Early HIV treatment and survival over six years of observation in the ANRS 12249 Treatment as Prevention Trial.

OBJECTIVES: Population-based universal test and treat (UTT) trials have shown an impact on population-level virological suppression. We followed the ANRS 12249 TasP trial population for 6 years to determine whether the intervention had longer-term survival benefits. METHODS: The TasP trial was a cluster-randomized trial in South Africa from 2012 to 2016. All households were offered 6-monthly home-based HIV testing. Immediate antiretroviral therapy (ART) was offered through trial clinics to all people living with HIV (PLHIV) in intervention clusters and according to national guidelines in control clusters. After the trial, individuals attending the trial clinics were transferred to the public ART programme. Deaths were ascertained through annual demographic surveillance. Random-effects Poisson regression was used to estimate the effect of trial arm on mortality among (i) all PLHIV; (ii) PLHIV aware of their status and not on ART at trial entry; and (iii) PHLIV who started ART during the trial. RESULTS: Mortality rates among PLHIV were 9.3/1000 and 10.4/1000 person-years in the control and intervention arms, respectively. There was no evidence that the intervention decreased mortality among all PLHIV [adjusted rate ratio (aRR) = 1.10, 95% confidence interval (CI) = 0.85-1.43, p = 0.46] or among PLHIV who were aware of their status but not on ART. Among individuals who initiated ART, the intervention decreased mortality during the trial (aRR = 0.49, 95% CI = 0.28-0.85, p = 0.01), but not after the trial ended. CONCLUSIONS: The 'treat all' strategy reduced mortality among individuals who started ART but not among all PLHIV. To achieve maximum benefit of immediate ART, barriers to ART uptake and retention in care need to be addressed.

Early ART Initiation Improves HIV Status Disclosure and Social Support in People Living with HIV, Linked to Care Within a Universal Test and Treat Program in Rural South Africa (ANRS 12249 TasP Trial).

We investigated the effect of early antiretroviral treatment (ART) initiation on HIV status disclosure and social support in a cluster-randomized, treatment-as-prevention (TasP) trial in rural South Africa. Individuals identified HIV-positive after home-based testing were referred to trial clinics where they were invited to initiate ART immediately irrespective of CD4 count (intervention arm) or following national guidelines (control arm). We used Poisson mixed effects models to assess the independent effects of (a) time since baseline clinical visit, (b) trial arm, and (c) ART initiation on HIV disclosure (n = 182) and social support (n = 152) among participants with a CD4 count > 500 cells/mm3 at baseline. Disclosure and social support significantly improved over follow-up in both arms. Disclosure was higher (incidence rate ratio [95% confidence interval]: 1.24 [1.04; 1.48]), and social support increased faster (1.22 [1.02; 1.46]) in the intervention arm than in the control arm. ART initiation improved both disclosure and social support (1.50 [1.28; 1.75] and 1.34 [1.12; 1.61], respectively), a stronger effect being seen in the intervention arm for social support (1.50 [1.12; 2.01]). Besides clinical benefits, early ART initiation may also improve psychosocial outcomes. This should further encourage countries to implement universal test-and-treat strategies.

Couples HIV counselling and couple relationships in India, Georgia and the Dominican Republic.

BACKGROUND: Couples HIV counseling and testing is essential for combination HIV prevention, but its uptake remains very low. We aimed to evaluate factors associated with couples HIV counseling uptake in India, Georgia and the Dominican Republic, as part of the ANRS 12127 Prenahtest intervention trial. METHODS: Pregnant women ≥15 years, attending their first antenatal care (ANC) session between March and September 2009, self-reporting a stable partner, and having received couple-oriented post-test HIV counseling (trial intervention) were included. Individuals and couple characteristics associated with the acceptability of couples HIV counseling were assessed using multivariable logistic regression for each study site. RESULTS: Among 711 women included (232, 240 and 239 in the Dominican Republic, Georgia and India, respectively), the uptake of couples HIV counseling was 9.1% in the Dominican Republic, 13.8% in Georgia and 36.8% in India. The uptake of couples HIV counseling was associated with women having been accompanied by their partner to ANC, and never having used a condom with their partner in the Dominican Republic; with women having been accompanied by their partner to ANC in India; with women having a higher educational level than their partner and having ever discussed HIV with their partner in Georgia. CONCLUSION: Couple HIV counseling uptake was overall low. Strategies adapted to local socio-cultural contexts, aiming at improving women's education level, or tackling gender norms to facilitate the presence of men in reproductive health services, should be considered. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01494961 . Registered December 15, 2011. (Retrospectively registered).

Uptake of Home-Based HIV Testing, Linkage to Care, and Community Attitudes about ART in Rural KwaZulu-Natal, South Africa: Descriptive Results from the First Phase of the ANRS 12249 TasP Cluster-Randomised Trial.

BACKGROUND: The 2015 WHO recommendation of antiretroviral therapy (ART) for all immediately following HIV diagnosis is partially based on the anticipated impact on HIV incidence in the surrounding population. We investigated this approach in a cluster-randomised trial in a high HIV prevalence setting in rural KwaZulu-Natal. We present findings from the first phase of the trial and report on uptake of home-based HIV testing, linkage to care, uptake of ART, and community attitudes about ART. METHODS AND FINDINGS: Between 9 March 2012 and 22 May 2014, five clusters in the intervention arm (immediate ART offered to all HIV-positive adults) and five clusters in the control arm (ART offered according to national guidelines, i.e., CD4 count ≤ 350 cells/µl) contributed to the first phase of the trial. Households were visited every 6 mo. Following informed consent and administration of a study questionnaire, each resident adult (≥16 y) was asked for a finger-prick blood sample, which was used to estimate HIV prevalence, and offered a rapid HIV test using a serial HIV testing algorithm. All HIV-positive adults were referred to the trial clinic in their cluster. Those not linked to care 3 mo after identification were contacted by a linkage-to-care team. Study procedures were not blinded. In all, 12,894 adults were registered as eligible for participation (5,790 in intervention arm; 7,104 in control arm), of whom 9,927 (77.0%) were contacted at least once during household visits. HIV status was ever ascertained for a total of 8,233/9,927 (82.9%), including 2,569 ascertained as HIV-positive (942 tested HIV-positive and 1,627 reported a known HIV-positive status). Of the 1,177 HIV-positive individuals not previously in care and followed for at least 6 mo in the trial, 559 (47.5%) visited their cluster trial clinic within 6 mo. In the intervention arm, 89% (194/218) initiated ART within 3 mo of their first clinic visit. In the control arm, 42.3% (83/196) had a CD4 count ≤ 350 cells/µl at first visit, of whom 92.8% initiated ART within 3 mo. Regarding attitudes about ART, 93% (8,802/9,460) of participants agreed with the statement that they would want to start ART as soon as possible if HIV-positive. Estimated baseline HIV prevalence was 30.5% (2,028/6,656) (95% CI 25.0%, 37.0%). HIV prevalence, uptake of home-based HIV testing, linkage to care within 6 mo, and initiation of ART within 3 mo in those with CD4 count ≤ 350 cells/µl did not differ significantly between the intervention and control clusters. Selection bias related to noncontact could not be entirely excluded. CONCLUSIONS: Home-based HIV testing was well received in this rural population, although men were less easily contactable at home; immediate ART was acceptable, with good viral suppression and retention. However, only about half of HIV-positive people accessed care within 6 mo of being identified, with nearly two-thirds accessing care by 12 mo. The observed delay in linkage to care would limit the individual and public health ART benefits of universal testing and treatment in this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT01509508.

"It is better to die": experiences of traditional health practitioners within the HIV treatment as prevention trial communities in rural South Africa (ANRS 12249 TasP trial).

The ANRS 12249 Treatment-as-Prevention (TasP) cluster-randomized trial in rural South Africa uses a "test and treat" approach. Home-based testing services and antiretroviral treatment initiation satellite clinics were implemented in every cluster as part of the trial. A social science research agenda was nested within TasP with the aim of understanding the social, economic and contextual factors that affect individuals, households, communities and health systems with respect to TasP. Considering the rural nature of the trial setting, we sought to understand community perceptions and experiences of the TasP Trial interventions as seen through the eyes of traditional health practitioners (THPs). A qualitative study design was adopted using four repeat focus group discussions conducted with nine THPs, combined with community walks and photo-voice techniques, over a period of 18 months. A descriptive, interpretive and explanatory approach to analysis was adopted. Findings indicate that THPs engaged with the home-based testing services and HIV clinics established for TasP. Specifically, home-based testing services were perceived as relatively successful in increasing access to HIV testing. A major gap observed by THPs was linkage to HIV clinics. Most of their clients, and some of the THPs themselves, found it difficult to use HIV clinics due to fear of labelling, stigma and discrimination, and the ensuing personal implications of unsolicited disclosure. On the one hand, a growing number of patients diagnosed with HIV have found sanctuary with THPs as alternatives to clinics. On the other hand, THPs in turn have been struggling to channel patients suspected of HIV into clinics through referrals. Therefore, acceptability of the TasP test and treat approach by THPs is a major boost to the intervention, but further success can be achieved through strengthened ties with communities to combat stigma and effectively link patients into HIV care, including partnerships with THPs themselves.

Men, masculinity, and engagement with treatment as prevention in KwaZulu-Natal, South Africa.

Men's poorer engagement with healthcare generally and HIV care specifically, compared to women, is well-described. Within the HIV public health domain, interest is growing in universal test and treat (UTT) strategies. UTT strategies refer to the expansion of antiretroviral therapy (ART) in order to reduce onward transmission and incidence of HIV in a population, through a "treatment as prevention" (TasP). This paper focuses on how masculinity influences engagement with HIV care in the context of an on-going TasP trial. Data were collected in January-November 2013 using 20 in-depth interviews, 10 of them repeated thrice, and 4 focus group discussions, each repeated four times. Analysis combined inductive and deductive approaches for coding and the review and consolidation of emerging themes. The accounts detailed men's unwillingness to engage with HIV testing and care, seemingly tied to their pursuit of valued masculinity constructs such as having strength and control, being sexually competent, and earning income. Articulated through fears regarding getting an HIV-positive diagnosis, observations that men preferred traditional medicine and that primary health centres were not welcoming to men, descriptions that men used lay measures to ascertain HIV status, and insinuations by men that they were removed from HIV risk, the indisposition to HIV care contrasted markedly with an apparent readiness to test among women. Gendered tensions thus emerged which were amplified in the context where valued masculinity representations were constantly threatened. Amid the tensions, men struggled with disclosing their HIV status, and used various strategies to avoid or postpone disclosing, or disclose indirectly, while women's ability to access care readily, use condoms, or communicate about HIV appeared similarly curtailed. UTT and TasP promotion should heed and incorporate into policy and health service delivery models the intrapersonal tensions, and the conflict, and poor and indirect communication at the micro-relational levels of couples and families.

Community perceptions of repeat HIV-testing: experiences of the ANRS 12249 Treatment as Prevention trial in rural South Africa.

In the context of the ANRS 12249 Treatment as Prevention (TasP) trial, we investigated perceptions of regular and repeat HIV-testing in rural KwaZulu-Natal (South Africa), an area of very high HIV prevalence and incidence. We conducted two qualitative studies, before (2010) and during the early implementation stages of the trial (2013-2014), to appreciate the evolution in community perceptions of repeat HIV-testing over this period of rapid changes in HIV-testing and treatment approaches. Repeated focus group discussions were organized with young adults, older adults and mixed groups. Repeat and regular HIV-testing was overall well perceived before, and well received during, trial implementation. Yet community members were not able to articulate reasons why people might want to test regularly or repeatedly, apart from individual sexual risk-taking. Repeat home-based HIV-testing was considered as feasible and convenient, and described as more acceptable than clinic-based HIV-testing, mostly because of privacy and confidentiality. However, socially regulated discourses around appropriate sexual behaviour and perceptions of stigma and prejudice regarding HIV and sexual risk-taking were consistently reported. This study suggests several avenues to improve HIV-testing acceptability, including implementing diverse and personalised approaches to HIV-testing and care, and providing opportunities for antiretroviral therapy initiation and care at home.

Factors associated with antiretroviral treatment initiation amongst HIV-positive individuals linked to care within a universal test and treat programme: early findings of the ANRS 12249 TasP trial in rural South Africa.

Prompt uptake of antiretroviral treatment (ART) is essential to ensure the success of universal test and treat (UTT) strategies to prevent HIV transmission in high-prevalence settings. We describe ART initiation rates and associated factors within an ongoing UTT cluster-randomized trial in rural South Africa. HIV-positive individuals were offered immediate ART in the intervention arm vs. national guidelines recommended initiation (CD4≤350 cells/mm(3)) in the control arm. We used data collected up to July 2015 among the ART-eligible individuals linked to TasP clinics before January 2015. ART initiation rates at one (M1), three (M3) and six months (M6) from baseline visit were described by cluster and CD4 count strata (cells/mm(3)) and other eligibility criteria: ≤100; 100-200; 200-350; CD4>350 with WHO stage 3/4 or pregnancy; CD4>350 without WHO stage 3/4 or pregnancy. A Cox model accounting for covariate effect changes over time was used to assess factors associated with ART initiation. The 514 participants had a median [interquartile range] follow-up duration of 1.08 [0.69; 2.07] months until ART initiation or last visit. ART initiation rates at M1 varied substantially (36.9% in the group CD4>350 without WHO stage 3/4 or pregnancy, and 55.2-71.8% in the three groups with CD4≤350) but less at M6 (from 85.3% in the first group to 96.1-98.3% in the three other groups). Factors associated with lower ART initiation at M1 were a higher CD4 count and attending clinics with both high patient load and higher cluster HIV prevalence. After M1, having a regular partner was the only factor associated with higher likelihood of ART initiation. These findings suggest good ART uptake within a UTT setting, even among individuals with high CD4 count. However, inadequate staffing and healthcare professional practices could result in prioritizing ART initiation in patients with the lowest CD4 counts.

Change of treatment guidelines and evolution of ART initiation in rural South Africa: data of a large HIV care and treatment programme.

BACKGROUND: While WHO recommendations are to treat people earlier and earlier, it will considerably increase the number of HIV infected people eligible for antiretroviral therapy (ART). In South Africa, a country which carries one of the highest HIV burden worldwide, very few studies are available on the impact of the ART guidelines on time to ART initiation in both individuals with low CD4 count and those newly eligible for ART. We thus aimed to describe ART initiation percentages in a large HIV programme in rural KwaZulu-Natal, South Africa, according to the temporal changes of national ART eligibility guidelines from 2007 to 2012. METHODS: Adults who accessed the decentralized Hlabisa HIV treatment programme in 2007-2012 were included. Three periods following the temporal change of ART eligibility guidelines were defined (Period 1: until April 2010; Period 2: April 2010 - July 2011; Period 3: from August 2011). Percentages of ART initiation within three months of programme entry were estimated in men, in women of childbearing age (<40 years old) and in older women, and stratifying by CD4 count. Trend tests and logistic regression models were used to study the effects of change of guidelines on ART initiation percentages. RESULTS: In individuals with CD4 count ≤200 cells/µL (N = 5709 men, N = 6743 women <40 years old and N = 2017 older women), percentages of ART initiation did not differ over time (p trend = 0.25; 0.28; and 0.14, respectively). In individuals with CD4 count = 201-350 cells/µL (N = 2680 men, N = 6086 women <40 years old and N = 1415 older women), percentages of ART initiation significantly increased over time (p trend <0.01 for the three groups): from 6 % in Period 1 to 20 % in Period 2 to 40 % in Period 3 in women of childbearing age, and from 7 % to 8-10 % to 42 % in men and in older women. CONCLUSIONS: As temporal changes of guidelines, percentages of ART initiation significantly increased in newly ART eligible people and did not decrease in individuals with very low CD4 counts. It will be crucial to continue verifying the evolution of these percentages of ART initiation with future recommendations reaching near-to-universal access to ART, to ensure that individuals most in need of ART receive it.

Addressing social issues in a universal HIV test and treat intervention trial (ANRS 12249 TasP) in South Africa: methods for appraisal.

BACKGROUND: The Universal HIV Test and Treat (UTT) strategy represents a challenge for science, but is also a challenge for individuals and societies. Are repeated offers of provider-initiated HIV testing and immediate antiretroviral therapy (ART) socially-acceptable and can these become normalized over time? Can UTT be implemented without potentially adding to individual and community stigma, or threatening individual rights? What are the social, cultural and economic implications of UTT for households and communities? And can UTT be implemented within capacity constraints and other threats to the overall provision of HIV services? The answers to these research questions will be critical for routine implementation of UTT strategies. METHODS/DESIGN: A social science research programme is nested within the ANRS 12249 Treatment-as-Prevention (TasP) cluster-randomised trial in rural South Africa. The programme aims to inform understanding of the (i) social, economic and environmental factors affecting uptake of services at each step of the continuum of HIV prevention, treatment and care and (ii) the causal impacts of the TasP intervention package on social and economic factors at the individual, household, community and health system level. We describe a multidisciplinary, multi-level, mixed-method research protocol that includes individual, household, community and clinic surveys, and combines quantitative and qualitative methods. DISCUSSION: The UTT strategy is changing the overall approach to HIV prevention, treatment and care, and substantial social consequences may be anticipated, such as changes in social representations of HIV transmission, prevention, HIV testing and ART use, as well as changes in individual perceptions and behaviours in terms of uptake and frequency of HIV testing and ART initiation at high CD4. Triangulation of social science studies within the ANRS 12249 TasP trial will provide comprehensive insights into the acceptability and feasibility of the TasP intervention package at individual, community, patient and health system level, to complement the trial's clinical and epidemiological outcomes. It will also increase understanding of the causal impacts of UTT on social and economic outcomes, which will be critical for the long-term sustainability and routine UTT implementation. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01509508; South African Trial Register: DOH-27-0512-3974.

Continuum in HIV care from entry to ART initiation in rural KwaZulu-Natal, South Africa.

OBJECTIVE: To quantify time from entry in HIV care until Antiretroviral therapy (ART) initiation and identify factors associated with ART initiation in rural KwaZulu-Natal, South Africa. METHODS: Adults ≥16 years entering the decentralised Hlabisa ART programme between 2007 and 2011 were followed until June 2013. Median survival times to ART initiation from date of programme entry and from date of ART eligibility were estimated with Kaplan-Meier methods. Associated factors were evaluated in Cox regressions, censoring for deaths. RESULTS: Of 37 749 adults (71.6% female), 17 638 (46.7%) initiated ART. Nearly half (46.9%) met the CD4 criteria for treatment eligibility at programme entry. Among the 20 039 individuals not yet ART-eligible at entry, only 62.5% were retained in care with at least one further CD4 measurement, of whom 6688 subsequently became ART-eligible. Overall, 65.5% of the 24 398 ART-eligible individuals initiated ART over the study period. ART initiation was more likely in women (P < 0.001), in individuals ≥ 25 years old (P < 0.001) and in patients with low CD4 count (P < 0.001). Patients who became eligible during follow up were significantly more likely to initiate ART than those eligible at programme entry (72.6% vs. 62.9%, Adjusted Hazard Ratio = 1.46; 95% Confidence Interval [1.41-1.51]), adjusting for sex, age, year and CD4 count at eligibility. CONCLUSIONS: In this rural programme, continuation of care remains challenging, especially in men and younger adults. ART initiation is more likely in those engaged prior eligibility than in those entering HIV care only late in their HIV disease.

HIV risk perception among pregnant women in western India: need for reducing vulnerabilities rather than improving knowledge!

Since the beginning of the HIV/AIDS epidemic in India, pregnant women attending antenatal clinics (ANC) have been considered as a low HIV risk population. Yet, a substantial proportion of new HIV infections are occurring among stable heterosexual couples. This paper sought to investigate the proportion and profile of women who, within the low-risk population, are potentially at higher risk of HIV infection. HIV risk perception of pregnant women enrolled within the ANRS 12127 Prenahtest trial was described and associated socio-behavioral characteristics, husband's characteristics, and HIV-related characteristics were analyzed using univariate and multivariate logistic regression models. Among 484 women enrolled, baseline data were collected for 479 women and 460 women with completed data were considered for the present analysis (96%). Eighty-nine (19.4%) women perceived themselves at risk of HIV. Women with educational level <11years (Adjusted Odds Ratio, AOR = 2.4 [CI = 1.28-4.53]), who stayed in joint families (AOR = 1.89 [CI = 1.12-3.12]), who had experienced insult or hurt from the partner (AOR = 1.91 [CI = 1.11-3.27]) and whose partner were alcoholic (AOR = 2.19 [CI = 1.31-3.66]) were significantly more likely to perceive themselves at risk of HIV. Women who had heard about sexually transmitted infections were also more likely to report HIV risk perception (AOR = 3.36 [CI = 1.83-6.18]). Substantial proportion of women (one out of five) perceived themselves at risk of HIV and most of these have reported some form of vulnerability in their couple relationship such as intimate partner violence, alcoholic partner, lack of communication, and spaces for communication with partner. Though awareness and knowledge is the first step for prevention, considering the vulnerabilities associated with HIV risk perception, HIV prevention interventions in India should target overall sources of vulnerability to HIV. Targeted risk reduction for women in ANC should be considered for primary HIV prevention among couples.

Effect of decentralising childhood tuberculosis diagnosis to primary health centre versus district hospital levels on disease detection in children from six high tuberculosis incidence countries: an operational research, pre-post intervention study.

Background: Childhood tuberculosis (TB) remains underdiagnosed largely because of limited awareness and poor access to all or any of specimen collection, molecular testing, clinical evaluation, and chest radiography at low levels of care. Decentralising childhood TB diagnostics to district hospitals (DH) and primary health centres (PHC) could improve case detection. Methods: We conducted an operational research study using a pre-post intervention cross-sectional study design in 12 DHs and 47 PHCs of 12 districts across Cambodia, Cameroon, Côte d'Ivoire, Mozambique, Sierra Leone and Uganda. The intervention included 1) a comprehensive diagnosis package at patient-level with tuberculosis screening for all sick children and young adolescents <15 years, and clinical evaluation, Xpert Ultra-testing on respiratory and stool samples, and chest radiography for children with presumptive TB, and 2) two decentralisation approaches (PHC-focused or DH-focused) to which districts were randomly allocated at country level. We collected aggregated and individual data. We compared the proportion of tuberculosis detection in children and young adolescents <15 years pre-intervention (01 August 2018-30 November 2019) versus during intervention (07 March 2020-30 September 2021), overall and by decentralisation approach. This study is registered with ClinicalTrials.gov, NCT04038632. Findings: TB was diagnosed in 217/255,512 (0.08%) children and young adolescent <15 years attending care pre-intervention versus 411/179,581 (0.23%) during intervention, (OR: 3.59 [95% CI 1.99-6.46], p-value<0.0001; p-value = 0.055 after correcting for over-dispersion). In DH-focused districts, TB diagnosis was 80/122,570 (0.07%) versus 302/86,186 (0.35%) (OR: 4.07 [1.86-8.90]; p-value = 0.0005; p-value = 0.12 after correcting for over-dispersion); and 137/132,942 (0.10%) versus 109/93,395 (0.11%) in PHC-focused districts, respectively (OR: 2.92 [1.25-6.81; p-value = 0.013; p-value = 0.26 after correcting for over-dispersion). Interpretation: Decentralising and strengthening childhood TB diagnosis at lower levels of care increases tuberculosis case detection but the difference was not statistically significant. Funding source: Unitaid, Grant number 2017-15-UBx-TB-SPEED.

Acceptability and feasibility of home and hospital follow-up in Burkina Faso and Guinea: A mixed-method study among patients of the COVID-19 Coverage-Africa clinical trial.

Patient experiences and perspectives on trial participation and follow-up may influence their compliance with research procedures or negatively impact their well-being. We aimed to explore the acceptability and feasibility of home-based and hospital-based follow-up modalities among COVID-19 patients enrolled in the ANTICOV ANRS COV33 Coverage-Africa trial in Burkina Faso and Guinea. The trial (2021-2022) evaluated the efficacy of treatments to prevent clinical worsening among COVID-19 patients with mild to moderate symptoms. Patients were either based at home or hospitalized, as per national recommendations, and followed-up through face-to-face visits and phone calls. We conducted a mixed-methods sub-study administering a questionnaire to all consenting participants and individually interviewing purposively selected participants. We performed descriptive analyses of Likert scale questions for the questionnaires and thematic analysis for the interviews. We conducted framework analysis and interpretation. Of the 400 trial patients, 220 completed the questionnaire (n = 182 in Burkina Faso, n = 38 in Guinea) and 24 were interviewed (n = 16 and n = 8, respectively). Participants were mostly followed-up at home in Burkina Faso; all patients from Guinea were first hospitalized, then followed-up at home. Over 90% of participants were satisfied with follow-up. Home follow-up was considered acceptable if (i) participants perceived they were not severely ill, (ii) it was combined with telemedicine, and (iii) the risk of stigma could be avoided. Hospital-based follow-up was viewed as a way to prevent contamination of family members, but could be badly experienced when mandatory and conflicting with family responsibilities and commitments. Phone calls were seen as reassuring and as a way to ensure continuity of care. These overall positive findings support the development of home-based follow-up for mildly ill patients in West-Africa, provided that both emotional and cognitive factors at individual, familial/inter-relational, healthcare and national levels be addressed when planning the implementation of a trial, or developing any public health strategy.

Implementation and effectiveness of a linkage to HIV care intervention in rural South Africa (ANRS 12249 TasP trial).

BACKGROUND: Timely linkage to care and ART initiation is critical to decrease the risks of HIV-related morbidity, mortality and HIV transmission, but is often challenging. We report on the implementation and effectiveness of a linkage-to-care intervention in rural KwaZulu-Natal, South Africa. METHODS: In the ANRS 12249 TasP trial on Universal Testing and Treatment (UTT) implemented between 2012-2016, resident individuals ≥16 years were offered home-based HIV testing every six months. Those ascertained to be HIV-positive were referred to trial clinics. Starting May 2013, a linkage-to-care intervention was implemented in both trial arms, consisting of tracking through phone calls and/or home visits to "re-refer" people who had not linked to care to trial clinics within three months of the first home-based referral. Fidelity in implementing the planned intervention was described using Kaplan-Meier estimation to compute conditional probabilities of being tracked and of being re-referred by the linkage-to-care team. Effect of the intervention on time to linkage-to-care was analysed using a Cox regression model censored for death, migration, and end of data follow-up. RESULTS: Among the 2,837 individuals (73.7% female) included in the analysis, 904 (32%) were tracked at least once, and 573 of them (63.4%) were re-referred. Probabilities of being re-referred was 17% within six months of first referral and 31% within twelve months. Compared to individuals not re-referred by the intervention, linkage-to-care was significantly higher among those with at least one re-referral through phone call (adjusted hazard ratio [aHR] = 1.82; 95% confidence interval [95% CI] = 1.47-2.25), and among those with re-referral through both phone call and home visit (aHR = 3.94; 95% CI = 2.07-7.48). CONCLUSIONS: Phone calls and home visits following HIV testing were challenging to implement, but appeared effective in improving linkage-to-care amongst those receiving the intervention. Such patient-centred strategies should be part of UTT programs to achieve the UNAIDS 95-95-95 targets.

Protocol: Implementation evaluation of a combination intervention for sustainable blood pressure control in rural KwaZulu-Natal, South Africa (IMPACT BP): A three-arm, unblinded, parallel group individually randomized clinical trial.

BACKGROUND: Hypertension is the primary risk factor for stroke and heart disease, which are leading causes of death in South Africa. Despite the availability of treatments, there is an implementation gap in how best to deliver hypertension care in this resource-limited region. METHODS: We describe a three-arm parallel group individually randomized control trial to evaluate the effectiveness and implementation of a technology-supported, community-based intervention to improve blood pressure control among people with hypertension in rural KwaZulu-Natal. The study will compare three strategies: 1) standard of care (SOC arm) clinic-based management, 2) home-based blood pressure management supported by community blood pressure monitors (CBPM arm) and a mobile health application to record blood pressure readings and enable clinic-based nurses to remotely manage care, and 3) an identical strategy to the CBPM arm, except that participants will use a cellular blood pressure cuff, which automatically transmits completed readings over cellular networks directly to clinic-based nurses (eCBPM+ arm). The primary effectiveness outcome is change in blood pressure from enrollment to 6 months. The secondary effectiveness outcome is the proportion of participants with blood pressure control at 6 months. Acceptability, fidelity, sustainability, and cost-effectiveness of the interventions will also be assessed. CONCLUSIONS: In this protocol, we report the development of interventions in partnership with the South Africa Department of Health, a description of the technology-enhanced interventions, and details of the study design so that our intervention and evaluation can inform similar efforts in rural, resource-limited settings. PROTOCOL: Version 3 November 9th, 2022. CLINICALTRIALS: gov Trial Registration: NCT05492955 SAHPRA Trial Number: N20211201. SANCTR Number: DOH-27-112,022-4895.

Acceptability of decentralizing childhood tuberculosis diagnosis in low-income countries with high tuberculosis incidence: Experiences and perceptions from health care workers in Sub-Saharan Africa and South-East Asia.

Decentralizing childhood tuberculosis services, including diagnosis, is now recommended by the WHO and could contribute to increasing tuberculosis detection in high burden countries. However, implementing microbiological tests and clinical evaluation could be challenging for health care workers (HCWs) in Primary Health Centers (PHCs) and even District Hospitals (DHs). We sought to assess the acceptability of decentralizing a comprehensive childhood tuberculosis diagnosis package from HCWs' perspective. We conducted implementation research nested within the TB-Speed Decentralization study. HCWs from two health districts of Cambodia, Cameroon, Côte d'Ivoire, Mozambique, Sierra Leone, and Uganda implemented systematic screening, nasopharyngeal aspirates (NPA) and stool sample collection with molecular testing, clinical evaluation and chest X-ray (CXR) interpretation. We investigated their experiences and perceptions in delivering the diagnostic package components in 2020-21 using individual semi-structured interviews. We conducted thematic analysis, supported by the Theoretical Framework of Acceptability. HCWs (n = 130, 55% female, median age 36 years, 53% nurses, 72% PHC-based) perceived that systematic screening, although increasing workload, was beneficial as it improved childhood tuberculosis awareness. Most HCWs shared satisfaction and confidence in performing NPA, despite procedure duration, need to involve parents/colleagues and discomfort for children. HCWs shared positive attitudes towards stool sample-collection but were frustrated by delayed stool collection associated with cultural practices, transport and distance challenges. Molecular testing, conducted by nurses or laboratory technicians, was perceived as providing quality results, contributing to diagnosis. Clinical evaluation and diagnosis raised self-efficacy issues and need for continuous training and clinical mentoring. HCWs valued CXR, however complained that technical and logistical problems limited access to digital reports. Referral from PHC to DH was experienced as burdensome. HCWs at DH and PHC-levels perceived and experienced decentralized childhood tuberculosis diagnosis as acceptable. Implementation however could be hampered by feasibility issues, and calls for innovative referral mechanisms for patients, samples and CXR.

Implementing an outpatient clinical trial on COVID-19 treatment in an emergency epidemic context: a mixed methods study among operational and research stakeholders within the Coverage trial, Bordeaux (France).

BACKGROUND: The emergency set-up and implementation of outpatient clinical trials on epidemic emerging infectious diseases such as COVID-19 raise many issues in terms of research structuration, regulations, and health systems organization. We aimed to describe the experience and points of view of different stakeholders involved in a French home-based outpatient trial on COVID-19 and to identify the early barriers and facilitators to the trial implementation. METHODS: We conducted a mixed-methods study in July 2020. A self-administered questionnaire was emailed to 213 clinical, operational and research stakeholders involved in the Coverage trial; individual semi-directed interviews were conducted among 14 stakeholders. Questionnaire data and written interview notes are presented together by key theme. RESULTS: One hundred fifty six stakeholders responded to the questionnaire. 53.4% did not have prior experience in clinical research. The motivation of most stakeholders to participate in the Coverage trial was to feel useful during the pandemic. 87.9% agreed that the trial had an unusual set-up timeframe, and many regretted a certain lack of regulatory flexibility. Mobile medical teams and specific professional skills were perceived as instrumental for outpatient research. CONCLUSIONS: The implementation of a home-based outpatient clinical trial on COVID-19 was perceived as relevant and innovative although requiring important adaptations of usual professional responsibilities and standard research procedures. Lessons learned from the Coverage trial underline the need for improved networks between hospital and community medicine, and call for a dedicated and reactive outpatient research platform on emerging or threatening infectious diseases.

Costs and economies of scale in repeated home-based HIV counselling and testing: Evidence from the ANRS 12249 treatment as prevention trial in South Africa.

Universal HIV testing is now recommended in generalised HIV epidemic settings. Although home-based HIV counselling and testing (HB-HCT) has been shown to be effective in achieving high levels of HIV status awareness, little is still known about the cost implications of universal and repeated HB-HCT. We estimated the costs of repeated HB-HCT and the scale economies that can be obtained when increasing the population coverage of the intervention. We used primary data from the ANRS 12249 Treatment as Prevention (TasP) trial in rural South Africa (2012-2016), whose testing component included six-monthly repeated HB-HCT. We relied on the dynamic system generalised method of moments (GMM) approach to produce unbiased short- and long-run estimates of economies of scale, using the number of contacts made by HIV counsellors for HB-HCT as the scale variable. We also estimated the mediating effect of the contact quality - measured as the proportion of HIV tests performed among all contacts eligible for an HIV test - on scale economies. The mean cost (standard deviation) of universal and repeated HB-HCT was $24.2 (13.7) per contact, $1694.3 (1527.8) per new HIV diagnosis, and $269.2 (279.0) per appropriate referral to HIV care. The GMM estimations revealed the presence of economies of scale, with a 1% increase in the number of contacts for HB-HCT leading to a 0.27% decrease in the mean cost. Our results also suggested a significant long-run relationship between mean cost and scale, with a 1% increase in the scale leading to a 0.36% decrease in mean cost in the long run. Overall, we showed that significant cost savings can be made from increasing population coverage. Nevertheless, there is a risk that this gain is made at the expense of quality: the higher the quality of HB-HCT activities, the lower the economies of scale.

Perceptions of COVID-19 among communities of Conakry (Guinea): a qualitative study exploring the context of the ANRS COV33 Coverage-Africa therapeutic trial.

OBJECTIVES: To explore communities' perceptions about COVID-19 in the context of the ANRS COV33 Coverage-Africa clinical trial evaluating the efficacy of treatments in preventing clinical worsening of COVID-19. DESIGN: Descriptive qualitative study using semistructured in-depth individual interviews conducted by telephone in French and Soussou between May and September 2021. Data were transcribed, translated in French when applicable and analysed with the thematic analysis method. SETTING: The eight neighbourhoods most affected by COVID-19 in Conakry's urban context, capital of Guinea. PARTICIPANTS: 4 community leaders acting as key informants-providing insights regarding population's opinions-and six community members, who were exposed to an information session conducted as part of Coverage-Africa. RESULTS: According to participants, community members have heterogeneous viewpoints about COVID-19: it exists and is dangerous; it is benign ('bad cold'); or it is fictitious (eg, government conspiracy). The fear of stigmatisation and social isolation of those sick or cured of COVID-19 was largely reported by participants, with illustrations of distressing situations for the victims. To avoid stigma, many patients seem to adopt strategies of discretion (eg, lying/hiding about the disease). Although community attitudes were reported to have evolved since the beginning of the epidemic, stigma remained a pervasive concern for many people. CONCLUSIONS: Community perceptions about COVID-19 in Conakry may be partly explained by the Guinean context of Ebola history and of sociopolitical tensions. Stigmatisation of COVID+ people seems to be aimed at protecting others against contamination. However, social avoidance can greatly affect the morale of stigmatised people, especially in collectivist cultures like Guinea. Further investigating stigma, including its role on seeking COVID-19 screening and treatment services, and its consequences on mental health among affected/exposed people, would contribute to identifying improved prevention and care interventions in preparation for future health threats, and to promoting participation in health research. TRIAL REGISTRATION NUMBER: NCT04920838 (Pre-results stage).