Evaluation of the impact of immediate versus WHO recommendations-guided antiretroviral therapy initiation on HIV incidence: the ANRS 12249 TasP (Treatment as Prevention) trial in Hlabisa sub-district, KwaZulu-Natal, South Africa: study protocol for a cluster randomised controlled trial

Background: Antiretroviral therapy (ART) suppresses HIV viral load in all body compartments and so limits the risk of HIV transmission. It has been suggested that ART not only contributes to preventing transmission at individual but potentially also at population level. This trial aims to evaluate the effect of ART initiated immediately after identification/diagnosis of HIV-infected individuals, regardless of CD4 count, on HIV incidence in the surrounding population. The primary outcome of the overall trial will be HIV incidence over two years. Secondary outcomes will include i) socio-behavioural outcomes (acceptability of repeat HIV counselling and testing, treatment acceptance and linkage to care, sexual partnerships and quality of life); ii) clinical outcomes (mortality and morbidity, retention into care, adherence to ART, virologic failure and acquired HIV drug resistance), iii) cost-effectiveness of the intervention. The first phase will specifically focus on the trial's secondary outcomes.Methods/design: A cluster-randomised trial in 34 (2 × 17) clusters within a rural area of northern KwaZulu-Natal (South Africa), covering a total population of 34,000 inhabitants aged 16 years and above, of whom an estimated 27,200 would be HIV-uninfected at start of the trial. The first phase of the trial will include ten (2 × 5) clusters. Consecutive rounds of home-based HIV testing will be carried out. HIV-infected participants will be followed in dedicated trial clinics: in intervention clusters, they will be offered immediate ART initiation regardless of CD4 count and clinical stage; in control clusters they will be offered ART according to national treatment eligibility guidelines (CD4 <350 cells/μL, World Health Organisation stage 3 or 4 disease or multidrug-resistant/extensively drug-resistant tuberculosis). Following proof of acceptability and feasibility from the first phase, the trial will be rolled out to further clusters.Discussion: We aim to provide proof-of-principle evidence regarding the effectiveness of Treatment-as-Prevention in reducing HIV incidence at the population level. Data collected from the participants at home and in the clinics will inform understanding of socio-behavioural, economic and clinical impacts of the intervention as well as feasibility and generalizability. © 2013 Iwuji et al.; licensee BioMed Central Ltd

HIV ascertainment through repeat home-based testing in the context of a treatment as prevention trial (ANRS 12249 TasP) in rural South Africa

International audienceBackgroundThe ANRS 12249 TasP cluster-randomised trial evaluates whether HIV testing of all members of a community, followed by immediate antiretroviral treatment (ART) for infected people, will prevent onward sexual transmission and reduce HIV incidence at population level. Ascertaining the HIV status of a high proportion of the population regularly and repeatedly is key to the success of any universal test and treat strategy, as the first step of the HIV cascade.MethodsBetween March 2012 and March 2014, we implemented three six-monthly rounds of home-based HIV counselling and testing in ten local communities (clusters). At each home visit, individual questionnaires were administered and a rapid HIV test offered to all trial participants. We report early results on rates of HIV ascertainment, defined as undergoing a rapid HIV test or HIV-positive self-report.ResultsOf 12,911 eligible individuals (resident in the trial area and ≥16 years), 10,007 were successfully contacted at least once. At first contact, HIV status was ascertained for 7,628 (76.2% [95% CI: 75.4-77.1]) individuals. At second contact, among the 5,885 individuals contacted a second time, HIV status was ascertained for 2,829 (85.0% [95% CI: 83.7-86.2]) of the 3,328 tested negative at first contact and for 543 (45.7% [95% CI: 42.9-48.6]) of the 1,188 who refused a rapid test at first contact. Overall, HIV ascertainment rate was 89.0% (5,239/5,885 [95% CI: 88.2-89.8]) among trial participants contacted twice.ConclusionsRepeat home-based HIV testing is acceptable and feasible in this rural area. Socio-demographic characteristics, behaviours, attitudes, household characteristics and experience of HIV infection and ART in the household will be explored for their association with HIV ascertainment uptake. This will inform whether this intervention reaches the individuals at higher risk in a rural South African region

Temporal trends of population viral suppression in the context of Universal Test and Treat: the ANRS 12249 TasP trial in rural South Africa

Introduction The universal test‐and‐treat (UTT) strategy aims to maximize population viral suppression (PVS), that is, the proportion of all people living with HIV (PLHIV) on antiretroviral treatment (ART) and virally suppressed, with the goal of reducing HIV transmission at the population level. This article explores the extent to which temporal changes in PVS explain the observed lack of association between universal treatment and cumulative HIV incidence seen in the ANRS 12249 TasP trial conducted in rural South Africa. Methods The TasP cluster‐randomized trial (2012 to 2016) implemented six‐monthly repeat home‐based HIV counselling and testing (RHBCT) and referral of PLHIV to local HIV clinics in 2 × 11 clusters opened sequentially. ART was initiated according to national guidelines in control clusters and regardless of CD4 count in intervention clusters. We measured residency status, HIV status, and HIV care status for each participant on a daily basis. PVS was computed per cluster among all resident PLHIV (≥16, including those not in care) at cluster opening and daily thereafter. We used a mixed linear model to explore time patterns in PVS, adjusting for sociodemographic changes at the cluster level. Results 8563 PLHIV were followed. During the course of the trial, PVS increased significantly in both arms (23.5% to 46.2% in intervention, +22.8, p < 0.001; 26.0% to 44.6% in control, +18.6, p < 0.001). That increase was similar in both arms (p = 0.514). In the final adjusted model, PVS increase was most associated with increased RHBCT and the implementation of local trial clinics (measured by time since cluster opening). Contextual changes (measured by calendar time) also contributed slightly. The effect of universal ART (trial arm) was positive but limited. Conclusions PVS was improved significantly but similarly in both trial arms, explaining partly the null effect observed in terms of cumulative HIV incidence between arms. The PVS gains due to changes in ART‐initiation guidelines alone are relatively small compared to gains obtained by strategies to maximize testing and linkage to care. The achievement of the 90‐90‐90 targets will not be met if the operational and implementational challenges limiting access to care and treatment, often context‐specific, are not properly addressed. Clinical trial number: NCT01509508 (clinicalTrials.gov)/DOH‐27‐0512‐3974 (South African National Clinical Trials Register)

Linkage to primary care after home-based blood pressure screening in rural KwaZulu-Natal, South Africa: a population-based cohort study

Objectives: The expanding burden of non-communicable diseases (NCDs) globally will require novel public health strategies. Community-based screening has been promoted to augment efficiency of diagnostic services, but few data are available on the downstream impact of such programmes. We sought to assess the impact of a home-based blood pressure screening programme on linkage to hypertension care in rural South Africa.  Setting: We conducted home-based blood pressure screening withinin a population cohort in rural KwaZulu-Natal, using the WHO Stepwise Approach to Surveillance (STEPS) protocol.  Participants: Individuals meeting criteria for raised blood pressure (≥140 systolic or ≥90 diastolic averaged over two readings) were referred to local health clinics and included in this analysis. We defined linkage to care based on self-report of presentation to clinic for hypertension during the next 2 years of cohort observation. We estimated the population proportion of successful linkage to care with inverse probability sampling weights, and fit multivariable logistic regression models to identify predictors of linkage following a positive hypertension screen.  Results: Of 11 694 individuals screened, 14.6% (n=1706) were newly diagnosed with elevated pressure. 26.9% (95% CI 24.5% to 29.4%) of those sought hypertension care in the following 2 years, and 38.1% (95% CI 35.6% to 40.7%) did so within 5 years. Women (adjusted OR (aOR) 2.41, 95% CI 1.68 to 3.45), those of older age (aOR 11.49, 95% CI 5.87 to 22.46, for 45–59 years vs <30) and those unemployed (aOR 1.71, 95% CI 1.10 to 2.65) were more likely to have linked to care.  Conclusions: Linkage to care after home-based identification of elevated blood pressure was rare in rural South Africa, particularly among younger individuals, men and the employed. Improved understanding of barriers and facilitators to NCD care is needed to enhance the effectiveness of blood pressure screening in the region

PLoS One

Introduction Patient-centered care (PCC) is an approach to involve patients in health care delivery, to contribute to quality of care, and to strengthen health systems responsiveness. This article aims to highlight patient perspectives by showcasing their perceptions of their experience of PCC at primary health facilities in two districts in Uganda. Methods A mixed methods cross-sectional study was conducted in three public and two private primary health care facilities in rural eastern Uganda. In total, 300 patient exit survey questionnaires, 31 semi-structured Interviews (SSIs), 5 Focus Group Discussions (FGDs) and 5 feedback meetings were conducted. Data analysis was guided by a conceptual framework focusing on (1) understanding patients’ health needs, preferences and expectations, (2) describing patients perceptions of their care experience according to five distinct PCC dimensions, and (3) reporting patient reported outcomes and their recommendations on how to improve quality of care. Results Patient expectations were shaped by their access to the facility, costs incurred and perceived quality of care. Patients using public facilities reported doing so because of their proximity (78.3% in public PHCs versus 23.3% in private PHCs) and because of the free services availed. On the other hand, patients attending private facilities did so because of their perception of better quality of care (84.2% in private PHCs versus 21.7% in public PHCs). Patients expectations of quality care were expressed as the availability of medication, shorter waiting times, flexible facility opening hours and courteous health workers. Analysis of the 300 responses from patients interviewed on their perception of the care they received, pointed to higher normalized scores for two out of the five PCC dimensions considered: namely, exploration of the patient’s health and illness experience, and the quality of the relationship between patient and health worker (range 62.1–78.4 out of 100). The qualitative analysis indicated that patients felt that communication with health workers was enhanced where there was trust and in case of positive past experiences. Patients however felt uncomfortable discussing psychological or family matters with health workers and found it difficult to make decisions when they did not fully understand the care provided. In terms of outcomes, our findings suggest that patient enablement was more sensitive than patient satisfaction in measuring the effect of interpersonal patient experience on patient reported outcomes. Discussion and conclusion Our findings show that Ugandan patients have some understanding of PCC related concepts and express a demand for it. The results offer a starting point for small scale PCC interventions. However, we need to be cognizant of the challenges PCC implementation faces in resource constrained settings. Patients’ expectations in terms of quality health care are still largely driven by biomedical and technical aspects. In addition, patients are largely unaware of their right to participate in the evaluation of health care. To mitigate these challenges, targeted health education focusing on patients’ responsibilities and patient’s rights are essential. Last but not least, all stakeholders must be involved in developing and validating methods to measure PCC

Novel roles for well-known players: from tobacco mosaic virus pests to enzymatically active assemblies

The rod-shaped nanoparticles of the widespread plant pathogen tobacco mosaic virus (TMV) have been a matter of intense debates and cutting-edge research for more than a hundred years. During the late 19th century, their behavior in filtration tests applied to the agent causing the \u27plant mosaic disease\u27 eventually led to the discrimination of viruses from bacteria. Thereafter, they promoted the development of biophysical cornerstone techniques such as electron microscopy and ultracentrifugation. Since the 1950s, the robust, helically arranged nucleoprotein complexes consisting of a single RNA and more than 2100 identical coat protein subunits have enabled molecular studies which have pioneered the understanding of viral replication and self-assembly, and elucidated major aspects of virus–host interplay, which can lead to agronomically relevant diseases. However, during the last decades, TMV has acquired a new reputation as a well-defined high-yield nanotemplate with multivalent protein surfaces, allowing for an ordered high-density presentation of multiple active molecules or synthetic compounds. Amino acid side chains exposed on the viral coat may be tailored genetically or biochemically to meet the demands for selective conjugation reactions, or to directly engineer novel functionality on TMV-derived nanosticks. The natural TMV size (length: 300 nm) in combination with functional ligands such as peptides, enzymes, dyes, drugs or inorganic materials is advantageous for applications ranging from biomedical imaging and therapy approaches over surface enlargement of battery electrodes to the immobilization of enzymes. TMV building blocks are also amenable to external control of in vitro assembly and re-organization into technically expedient new shapes or arrays, which bears a unique potential for the development of \u27smart\u27 functional 3D structures. Among those, materials designed for enzyme-based biodetection layouts, which are routinely applied, e.g., for monitoring blood sugar concentrations, might profit particularly from the presence of TMV rods: Their surfaces were recently shown to stabilize enzymatic activities upon repeated consecutive uses and over several weeks. This review gives the reader a ride through strikingly diverse achievements obtained with TMV-based particles, compares them to the progress with related viruses, and focuses on latest results revealing special advantages for enzyme-based biosensing formats, which might be of high interest for diagnostics employing \u27systems-on-a-chip\u27