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2.8. Functional Capacity and Physical Fitness Assessment | Functional capacity was assessed by a battery of functional tests, including two versions of the “Sit-to-Stand Tests” (STS-5 and STS-60) and the “Timed Up-and-Go Test” [Maximal oxygen uptake (VO | PMC10386647 |
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2.9. Statistical Analysis | The Kolmogorov–Smirnov test was used to assess normality of distribution. Repeated measures ANOVA (group × time) were used to analyze the results. Tukey post hoc tests were used to determine pairwise differences wherever repeated measures ANOVA showed statistical significance | PMC10386647 |
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3. Results | No side effects of the supplementation were reported during the 8-week intervention while all participants showed a compliance of >90%. No differences were found in any examined variable between the two groups at baseline. | PMC10386647 |
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3.1. Effects on Anthropometry and Body Composition | The results for anthropometry and body composition parameters are presented in | PMC10386647 |
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3.2. Effects on Resting Metabolic Rate | The results for RMR measurements are demonstrated in | PMC10386647 |
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3.3. Effects on Respiratory Quotient | The results showed no significant interaction effect between group and time, F | PMC10386647 |
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3.4. Effects on Thyroid Hormones | The results for the thyroid hormones are presented in | PMC10386647 |
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3.5. Effects on Selenium and Zinc Serum Levels | Se and Zn serum results are shown in | PMC10386647 |
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3.6. Effects on Physical Fitness and Functional Capacity | The results for the physical fitness tests and functional capacity are presented in Regarding the Sit-to-Stand 5 test, no significant interaction effect between group and time was found, FFor Sit-to-Stand 30, the analysis showed no significant interaction effect between group and time (FNo significant interaction effect between group and time was found for Sit-to-Stand 60 (FFor handgrip strength, no significant interaction effect between group and time was found for the left arm (F | PMC10386647 |
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4. Discussion | obesity, muscle mass, inflammation, mitochondrial dysfunction, weight loss | OBESITY, INFLAMMATION, OXIDATIVE STRESS, MITOCHONDRIAL DYSFUNCTION | In the present study, the Zn/Se co-administration enhanced RMR of the participants and increased Se serum levels and TUG performance. However, compared to the placebo group, there were no additional benefits of Zn/Se co-administration on thyroid hormones, body composition, physical fitness, and the remaining functional capacity.The most important finding in the present study was that Zn/Se co-administration enhanced RMR. Specifically, RMR in the supplementation group increased by 22.9%, while RMR in the placebo group decreased with weight loss. The placebo group results contrast other studies, where RMR had significantly decreased after weight loss attempts [The average increase in RMR of the participants in the Zn/Se co-administration group was 441 kcal/day. A positive effect of Zn and Se co-supplementation on the Basal Metabolic Rate (BMR) has also been reported by Federico et al. [In people with obesity, the increased oxidative stress, as a result of the inflammation process, can have a negative impact on mitochondrial function, with the mitochondria being unable to generate sufficient adenosine triphosphate (ATP) levels [The possible effects of Zn levels on RMR have been demonstrated in non-experimental studies. For example, Wang et al. [When discussing the effects of Zn and Se supplements on RMR, the two micronutrients’ role on oxidative stress management should also be addressed due to the effect of oxidative stress on mitochondrial dysfunction. Hasani et al. [Some interesting findings by Hasani et al. [A difference between the study conducted by Mahmoodianfard et al. [The Zn/Se combination in this work did not affect thyroid hormones since both groups’ TSH, FT3, and FT4 remained unchanged. In agreement with our study, Mahmoodianfrad et al. [Even though thyroid hormones might not be the most critical hormones associated with RMR [A lot of money is spent annually on weight loss supplements [In the present study, the body composition in the Zn/Se co-administration group improved more than the placebo group, though this difference was not statistically significant. Body mass decreased by 1.33 kg and 0.95 kg for Zn/Se co-administration and placebo group, respectively, at the end of the intervention with a mean difference of approximately 0.4 kg between groups. This number is very close to what was reported in a meta-analysis by Abdollahi et al. [In the present study, it is worth mentioning that the fat-free mass and muscle mass in the supplementation group increased by 0.61 kg and 0.58 kg, respectively. This was an unexpected finding, considering that the participants were on a hypocaloric diet and did not participate in a resistance training intervention. On the contrary, fat-free and muscle mass in the control group slightly decreased. Even though not statistically significant, the increased fat-free mass in the intervention group might have contributed to the effects of Se/Zn co-administration on body weight between groups. In line with the present study, positive results of the two micronutrients on fat-free mass and muscle mass have also been reported in previous studies. For example, in a cohort study, Zn was associated with muscle mass in an elderly population [Regarding Se’s effects on muscle mass, Cavedon et al. [In the present study, Zn/Se co-administration was found to affect functional capacity by improving the TUG performance in the intervention group by 8.8%. Furthermore, a main effect of time was detected for all functional capacity outcomes at the end of the intervention period as compared to the baseline measurement. Notably, the participants in the supplementation group improved their performance in all tests more than the control group. However, this difference was insignificant since no time x group effects were found. One study examining the relationship between Se intake and musculoskeletal function in older adults found that low Se intake was associated with a lower TUG and handgrip performance than high Se intake [A cross-sectional study examined the association between physical function (TUG performance, activities of daily leaving measurement, and handgrip and quadriceps muscle strength) and Zn levels in older people [A limitation of the present work was that we could not include separate Se and Zn groups in order to examine the effects of each micronutrient alone. This is proposed for future research. Furthermore, although the participants were instructed not to change their physical activity levels, these were not assessed during the study. A strength of the present study was that Se and Zn serum measurements were included to determine the effects of supplementation on blood levels of these micronutrients and to compare them with other studies. Furthermore, with an individualized diet plan, daily intake of Zn and Se was strictly controlled and kept below the upper limits for the two micronutrients. An advantage of the present study was that indirect calorimetry was used for the determination of RMR instead of predictive equations, which typically either overestimate or underestimate resting energy expenditure [ | PMC10386647 |
5. Conclusions | The present study found a significant increase in the RMR after co-administration of 200 mcg of selenium L-selenomethionine and 25 mg of Zn gluconate, with the thyroid function hormones remaining unaffected. Furthermore, significant improvements in Se status and TUG performance were detected in the supplementation group compared to the placebo group. However, despite the larger improvements in body composition, cardiorespiratory fitness, and most of the remaining functional capacity outcomes of the intervention group, no time × group effect was found. Finally, even though the duration of the intervention, the dosages, and the forms of Se and Zn supplements used in the present study were effective, more research is needed to reveal the most effective combinations of the two micronutrients. | PMC10386647 |
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Author Contributions | Conceptualization, C.D.G., E.A. and A.Z.; methodology, C.D.G. and E.A.; formal analysis, A.Z., E.A. and C.D.G.; investigation, A.Z, G.A., Z.R. and E.A.; data curation, A.Z. and C.D.G.; writing—original draft preparation, A.Z. and C.D.G.; writing—review and editing, A.Z., G.A., C.D.G., E.A., G.C.B., G.K.S. and Z.R.; supervision, E.A., Z.R. and C.D.G.; project administration, E.A. and C.D.G. All authors have read and agreed to the published version of the manuscript. | PMC10386647 |
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Institutional Review Board Statement | The study was conducted in accordance with the Declaration of Helsinki and was approved by the Cyprus National Ethics Committee (ΕΕΒΚ/ΕΠ/2020/18). | PMC10386647 |
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Informed Consent Statement | Informed consent was obtained from all subjects involved in the study. | PMC10386647 |
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Data Availability Statement | All data and materials of this study are available upon request. | PMC10386647 |
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Conflicts of Interest | The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. | PMC10386647 |
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References | Consort 2010 Flow Diagram.Resting metabolic rate changes after the intervention period. * Significant time × group interaction.Basic characteristics and body composition data divided into two groups according to the assigned intervention (bold indicates statistical significance). All data are mean ± SD.Resting metabolic rate, thyroid hormones, and blood selenium and zinc levels before (baseline) and after the intervention (post) in the two groups (bold indicates statistical significance). Data are mean ± SD.Cardiorespiratory fitness and functional capacity for the two groups.Abbreviations: VO | PMC10386647 |
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Objectives: | The CHARM2 (Counseling Husbands and wives to Achieve Reproductive Health and Marital Equity) intervention engages health care providers to deliver gender-equity and family planning sessions to couples using a person-centered shared decision-making approach for contraception counseling. We previously showed that the intervention improved contraceptive use at 9-month follow-up. We sought to assess whether the intervention was further associated with the quality of care reported by participants and whether the quality of care reported mediated the effect of the intervention on contraceptive use. | PMC10695301 |
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Study design: | REGRESSION, SECONDARY | This is a planned secondary analysis of the effect of the CHARM2 intervention on 1201 married couples in rural Maharashtra, India in a cluster randomized controlled trial completed between 2018 and 2020. We assessed the effect of CHARM2 on perceived quality of care as measured by the Interpersonal Quality of Family Planning (IQFP) scale using a difference-in-differences linear regression approach including a mixed-effects model with nested random effects to account for clustering. We assessed whether the association between CHARM2 and modern contraceptive use was mediated by quality of family planning care. | PMC10695301 |
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Results: | Intervention participants had higher mean IQFP scores than control participants at 9-month follow-up (intervention 3.2, SD 0.6 vs. control 2.3 mean, SD 0.9, | PMC10695301 |
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Conclusion: | Family planning interventions such as CHARM2, which utilize person-centered shared decision-making contraceptive counseling approaches improve women’s perceived quality of care. Effects on quality of care mediate observed effects of the intervention on contraceptive use. | PMC10695301 |
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Implications: | Contraceptive interventions should focus on improving person-centered outcomes, such as quality of care, rather than contraceptive use targets. By focusing on improving person-centered care, interventions will improve contraceptive use among those who desire a method while meeting the holistic reproductive health needs of clients and couples. | PMC10695301 |
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Introduction | ’ contraceptive communication | Provision of person-centered, high-quality, contraceptive counseling has the potential to better meet the reproductive needs of women and couples and has been associated with increased contraceptive use [Gender based power dynamics, including traditional gender norms, male control of and even violence against female partners, son preference, and gender-based inequality in decision-making in households, affect women’s reproductive agency (the capacity to enact choice) and contraceptive use in India [Recent evaluation of the CHARM2 intervention demonstrated significant improvements in couples’ contraceptive communication and women’s contraceptive agency or perceived ability to use a chosen method over 18-month follow-up, as well as a significant effect on contraceptive use at 9-month follow-up [ | PMC10695301 |
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Methods | SECONDARY | This is an a priori planned secondary analysis of the CHARM2 study described elsewhere in detail [In this cluster randomized trial, 1201 young couples across 40 geographic clusters were randomized to the CHARM2 intervention or control condition (standard of care). Inclusion criteria for the CHARM2 study included married couples with women aged 18 to 29 years, both partners nonsterilized, living together for at least six months.We recruited couples from the rural Pune district of Maharashtra, India from September 2018–June 2019 via random selection from household rosters and approached and interviewed them in their homes. We collected data at three time points: baseline, 9-month, and 18-month follow-up. At 9-month follow-up, 1089 women provided survey responses, full couple retention at nine months was 90.2% (Our independent variable was intervention condition. Couples in the intervention clusters received counseling sessions from CHARM2 providers between baseline and 9-month follow-up. Gender-matched health providers delivered two gender-equity and family planning counseling sessions with married husbands and wives separately in parallel, and a final session was delivered to the couple together, by either the male or female provider who delivered the individual sessions, whichever was available and/or preferred by the couple.CHARM2 providers included public and private health providers within the couples’ geographic cluster area who were trained in the CHARM2 curriculum inclusive of gender equity and person-centered contraceptive counseling using a shared decision-making approach. Counseling sessions were supported by a desktop flip chart and contraceptive flash cards to facilitate patient-centered shared decision-making. Couples in the control condition were informed about local family planning services available at no cost from the public health sector. Control participants were not required to obtain contraceptive counseling or care.We utilized the Interpersonal Quality of Family Planning (IQFP) scale to measure our dependent variable, perceived quality of care. IQFP consists of 11 items assessing client perceptions of interpersonal connection, receiving adequate information, and decision support in their most recent family planning counseling ( | PMC10695301 |
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Analysis | REGRESSION | First, we assessed descriptive statistics including demographics and IQFP at each time point by intervention group. We utilized two-sided We evaluated the IQFP scale as a continuous mean score and as a categorical average response in descriptive analyses, and as a continuous mean score only in unadjusted and adjusted regression analyses. We recorded the mean score as “Poor/Fair” (average score 1–2.5), “Good” (average score 2.51–3.5), and “Very good/Excellent” (average score 4.51–5) for the categorical response.To assess potential mediation of improved quality of family planning care on other observed CHARM2 treatment effects [Assuming a baseline average IQFP score (2.62) [ | PMC10695301 |
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Results | At baseline, 504 of 1201 women (42%) reported seeing a family planning provider in the previous 9 months; 38% of intervention and 46% of control participants (All five counseling sessions were received by 87.5% of couples in the intervention arm; an additional 7.3% of women and 5.3% of men received at least one session. Only 3.0% of couples in the intervention arm received no sessions.Among women who reported seeing a family planning provider in the prior 9 months, most provided responses to all IQFP items; 491 of 504 at baseline (97%), 723 of 724 at 9-month (99%), and 213 of 213 at 18-month follow-up (100%) (Thus, the final analytic sample for this study includes 491 women at baseline, 723 women at 9-month follow-up, and 213 women at 18-month follow-up; 948 unique women providing data at one time point at least, with 55 women providing data at all three time points. Women in the intervention group were more likely to be Hindu than women in the control group (96.9 vs. 85.2%, At baseline, the average IQFP score was 2.6 out of 5 (SD 0.9), equivalent to a rating between “fair” and “good” (At 9-month follow-up, the average IQFP score was 2.9 out of 5 (SD 0.8), equivalent to a rating of approximately “good.” Intervention participants had significantly higher mean IQFP scores than control participants at 9-month follow-up (intervention mean 3.2, SD 0.6 vs. control mean 2.3, SD 0.9, At 18-month follow-up, the average IQFP score was 3.0 out of 5 (SD 0.7), equivalent to a rating of “good.” Intervention participants had significantly higher mean IQFP scores than control participants at 18-month follow-up (intervention mean 3.2, SD 0.6 vs. control mean 2.8, SD 0.7, In minimally adjusted models (accounting for time, treatment status, and geographic cluster), intervention relative to control condition was associated with a one-point increase in IQFP score from baseline at 9-month follow-up (1.05, 95% CI 0.61–1.48, In analyses assessing mediation of CHARM2 treatment effects by improved QOC at 9-month follow-up, we found evidence of significant mediation of the treatment effect on current modern contraceptive use (indirect effect coefficient 0.29, 95% CI 0.07–0.50). We did not observe statistically significant mediation of any other assessed outcome including wife’s reports of contraceptive communication, self-efficacy, and equal right to decide to use contraception as her husband (data not shown). | PMC10695301 |
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Discussion | We found that the CHARM2 intervention had a significant effect on women’s perceptions of interpersonal quality of care received from their family planning providers and that this effect on quality of care mediated observed effects of the CHARM2 intervention on contraceptive use. Interestingly, quality of care did not demonstrate mediation effects on contraceptive communication and contraceptive self-efficacy outcomes; these outcomes may be more attributable to engagement of men in the CHARM2 intervention rather than the quality of care women report. However, our study design does not allow us to compare male engagement components to women’s person-centered counseling components. These findings indicate the value of the person-centered shared decision-making approach utilized in CHARM2 to support quality of care in family planning counseling for women and that this care can increase women’s uptake of contraceptive use, corresponding to prior evidence showing an association with person-centered care and contraceptive use [We found low mean IQFP scores for both groups at baseline, and for the control group throughout the study, highlighting the need for more person-centered counseling methods, like CHARM2, in this population. Our findings support the capacity for health systems to support person-centered care for women while engaging men in family planning counseling simultaneously, with gender synchronized sessions. Concerns regarding male partner engagement as compromising female reproductive agency [Our study has several limitations. Outcomes were reliant on self-report and collected by interview, and are, therefore, vulnerable to recall and social desirability biases. High follow-up rates (> 80%) reduce follow-up biases, though the sample is reduced in analyses restricted to women who reported receiving family planning care in the prior 9 months. At 9-month follow-up, all women in the intervention arm who received at least one intervention session (95% of intervention participants) had in fact seen a family planning provider in the prior 9 months; however, this item was asked directly of women and 33 women who received sessions reported they had not seen a provider and did not provider IQFP scale responses. This may be due to issues of recall or misunderstanding the question.Another limitation is that we cannot ascribe the quality of care outcomes to CHARM2 intervention participation with certainty (respondents were not asked to name the provider for whom they were rating quality of care). Treatment condition respondents would most likely have seen a CHARM2 provider in the prior 9 months at 9-month follow-up due to the nature and timing of the intervention, and would likely revisit that provider given an established relationship, physical proximity, free services, and continuity of care, particularly if perceived quality of care was high. Additionally, observed intervention effects, particularly at 18-month follow-up, may be attributable to women more effectively engaging with providers subsequent to CHARM2 receipt, whether or not the provider was trained in the CHARM2 intervention. Findings from this study have limited generalizability, to the region of India in which we worked and to rural young married couples. Nonetheless, findings may inform efforts to increase person-centered contraceptive care and use of preference-aligned outcome indicators to assess intervention effects in other contexts and populations, particularly within India. While our rigorous cluster randomized controlled trial design is a strength of the study, multiple arms to compare intervention components would offer greater insight into the mechanisms by which the intervention led to significant improvements in outcomes. Data collection at follow-up encompassed the period of the COVID-19 pandemic and subsequent lockdown periods in India, and the pandemic may have affected access to contraceptives as well as women’s agency [In summary, gender equity focused family planning interventions such as CHARM2, which utilize person-centered care models improve women’s perceived quality of care. Effects on quality of care mediate the observed effects of the intervention on contraceptive use. These findings highlight the value of shared decision-making counseling strategies to support male engagement interventions while still prioritizing women’s reproductive agency and the importance of utilizing preference-aligned outcome measures to assess the effect of family planning interventions. | PMC10695301 |
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Supplementary Material | PMC10695301 |
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Funding: | This work was supported by the National Institutes of Health, Grants R01HD084453 and K12HD001259. The funder had no role in the design and conduct of the study, collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.Declaration of Competing Interest: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article.Supplementary materialsSupplementary material associated with this article can be found, in the online version, at doi: | PMC10695301 |
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References | REGRESSION | Interpersonal Quality of Family Planning (IQFP) items.Female participant IQFP item response by CHARM2 intervention group (Mean Interpersonal Quality of Family Planning (IQFP) score over time, by treatment group (Baseline characteristics of CHARM2 intervention participants who provided IQFP scale response for at least one time point (Interpersonal Quality of Family Planning score by treatment group and time among women participating in the CHARM2 intervention in rural India (n = 948) Maharashtra, India 2018–2020Intervention vs. control; Mixed effects linear regression difference-in-differences models of average IQFP score (p < 0.05.p < 0.01.p < 0.001. | PMC10695301 |
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Background | DSD, viral suppression | Of the 8 million people in South Africa living with HIV, 74% of persons living with HIV are on antiretroviral therapy (ART) and 65% are virally suppressed. Detectable viral load results in HIV-associated morbidity and mortality and HIV transmission. Patient barriers to care, such as missed wages, transport costs, and long wait times for clinic visits and ART refills, are associated with detectable viral load. HIV differentiated service delivery (DSD) has simplified ART delivery for clients who achieve viral suppression and engage in care. However, DSD needs adaptation to serve clients who are not engaged in care. | PMC9842495 |
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Methods | DSD | A Sequential Multiple Assignment Randomized Trial will be undertaken in KwaZulu-Natal, South Africa, to test adaptive ART delivery for persons with detectable viral load and/or who are not engaged in care. The types of differentiated service delivery (DSD) which will be examined in this study are clinic-based incentives, community-based smart lockers, and home delivery. The study plans to enroll up to 900 participants-people living with HIV, eligible for ART, and who are not engaged in care. The study aims to assess the proportion of ART-eligible persons living with HIV who achieve viral suppression at 18 months. The study will also evaluate the preferences of clients and providers for differentiated service delivery and evaluate the cost-effectiveness of adaptive HIV treatment for those who are not engaged in care. | PMC9842495 |
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Discussion | DSD, viral suppression | To increase population-level viral suppression, persons with detectable viral load need responsive DSD interventions. A Sequential Multiple Assignment Randomized Trial (SMART) design facilitates the evaluation of a stepped, adaptive approach to achieving viral suppression with “right-sized” interventions for patients most in need of effective and efficient HIV care delivery strategies. | PMC9842495 |
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Keywords | PMC9842495 |
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Introduction | PMC9842495 |
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Background and rationale {6a} | DSD, viral suppression, HIV better, HIV is a client-centered approach, chronic disease | CHRONIC DISEASE | HIV care programs have evolved into a chronic disease care model in South Africa, where eight million people are living with HIV [Differentiated service delivery (DSD), also known as differentiated care, for HIV is a client-centered approach that simplifies and adapts HIV services across the HIV care continuum, in ways that both serve the needs of people living with HIV better and reduce unnecessary burdens on the health system [DSD models have been implemented across sub-Saharan Africa that differ from standard clinic-based care and are targeted to stable patients (i.e., clients with suppressed viral loads) on ART [These DSD models differ in the intensity of service provision and, consequently, in the resources required. For example, lottery incentives are low cost to implement but have a short-term effect increasing ART initiation but not long-term viral suppression [The simplification and client-centeredness of DSD approaches could be adapted to help those who are struggling instead of succeeding. As HIV services, specifically supplying ART and conducting monitoring, mature, the most pressing need is for clients to access ART over their lifetimes—i.e., services to support lifelong retention. However, 5-year retention in care in South Africa is 60% [We and others found that DSD, as currently implemented, often costs effectively the same as standard models [“Right-sizing” DSD to fit client needs and provider services so that more intensive services reach clients that would benefit from simplification and client-centered approachesA unique opportunity exists to evaluate the impact of strategies to reengage and retain people living with HIV with detectable viral load and/or otherwise not engaged in care, specifically by providing enhanced services to clients with detectable viral load and/or who are not engaged in care. To address gaps in care, the South African National Department of Health (NDOH) clinics are rolling out interventions to increase viral suppression and retention in care. For example, Médecins Sans Frontières (MSF) has piloted a “Welcome Back” service at HIV clinics in the Western Cape to reengage clients in care who have previously been lost to follow-up or who have detectable viral load and this service is being further refined and adapted at other clinics. The Welcome Back service has three pillars: (1) identification and linkage, (2) medical support including care for advanced HIV, and (3) psychological support including adherence support. Working with MSF, we will adapt their clinic staff training and client materials to support best clinic practices. In the proposed study, we will work with clinic teams to implement the MSF Welcome Back services and other evidence-based clinic interventions, specifically adequate stock of ART, fast-track ART, time for clients, and kind providers which have been associated with higher retention in care [DSD approaches work for persons not engaged in care. Building on best clinic practices, lottery incentives shorten time to ART initiation [ | PMC9842495 |
Objectives {7} | SECONDARY | Our clinical trial aims to determine whether community-based ART initiation and maintenance increase the proportion of ART-eligible persons living with HIV who achieve viral suppression at 18 months. We will also evaluate as secondary objectives the (1) qualitative preferences of clients and providers for differentiated service delivery intensification and (2) cost, budget impact, and cost-effectiveness of an adaptative HIV treatment strategy for persons living with HIV who are not engaged in care to support viral suppression. | PMC9842495 |
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Trial design {8} | The SMART ART study is a Sequential Multiple Assignment Randomized Trial (SMART) to test an adaptive treatment strategy for persons living with HIV who are not virally suppressed within existing clinic services (Fig. SMART ART trial design | PMC9842495 |
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Methods: participants, interventions, and outcomes | PMC9842495 |
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Study setting {9} | Greater Edendale Area within the Umgungundlovu District in KwaZulu-Natal, South Africa. | PMC9842495 |
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Eligibility criteria {10} | ACTIVE TUBERCULOSIS | To be eligible, participants•Age 18 years or older•Able and willing to provide informed consent for study procedures•Intend to reside in the study community for the duration of follow-up•Living with HIV and eligible for ART by national guidelinesHave a detectable viral load greater than the lower limit of detection and/or not engaged in careAre stable clinically (CD4>100 cells/μL, no moderate/severe screening laboratory abnormalities for kidney function, not receiving treatment for active tuberculosis or other opportunistic infections)There are no separate exclusion criteria. | PMC9842495 |
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Who will take informed consent? {26a} | ICH | EVENT | A study counselor will review the study information sheets (screen consent and when applicable enrolment consent) with all potential participants and discuss emerging questions with the individual. In the event that informed consent is being discussed with a couple rather than an individual, each partner will be asked to provide separate independent informed consent for study participation. If the participant is illiterate, a witness will be present when informed consent is verbally administered and a checkmark is obtained. If electronic consent is unavailable due to technical challenges, then paper back consents will be used. Separate electronic informed consents complying to ICH guidelines E6 4.8. will be completed for screening and for enrolment of eligible participants. | PMC9842495 |
Additional consent provisions for collection and use of participant data and biological specimens {26b} | All participants completing the enrollment consent are given the option of agreeing to future contact for either new research protocols or to receive general information about research findings. Participants are also asked whether they agree or not to be contacted by text message or phone for appointment reminders and receiving of test results. | PMC9842495 |
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Interventions | PMC9842495 |
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Explanation for the choice of comparators {6b} | DSD | The innovation advanced in this study is testing adaptive DSD strategies. The “supply (dissemination) – demand (diffusion) – infrastructure (delivery) model” provides a useful framework to organize activities and bridge the translational research-practice gap [ | PMC9842495 |
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Intervention description {11a} | We will conduct a Sequential Multiple Assignment Randomized Trial (SMART) with participants presenting with a viral load above the limit of detection for the assay or who are not engaged in care/lost to follow-up (LFTU). To classify as not engaged, participants must meet one of the following criteria: (1) more than 6 months have passed since they were referred to the clinic and they have not attended, (2) they have missed a clinic appointment and have not rescheduled, (3) they have missed ART pick-ups without re-attempting pick-up, (4) they are on the clinic list for tracking, or (5) they report two or more barriers to engaging in standard clinic-based care (logistics including clinic hours, transportation costs, and wait times, stigma, not wanting to visit the clinic, and concerned about being treated with respect at the clinic). | PMC9842495 |
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Participants randomized to best clinic practices without lottery incentives | AIDS | AIDS | Enrolled participants will first be randomly assigned to low-intensity interventions: either best clinic practices or best clinic practices with a conditional lottery incentive. Participants randomized to the standard of care (SOC) best clinic practice group receive a clinic referral letter including the date of the HIV test, information on the clinical screening, and that they are being referred to the clinic for ART initiation. The study team will work with the clinics in the study area to provide training on the “Welcome Back” Campaign that was launched by the South African Department of Health in December 2020 on World AIDS Day. The Welcome Back service is a model of HIV care that aims to improve engagements in HIV services and promote long-term retention and care. The program focuses on those patients that leave care and return to care on their own and ensures that they are welcomed back to the clinic in a non-judgmental way. Welcome Back services include text message reminders/outreach; optimized ART pharmacy refills, including fast-track refills and multi-month dispensing as provided by the clinic; and adherence support. Participants are asked to notify the study team when they start ART, and receive phone calls every 3 months to assess linkage to care. Participants will schedule their month 6 follow-up visit to determine if rerandomization is required. | PMC9842495 |
Participants randomized to best clinic practices with lottery incentives | Participants randomized to the SOC with lottery incentives group will receive a clinic referral letter including the date of the HIV test, information on the clinical screening, and that they are being referred to the clinic for ART initiation. Participants will be asked to scan their barcode at the clinic or notify the study team of their visit and the reason for the visit (ART initiation, refill, or follow-up). Participants will be notified by text message that they have been entered into the lottery, and within a week, they will be notified whether they have won. All participants will be notified of when there is an (anonymous) lottery winner. Lottery winners are predetermined through a random selection to ensure that winning may occur in a timely manner linked to behavior. If participants do not notify the study or scan their barcode, at their quarterly phone call follow-up, they would be entered into the lottery if they are eligible. The lottery prize will be a pre-loaded smart phone or equivalent with an approximate value of 1000 ZAR (~71 USD). Participants also will receive phone calls after 3 months to assess linkage to care. Participants will schedule their month 6 follow-up visit to determine if rerandomization is required. | PMC9842495 |
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Six-month study visit to determine eligibility for the second randomization | TB | CRYPTOCOCCAL MENINGITIS | After the initial 6-month stage, a visit will take place at a location of the participant’s choice with options for the visit to take place at home, at a mobile van, a location in the community, or at the clinic. Participants will complete questionnaires to assess engagement in care and barriers to accessing care. To further determine eligibility, specimens will be collected for viral load testing (either plasma or point-of-care viral load testing, if available). Participant clinic and pharmacy records will be checked for missed clinic appointments and/or missed ART refills. Participants who are virally suppressed and engaged in care at month 6 will continue in their original group, receive quarterly phone calls, and schedule their exit visit at month 18. Locator information will be confirmed. Participants who meet the criteria for not engaged in care or LTFU will receive their second randomization once the questionnaire is complete. Viral load results will be provided either immediately if using a point-of-care test or within a week to facilitate rerandomization for participants who are engaged in care. Once it has been determined that the participant is eligible to be rerandomized, the first step will be to determine whether or not ART has been initiated. If the participant is not engaged in care but ART has been initiated, the clinical screen will be conducted to exclude symptoms of active TB or cryptococcal meningitis, point-of-care creatinine will be checked, and a 3-month refill will be provided. Participants will be taught to self-collect DBS for viral load testing at this visit. | PMC9842495 |
Participants initiating ART at the month 6 visit | ADVERSE EFFECTS | For participants requiring ART initiation, a study nurse will initiate ART at home or in a mobile van. The study nurse will review the participant’s eligibility for ART initiation at home, provide counseling on adherence and adverse effects, and will dispense the first 90 days of medication. The study staff member will register the participant at the clinic so that the participant records are available at the clinic should the participant seek care there for any reason. The registration will either be done electronically or through paper forms, depending on the clinic capacity to receive electronic referrals. If appropriate, the participant may be transferred to the HSRC via | PMC9842495 |
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Community (smart locker) delivery | If participants are randomized to the community (smart locker) delivery group, they will receive ART refill delivery via a smart locker in a secure location. They will complete their clinical screen via telehealth, including an option for a secure video link, and self-collect specimens for viral load screening. If the participant is not able to access the smart locker due to the geographic location, mobile smart lockers will be provided via a mobile van at the time of delivery. | PMC9842495 |
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Home ART delivery | Participants randomized to the home ART delivery group will receive ART delivery at home or at a location of their choice, such as a community center. At ART delivery visits, a clinical screening questionnaire will be completed, and blood collected for viral load and creatinine tested as indicated by the clinical monitoring schedule following local guidelines. These procedures will be conducted by a study team member in person, with oversight from a nurse, or via telehealth with a nurse. If no-contact delivery is necessary due to COVID-19 restrictions, the participant will self-collect DBS for viral load testing and provide that when the medication is delivered. Participants will have a home delivery appointment scheduled 3 months after ART initiation. | PMC9842495 |
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Criteria for discontinuing or modifying allocated interventions {11b} | tuberculosis | OPPORTUNISTIC INFECTIONS, ADVERSE EVENTS, TUBERCULOSIS, STIS, ADVERSE EFFECTS, ADVERSE EVENT | Participants will be encouraged to visit the clinic for medical concerns outside of ART monitoring and adherence counseling. During participant ART resupply and monitoring visits, they will complete a standardized symptom screening questionnaire for adverse effects of ART, tuberculosis, opportunistic infections, and STIs. Furthermore, all participants on TDF/FTC or 3TC/TDF will receive the standard ART lab monitoring, including a creatinine test to monitor their renal function. Participants who have severe (grade 3/4) adverse effects, according to the DAIDS guidelines and serious adverse effects, will be referred to the clinic for medical evaluation and appropriate diagnostic testing. We have established relationships with the clinics who expect to see study participants. All participants who experience adverse events will receive follow-up until the adverse event is resolved. The SMART ART study clinical monitor, based at the University of Washington Coordinating Center, will review all severe (grade 3/4) and serious adverse events to ensure follow-up and reporting. Participants who have two viral loads with >1500 copies/mL will be referred to the participating local HIV clinic(s) for evaluation for drug resistance and initiation of second-line ART. Participants who are referred back to the clinic will continue to receive their study follow-up visits and can return to home delivery or smart locker delivery with ART monitoring and refills once they are clinically stable. | PMC9842495 |
Strategies to improve adherence to interventions {11c} | Participants will receive a non-identifying text message within 1 week of viral load testing to communicate that “all is going well” (i.e., if their viral load is suppressed), contacting them to have additional adherence counseling—“contact us for more information” (i.e., if first viral load not suppressed), or asking them to come into the clinic for assessment for treatment failure (i.e., if two viral loads are not suppressed following intervening adherence counseling). Adherence counseling for participants with VL>1500 copies/mL will identify barriers and strategies to increase ART adherence. | PMC9842495 |
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Relevant concomitant care permitted or prohibited during the trial {11d} | ART, TPT, and other chronic meds will be dispensed. | PMC9842495 |
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Provisions for post-trial care {30} | Participants who suffer harm from participating in this study will be offered a referral to one of the study site’s referral partners or, if appropriate, care at the HSRC site clinic, free of charge. No monetary compensation will be provided. If a participant requires medical care that the study clinic cannot provide, the study doctors will refer participants to the appropriate services or organizations that can provide care for the injury or harm. | PMC9842495 |
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Outcomes {12} | viral suppression | SECONDARY | The primary outcome of this trial is viral suppression at 18 months, comparing (i) all individuals randomized to clinic-based care with or without lottery incentives for the full 18 months and (ii) nonresponding individuals rerandomized to home- or community-based care to those rerandomized to clinic-based care. The secondary outcomes are (a) retention in care (defined as the proportion of clinical visits and medication refills missed over the last 12 months of the intervention) and (b) time to ART initiation, and additional analyses will include (c) impact of the adaptive interventions among men; (d) impact among the two subgroups at enrollment (persons with detectable viral load and persons not engaged in care); (e) assessment of how baseline variables influence the difference between adaptive interventions; and (f) comparison of viral suppression and retention outcomes between local clinics. For home delivery, missed ART deliveries, total miles traveled, and CO | PMC9842495 |
Participant timeline {13} | The flow of participants through the study at associated time points is presented in Fig. The flow of participants through the study at associated time points | PMC9842495 |
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Sample size {14} | With a sample size of | PMC9842495 |
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Recruitment {15} | RECRUITMENT | Prior to recruitment, community mobilizers will visit communities to provide details about the study including the community-based HIV testing and approximate dates available in that community and at the clinic. Site teams are experienced in HTC and are well known to the clinic staff and community leaders. We will identify participants for recruitment through two means: (1) clinic recruitment and (2) community-based HIV testing and counseling through home and mobile testing. | PMC9842495 |
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Recruitment at HIV clinics | RECRUITMENT | Outreach for recruitment will be conducted by study staff at HIV clinics to identify persons living with HIV who are presenting at the clinic for the first time and are not yet engaged in care. Participants recruited at the clinic will be eligible to continue with study procedures outlined below. For Clinic Outreach Team recruitment, we have worked closely with the Caluza Clinic who have identified clients who have had a detectable viral load and/or who have not been engaged in care. Under new guidance to offer “Welcome Back” services, clinic outreach teams will contact these clients to ensure that they are not engaged in care elsewhere. Clients will be informed about the study and referred to the SMART ART study team for information and, if they choose, study enrollment. Informed consent may take place at the clinic or at an alternate location of the participant’s choice, such as a community center. | PMC9842495 |
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Community-based HTC | PMC9842495 |
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Home HTC | Counseling and testing in home HTC is conducted in a private environment either inside the participant’s home or outside. During community mobilization, mobilizers will inform household members of the day and time of home HTC visits. For the home HTC visit, trained counselors will visit contiguous homes within the community. | PMC9842495 |
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Mobile HTC | RECRUITMENT | Counseling and testing in mobile HTC is conducted in mobile testing centers in a private environment either inside the testing van or outside. Mobile HTC will be provided from mobile counseling and testing units and within suitable community venues identified during the community entry and consultation process. The community mapping process will be used to identify high-traffic spots in the community. This will include taxi ranks, popular shops, kiosks, weekly markets, communal service, and social venues such as churches, sports grounds, etc. A list of possible community testing venues will be developed and reviewed to ensure walking-distance coverage of all the settlement clusters in the community. These high-traffic spots will be used for mobilization activities. A suitable open space of land for the siting of the mobile testing unit will be identified proximal to the mobilization area. Where available and suitable, nearby community buildings or informal structures such as tents may be used to provide counseling and testing. Mobile HTC will be offered at high-traffic areas such as taxi ranks to identify persons who have not yet virally suppressed despite knowing their status and visiting the clinic in the last 6 months. Community-based HTC approaches for recruitment will allow us to recruit participants who do not come to the clinic despite knowing their status and clients who have attended the clinic but are not yet virally suppressed and engaged in care. | PMC9842495 |
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HIV self-testing (HIVST) | EVENTS | In order to further identify persons, particularly men, in the community who are less likely to participate in community-based HTC, we will provide HIV testing kits for self-administered testing and clear guidance for follow-up of persons electing to use the test kits. Persons who have a positive test using the kits will be invited to participate in SMART ART, receive confirmatory testing, and enroll in SMART ART if confirmed to be living with HIV. Kits for self-administered HIV testing (BioSure HIV Self Test, OraQuick, or other approved HIV Self Tests) will be distributed at the following venues: (1) HIV testing at the mobile van, which is often oversubscribed with some people having to wait or leave without a test, (2) providing HIV self-test kits to men and women in the SMART ART study to facilitate partner testing, and (3) HIV testing at outreach venues to reach men (men’s health events including multi-disease screening; peer ambassadors; work place testing; churches; music venues; and soccer games). Participants using self-test kits will watch a demonstration of the self-test kit, have the option of using a chatbot to help with self-testing, and receive information about the test kit, the need for confirmatory testing, and options for clinic-based services or SMART ART study enrollment to provide ART for persons testing positive. Persons electing to participate in self-testing will be encouraged to contact the study team for further information about linking to HIV treatment or prevention, including information about enrolling in the SMART ART study. Results of HIV self-testing will be confirmed with provider-conducted testing to determine eligibility in the SMART ART study. | PMC9842495 |
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Assignment of interventions: allocation | PMC9842495 |
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Sequence generation {16a} | RECRUITMENT | We plan to enrol approximately 900 participants and randomize them initially at a ratio of 1:1 using varying size block randomization. At 6 months into the study, rerandomization of eligible participants will take place at a ratio of 2:1:1 again using varying size block randomization. Due to the intermittent availability of Internet access, envelopes will be used to randomize participants. Two recruitment teams will be used and therefore two different packets of envelopes were prepared, one set for each team. | PMC9842495 |
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Concealment mechanism {16b} | The randomization sequence will be predetermined and available through sealed envelopes for each participant/household enrolled. The randomization group will not be determined until the participant has completed all screening procedures. The randomization will be designed at the University of Washington International Clinical Research Center (ICRC) Coordinating Center and will be provided via sealed envelopes, with UW ICRC oversight. | PMC9842495 |
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Implementation {16c} | The allocation sequence will be generated by the unblinded biostatistician. The screening and enrolling nurse will assign participants who are eligible to the available interventions. | PMC9842495 |
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Assignment of interventions: blinding | PMC9842495 |
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Who will be blinded {17a} | Because of the difficulty masking study team and study participants to group allocation, the study is unblinded. However, staff assessing the primary outcome will be masked to the allocation of participants, as will study investigators. | PMC9842495 |
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Procedure for unblinding if needed {17b} | This study is unblinded with respect to the study group. | PMC9842495 |
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Data collection and management | PMC9842495 |
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Plans for assessment and collection of outcomes {18a} | PMC9842495 |
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Screening and baseline | PMC9842495 |
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Screening questionnaire | HIV testing behavior | After consent is obtained and locator information documented, the core set of risk assessment questions will be administered, including socio-demographic information; sexual and risk behavior; hypothetical risk and Belief in Medicines questionnaires; quality of life survey; knowledge, attitudes, and practices of HIV testing behavior; engagement in HIV treatment and prevention; clinical HIV history; costs of engaging in care; and related health activities. The staff member will administer the screening questionnaire to each individual in a confidential area. | PMC9842495 |
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Testing | hypertension, diabetes | BLOOD, HYPERTENSION, DIABETES | Home testing and counseling (HTC) and mobile HTC will be conducted in communities in South Africa. Additional health services, specifically measurement of blood pressure and hemoglobin A1C testing for hypertension and diabetes screening, may be offered to all participants following local screening guidelines. Blood pressure will be measured two or three times, with a rest in-between reading, using an automated cuff and the lowest reading used to refer the participant for further medical care. Hemoglobin A1C will be the measured using a finger-prick specimen. Height and weight will be measured to calculate the body mass index of all participants. If BMI is measured, participants will receive information on maintaining a healthy weight through lifestyle interventions (e.g., diet and exercise). The screening results and referral to local clinics will be provided to participants who choose to engage in additional health screens. | PMC9842495 |
HIV counseling and testing | EVENT | Subsequently, the counselor will conduct individual counseling and HIV testing according to national guidelines. HIV results will be recorded. If necessary, for quality assurance (QA) of rapid HIV tests, dried blood spots will be collected. In the event that two individuals within a partnership test, the study staff will ask partners if they are interested in disclosing their test results to each other. Partners are encouraged to disclose their results, with the counselor facilitating disclosure, but are not required to disclose; for disclosure to take place, both partners must agree to disclose their results. If disclosure is agreed upon, the participants will be brought back together and disclosure counseling will occur. Once testing has been completed for a couple, and both members of the couple choose to disclose their results, disclosure counseling will be done. All HIV-negative participants will receive HIV prevention counseling and will be informed their participation in the study is complete. Participant who test negative for HIV may be referred to available HIV prevention studies. All participants will receive counseling on positive prevention and the benefits of engagement in HIV care. Persons living with HIV not on ART will continue with the screening process. | PMC9842495 |
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Screening for persons living with HIV not on ART | HIV infection | HIV INFECTION, RECRUITMENT | Persons living with HIV identified through home HTC, mobile HTC, or clinic recruitment and who are not on ART will be screened to stage their HIV infection by CD4 testing and the World Health Organization (WHO) symptomatic screen. To minimize the time to ART initiation, costs, and loss to follow-up, point-of-care tests will be used where possible, including for CD4 and creatinine. | PMC9842495 |
CD4 testing | The CD4 test is a measure of immune function and is used to determine eligibility into SMART ART. Participants will be offered a point-of-care (POC) CD4 test, which will be obtained from a fingertip sample by lancet. If necessary for quality assurance (QA) of POC CD4 testing under field settings or if the POC CD4 test is not available, blood may also be collected at this time for standard laboratory CD4 count measurement by flow cytometry. The QA protocol is predetermined by the study sites to ensure reliable CD4 results. | PMC9842495 |
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WHO symptom screen and HIV engagement in care questionnaire | PCP pneumonia, tuberculosis | CRYPTOCOCCAL MENINGITIS, SEXUALLY TRANSMITTED INFECTIONS, OPPORTUNISTIC INFECTIONS, TUBERCULOSIS | Participants will be screened for symptoms of tuberculosis, opportunistic infections (e.g., cryptococcal meningitis, PCP pneumonia), sexually transmitted infections, and clinical HIV through a set of standard WHO questions. Persons living with HIV will complete an HIV engagement in care questionnaire on previous HIV testing, CD4 count testing, clinical management, cost of engaging in care, ART use, and risk behavior. | PMC9842495 |
Pregnancy testing | A urine pregnancy test will be performed, with urine collection done in a private setting. Women who have a positive pregnancy test will be eligible to participate in the study and will be linked to antenatal care at the clinic and followed until they link. | PMC9842495 |
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Creatinine testing | TAF | Persons living with HIV who are ART eligible will receive a point-of-care creatinine (Cr) test (using a lancet for finger-stick blood collection) to evaluate renal function for the common first-line regimens that include tenofovir (TDF) or tenofovir alafenamide (TAF). If an alternate first-line regimen is available following national treatment guidelines, appropriate screening will be conducted prior to ART initiation. A validated point-of-care test for monitoring creatinine will be used. If necessary for quality control (QC) of POC creatinine testing under field settings or if the POC creatinine test is not available, 5 mL of blood may also be collected at this time for standard laboratory creatinine measurement. | PMC9842495 |
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Tuberculosis (TB) testing | TB | AMPLIFICATION | For persons reporting symptoms consistent of active TB, we will use a point-of-care TB test once available. The Cepheid GeneXpert test (Sunnyvale, CA) is approved for use in South Africa, and a portable version (Omni) is expected to be available. Both the GeneXpert and the Omni systems use sputum specimens (2 mL unprocessed sputum) that are processed for TB detection by Cartridge Based Nucleic Acid Amplification testing (CB-NAAT) using Xpert MTB/RiF assay technology. Persons who screen positive for active TB will be provided their test results and referred to the clinic or appropriate clinical study for further workup and treatment. Until this test is available, we will use symptom screening for active TB though it is non-specific and may exclude persons who are eligible for ART. | PMC9842495 |
Cryptococcal testing | cryptococcal infection, cryptococcal disease, co-infections | While ART is recommended for all persons living with HIV, for participants who have co-infections, ART initiation may be delayed with cryptococcal disease, which is most commonly seen when the CD4 count is ≤100 cells/μL. A point-of-care assay for cryptococcal infection is currently being evaluated and will be included in the screening protocol once it is available to facilitate referral of participants for appropriate evaluation and management. The point-of-care cryptococcal antigen test uses a finger-stick sample of whole blood. Persons who screen positive for cryptococcal antigen will receive their results as part of their referral to the clinic for further evaluation and management. | PMC9842495 |
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Screening viral load and ART testing | Two dried blood spot (DBS) cards will be collected at screening and stored for testing for HIV viral load and antiretroviral therapy. The maximum volume of blood to be collected is 0.5mL [2 spots on the first card and three spots on the second]. The cards will be stored at the study sites under appropriate conditions. If validated viral load testing through point-of-care viral load testing is available, it may be used instead of DBS. | PMC9842495 |
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Volume of specimens | For most participants for whom point-of-care tests will be used, 1.5 mL of blood will be collected. A maximum of 12mL of blood will be collected for testing for CD4, creatinine, DBS, and viral load including specimens for QA/QC. The specimens will be disposed of after testing. | PMC9842495 |
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Chart abstraction | For all study groups, engagement in care (clinic visits, ART initiation, and pharmacy refills) may be abstracted from clinic records or ART refills confirmed by participant report and/or staff member confirming ART supplies either in person or via phone/telehealth. | PMC9842495 |
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Six-month visit | PMC9842495 |
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Specimen collection | Participants will have specimens collected for ART monitoring at the month 6 visit, specifically creatinine and viral load. Volumes and frequency of laboratory monitoring are described below. | PMC9842495 |
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Community (smart locker) delivery | If participants are randomized to the community (smart locker) delivery group, they will receive ART refill delivery via a smart locker in a secure location. They will complete their clinical screen via telehealth, including an option for a secure video link, and self-collect specimens for viral load screening. If the participant is not able to access the smart locker due to the geographic location, mobile smart lockers will be provided via a mobile van at the time of delivery. | PMC9842495 |
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Home ART delivery | Participants randomized to the home ART delivery group will receive ART delivery at home or at a location of their choice, such as a community center. At ART delivery visits, a clinical screening questionnaire will be completed, and blood collected for viral load and creatinine tested as indicated by the clinical monitoring schedule following local guidelines. These procedures will be conducted by a study team member in person, with oversight from a nurse, or via telehealth with a nurse. If no-contact delivery is necessary due to COVID-19 restrictions, the participant will self-collect DBS for viral load testing and provide that when the medication is delivered. | PMC9842495 |
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Follow-up (9, 12, and 15 months) | PMC9842495 |
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Follow-up procedures for participants in the home ART group | ADVERSE EVENTS, ADVERSE EVENT | Follow-up visits at months 9, 12, and 15 will take place at the home or a location of the participant’s choice. Appointments for the home delivery, i.e., date and time that it will be available at home or a location easily accessible to the participants for follow-up, will be made at the time of ART initiation. Appointments will be made prior to ART supply running out, and confidential, neutral text message reminders will be provided for participants who have access to private messaging and phone calls. Participants will be able to reschedule their appointments by text message. Contact information will be provided for study staff, who participants can contact with questions. Clinic details will be provided to the participant who can contact the clinic at any time.At the follow-up visits, participants will have their identification confirmed and GPS location collected, complete a questionnaire including adverse event and social harm screening, complete labs for ART and TPT monitoring, and collect ART resupply, and counselors will answer questions and provide support for HIV care. Participants will have their blood pressure measured if indicated. Participants will receive counseling and be referred to local clinics for further evaluation and treatment as needed. Participants will complete a questionnaire on clinical review, their experience accessing care, including barriers to care, linkage to care, uptake of ART, adherence, adverse events, lab testing, social harms, risk behavior, cost of engaging in care, HIV clinical care, and knowledge about HIV treatment for clinical and prevention benefits. Deliveries may be conducted as no-contact deliveries, with visits via telehealth and self-collected DBS specimens for monitoring if COVID-19 restrictions or other limitations on mobility are put in place. | PMC9842495 |
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Follow-up procedures for participants in the community (smart locker) group | tuberculosis | TUBERCULOSIS | Follow-up visits at months 9, 12, and 15 will take place via telehealth with ART provided at the smart locker and the participant depositing their self-collected specimens at the smart locker for collection. Smart locker ART pick-up windows will be made for ART refills and monitoring prior to their ART supply running out, and confidential, neutral text message reminders will be provided for participants who have access to private messaging and phone calls. Participants will be able to reschedule their telehealth appointments and locker pick-up by text message. Contact information will be provided for study staff, who participants can contact with questions. Clinic details will be provided to the participant who can contact the clinic at any time. With each ART delivery, the following procedures will happen:Collection of the GPS coordinate of the delivery locationART, tuberculosis preventive treatment (TPT), and other chronic meds will be dispensedSchedule next delivery or visit as indicatedParticipants will have refills every 3 monthsHealth questionnaires will be completedBlood draw or self-collected DBS (if necessary, for POC creatinine and viral load (up to 12.5mL))Participants may have their medical records reviewed by the study team to record any visits to the clinic and the reason | PMC9842495 |
Follow-up procedures for ART monitoring in the community (smart locker) and home delivery groups | BLOOD | Blood specimens will be collected for viral load and creatinine monitoring according to national guidelines. In the smart locker group, participants will self-collect DBS for viral load testing. In the home ART delivery group, specimens will either be collected by staff or, for no contact deliveries, by participants. For participants on fixed dose combination TDF/3TC/DGT, the first-line regimen in South Africa, safety labs will consist of viral load monitoring at months 6 and 12 and creatinine monitoring following local guidelines. Creatinine monitoring will be conducted using the StatSensor. If the StatSensor is not available, 5mL of blood will be collected for creatinine testing in the lab and the result made available to the participant. Participants with significantly raised creatinine levels (an increase of >0.5 mg/dL) will be referred to the clinic for investigation and management.HIV viral load testing will use the gold standard PCR viral load test, using plasma or DBS specimen) or the validated Xpert assay. The viral load result will be made available to the participant, with counseling to help with the interpretation of the result.Participants will receive a non-identifying text message within 1 week to communicate that “all is going well” (i.e., if their viral load is suppressed), contacting them to have additional adherence counseling—“contact us for more information” (i.e., if first viral load not suppressed), or asking them to come into the clinic for assessment for treatment failure (i.e., if two viral loads are not suppressed following intervening adherence counseling). Adherence counseling for participants with VL > 1500 copies/mL will identify barriers and strategies to increase ART adherence.If indicated by local guidelines, cotrimoxazole (Bactrim) and/or isoniazid prophylaxis will be provided to participants following national guidelines and for whom it is not contra-indicated. At each study visit, female participants will be asked about pregnancy and referred for antenatal care if they report missed periods and/or signs or symptoms of pregnancy. They will be encouraged to remain on ART to decrease the risk for mother to child transmission of HIV. Pregnant participants are eligible to remain in the study and will continue to have follow-up visits. | PMC9842495 |
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Follow-up procedures for the SOC clinic group (with and without lottery incentives) | ADVERSE EVENTS, OPPORTUNISTIC INFECTIONS | Participants will initiate ART at the clinic and, if feasible, receive quarterly chart review (either paper charts or through electronic medical records (EMRs) where available) to review safety labs (creatinine at 3, 6, and 12 months after ART initiation, for participants on TDF, and viral load 6 and 12 months after ART initiation), adherence data, ART refills, and engagement in clinical care. A study team member will facilitate linkages of the participant to the study to enable follow-up and chart extraction. Participants will complete a questionnaire on opportunistic infections, engagement in care, adverse events, and, if they have started ART, ART symptoms either by phone or in person at the clinic at months 3, 6, 9, 12, and 15. Participants will receive an 18-month follow-up visit during which they will complete the follow-up questionnaire (month 18 visit detailed below). | PMC9842495 |
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Procedures for 18-month or exit visit for all participants | Examination of HIV care documentation | ADVERSE EVENTS | Follow-up visits at month 18 or exit will take place in person at the mobile van, home, or clinic, by participant choice. At the follow-up visits, counselors will answer questions and provide support for HIV care. Participants will complete a questionnaire on their experience accessing care, including barriers to care, linkage to care, uptake of ART, adherence, adverse events, reasons for loss to follow-up, CD4 and viral load testing, social harms, risk behavior, cost of engaging in care, HIV clinical care including co-infections, and knowledge of HIV treatment and prevention. Examination of HIV care documentation (e.g., registration card from HIV care clinic) and recording of medications (e.g., HIV care medications and ART) will take place. If feasible, chart extraction will be conducted to record engagement in HIV care and lab monitoring for all participants. A maximum of 11 mL of blood (2 teaspoons) will be collected for viral load and creatinine testing. The specimens will be disposed of after testing has taken place. HIV viral load testing will use the gold standard PCR viral load test or the validated alternate approach. The viral load result will be made available to the participant, with counseling to help with the interpretation of the result. | PMC9842495 |
Plans to promote participant retention and complete follow-up {18b} | TB | ADVERSE EFFECTS, PNEUMOCYSTIS PNEUMONIA, TUBERCULOSIS (TB) | Screening and enrolment will be conducted in person and will be followed by quarterly visits thereafter for 18 months. Participants will also receive a phone call 7 days and 30 days after initiating ART to complete a standard symptom screen for ART adverse effects and referred to clinic care if necessary. If indicated, tuberculosis (TB) preventive treatment (TPT) and trimethoprim-sulfamethoxazole will be provided to prevent TB and pneumocystis pneumonia. Tracking and tracing activities will be undertaken by the community engagement team who will keep an active presence in study communities for the duration of the trial. Every effort will be made to retain all participants at the 18-month exit visit to ensure high-quality data and that continuity of care can be put in place before the study exit. We will follow well-established practices of notifying participants of their study follow-up visits via SMS and WhatsApp messaging and telephone calls. | PMC9842495 |
Data management {19} | VIRUS, EVENT | Screening and enrolment questionnaires will be administered to all participants using REDCap (Research Electronic Data Capture). REDCap was developed through a National Institutes of Health grant to Vanderbilt University. It is free and consists of a secure web-based application and associated mobile phone app. It is used globally to support data capture for research studies and provides a graphical interface for survey development, data entry validation, audit trails and a change log of all data edits, and the ability to export data in formats that can be easily read by common statistical packages. REDCap uses role permissions to ensure only authorized staff have access to appropriate data and functions.The HIV questionnaires are also available on REDCap and consist of questions which will be administered to persons living with HIV identified through HIV testing. Checks will be placed to ensure correct information has been entered. Data from laboratory testing (e.g., plasma HIV viral load) will be collected by participant ID number and merged into the database.All questionnaires will be loaded onto the REDCap mobile app which will allow for offline data collection. Both the mobile phone and REDCap are password protected to ensure data safety in the event a handset is lost. Surveys are then uploaded to the secured UW server. The de facto standard for securing network traffic is Secure Sockets Layering (SSL). This technology is fully supported by the handsets used in this study and ensures that all data transferred between the device and the server is encrypted. Similarly, when reviewing, exporting or managing data all communications between browser and server are encrypted. All data will be encrypted. Servers are secured by firewalls to prevent unauthorized access and denial of service attacks. Data is protected from virus threats using anti-virus technology. The study database will be backed-up regularly. | PMC9842495 |
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