El-Sadr 5, Tsitsi Apollo 6, Miriam [...]

Author(s): Jan A. C. Hontelez 1,2,*, Caroline A. Bulstra 1,2, Anna Yakusik 3, Erik Lamontagne 3,4, Till W. Bärnighausen 1,5,6, Rifat Atun 7 Summary points Sustainable Development Goal 3 aims [...]

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. [ABSTRACT FROM AUTHOR]

Author(s): Evelinn Mikkelsen 1, Jan A. C. Hontelez 2,3,4,*, Maarten P. M. Jansen 1, Till Bärnighausen 2,4,5, Katharina Hauck 6, Kjell A. Johansson 7,8, Gesine Meyer-Rath 9,10, Mead Over 11, [...]

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. [ABSTRACT FROM AUTHOR]

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., Introduction South Africa is home to the largest population of HIV-infected individuals worldwide, with nearly 6 million people living with HIV in 2010 [1]. Although extensive efforts to curb the [...]

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. Please see later in the article for the Editors' Summary., Introduction There has recently been increasing interest in expanding provision of antiretroviral therapy (ART) as a tool for reducing the spread of HIV in generalised epidemics in sub-Saharan Africa [1-5]. [...]

Background: Human papillomavirus (HPV) vaccination and the implementation of primary HPV screening in the Netherlands will lead to a lower cervical disease burden. For evaluation and further improvement of prevention, it is important to estimate the magnitude and timing of health benefits of current and alternative vaccination strategies such as vaccination of boys or adults. Methods and findings: We evaluated the impact of the current girls-only vaccination program and alternative strategies on cervical disease burden among the first four vaccinated five-year birth cohorts, given the context of primary HPV screening. We integrated the existing microsimulation models STDSIM (HPV transmission model) and MISCAN-Cervix (cervical cancer screening model). Alternative vaccination strategies include: improved vaccination uptake, including routine boys vaccination, and offering adult vaccination at sexual health clinics. Our models show that the current vaccination program is estimated to reduce cervical cancers and cancer deaths by about 35% compared to primary HPV screening in the absence of vaccination. The number needed to vaccinate (NNV) to gain 1 life year is 45. The most efficient alternative vaccination strategies are: 1) improving coverage of girls to 80% (NNV = 42); and 2) routine vaccination for girls and boys at 80% coverage (incremental NNV = 155), with cervical cancer mortality reductions estimated at 50% and 60% respectively. Conclusions: While the current program already substantially reduces cervical cancer incidence and mortality, prevention can be further improved by increasing vaccination uptake and extending vaccination to boys. As not all cervical cancer deaths will be prevented, screening participation should still be encouraged. [ABSTRACT FROM AUTHOR]

Background: The control or elimination of neglected tropical diseases (NTDs) has targets defined by the WHO for 2020, reinforced by the 2012 London Declaration. We estimated the economic impact to individuals of meeting these targets for human African trypanosomiasis, leprosy, visceral leishmaniasis and Chagas disease, NTDs controlled or eliminated by innovative and intensified disease management (IDM). Methods: A systematic literature review identified information on productivity loss and out-of-pocket payments (OPPs) related to these NTDs, which were combined with projections of the number of people suffering from each NTD, country and year for 2011–2020 and 2021–2030. The ideal scenario in which the WHO’s 2020 targets are met was compared with a counterfactual scenario that assumed the situation of 1990 stayed unaltered. Economic benefit equaled the difference between the two scenarios. Values are reported in 2005 US$, purchasing power parity-adjusted, discounted at 3% per annum from 2010. Probabilistic sensitivity analyses were used to quantify the degree of uncertainty around the base-case impact estimate. Results: The total global productivity gained for the four IDM-NTDs was I$ 23.1 (I$ 15.9 –I$ 34.0) billion in 2011–2020 and I$ 35.9 (I$ 25.0 –I$ 51.9) billion in 2021–2030 (2.5th and 97.5th percentiles in brackets), corresponding to US$ 10.7 billion (US$ 7.4 –US$ 15.7) and US$ 16.6 billion (US$ 11.6 –US$ 24.0). Reduction in OPPs was I$ 14 billion (US$ 6.7 billion) and I$ 18 billion (US$ 10.4 billion) for the same periods. Conclusions: We faced important limitations to our work, such as finding no OPPs for leprosy. We had to combine limited data from various sources, heterogeneous background, and of variable quality. Nevertheless, based on conservative assumptions and subsequent uncertainty analyses, we estimate that the benefits of achieving the targets are considerable. Under plausible scenarios, the economic benefits far exceed the necessary investments by endemic country governments and their development partners. Given the higher frequency of NTDs among the poorest households, these investments represent good value for money in the effort to improve well-being, distribute the world’s prosperity more equitably and reduce inequity. [ABSTRACT FROM AUTHOR]

Background: Lymphatic filariasis (LF), onchocerciasis, schistosomiasis, soil-transmitted helminths (STH) and trachoma represent the five most prevalent neglected tropical diseases (NTDs). They can be controlled or eliminated by means of safe and cost-effective interventions delivered through programs of Mass Drug Administration (MDA)—also named Preventive Chemotherapy (PCT). The WHO defined targets for NTD control/elimination by 2020, reinforced by the 2012 London Declaration, which, if achieved, would result in dramatic health gains. We estimated the potential economic benefit of achieving these targets, focusing specifically on productivity and out-of-pocket payments. Methods: Productivity loss was calculated by combining disease frequency with productivity loss from the disease, from the perspective of affected individuals. Productivity gain was calculated by deducting the total loss expected in the target achievement scenario from the loss in a counterfactual scenario where it was assumed the pre-intervention situation in 1990 regarding NTDs would continue unabated until 2030. Economic benefits from out-of-pocket payments (OPPs) were calculated similarly. Benefits are reported in 2005 US$ (purchasing power parity-adjusted and discounted at 3% per annum from 2010). Sensitivity analyses were used to assess the influence of changes in input parameters. Results: The economic benefit from productivity gain was estimated to be I$251 billion in 2011–2020 and I$313 billion in 2021–2030, considerably greater than the total OPPs averted of I$0.72 billion and I$0.96 billion in the same periods. The net benefit is expected to be US$ 27.4 and US$ 42.8 for every dollar invested during the same periods. Impact varies between NTDs and regions, since it is determined by disease prevalence and extent of disease-related productivity loss. Conclusion: Achieving the PCT-NTD targets for 2020 will yield significant economic benefits to affected individuals. Despite large uncertainty, these benefits far exceed the investment required by governments and their development partners within all reasonable scenarios. Given the concentration of the NTDs among the poorest households, these investments represent good value for money in efforts to share the world’s prosperity and reduce inequity. [ABSTRACT FROM AUTHOR]

Background: The effect of the rapid scale-up of vertical antiretroviral treatment (ART) programs for HIV in sub-Saharan Africa on the overall health system is under intense debate. Some have argued that these programs have reduced access for people suffering from diseases unrelated to HIV because ART programs have drained human and physical resources from other parts of the health system; others have claimed that the investments through ART programs have strengthened the general health system and the population health impacts of ART have freed up health care capacity for the treatment of diseases that are not related to HIV. To establish the population-level impact of ART programs on health care utilization in the public-sector health system, we compared trends in health care utilization among HIV-infected people receiving and not receiving ART with HIV-uninfected people during a period of rapid ART scale-up. Methods and Findings: We used data from the Wellcome Trust Africa Centre for Population Health, which annually elicited information on health care utilization from all surveillance participants over the period 2009–2012 (N = 32,319). We determined trends in hospitalization, and public-sector and private-sector primary health care (PHC) clinic visits for HIV-infected and -uninfected people over a time period of rapid ART scale-up (2009–2012) in this community. We regressed health care utilization on HIV status and ART status in different calendar years, controlling for sex, age, and area of residence. The proportion of people who reported to have visited a public-sector primary health care (PHC) clinic in the last 6 months increased significantly over the period 2009–2012, for both HIV-infected people (from 59% to 67%; p<0.001), and HIV-uninfected people (from 41% to 47%; p<0.001). In contrast, the proportion of HIV-infected people visiting a private-sector PHC clinic declined from 22% to 12% (p<0.001) and hospitalization rates declined from 128 to 82 per 1000 PY (p<0.001). For HIV-uninfected people, the proportion visiting a private-sector PHC clinic declined from 16% to 9%, and hospitalization rates declined from 78 to 44 per 1000 PY (p<0.001). After controlling for potential confounding factors, all trends remained of similar magnitude and significance. Conclusions: Our results indicate that the ART scale-up in this high HIV prevalence community has shifted health care utilization from hospitals and private-sector primary care to public-sector primary care. Remarkably, this shift is observed for both HIV-infected and -uninfected populations, supporting and extending hypotheses of ‘therapeutic citizenship’ whereby HIV-infected patients receiving ART facilitate primary care access for family and community members. One explanation of our findings is that ART has improved the capacity or quality of primary care in this community and, as a consequence, increasingly met overall health care needs at the primary care level rather than at the secondary level. Future research needs to confirm this causal interpretation of our findings using qualitative work to understand causal mechanisms or quasi-experimental quantitative studies to increase the strength of causal inference. [ABSTRACT FROM AUTHOR]

Background: The London Declaration (2012) was formulated to support and focus the control and elimination of ten neglected tropical diseases (NTDs), with targets for 2020 as formulated by the WHO Roadmap. Five NTDs (lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminths and trachoma) are to be controlled by preventive chemotherapy (PCT), and four (Chagas’ disease, human African trypanosomiasis, leprosy and visceral leishmaniasis) by innovative and intensified disease management (IDM). Guinea worm, virtually eradicated, is not considered here. We aim to estimate the global health impact of meeting these targets in terms of averted morbidity, mortality, and disability adjusted life years (DALYs). Methods: The Global Burden of Disease (GBD) 2010 study provides prevalence and burden estimates for all nine NTDs in 1990 and 2010, by country, age and sex, which were taken as the basis for our calculations. Estimates for other years were obtained by interpolating between 1990 (or the start-year of large-scale control efforts) and 2010, and further extrapolating until 2030, such that the 2020 targets were met. The NTD disease manifestations considered in the GBD study were analyzed as either reversible or irreversible. Health impacts were assessed by comparing the results of achieving the targets with the counterfactual, construed as the health burden had the 1990 (or 2010 if higher) situation continued unabated. Principle Findings/Conclusions: Our calculations show that meeting the targets will lead to about 600 million averted DALYs in the period 2011–2030, nearly equally distributed between PCT and IDM-NTDs, with the health gain amongst PCT-NTDs mostly (96%) due to averted disability and amongst IDM-NTDs largely (95%) from averted mortality. These health gains include about 150 million averted irreversible disease manifestations (e.g. blindness) and 5 million averted deaths. Control of soil-transmitted helminths accounts for one third of all averted DALYs. We conclude that the projected health impact of the London Declaration justifies the required efforts. [ABSTRACT FROM AUTHOR]

Background: Knowledge of the natural history of human papillomavirus (HPV), in particular the role of immunity, is crucial in estimating the (cost-) effectiveness of HPV vaccination and cervical cancer screening strategies, because naturally acquired immunity after clearing an infection may already protect part of the risk population against new HPV infections. Methods: We used STDSIM, an established stochastic microsimulation model, quantified to the Netherlands. We explored different assumptions regarding the natural history of HPV-16 and HPV-18, and estimated the transmission probabilities and durations of acquired immunity necessary to reproduce age-specific prevalence. Results: A model without acquired immunity cannot reproduce the age-specific patterns of HPV. Also, it is necessary to assume a high degree of individual variation in the duration of infection and acquired immunity. According to the model estimates, on average 20% of women are immune for HPV-16 and 15% for HPV-18. After an HPV-16 infection, 50% are immune for less than 1 year, whereas 20% exceed 30 years. For HPV-18, up to 12% of the individuals are immune for less than 1 year, and about 50% over 30 years. Almost half of all women will never acquire HPV-16 or HPV-18. Conclusions: Acquired immunity likely plays a major role in HPV epidemiology, but its duration shows substantial variation. Combined with the lifetime risk, this explains to a large extent why many women will never develop cervical cancer. [ABSTRACT FROM AUTHOR]

Background: Since November 2009, WHO recommends that adults infected with HIV should initiate antiretroviral therapy (ART) at CD4+ cell counts of ≤350 cells/µl rather than ≤200 cells/µl. South Africa decided to adopt this strategy for pregnant and TB co-infected patients only. We estimated the impact of fully adopting the new WHO guidelines on HIV epidemic dynamics and associated costs. Methods and Finding: We used an established model of the transmission and control of HIV in specified sexual networks and healthcare settings. We quantified the model to represent Hlabisa subdistrict, KwaZulu-Natal, South Africa. We predicted the HIV epidemic dynamics, number on ART and program costs under the new guidelines relative to treating patients at ≤200 cells/µl for the next 30 years. During the first five years, the new WHO treatment guidelines require about 7% extra annual investments, whereas 28% more patients receive treatment. Furthermore, there will be a more profound impact on HIV incidence, leading to relatively less annual costs after seven years. The resulting cumulative net costs reach a break-even point after on average 16 years. Conclusions: Our study strengthens the WHO recommendation of starting ART at ≤350 cells/µl for all HIV-infected patients. Apart from the benefits associated with many life-years saved, a modest frontloading appears to lead to net savings within a limited time-horizon. This finding is robust to alternative assumptions and foreseeable changes in ART prices and effectiveness. Therefore, South Africa should aim at rapidly expanding its healthcare infrastructure to fully embrace the new WHO guidelines. [ABSTRACT FROM AUTHOR]