Community-randomized Trial Research Articles

Identification of antibody targets associated with lower HIV viral load and viremic control.

High HIV viral loads (VL) are associated with increased morbidity, mortality, and on-going transmission. HIV controllers maintain low VLs in the absence of antiretroviral therapy (ART). We previously used a massively multiplexed antibody profiling assay (VirScan) to compare antibody profiles in HIV controllers and persons living with HIV (PWH) who were virally suppressed on ART. In this report, we used VirScan to evaluate whether antibody reactivity to specific HIV targets and broad reactivity across the HIV genome was associated with VL and controller status 1-2 years after infection. Samples were obtained from participants who acquired HIV infection in a community-randomized trial in Africa that evaluated an integrated strategy for HIV prevention (HPTN 071 PopART). Controller status was determined using VL and antiretroviral (ARV) drug data obtained at the seroconversion visit and 1 year later. Viremic controllers had VLs <2,000 copies/mL at both visits; non-controllers had VLs >2,000 copies/mL at both visits. Both groups had no ARV drugs detected at either visit. VirScan testing was performed at the second HIV-positive visit (1-2 years after HIV infection). The study cohort included 13 viremic controllers and 64 non-controllers. We identified ten clusters of homologous peptides that had high levels of antibody reactivity (three in gag, three in env, two in integrase, one in protease, and one in vpu). Reactivity to 43 peptides (eight unique epitopes) in six of these clusters was associated with lower VL; reactivity to six of the eight epitopes was associated with HIV controller status. Higher aggregate antibody reactivity across the eight epitopes (more epitopes targeted, higher mean reactivity across all epitopes) and across the HIV genome was also associated with lower VL and controller status. We identified HIV antibody targets associated with lower VL and HIV controller status 1-2 years after infection. Robust aggregate responses to these targets and broad antibody reactivity across the HIV genome were also associated with lower VL and controller status. These findings provide novel insights into the relationship between humoral immunity and viral containment that could help inform the design of antibody-based approaches for reducing HIV VL.

Newborn community health advancements among Ethiopian Orthodox Christian women in North Gondar, Ethiopia: community-based randomised trial protocol

IntroductionDespite significant progress over past decades, neonatal and infant morbidity and mortality remain unacceptably high in Ethiopia. Simple interventions have been shown to improve the health of children and reduce...

Investigation of the relationship between air pollution and gestational diabetes

Background Gestational diabetes mellitus (GDM) can have negative effects on both the pregnancy and perinatal outcomes, as well as the long-term health of the mother and the child. It has been suggested that exposure to air pollution may increase the risk of developing GDM. This study investigated the relationship between exposure to air pollutants with gestational diabetes. Methods The present study is a retrospective cohort study. We used data from a randomised community trial conducted between September 2016 and January 2019 in Iran. During this period, data on air pollutant levels of five cities investigated in the original study, including 6090 pregnant women, were available. Concentrations of ozone (O3), nitric oxide (NO), nitrogen dioxide (NO2), nitrogen oxides (NOx), sulphur dioxide (SO2), carbon monoxide (CO), particulate matter < 2.5 (PM2.5) or <10 μm (PM10) were obtained from air pollution monitoring stations. Exposure to air pollutants during the three months preceding pregnancy and the first, second and third trimesters of pregnancy for each participant was estimated. The odds ratio was calculated based on logistic regression in three adjusted models considering different confounders. Only results that had a p < .05 were considered statistically significant. Results None of the logistic regression models showed any statistically significant relationship between the exposure to any of the pollutants and GDM at different time points (before pregnancy, in the first, second and third trimesters of pregnancy and 12 months in total) (p > .05). Also, none of the adjusted logistic regression models showed any significant association between PM10 exposure and GDM risk at all different time points after adjusting for various confounders (p > .05). Conclusions This study found no association between GDM risk and exposure to various air pollutants before and during the different trimesters of pregnancy. This result should be interpreted cautiously due to the lack of considering all of the potential confounders.

Incidence of self-reported tuberculosis treatment with community-wide universal testing and treatment for HIV and tuberculosis screening in Zambia and South Africa: A planned analysis of the HPTN 071 (PopART) cluster-randomised trial.

HIV is a potent risk factor for tuberculosis (TB). Therefore, community-wide universal testing and treatment for HIV (UTT) could contribute to TB control, but evidence for this is limited. Community-wide TB screening can decrease population-level TB prevalence. Combining UTT with TB screening could therefore significantly impact TB control in sub-Saharan Africa, but to our knowledge there is no evidence for this combined approach. HPTN 071 (PopART) was a community-randomised trial conducted between November 2013 to July 2018; 21 Zambian and South African communities (with a total population of approximately 1 million individuals) were randomised to arms A (community-wide UTT and TB screening), B (community-wide universal HIV testing with treatment following national guidelines and TB screening), or C (standard-of-care). In a cohort of randomly selected adults (18 to 44 years) enrolled between 2013 and 2015 from all 21 communities (total size 38,474; 27,139 [71%] female; 8,004 [21%] HIV positive) and followed-up annually for 36 months to measure the population-level impact of the interventions, data on self-reported TB treatment in the previous 12 months (self-reported TB) were collected by trained research assistants and recorded using a structured questionnaire at each study visit. In this prespecified analysis of the trial, self-reported TB incidence rates were measured by calendar year between 2014 and 2017/2018. A p-value ≤0.05 on hypothesis testing was defined as reaching statistical significance. Between January 2014 and July 2018, 38,287 individuals were followed-up: 494 self-reported TB during 104,877 person-years. Overall incidence rates were similar across all arms in 2014 and 2015 (0.33 to 0.46/100 person-years). In 2016 incidence rates were lower in arm A compared to C overall (adjusted rate ratio [aRR] 0.48 [95% confidence interval (95% CI) 0.28 to 0.81; p = 0.01]), with statistical significance reached. In 2017/2018, while incidence rates were lower in arm A compared to C, statistical significance was not reached (aRR 0.58 [95% CI 0.27 to 1.22; p = 0.13]). Among people living with HIV (PLHIV) incidence rates were lower in arm A compared to C in 2016 (RR 0.56 [95% CI 0.29 to 1.08; p = 0.08]) and 2017/2018 (RR 0.50 [95% CI 0.26 to 0.95; p = 0.04]); statistical significance was only reached in 2017/2018. Incidence rates in arms B and C were similar, overall and among PLHIV. Among HIV-negative individuals, there were too few events for cross-arm comparisons. Study limitations include the use of self-report which may have been subject to under-reporting, limited covariate adjustment due to the small number of events, and high losses to follow-up over time. In this study, community-wide UTT and TB screening resulted in substantially lower TB incidence among PLHIV at population-level, compared to standard-of-care, with statistical significance reached in the final study year. There was also some evidence this translated to a decrease in self-reported TB incidence overall in the population. Reduction in arm A but not B suggests UTT drove the observed effect. Our data support the role of UTT in TB control, in addition to HIV control, in high TB/HIV burden settings. ClinicalTrials.gov: NCT01900977.

Low methylation marker levels among human papillomavirus-vaccinated women with cervical high-grade squamous intraepithelial lesions.

Cervical cancer screening programs, including triage tests, need redesigning as human papillomavirus (HPV)-vaccinated women are entering the programs. Methylation markers offer a potential solution to reduce false-positive rates by identifying clinically relevant cervical lesions with progressive potential. In a nested case-control study, 9242 women who received the three-dose HPV16/18-vaccine at ages 12-15 or 18 in a community-randomized trial were included. Subsequently, they were re-randomized for either frequent or infrequent cervical cancer screening trials. Over a 15-year post-vaccination follow-up until 2022, 17 high-grade squamous intraepithelial lesion (HSIL) and 15 low-grade (LSIL) cases were identified at the 25-year screening round, alongside 371 age and community-matched HPV16/18-vaccinated controls. Methylation analyses were performed on cervical samples collected at age 25, preceding histologically confirmed LSIL or HSIL diagnoses. DNA methylation of viral (HPV16/18/31/33) and host-cell genes (EPB41L3, FAM19A4, and miR124-2) was measured, along with HPV-genotyping. No HPV16/18 HSIL cases were observed. The predominant HPV-genotypes were HPV52 (29.4%), HPV59/HPV51/HPV58 (each 23.5%), and HPV33 (17.7%). Methylation levels were generally low, with no significant differences in mean methylation levels of viral or host-cell genes between the LSIL/HSIL and controls. However, a significant difference in methylation levels was found between HSIL cases and controls when considering a combination of viral genes and EPB41L3 (p value = .0001). HPV-vaccinated women with HSIL had HPV infections with uncommon HPV types that very rarely cause cancer and displayed low methylation levels. Further investigation is warranted to understand the likely regressive nature of HSIL among HPV-vaccinated women and its implications for management.

Examining local smoke-free coalitions in Armenia and Georgia: context and outcomes of a matched-pairs community-randomised controlled trial

IntroductionLocal coalitions can advance public health initiatives such as smoke-free air but have not been widely used or well-studied in low-income and middle-income countries.MethodsWe conducted a matched-pairs community-randomised controlled trial...

Improvements in dietary intake, behaviors, and psychosocial measures in a community-randomized cardiovascular disease risk reduction intervention: Strong Hearts, Healthy Communities 2.0

BackgroundCardiovascular disease (CVD) prevalence has disproportionately risen among midlife and older female adults of rural communities, partly due to poor diet and diet-related behaviors and psychosocial factors that impede healthy eating. ObjectivesThis study aimed to evaluate the impact of Strong Hearts Healthy Communities 2.0 (SHHC-2.0) on secondary diet-related outcomes between intervention and control participants that align with the dietary goal and behavioral aims of the SHHC-2.0, a CVD risk reduction program. MethodsA community-randomized controlled trial was conducted in rural, medically underserved communities. Participants were female adults ≥40 y who were classified as obese or both overweight and sedentary. Communities were randomized to SHHC-2.0 intervention (n = 5 communities; n = 87 participants) or control (with delayed intervention) (n = 6 communities; n = 95 participants). SHHC-2.0 consisted of 24 wk of twice-weekly experiential nutrition education and group-based physical activity classes led by local health educators. Changes between baseline and end point (24 wk) in dietary intake (24-h recalls), dietary behaviors (e.g., Rapid Eating Assessment for Participants-Short Version [REAP-S] scores) and diet-related psychosocial measures (e.g., Three Factor Eating questionnaire) between groups were analyzed using linear mixed-effects multilevel models. ResultsAt 24 wk, participants from the 5 intervention communities, compared with controls, consumed fewer calories (mean difference [MD]= −211 kcal, 95% CI: −412, −110, P = 0.039), improved overall dietary patterns measured by REAP-S scores (MD: 3.9; 95% CI: 2.26, 5.6; P < 0.001), and improved psychosocial measures (healthy eating attitudes, uncontrolled eating, cognitive restraint, and emotional eating). ConclusionsSHHC-2.0 has strong potential to improve diet patterns and diet-related psychosocial wellbeing consistent with improved cardiovascular health.This trial was registered at www.clinicaltrials.gov as NCT03059472.

Starting point for improving the approach to vertigo in primary care.

Benign paroxysmal positional vertigo (BPPV) is a prevalent and disabling pathology. Its diagnosis and treatment according to clinical practice guidelines is carried out through canalicular repositioning maneuvers, but these maneuvers are not performed routinely in primary care consultations. To analyse the baseline data from the VERTAP randomised community trial that evaluates whether a blended course is effective in improving the adherence of primary care physicians to clinical practice guidelines. Baseline data 2021. 20 primary healthcare centers with an assigned population of 514157. sex, age, diagnoses related to vertigo/dizziness, anti-vertigo medications prescribed, number of referrals to the otolaryngologist and neurologist, complementary examinations, and sick leave. Vertigo/dizziness-related diagnoses totaled 21 359 cases, with a prevalence of 4.15%. Women made up 51.49% of cases. Median age was 52.00 (41.00, 65.00) years. Non-specific diagnoses totaled 18 617 (87.16%), including dizziness (n = 13 846, 64.83%), unspecified vestibular function disorder (n = 962, 4.50%), aural vertigo (n = 7, 0.03%), and other (n = 3802, 17.80%). Specific diagnoses totalled 2742 (12.84%), including BPPV (n = 1665, 7.80%), vestibular neuritis (n = 24, 0.11%), Menière's disease (n = 992, 4.64%), and central vertigo (n = 61, 0.29%). Anti-vertigo drugs prescribed included betahistine (n = 13 338, 62.45%), sulpiride (n = 3379, 15.82%), and dimenhydrinate (n = 20, 0.093%). Complementary examinations included computed tomography (n = 5704, 26.70%) and magnetic resonance (n = 604, 2.83%). One temporary disability for work (n = 1468, 6.87%); ≥2 temporary disability for work (n = 275, 1.29%). The majority of diagnostic records related to vertigo/dizziness were non-specific (9 out of 10). The number of prescriptions for betahistine, and referrals, mainly to an otolaryngologist, are considerable and an avoidable expense. Better knowledge about vertigo/dizziness in care could improve the diagnostic and therapeutic accuracy of this pathology as well as the social and health costs it produces.

Tobacco Use Patterns From Adolescence to Young Adulthood Among Latinx Youth From Rural Communities

PurposeTo examine patterns in adolescent and young adult tobacco use, comparing Latinx foreign-born children and children of foreign-born parents (i.e., children of immigrants(COI)) to Latinx US-born children of US-born parents (i.e., children of nonimmigrants,(CONI)) and to CONI White youth who grew up in small and rural towns. MethodsData were from youth who lived in control communities that participated in a community-randomized trial of the Communities That Care prevention system. We compared Latinx CONI (n = 154) with Latinx COI (n = 316) and with non-Latinx White CONI (n = 918). We examined tobacco use in adolescence (any adolescent use, early onset, and chronic use) and young adulthood (any past-year tobacco use, any daily smoking, any nicotine dependence symptoms) with mixed-effects logistic regressions. ResultsIn adolescence, Latinx CONI had a higher prevalence of any and chronic tobacco use relative to Latinx COI, and of any and early onset tobacco use relative to non-Latinx White CONI. In young adulthood, Latinx CONI were more likely to report tobacco use in the past year, any symptoms of nicotine dependence, and daily smoking relative to Latinx COI; and more likely to report daily smoking relative to non-Latinx White CONI. Generation differences in young adult tobacco use were explained by chronic tobacco use in adolescence. DiscussionThe study suggests targeting chronic tobacco use in adolescence to prevent disparities in tobacco outcomes among Latinx young adults from rural communities.

Targeted Mass Azithromycin Distribution for Trachoma: A Community-Randomized Trial (TANA II).

Current guidelines recommend annual community-wide mass administration of azithromycin for trachoma. Targeting treatments to those most likely to be infected could reduce the amount of unnecessary antibiotics distributed. In a cluster-randomized trial conducted from 1 November 2010 through 8 November 2013, 48 Ethiopian communities previously treated with annual mass azithromycin distributions for trachoma were randomized in equal numbers to (1) annual azithromycin distributions targeted to children aged 0-5 years, (2) annual azithromycin distributions targeted to households with a child aged 0-5 years found to have clinically active trachoma, (3) continued annual mass azithromycin distributions to the entire community, or (4) cessation of treatment. The primary outcome was the community prevalence of ocular chlamydia infection among children aged 0-9 years at month 36. Laboratory personnel were masked to treatment allocation. The prevalence of ocular chlamydia infection among children aged 0-9 years increased from 4.3% (95% confidence interval [CI], .9%-8.6%) at baseline to 8.7% (95% CI, 4.2%-13.9%) at month 36 in the age-targeted arm, and from 2.8% (95% CI, .8%-5.3%) at baseline to 6.3% (95% CI, 2.9%-10.6%) at month 36 in the household-targeted arm. After adjusting for baseline chlamydia prevalence, the 36-month prevalence of ocular chlamydia was 2.4 percentage points greater in the age-targeted group (95% CI, -4.8% to 9.6%; P = .50; prespecified primary analysis). No adverse events were reported. Targeting azithromycin treatment to preschool children was no different than targeting azithromycin to households with a child with clinically active trachoma. Neither approach reduced ocular chlamydia over the 3-year study. NCT01202331.

One-step versus two-step screening for diagnosis of gestational diabetes mellitus in Iranian population: A randomized community trial.

There is considerable worldwide controversy regarding optimal screening and diagnostic approaches for GDM. This study aimed to compare the prevalence, maternal and neonatal outcomes of a One-step with a Two-step approach for the screening and diagnosis of GDM in a large community sample of pregnant women. We conducted a secondary analysis of a randomized community non-inferiority trial of GDM screening in Iran. For the current study, all pregnant women who met the inclusion criteria were randomized into two groups for GDM screening. The first group of women (n = 14611) was screened by a One-step screening approach [75-g 2-h oral glucose tolerance test (OGTT)] and the second group (n = 14160) by a Two-step method (the 50-g glucose challenge test followed by the 100-g OGTT). All study participants were followed up until delivery, and the adverse maternal and neonatal outcomes were recorded in detail. GDM was diagnosed in 9.3% of the pregnant women who were assigned to the One-step and in 5.4% of those assigned to the Two-step approach with a statistically significant difference between them (p < 0.001). Intention-to-treat analyses showed no significant differences between the One-step and the Two-step group in the unadjusted risks of the adverse pregnancy outcomes of macrosomia, primary cesarean-section, preterm birth, hypoglycemia, hypocalcemia, hyperbilirubinemia, preeclampsia, neonatal intensive care unit admission, birth trauma, low birth weight, and intrauterine fetal death. Results remained unchanged after adjustment for potential confounder variables including gestational age at enrollment and delivery, maternal body mass index, gestational weight gain, type of delivery, treatment modality, and GDM diagnosis in the first trimester. We found that although the rates of GDM more than doubled with the One-step strategy, the One-step approach was similar to the Two-step approach in terms of maternal and neonatal outcomes. These findings may warn that more caution should be exercised in adopting the One-step method worldwide. Future research is needed to assess the long-term harm and benefits of those approaches to GDM screening for both mothers and their offspring. https://www.irct.ir/trial/518, identifier (IRCT138707081281N1).

Achieving the UNAIDS 90–90-90 targets: a comparative analysis of four large community randomised trials delivering universal testing and treatment to reduce HIV transmission in sub-Saharan Africa

BackgroundFour large community-randomized trials examining universal testing and treatment (UTT) to reduce HIV transmission were conducted between 2012–2018 in Botswana, Kenya, Uganda, Zambia and South Africa. In 2014, the UNAIDS 90–90-90 targets were adopted as a useful metric to monitor coverage. We systematically review the approaches used by the trials to measure intervention delivery, and estimate coverage against the 90–90-90 targets. We aim to provide in-depth understanding of the background contexts and complexities that affect estimation of population-level coverage related to the 90–90-90 targets.MethodsEstimates were based predominantly on “process” data obtained during delivery of the interventions which included a combination of home-based and community-based services. Cascade coverage data included routine electronic health records, self-reported data, survey data, and active ascertainment of HIV viral load measurements in the field.ResultsThe estimated total adult populations of trial intervention communities included in this study ranged from 4,290 (TasP) to 142,250 (Zambian PopART Arm-B). The estimated total numbers of PLHIV ranged from 1,283 (TasP) to 20,541 (Zambian PopART Arm-B). By the end of intervention delivery, the first-90 target (knowledge of HIV status among all PLHIV) was met by all the trials (89.2%-94.0%). Three of the four trials also achieved the second- and third-90 targets, and viral suppression in BCPP and SEARCH exceeded the UNAIDS target of 73%, while viral suppression in the Zambian PopART Arm-A and B communities was within a small margin (~ 3%) of the target.ConclusionsAll four UTT trials aimed to implement wide-scale testing and treatment for HIV prevention at population level and showed substantial increases in testing and treatment for HIV in the intervention communities. This study has not uncovered any one estimation approach which is superior, rather that several approaches are available and researchers or policy makers seeking to measure coverage should reflect on background contexts and complexities that affect estimation of population-level coverage in their specific settings.All four trials surpassed UNAIDS targets for universal testing in their intervention communities ahead of the 2020 milestone. All but one of the trials also achieved the 90–90 targets for treatment and viral suppression. UTT is a realistic option to achieve 95–95-95 by 2030 and fast-track the end of the HIV epidemic.

Effect of household couple counselling for male involvement on the utilization of postnatal services at 1 week in Ibanda district, Uganda; A cluster randomized community trial

Introduction: Prompt and Skilled postnatal care attendance coupled with skilled Antenatal and delivery care can drastically reduce maternal morbidity and mortality and also improve newborn outcomes. Research shows that men are decision makers in the home but they may also restrict resources, hence preventing women and children from health care seeking. But however if involved men may lead to better health care seeking behavior and better utilization of Antenatal care, delivery and postnatal care services. The postnatal care attendance at 1 week is low in Uganda, Ibanda district reported 4% in 2018. The aim of this study was to innovate, implement and document an intervention of house hold couple counseling for male involvement and compare the intervention and control clusters on the utilization of postnatal care services at 1 week. Methods: This was a two arm cluster randomized Community trial with a parallel design with the aim of comparing utilization of postnatal care services. It was carried out in two intervention parishes and two control parishes and was a superiority trial to test if the intervention of household couple counseling would improve utilization of postnatal care services. Results: The intervention arm had 200 respondents while the control had 213. The mean age was 27.3years (SD 6.8). Ninety one point five percent of mother had used skilled delivery services in the intervention compared to 78.4% in the control. Seventy Five percent attended postnatal care at 1week in the intervention as compared to 21.1% in the control (OR 11.2, P&lt;0.001). The activity that are statistically significantly associated with utilization of postnatal services utilization is providing transport to the postnatal clinic (AOR 30.8, P&lt;0.001) comparing the intervention and control clusters. The others included; accompanying to antenatal clinic, partner attending antenatal clinic, providing transport for delivery, escorting partner for delivery, providing psychological support during delivery and providing necessary drugs during delivery and PNC period but these were not statistically significant. Conclusion: The study demonstrated that the intervention of household couple counseling for increased male partner involvement improved significantly utilization of postnatal care services. Interventions to improve utilization of postnatal care services should focus on involving male partners to do the supportive activities which help their partners utilize the health care services.

Abstract 13183: Effectiveness of a Telehealth-Based Behavioral Lifestyle Program for Hypertension Control in African Americans: Results From Heals Med-Tech Randomized Controlled Study

Background: Hypertension (HTN) is a great concern because of its widespread prevalence, and associated racial health disparities. HTN is higher among African Americans (AAs) than whites. Among the many barriers to control HTN is poor adherence to needed lifestyle changes. The efficacy-tested HEALS Med-Tech behavioral lifestyle HTN control program may provide some solutions. We present the findings from the 1-year HEALS Med-Tech program in AAs. Methods: This is a randomized control community trial implemented in a primary care setting. HEALS Med-Tech program includes a) HEALS (Healthy Eating and Living Spiritually), a 12-month program modified from DASH and PREMIER programs; b) Med-component provides medications and social support; and c) Tech-component provides interactive telehealth contact. Primary outcomes of interest is change in systolic BP (SBP). Mixed Model repeated measure method was used for outcome analysis. Results: 61 participants (50 females, 11 males) were enrolled and randomized to either HEALS Med-Tech or standard care (control). Participants’ mean age is 62.8 ± 10.8 years, majority (90%) had a family history of CVD and 26.5% had diabetes. At the baseline, the SBP was 139.52 mmHg and 146 mmHg for the HEALS and control groups, respectively (Figure 1), which significantly reduced after 1 year (p=0.0134) in HEALS group. Similarly, the DBP was 82.78 mmHg and 84.32 mmHg for HEALS and control groups, respectively, at the baseline (not shown). For DBP and SBP, the results showed a significant difference between the HEALS and Control groups at 6 and 12 weeks. Conclusion: HEALS Med-Tech behavioral lifestyle program could serve as an effective and sustainable model for BP among marginalized AAs. There is a need for implementation studies of longer duration, such as HEALS Med-Tech, to address social determinants for the programs to be sustainable. Further research is needed to explore the potential implementation of HEALS Med-Tech program into clinical practice.

Impact of universal testing and treatment on sexual risk behaviour and herpes simplex virus type 2: a prespecified secondary outcomes analysis of the HPTN 071 (PopART) community-randomised trial

Comprehensive HIV prevention strategies have raised concerns that knowledge of interventions to reduce risk of HIV infection might mitigate an individual's perception of risk, resulting in riskier sexual behaviour. We investigated the prespecified secondary outcomes of the HPTN 071 (PopART) trial to determine whether a combination HIV prevention strategy, including universal HIV testing and treatment, changed sexual behaviour; specifically, we investigated whether there was evidence of sexual risk compensation. HPTN 071 (PopART) was a cluster-randomised trial conducted during 2013-18, in which we randomly assigned 21 communities with high HIV prevalence in Zambia and South Africa (total population, approximately 1 million) to combination prevention intervention with universal antiretroviral therapy (ART; arm A), prevention intervention with ART provided according to local guidelines (universal since 2016; arm B), or standard of care (arm C). The trial included a population cohort of approximately 2000 randomly selected adults (aged 18-44 years) in each community (N=38 474 at baseline) who were followed up for 36 months. A prespecified secondary objective was to evaluate the impact of the PopART intervention compared with standard of care on herpes simplex virus type 2 (HSV-2) and sexual behaviour (N=20 422 completed final visit). Secondary endpoints included differences in sexual risk behaviour measures at 36 months and were assessed using a two-stage method for matched cluster-randomised trials. This trial is registered with ClinicalTrials. gov, number NCT01900977. The PopART intervention did not substantially change probability of self-reported multiple sex partners, sexual debut, or pregnancy in women at 36 months. Adjusted for baseline community prevalence, reported condomless sex was significantly lower in arm A versus arm C (adjusted prevalence ratio 0·80 [95% CI 0·64-0·99]; p=0·04) but not in arm B versus arm C (0·94 [0·76-1·17]; p=0·55). 3-year HSV-2 incidence was reduced in arm B versus arm C (adjusted risk ratio 0·76 [95% CI 0·63-0·92]; p=0·010); no significant change was shown between arm A versus arm C (0·89 [0·73-1·08]; p=0·199). We found little evidence of any change in sexual behaviour owing to the PopART interventions, and reassuringly for public health, we saw no evidence of sexual risk compensation. The findings do not help to explain the differences between the two intervention groups of the HPTN 071 (PopART) trial. National Institute of Allergy and Infectious Diseases, the National Institutes of Health, the International Initiative for Impact Evaluation (3ie), the Bill &amp; Melinda Gates Foundation, the US President's Emergency Plan for AIDS Relief, and the Medical Research Council UK.

Viral suppression and self-reported ART adherence after 3 years of universal testing and treatment in the HPTN 071 (PopART) community-randomised trial in Zambia and South Africa: a cross-sectional analysis

In 2014, UNAIDS set the target that 90% of individuals on antiretroviral therapy (ART) be virally suppressed. Here, we use data from the HPTN 071 (PopART) trial to report whether the introduction of universal testing and treatment has affected viral suppression or treatment adherence among individuals who self-reported they were taking ART, and identify risk factors for these outcomes. This was a cross-sectional study nested within the randomly selected population cohort of the PopART trial. The trial took place in 21 communities in Zambia and South Africa. Analyses included 3570 HIV-positive participants who were seen at the second follow-up visit in 2016-17 and who self-reported that they were currently taking ART. Viral suppression was defined as HIV RNA of less than 400 copies per mL from a blood sample collected during the cohort visit, and ART adherence was measured using self-reporting (reported as no missed pills in last 7 days). Prevalences of these outcomes were compared across three trial arms using a two-stage approach suitable for clustered data. Each arm consisted of seven communities, with one arm receiving a combination HIV prevention package including immediate ART initiation, one receiving a combination HIV prevention package excluding immediate ART initiation and one arm receving standard of care. Risk factors for each of the outcomes were assessed using logistic regression. Among the 3570 participants who self-reported that they were currently on ART, 416 (11·7%) of 3554 were not virally suppressed (16 were missing viral suppression status) and 345 (9·7%) of 3566 reported being non-adherent to ART (four were missing adherence status). The proportion not virally suppressed was higher in communities in South Africa (195 [16·4%] of 1191) than in Zambia (221 [9·4%] of 2363). There was no evidence that the prevalence of the outcomes differed between trial arms. There was evidence that men, younger individuals, individuals who reported participating in harmful alcohol use, and those who reported internalised stigma were more likely to be non-adherent, and not virally suppressed. The results assuaged concerns that early ART initiation in a universal testing and treatment setting could lead to reduced adherence and viral suppression. US National Institute of Allergy and Infectious Diseases (which is a part of the National Institutes of Health), the International Initiative for Impact Evaluation with support from the Bill &amp; Melinda Gates Foundation, US President's Emergency Plan for AIDS Relief, and Medical Research Council UK.

Antiretroviral Drug Detection in a Community-Randomized Trial of Universal HIV Testing and Treatment: HPTN 071 (PopART).

Antiretroviral therapy (ART) reduces human immunodeficiency virus (HIV) transmission risk. The primary aim of this study was to evaluate ART uptake in a trial in Zambia and South Africa that implemented a community-wide universal testing and treatment package to reduce HIV incidence. Study communities were randomized to 3 arms: A, combination-prevention intervention with universal ART; B, combination-prevention intervention with ART according to local guidelines; and C, standard of care. Samples were collected from people with HIV (PWH) during a survey visit conducted 2 years after study implementation: these samples were tested for 22 antiretroviral (ARV) drugs. Antiretroviral therapy uptake was defined as detection of ≥1 ARV drug. Resistance was evaluated in 612 randomly selected viremic participants. A 2-stage, cluster-based approach was used to assess the impact of the study intervention on ART uptake. Antiretroviral drugs were detected in 4419 of 6207 (71%) samples (Arm A, 73%; Arm B, 70%; Arm C, 60%); 4140 (94%) of samples with ARV drugs had viral loads <400 copies/mL. Drug resistance was observed in 237 of 612 (39%) viremic participants (95 of 102 [93%] with ARV drugs; 142 of 510 [28%] without drugs). Antiretroviral therapy uptake was associated with older age, female sex, enrollment year, seroconverter status, and self-reported ART (all P < .001). The adjusted risk ratio for ART uptake was similar for Arm A versus C (1.21; 95% confidence interval [CI], .94-1.54; P = .12) and Arm B versus C (1.14; 95% CI, .89-1.46; P = .26). At the 2-year survey, 71% of PWH were on ART and 94% of those participants were virally suppressed. Universal testing and treatment was not significantly associated with increased ART uptake in this cohort.

HIV Incidence in Botswana Rural Communities With High Antiretroviral Treatment Coverage: Results From the Botswana Combination Prevention Project, 2013-2017.

The Botswana Combination Prevention Project demonstrated a 30% reduction in community HIV incidence through expanded HIV testing, enhanced linkage to care, and universal antiretroviral treatment and exceeded the Joint United Nations Programme on HIV/AIDS 90-90-90 targets. We report rates and characteristics of incident HIV infections. The Botswana Combination Prevention Project was a community-randomized controlled trial conducted in 30 rural/periurban Botswana communities from 2013 to 2017. Home-based and mobile HIV-testing campaigns were conducted in 15 intervention communities, with 39% of participants testing at least twice. We assessed the HIV incidence rate [IR; number of new HIV infections per 100 person-years (py) at risk] among repeat testers and risk factors with a Cox proportional hazards regression model. During 27,517 py, 195 (women: 79%) of 18,597 became HIV-infected (0.71/100 py). Women had a higher IR (1.01/100 py; 95% confidence interval: 0.99 to 1.02) than men (0.34/100 py; 95% confidence interval: 0.33 to 0.35). The highest IRs were among women aged 16-24 years (1.87/100 py) and men aged 25-34 years (0.56/100 py). The lowest IRs were among those aged 35-64 years (women: 0.41/100 py; men: 0.20/100 py). The hazard of incident infection was the highest among women aged 16-24 years (hazard ratio = 7.05). Sex and age were significantly associated with incidence (both P < 0.0001). Despite an overall reduction in HIV incidence and approaching the United Nations Programme on HIV/AIDS 95-95-95 targets, high HIV incidence was observed in adolescent girls and young women. These findings highlight the need for additional prevention services (pre-exposure prophylaxis and DREAMS) to achieve epidemic control in this subpopulation and increased efforts with men with undiagnosed HIV.

Smoking Cessation Programs Are Less Effective in Smokers with Low Socioeconomic Status Even When Financial Incentives for Quitting Smoking Are Offered-A Community-Randomized Smoking Cessation Trial in Denmark.

Financial incentives offered to those who quit smoking have been found effective, also in persons with low socioeconomic status (SES), but no previous study has investigated who benefits most: smokers with low or high SES. In this community-randomized trial (“Richer without smoking”), three Danish municipalities were randomized to reward persons who were abstinent when attending the municipal smoking cessation program (FIMs) and three municipalities were randomized to spend the same amount on smoking cessation campaigns recruiting smokers to the smoking cessation program (CAMs). The municipalities each received approximately USD 16,000. An intention-to-treat approach was used in analyses. In regression analyses adjusted for individual- and municipal-level differences, we found that smokers with high SES living in FIMs had significantly higher proportion of validated long-term successful quitters (OR (95% CI): 2.59 (1.6–4.2)) than high-SES smokers living in CAM. Smokers with low SES, however, did not experience the same benefit of financial incentives as smokers with high SES. Neither the FIMs nor the CAMs succeeded in attracting more smokers with low SES during the intervention year 2018 than the year before. Our study showed that smokers with low SES did not experience the same benefit of financial incentives as smokers with high SES.

Iodine Concentration Effects on Linear Growth of Children after Nutrition Behavior intervention, Central Highland of Ethiopia: A Cluster Randomized Community Trial

Background: To improve the iodine status and growth of children was not documented in Ethiopia. This study aimed to determine the effects of nutrition behavior communication change (BCC) on improving iodine status and growth of children 6 to 59 months.&#x0D; Methods: A community cluster randomized trial with a single treatment arm was conducted from February 2018 to April 2020. “Kebeles” [lower administrative units] were randomly assigned to either the intervention or the control cluster. Mothers and their paired children were randomly selected from kebeles. Anthropometry data and urine samples were collected at baseline and end-line surveys. Percentile rank and Independent t-test were used to determine the difference between arms. Finally, Generalized Estimating Equation (GEE) is used to isolate independent predictors.&#x0D; Results: At baseline, 97.83 % (n = 812) mothers/ caregivers and paired children were enrolled for the trial study, but at the end-line, 88.05% (n =715) of children completed the intervention. Iodine deficiency prevalence was higher (11.82%, n = 96) at baseline and reduced to 6.15 % (n =44) at the end-line. The growth defect among children was 41 %( n = 332) at the baseline and declined to 28.67 %( n=205) at the end-line, while among interventions reduced by more than two times (39% to 12.81%). At the baseline, the median UIC among the intervention group was 106.0µg/L and increased to 207.190µg/L. The prevalence of iodine deficiency among intervention was 14.29% (n = 58) at the baseline and lowered to 3.45% (n=14) at the end-line, but a slight increment observed among control from 9.36% to 9.71% at end-line. The end-line median UIC was very high (210.56µg/L ± 150 compared to the baseline median UIC (107µg/L ± 8.66). Most (43.6%) of the intervention group found in the 4th and 5th percentile ranks factions of UIC by Height (Ht) mean differences. Being an intervention group increased Ht by 10.85cm (β =10.85, Std. E = 0.33). Likewise, for 1µg/l UIC change a 1cm (β = 1.0, p = &lt;0.05) Ht change predicted at the end-line.&#x0D; Conclusions: Findings from this trial enhance nutrition behavior communication to improve the iodine status and growth of young children in the community. Longitudinal studies are needed to determine the level of iodine deficiency disorders in the community.