Preventing tuberculosis with community-based care in an HIV-endemic setting: a modelling analysis.

INTRODUCTION: Antiretroviral therapy (ART) and tuberculosis preventive treatment (TPT) both prevent tuberculosis (TB) disease and deaths among people living with HIV. Differentiated care models, including community-based care, can increase the uptake of ART and TPT to prevent TB in settings with a high burden of HIV-associated TB, particularly among men. METHODS: We developed a gender-stratified dynamic model of TB and HIV transmission and disease progression among 100,000 adults ages 15-59 in KwaZulu-Natal, South Africa. We drew model parameters from a community-based ART initiation and resupply trial in sub-Saharan Africa (Delivery Optimization for Antiretroviral Therapy, DO ART) and other scientific literature. We simulated the impacts of community-based ART and TPT care programmes during 2018-2027, assuming that community-based ART and TPT care were scaled up to similar levels as in the DO ART trial (i.e. ART coverage increasing from 49% to 82% among men and from 69% to 83% among women) and sustained for 10 years. We projected the number of TB cases, deaths and disability-adjusted life years (DALYs) averted relative to standard, clinic-based care. We calculated programme costs and incremental cost-effectiveness ratios from the provider perspective. RESULTS: If community-based ART care could be implemented with similar effectiveness to the DO ART trial, increased ART coverage could reduce TB incidence by 27.0% (range 21.3%-34.1%) and TB mortality by 34.6% (range 24.8%-42.2%) after 10 years. Increasing both ART and TPT uptake through community-based ART with TPT care could reduce TB incidence by 29.7% (range 23.9%-36.0%) and TB mortality by 36.0% (range 26.9%-43.8%). Community-based ART with TPT care reduced gender disparities in TB mortality rates, with a projected 54 more deaths annually among men than women (range 11-103) after 10 years of community-based care versus 109 (range 41-182) in standard care. Over 10 years, the mean cost per DALY averted by community-based ART with TPT care was $846 USD (range $709-$1012). CONCLUSIONS: By substantially increasing coverage of ART and TPT, community-based care for people living with HIV could reduce TB incidence and mortality in settings with high burdens of HIV-associated TB and reduce TB gender disparities.

Delivering integrated strategies from a mobile unit to address the intertwining epidemics of HIV and addiction in people who inject drugs: the HPTN 094 randomized controlled trial protocol (the INTEGRA Study).

BACKGROUND: Persons with opioid use disorders who inject drugs (PWID) in the United States (US) face multiple and intertwining health risks. These include interference with consistent access, linkage, and retention to health care including medication for opioid use disorder (MOUD), HIV prevention using pre-exposure prophylaxis (PrEP), and testing and treatment for sexually transmitted infections (STIs). Most services, when available, including those that address substance misuse, HIV prevention, and STIs, are often provided in multiple locations that may be difficult to access, which further challenges sustained health for PWID. HPTN 094 (INTEGRA) is a study designed to test the efficacy of an integrated, "whole-person" strategy that provides integrated HIV prevention including antiretroviral therapy (ART), PrEP, MOUD, and STI testing and treatment from a mobile health delivery unit ("mobile unit") with peer navigation compared to peer navigation alone to access these services at brick and mortar locations. METHODS: HPTN 094 (INTEGRA) is a two-arm, randomized controlled trial in 5 US cities where approximately 400 PWID without HIV are assigned either to an experimental condition that delivers 26 weeks of "one-stop" integrated health services combined with peer navigation and delivered in a mobile unit or to an active control condition using peer navigation only for 26 weeks to the same set of services delivered in community settings. The primary outcomes include being alive and retained in MOUD and PrEP at 26 weeks post-randomization. Secondary outcomes measure the durability of intervention effects at 52 weeks following randomization. DISCUSSION: This trial responds to a need for evidence on using a "whole-person" strategy for delivering integrated HIV prevention and substance use treatment, while testing the use of a mobile unit that meets out-of-treatment PWID wherever they might be and links them to care systems and/or harm reduction services. Findings will be important in guiding policy for engaging PWID in HIV prevention or care, substance use treatment, and STI testing and treatment by addressing the intertwined epidemics of addiction and HIV among those who have many physical and geographic barriers to access care. TRIAL REGISTRATION: ClinicalTrials.gov NCT04804072 . Registered on 18 March 2021.

Preventing tuberculosis with community-based care in an HIV-endemic setting: a modeling analysis.

Introduction: Antiretroviral therapy (ART) and TB preventive treatment (TPT) both prevent tuberculosis (TB) disease and deaths among people living with HIV. Differentiated care models, including community-based care, can increase uptake of ART and TPT to prevent TB in settings with a high burden of HIV-associated TB, particularly among men. Methods: We developed a gender-stratified dynamic model of TB and HIV transmission and disease progression among 100,000 adults ages 15-59 in KwaZulu-Natal, South Africa. We drew model parameters from a community-based ART initiation and resupply trial in sub-Saharan Africa (Delivery Optimization for Antiretroviral Therapy, DO ART) and other scientific literature. We simulated the impacts of community-based ART and TPT care programs during 2018-2027, assuming that community-based ART and TPT care were scaled up to similar levels as in the DO ART trial (i.e., ART coverage increasing from 49% to 82% among men and from 69% to 83% among women) and sustained for ten years. We projected the number of TB cases, deaths, and disability-adjusted life years (DALYs) averted relative to standard, clinic-based care. We calculated program costs and incremental cost-effectiveness ratios from the provider perspective. Results: If community-based ART care could be implemented with similar effectiveness to the DO ART trial, increased ART coverage could reduce TB incidence by 27.0% (range 21.3% - 34.1%) and TB mortality by 36.0% (range 26.9% - 43.8%) after ten years. Increasing both ART and TPT uptake through community-based ART with TPT care could reduce TB incidence by 29.7% (range 23.9% - 36.0%) and TB mortality by 36.0% (range 26.9% - 43.8%). Community-based ART with TPT care reduced gender disparities in TB mortality rates by reducing TB mortality among men by a projected 39.8% (range 32.2% - 46.3%) and by 30.9% (range 25.3% - 36.5%) among women. Over ten years, the mean cost per DALY averted by community-based ART with TPT care was $846 USD (range $709 - $1,012). Conclusions: By substantially increasing coverage of ART and TPT, community-based care for people living with HIV could reduce TB incidence and mortality in settings with high burdens of HIV-associated TB and reduce TB gender disparities.

Population-level impact of expanding PrEP coverage by offering long-acting injectable PrEP to MSM in three high-resource settings: a model comparison analysis.

INTRODUCTION: Long-acting injectable cabotegravir (CAB-LA) demonstrated superiority to daily tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for HIV pre-exposure prophylaxis (PrEP) in the HPTN 083/084 trials. We compared the potential impact of expanding PrEP coverage by offering CAB-LA to men who have sex with men (MSM) in Atlanta (US), Montreal (Canada) and the Netherlands, settings with different HIV epidemics. METHODS: Three risk-stratified HIV transmission models were independently parameterized and calibrated to local data. In Atlanta, Montreal and the Netherlands, the models, respectively, estimated mean TDF/FTC coverage starting at 29%, 7% and 4% in 2022, and projected HIV incidence per 100 person-years (PY), respectively, decreasing from 2.06 to 1.62, 0.08 to 0.03 and 0.07 to 0.001 by 2042. Expansion of PrEP coverage was simulated by recruiting new CAB-LA users and by switching different proportions of TDF/FTC users to CAB-LA. Population effectiveness and efficiency of PrEP expansions were evaluated over 20 years in comparison to baseline scenarios with TDF/FTC only. RESULTS: Increasing PrEP coverage by 11 percentage points (pp) from 29% to 40% by 2032 was expected to avert a median 36% of new HIV acquisitions in Atlanta. Substantially larger increases (by 33 or 26 pp) in PrEP coverage (to 40% or 30%) were needed to achieve comparable reductions in Montreal and the Netherlands, respectively. A median 17 additional PYs on PrEP were needed to prevent one acquisition in Atlanta with 40% PrEP coverage, compared to 1000+ in Montreal and 4000+ in the Netherlands. Reaching 50% PrEP coverage by 2032 by recruiting CAB-LA users among PrEP-eligible MSM could avert >45% of new HIV acquisitions in all settings. Achieving targeted coverage 5 years earlier increased the impact by 5-10 pp. In the Atlanta model, PrEP expansions achieving 40% and 50% coverage reduced differences in PrEP access between PrEP-indicated White and Black MSM from 23 to 9 pp and 4 pp, respectively. CONCLUSIONS: Achieving high PrEP coverage by offering CAB-LA can impact the HIV epidemic substantially if rolled out without delays. These PrEP expansions may be efficient in settings with high HIV incidence (like Atlanta) but not in settings with low HIV incidence (like Montreal and the Netherlands).

Implementation and scale-up of a single-visit, screen-and-treat approach with thermal ablation for sustainable cervical cancer prevention services: a protocol for a stepped-wedge cluster randomized trial in Kenya.

BACKGROUND: An important cervical cancer prevention strategy in low- and middle-income countries (LMICs) has been single-visit screen-and-treat (SV-SAT) approach, using visual inspection with acetic acid (VIA) and ablative treatment with cryotherapy to manage precancerous lesions. While SV-SAT with VIA and cryotherapy have established efficacy, its population level coverage and impact on reducing cervical cancer burden remains low. In Kenya, the estimated cervical cancer screening uptake among women aged 30-49 is 16% and up to 70% of screen-positive women do not receive treatment. Thermal ablation for treatment of precancerous lesions of the cervix is recommended by the World Health Organization and has the potential to overcome logistical challenges associated with cryotherapy and facilitate implementation of SV-SAT approach and increase treatment rates of screen-positive women. In this 5-year prospective, stepped-wedge randomized trial, we plan to implement and evaluate the SV-SAT approach using VIA and thermal ablation in ten reproductive health clinics in central Kenya. METHODS: The study aims to develop and evaluate implementation strategies to inform the national scale-up of SV-SAT approach with VIA and thermal ablation through three aims: (1) develop locally tailored implementation strategies using multi-level participatory method with key stakeholders (patient, provider, system-level), (2) implement SV-SAT approach with VIA and thermal ablation and evaluate clinical and implementation outcomes, and (3) assess the budget impact of SV-SAT approach with VIA and thermal ablation compared to single-visit, screen-and-treat method using cryotherapy. DISCUSSION: Our findings will inform national scale-up of the SV-SAT approach with VIA and thermal ablation. We anticipate that this intervention, along with tailored implementation strategies will enhance the adoption and sustainability of cervical cancer screening and treatment compared to the standard of care using cryotherapy. TRIAL REGISTRATION: NCT05472311.

Assessment of a viral load result-triggered automated differentiated service delivery model for people taking ART in Lesotho (the VITAL study): Study protocol of a cluster-randomized trial.

INTRODUCTION: To sustainably provide good quality care to increasing numbers of people living with HIV (PLHIV) receiving antiretroviral therapy (ART) in resource-limited settings, care delivery must shift from a "one-size-fits-all" approach to differentiated service delivery models. Such models should reallocate resources from PLHIV who are doing well to groups of PLHIV who may need more attention, such as those with treatment failure. The VIral load Triggered ART care Lesotho (VITAL) trial assesses a viral load (VL)-, participant's preference-informed, electronic health (eHealth)-supported, automated differentiated service delivery model (VITAL model). With VITAL, we aim to assess if the VITAL model is at least non-inferior to the standard of care in the proportion of participants engaged in care with viral suppression at 24 months follow-up and if it is cost-saving. METHODS: The VITAL trial is a pragmatic, multicenter, cluster-randomized, non-blinded, non-inferiority trial with 1:1 allocation conducted at 18 nurse-led, rural health facilities in two districts of northern Lesotho, enrolling adult PLHIV taking ART. In intervention clinics, providers are trained to implement the VITAL model and are guided by a clinical decision support tool, the VITALapp. VITAL differentiates care according to VL results, clinical characteristics, sub-population and participants' and health care providers' preferences. EXPECTED OUTCOMES: Evidence on the effect of differentiated service delivery for PLHIV on treatment outcomes is still limited. This pragmatic cluster-randomized trial will assess if the VITAL model is at least non-inferior to the standard of care and if it is cost saving. TRIAL REGISTRATION: The study has been registered with clinicaltrials.gov (Registration number NCT04527874; August 27, 2020).

Impact of SMS Text Messaging Reminders on Helmet Use Among Motorcycle Drivers in Dar es Salaam, Tanzania: Randomized Controlled Trial.

BACKGROUND: Road traffic injury is a pressing public health issue in Tanzania. Increasing helmet use among motorcycle drivers can help reduce the burden due to road traffic injuries in the country. Helmet adherence can be supported through mobile health interventions. OBJECTIVE: The aim of this study is to evaluate the comparative impact of two different types of SMS text messaging reminders on motorcycle helmet use. METHODS: Participants were 391 commercial motorcycle taxi drivers in Dar es Salaam, Tanzania. Participants were randomized into three groups, each receiving a different set of messages: (1) social norming messages aimed at emphasizing society's positive stance on helmet wearing, (2) fear appeal messages that emphasized the dangers of riding without a helmet, and (3) control group messages, which included basic road safety messages unrelated to helmet use. Every participant received the control messages. Adherence to helmet use was evaluated by self-report through surveys conducted at baseline, 3 weeks, and 6 weeks. RESULTS: At 6 weeks, the odds of self-reporting consistent helmet use were estimated to be 1.58 times higher in the social norming group than in the control group (P=.04), though this difference was not significant after accounting for multiple testing. There was little difference between fear appeal and control group recipients (odds ratio 1.03, P=.47). Subgroup analysis suggests that both fear appeal and social norming message types might have been associated with increased helmet use among participants who did not consistently wear helmets at baseline (odds ratio 1.66 and odds ratio 1.84, respectively), but this was not significant (P=.11 and P=.07, respectively). Among those who were consistent wearers at baseline, the social norming messages performed better than the fear appeal messages, and this difference reached traditional significance (P=.03), but was not significant after accounting for multiple testing. CONCLUSIONS: The use of SMS text messaging reminders may improve helmet use among motorcycle drivers when framed as social norming messages. Given that nearly half of the drivers in our sample did not consistently wear their helmets on every trip, strategies to increase consistent usage could greatly benefit public safety. TRIAL REGISTRATION: ClinicalTrials.gov NCT02120742; https://clinicaltrials.gov/ct2/show/NCT02120742.

Effect of a Text Messaging-Based Educational Intervention on Cesarean Section Rates Among Pregnant Women in China: Quasirandomized Controlled Trial.

BACKGROUND: Consensus exists that appropriate regional cesarean rates should not exceed 15% of births, but China's cesarean rate exceeds 50% in some areas, prompting numerous calls for its reduction. At present, China's 2016 two-child policy has heightened the implications of national cesarean section trends. OBJECTIVE: This study leveraged pervasive cellular phone access amongst Chinese citizens to test the effect of a low-cost and scalable prenatal advice program on cesarean section rates. METHODS: Participants were pregnant women presenting for antenatal care at a clinic in Xi'an, China. Assignment was quasirandomized and utilized factorial assignment based on the expecting mother's birthday. Participants were assigned to one of the following four groups, with each receiving a different set of messages: (1) a comparison group that received only a few "basic" messages, (2) a group receiving messages primarily regarding care seeking, (3) a group receiving messages primarily regarding good home prenatal practices, and (4) a group receiving text messages of all groups. Messages were delivered throughout pregnancy and were tailored to each woman's gestational week. The main outcome was the rates of cesarean delivery reported in the intervention arms. Data analysts were blinded to treatment assignment. RESULTS: In total, 2115 women completed the trial and corresponding follow-up surveys. In the unadjusted analysis, the group receiving all texts was associated with an odds ratio of 0.77 (P=.06), though neither the care seeking nor good home prenatal practice set yielded a relevant impact. Adjusting for potentially confounding covariates showed that the group with all texts sent together was associated with an odds ratio of 0.67 (P=.01). Notably, previous cesarean section evoked an odds ratio of 11.78 (P<.001), highlighting that having a cesarean section predicts future cesarean section in a subsequent pregnancy. CONCLUSIONS: Sending pregnant women in rural China short informational messages with integrated advice regarding both care-seeking and good home prenatal practices appears to reduce women's likelihood of undergoing cesarean section. Reducing clear medical indications for cesarean section seems to be the strongest potential pathway of the effect. Cesarean section based on only maternal request did not seem to occur regularly in our study population. Preventing unnecessary cesarean section at present may have a long-term impact on future cesarean section rates. TRIAL REGISTRATION: ClinicalTrials.gov NCT02037087; https://clinicaltrials.gov/ct2/show/NCT02037087. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2015-011016.

Predicted COVID-19 fatality rates based on age, sex, comorbidities and health system capacity.

Early reports suggest the fatality rate from COVID-19 varies greatly across countries, but non-random testing and incomplete vital registration systems render it impossible to directly estimate the infection fatality rate (IFR) in many low- and middle-income countries. To fill this gap, we estimate the adjustments required to extrapolate estimates of the IFR from high-income to lower-income regions. Accounting for differences in the distribution of age, sex and relevant comorbidities yields substantial differences in the predicted IFR across 21 world regions, ranging from 0.11% in Western Sub-Saharan Africa to 1.07% for high-income Asia Pacific. However, these predictions must be treated as lower bounds in low- and middle-income countries as they are grounded in fatality rates from countries with advanced health systems. To adjust for health system capacity, we incorporate regional differences in the relative odds of infection fatality from childhood respiratory syncytial virus. This adjustment greatly diminishes but does not entirely erase the demography-based advantage predicted in the lowest income settings, with regional estimates of the predicted COVID-19 IFR ranging from 0.37% in Western Sub-Saharan Africa to 1.45% for Eastern Europe.

The Effects on Inappropriate Weight for Gestational Age of an SMS Based Educational Intervention for Pregnant Women in Xi'an China: A Quasi-Randomized Controlled Trial.

BACKGROUND: The aim of this study was to estimate the effects of maternal text messages on inappropriate weight for gestational age (IWGA) in newborns in rural China. METHODS: Participants were pregnant women presenting for antenatal care at a Maternal and Child Health Center in Xi'an, China during the 2013-2015 period. In total, 2115 women completed the program with follow-up information included in the final analyses. All mothers were divided into four groups, including (1) a control group that received only a few "Basic" messages, (2) a Care-Seeking (CS) message group, (3) Good Household Prenatal Practices (GHPP) message group, and (4) a group receiving all 148 text messages. The primary outcome was IWGA, including small for gestational age (SGA) and macrosomia (weighing ≥4000g at birth). Multivariable logistic regression using an intent-to-treat estimate was utilized. RESULTS: In total, 19.5% of newborns were IWGA. The risk of IWGA was 23.0% in the control group, 19.6% in the CS group, 18.9% in the GHPP group, and 16.5% in the group with All Texts. Compared to the control group, the odds ratio of IWGA was 0.65 (0.48-0.89) for the group receiving All Texts, which remained statistically significant after performing the Holm-Bonferroni correction. The odds ratio of macrosomia was 0.54 (0.34-0.87) and 0.57 (0.36-0.49) for the Care Seeking message group and the All Texts group, respectively, with statistical significance. CONCLUSION: A package of free informational text messages, including advice for good household prenatal practices and care seeking, may prevent the inappropriate weight for gestational age through a protective effect on macrosomia. Advice to encourage care seeking in pregnancy may prevent macrosomia among neonates in rural China as well.

Catastrophic healthcare expenditure and its inequality for households with hypertension: evidence from the rural areas of Shaanxi Province in China.

BACKGROUND: China has been undergoing tremendous demographic and epidemiological transitions during the past three decades and increasing burden from non-communicable diseases and an ageing population have presented great health-care challenges for the country. Numerous studies examine catastrophic healthcare expenditures (CHE) worldwide on whole populations rather than specific vulnerable groups. As hypertension and other chronic conditions impose a growing share of the disease burden in China, they will become an increasingly important component of CHE. This study aims to estimate households with hypertension incurring CHE and its income-related inequality in the rural areas of Shaanxi Province. METHODS: Data were obtained from the National Household Health Service Surveys of Shaanxi Province conducted in 2013 and 13104 households were identified for analysis. The households were classified into three types: households with non-chronic diseases, households with hypertension only and households with hypertension plus other chronic diseases. CHE was measured according to the proportion of out-of-pocket health payments to non-food household expenditures and the concentration index was employed to measure the extent of income-related inequality in CHE. A decomposition method based on a probit model was used to decompose the concentration index into its determining components. RESULTS: The incurring of CHE of households with hypertension is at a disconcerting level compared to households with non-chronic diseases. Households with hypertension only and households with hypertension plus other chronic diseases incurred CHE in 23.48% and 34.01% of cases respectively whereas households with non-chronic diseases incurred CHE in only 13.33%. The concentration index of households with non-chronic diseases is -0.4871. However, the concentration index of households with hypertension only and households with hypertension plus other chronic diseases is -0.4645 and -0.3410 respectively. The majority of observed inequalities in CHE were explained by household economic status and having elder members. CONCLUSIONS: The proportion of households incurring CHE in the rural areas of Shaanxi Province was considerably high in all three types of households and households with hypertension were at a higher risk of incurring CHE. Furthermore, there existed a strong pro-poor inequality of CHE in all three types of households and the results implied more inequality in households with non-chronic diseases compared with two other groups. Our study suggests that more concern needs to be directed toward households with hypertension plus other chronic diseases and households having elder members.

Impact of an SMS advice programme on maternal and newborn health in rural China: study protocol for a quasi-randomised controlled trial.

INTRODUCTION: Expectant mothers in low-income and middle-income countries often lack access to vital information about pregnancy, preparation for birth and best practices when caring for their newborn. Innovative solutions are needed to bridge this knowledge gap and dramatically improve maternal and neonatal health in these settings. This study aims to evaluate the impact of an innovative text messaging intervention on maternal and neonatal health outcomes. METHODS AND ANALYSIS: This study offers expectant mothers in rural China a package of free short messages via cell phone regarding pregnancy and childbirth. These messages are tailored to each mother's gestational week. It is hypothesised that delivering these short advice messages to pregnant women can improve maternal and newborn health. The study uses factorial quasi-randomisation to compare psychological, behavioural and health outcomes between 4 groups: 2 groups receiving different sets of short message interventions (ie, good household prenatal practices and healthcare seeking), a group receiving both interventions and a control group. Treatment assignment occurs at the individual level. The primary outcome is newborn health, measured by appropriateness of weight for gestational age. Secondary outcomes include severe neonatal and maternal morbidity as well as psychological and behavioural measures. This study has enrolled pregnant women who attend county maternal and child health centres for their prenatal visits. DISCUSSION: This pilot is the first large-scale effort to build a comprehensive evidence base on the impact of prenatal text messages via cell phone on maternal and newborn health outcomes in China. The study has broad implications for public health policy in China and the implementation of mobile health interventions in low-resource settings around the world. ETHICS: This study was approved by the Ethics Committee of the School of Medicine at Xi'an Jiaotong University on 18 January 2013. TRIAL REGISTRATION NUMBER: NCT02037087; Pre-results.

Evaluating the cost-effectiveness of preventive zinc supplementation.

BACKGROUND: Even though the WHO currently recommends zinc for diarrhea management, no consensus has been reached with respect to routine distribution of zinc for preventive reasons. We reviewed the health impact of preventive zinc interventions, and evaluated the relative cost effectiveness of currently feasible interventions. METHODS: Using the latest relative risk estimates reported in the literature, we parameterized a health impact model, and calculated the expected benefits of zinc supplementation in a representative low-income country. We then computed the cost and cost-effectiveness for three delivery mechanisms: the direct distribution of zinc supplements, the distribution of micronutrient biscuits including zinc, and the distribution of zinc through water filtration systems. RESULTS: Combining all health outcomes and impact estimates, we find that systematic zinc supplementation among children of ages one to five would avert 1.423 DALYs per 100 households and year in least developed countries. The estimated cost per DALY is US$ 606 for pill supplementation, US$ 1211 for micronutrient biscuits, and US$ 879 per DALY saved for water filtration systems. CONCLUSIONS: Preventive zinc supplementation to children of ages 1-5 appears to be a highly cost-effective intervention in typical developing country settings. More research will be needed to determine the most effective mechanism to deliver zinc to this target population.