Assessment of the impact of a personalised nutrition intervention in impaired glucose regulation over 26 weeks: a randomised controlled trial.

Dietary interventions can reduce progression to type 2 diabetes mellitus (T2DM) in people with non-diabetic hyperglycaemia. In this study we aimed to determine the impact of a DNA-personalised nutrition intervention in people with non-diabetic hyperglycaemia over 26 weeks. ASPIRE-DNA was a pilot study. Participants were randomised into three arms to receive either (i) Control arm: standard care (NICE guidelines) (n = 51), (ii) Intervention arm: DNA-personalised dietary advice (n = 50), or (iii) Exploratory arm: DNA-personalised dietary advice via a self-guided app and wearable device (n = 46). The primary outcome was the difference in fasting plasma glucose (FPG) between the Control and Intervention arms after 6 weeks. 180 people were recruited, of whom 148 people were randomised, mean age of 59 years (SD = 11), 69% of whom were female. There was no significant difference in the FPG change between the Control and Intervention arms at 6 weeks (- 0.13 mmol/L (95% CI [- 0.37, 0.11]), p = 0.29), however, we found that a DNA-personalised dietary intervention led to a significant reduction of FPG at 26 weeks in the Intervention arm when compared to standard care (- 0.019 (SD = 0.008), p = 0.01), as did the Exploratory arm (- 0.021 (SD = 0.008), p = 0.006). HbA1c at 26 weeks was significantly reduced in the Intervention arm when compared to standard care (- 0.038 (SD = 0.018), p = 0.04). There was some evidence suggesting prevention of progression to T2DM across the groups that received a DNA-based intervention (p = 0.06). Personalisation of dietary advice based on DNA did not result in glucose changes within the first 6 weeks but was associated with significant reduction of FPG and HbA1c at 26 weeks when compared to standard care. The DNA-based diet was effective regardless of intervention type, though results should be interpreted with caution due to the low sample size. These findings suggest that DNA-based dietary guidance is an effective intervention compared to standard care, but there is still a minimum timeframe of adherence to the intervention before changes in clinical outcomes become apparent.Trial Registration: www.clinicaltrials.gov.uk Ref: NCT03702465.

Multimorbidity in elderly people living with HIV: how do general practitioners manage? / Polypathologie des personnes âgées vivant avec le VIH : quelle gestion en médecine générale ?

INTRODUCTION: The occurrence of multimorbidity concerns more and more people living with HIV (PLWHIV) and its frequency increases with age. General practitioners should occupy a central place in the out-of-hospital follow-up of elderly PLWHIV with multimorbidities. Our study aims to understand the actual position of general practitioners and the barriers they encounter in the management of elderly PLWHIV with multimorbidities. METHODS: This sub-study of the ANRS EP66-SEPTAVIH sancillary tudy, which assesses frailty in PLWHIV aged 70 years and over, is based on in-depth interviews with general practitioners and PLWHIV aged 70 years and over. The data were processed manually. Themes and sub-themes were identified and tabulated before being subjected to a cross-sectional thematic analysis. RESULTS: Based on 30 interviews conducted between April 2020 and June 2021 with 10 general practitioners and 20 PLWHIV aged 70 years and over and with multiple diseases, this study identifies the difficulties that general practitioners encounter in fully participating in the care. The follow-up of these patients is characterized by symbolic partitions between groups of professionals: organizational fragmentation between general practitioners and specialists, fear of encroaching on the role of the other health professionals, and frequent absence of formalization of roles in the coordination of care. CONCLUSIONS: In order to promote optimal follow-up and improve the experience of elderly PLWHIV, it is important that the role of each stakeholder be better defined for better shared follow-up.

Introduction: La polypathologie est une problématique de santé qui concerne de plus en plus de personnes vivant avec le VIH (PVVIH) et dont la fréquence augmente avec l'âge. Le recul actuel de l'hospitalo-centrisme devrait amener le médecin généraliste à occuper une place centrale dans le suivi extra-hospitalier des PVVIH âgées et polypathologiques. Notre étude cherche à comprendre la place qu'occupent réellement les médecins généralistes et les barrières qu'ils rencontrent dans la prise en charge des PVVIH âgées et polypathologiques. Méthodes: Nous présentons ici les résultats d'une étude ancillaire d'une précédente recherche (ANRS EP66-SEPTAVIH) qui évalue la fragilité chez les PVVIH âgées de 70 ans et plus. Elle repose sur des entretiens approfondis réalisés auprès de médecins généralistes et de PVVIH âgées de 70 ans et plus. Les données ont fait l'objet d'un traitement manuel et les thèmes et sous-thèmes identifiés ont été classés dans un tableau sous forme de grilles d'être soumis à une analyse thématique transversale. Résultats: À partir de 30 entretiens réalisés d'avril 2020 à juin 2021 auprès de 10 médecins généralistes et 20 PVVIH âgées de 70 ans et plus et polypathologiques, cette étude identifie les difficultés que les médecins généralistes rencontrent pour intervenir pleinement dans la prise en charge de ces patients. Leur suivi est caractérisé par des cloisonnements symboliques entre groupes de professionnels : morcellement organisationnel entre médecins généralistes et spécialistes, peur d'empiéter sur le rôle de l'autre professionnel de santé et absence fréquente de formalisation des rôles dans la coordination des soins. Conclusions: Afin de favoriser un suivi optimal et d'améliorer le vécu des PVVIH âgées, il est important que le rôle de chaque intervenant soit mieux défini pour un meilleur suivi partagé.

Intensified tuberculosis treatment to reduce the mortality of HIV-infected and uninfected patients with tuberculosis meningitis (INTENSE-TBM): study protocol for a phase III randomized controlled trial.

BACKGROUND: Tuberculous meningitis (TBM) is the most lethal and disabling form of tuberculosis (TB), particularly in sub-Saharan Africa. Current anti-TB treatment is poorly effective since TBM mortality reaches 40% in HIV-negative patients and up to 70% in HIV-co-infected patients. To reduce TBM-induced morbidity and mortality, the INTENSE-TBM trial evaluates two interventions in both HIV-infected and uninfected patients: an anti-TB treatment intensification using oral high-dose rifampicin (35 mg/kg daily) and linezolid (1200 mg daily and then 600 mg daily) during the first 8 weeks of the anti-TB treatment and the use of adjunctive aspirin (200 mg daily). METHODS: This is a randomized controlled, phase III, multicenter, 2 × 2 factorial plan superiority trial. The trial has four arms, combining the two experimental treatments (intensified TBM regimen and aspirin) with the two reference treatments (WHO standard TB treatment and placebo), and is open-label for anti-TB treatment and double-blind placebo-controlled for aspirin treatment. This trial is conducted in adults or adolescents of age ≥15 years with TBM defined as "definite," "probable," or "possible" using Tuberculosis Meningitis International Research Consortium criteria, in four African countries: Ivory Coast, Madagascar, Uganda, and South Africa. The primary outcome is all-cause death between inclusion and week 40. DISCUSSION: The INTENSE-TBM trial represents a key opportunity to enhance TBM treatment with widely available existing drugs notably in high-incidence settings of both TB and HIV. The trial design is pragmatic and the results will permit early and effective applications in TBM patient care, in both HIV and TB high-incidence countries. TRIAL REGISTRATION: ClinicalTrials.gov NCT04145258. Registered on October 30, 2019.

Implementation of HPV-based screening in Burkina Faso: lessons learned from the PARACAO hybrid-effectiveness study.

BACKGROUND: Cervical cancer screening in sub-Saharan countries relies on primary visual inspection with acetic acid (VIA). Primary human papillomavirus (HPV)-based screening is considered a promising alternative. However, the implementation and real-life effectiveness of this strategy at the primary-care level in limited-resource contexts remain under explored. In Ouagadougou, Burkina Faso, free HPV-based screening was implemented in 2019 in two primary healthcare centers. We carried out a process and effectiveness evaluation of this intervention. METHODS: Effectiveness outcomes and implementation indicators were assessed through a cohort study of screened women, observations in participating centers, individual interviews with women and healthcare providers and monitoring reports. Effectiveness outcomes were screening completeness and women's satisfaction. Logistic regression models and concurrent qualitative analysis explored how implementation variability, acceptability by women and the context affected effectiveness outcomes. RESULTS: After a 3-month implementation period, of the 350 women included in the cohort, 94% completed the screening, although only 26% had their screening completed in a single visit as planned in the protocol. The proportion of highly satisfied women was higher after result disclosure (95%) than after sampling (65%). A good understanding of the screening results and recommendations increased screening completeness and women's satisfaction, while time to result disclosure decreased satisfaction. Adaptations were made to fit healthcare workers' workload. CONCLUSION: Free HPV-based screening was successfully integrated within primary care in Ouagadougou, Burkina Faso, leading to a high level of screening completeness despite the frequent use of multiple visits. Future implementation in primary healthcare centers needs to improve counseling and reduce wait times at the various steps of the screening sequence.

The multidimensional vulnerability of people with disability to HIV infection: Results from the handiSSR study in Bujumbura, Burundi.

BACKGROUND: In resource-limited contexts, available data indicate that people with disability are disproportionally affected by the HIV epidemic. While disability resulting from chronic HIV infection has received some attention, few epidemiologic studies have examined the vulnerability of people with disability to HIV acquisition. The aims of the study were as follows: to estimate and compare HIV prevalence among people with and without disability living in Bujumbura, Burundi; to examine how the interaction among disability, gender and socioeconomic environment shapes vulnerability to HIV; and to identify potential pathways to higher HIV risk. METHODS: In this cross-sectional population-based study, 623 persons with disability (302 with disability onset ≤10 years ["early disability"]) and 609 persons without disability matched for age, sex and location were randomly selected to be tested for HIV and to participate in an interview about their life history, their social environment and their knowledge of sexual health. FINDINGS: A total of 68% of men and 75% of women with disability were affected by multidimensional poverty compared to 54% and 46% of their peers without disability (p<0.0001). Higher HIV prevalence was observed among women with disability (12.1% [8.2-16]) than among those without (3.8% [1.7-6], ORa 3.8, p<0.0001), while it was similar among men with disability and those without (p = 0·8). Women with disability were also at higher risk of sexual violence than were those without (ORa 2.7, p<0.0001). The vulnerability of women with early disability to HIV was higher among those who were socially isolated (HIV prevalence in this group: 19% [12-27]). In addition, education level and sexual violence mediated 53% of the association between early disability and HIV (p = 0.001). INTERPRETATION: This study highlights how the intersection of disability, gender and social environment shapes vulnerability to HIV. It also shows that the vulnerability to HIV of women who grew up with a disability is mediated by sexual violence. FUNDING: This research was funded by the Netherlands Organization for Scientific Research (Grant W08.560.005) and the Initiative HIV-TB-Malaria (new name of the organisation).

Acceptability of HPV screening among HIV-infected women attending an HIV-dedicated clinic in Abidjan, Côte d'Ivoire.

BACKGROUND: Cervical cancer incidence is high among women living with HIV due to high-risk HPV persistence in the cervix. In low-income countries, cervical cancer screening is based on visual inspection with acetic acid. Implementing human papilloma virus (HPV) screening through self-sampling could increase women's participation and screening performance. Our study aims to assess the preintervention acceptability of HPV screening among HIV-infected women in Abidjan, Côte d'Ivoire. METHODS: Applying the Health Belief Model theoretical framework, we collected qualitative data through in-depth interviews with 21 HIV-infected women treated in an HIV-dedicated clinic. Maximum variation sampling was used to achieve a diverse sample of women in terms of level of health literacy. Interviews were recorded and transcribed with the participants' consent. Data analysis was performed using NVivo 12. RESULTS: Screening acceptability relies on cervical cancer representations among women. Barriers were the fear of diagnosis and the associated stigma disregard for HIV-associated health conditions, poor knowledge of screening and insufficient resources for treatment. Fees removal, higher levels of knowledge about cervical cancer and of the role of HIV status in cancer were found to facilitate screening. Healthcare providers are obstacle removers by their trusting relationship with women and help navigating through the healthcare system. Self-confidence in self-sampling is low. CONCLUSIONS: Free access to cervical screening, communication strategies increasing cervical cancer knowledge and healthcare provider involvement will foster HPV screening. Knowledge gathered through this research is crucial for designing adequate HPV-based screening interventions for women living with HIV in this setting.

Disability and Access to Sexual and Reproductive Health Services in Cameroon: A Mediation Analysis of the Role of Socioeconomic Factors.

There is growing evidence showing that people with disabilities face more frequently socioeconomic inequities than their non-disabled peers. This study aims to examine to what extent socioeconomic consequences of disability contribute to poorer access to sexual and reproductive health (SRH) services for Cameroonian with disabilities and how these outcomes vary with disabilities characteristics and gender. It uses data from a population-based survey conducted in 2015 in Yaounde, Cameroon. Mediation analysis was performed to determine how much of the total association between disability and the use, satisfaction and difficulties to access SRH services was mediated by education level, material wellbeing lifetime work participation and availability of social support. Overall, disability was associated with deprivation for all socioeconomic factors assessed though significant variation with the nature and severity of the functional limitations was observed. Lower education level and restricted lifetime work mediated a large part of the association between disability and lower use of HIV testing and of family planning. By contrast, while people with disabilities reported more difficulties to use a SRH service, no mediating was identified. In conclusion, Cameroonians with disabilities since childhood have restricted access to SRH services resulting from socioeconomic factors occurring early during the life-course.

Residual or Recurrent Precancerous Lesions After Treatment of Cervical Lesions in Human Immunodeficiency Virus-infected Women: A Systematic Review and Meta-analysis of Treatment Failure.

BACKGROUND: Screening and treating premalignant cervical lesions (cervical intraepithelial neoplasia 2+ [CIN2+]) is an effective way to prevent cervical cancer, and recommendations exist for the monitoring of treatment success. Yet, there is no specific recommendation for human immunodeficiency virus (HIV)-infected women, who are at a known, increased risk of cervical cancer. METHODS: A systematic review was performed by searching MEDLINE, EMBASE, and Web of Science for studies published from January 1980 through May 2018. Eligible studies described the prevalence of histologically- and/or cytologically-defined lesions in HIV-infected women at least 6 months post-treatment. The primary endpoint was treatment failure, defined as the presence of residual and/or recurrent high-grade CIN2+/high-grade squamous intraepithelial lesions post-treatment. The pooled prevalence in HIV-infected women and the odds ratios (ORs) for HIV-infected compared to HIV-uninfected women were estimated using random-effects models. RESULTS: Among 40 eligible studies, the pooled prevalence of treatment failure in HIV-infected women was 21.4% (95% confidence interval [CI] 15.8-27.0). There was no significant difference in the treatment failure prevalence for cryotherapy (13.9%, 95% CI 6.1-21.6) versus loop electrosurgical excision procedure (13.8%, 95% CI 8.9-18.7; P = .9), but the treatment failure prevalence was significantly higher in women with positive (47.2%, 95% CI 22.0-74.0) than with negative (19.4%, 95% CI 11.8-30.2) excision margin (OR 3.4, 95% CI 1.5-7.7). Treatment failure was significantly increased in HIV-infected versus HIV-uninfected women, both overall (OR 2.7, 95% CI 2.0-3.5) and in all sub-group analyses. CONCLUSIONS: There is strong evidence for an increased risk of treatment failure in HIV-infected women, in comparison to their HIV-negative counterparts. The only significant predictor of treatment failure in HIV-infected women was a positive margin status, but further data is needed on long-term outcomes after ablative treatment in HIV-infected women.

Neurodevelopmental outcomes in HIV-infected and uninfected African children.

OBJECTIVE: HIV infection is associated with cognitive impairments, but outcomes are poorly explored in children starting antiretroviral therapy (ART) early or in those exposed but uninfected. DESIGN: Nested cross-sectional evaluation of the neurocognitive and behavioural outcomes of HIV-infected, HIV-exposed uninfected (HEU) and HIV-unexposed (HUU) Cameroonian children at age 4-9 years prospectively followed. METHODS: Cognitive development was assessed in 127 HIV-infected, 101 HEU, 110 HUU children using the KABC-II, neurologic dysfunction using the Touwen examination and behavioural difficulties using the Strength and Difficulties Questionnaire (SDQ). Analyses were adjusted for children age, sex and primary language. Contextual factors were included in a second step to assess their effects on outcomes. RESULTS: All HIV-infected children were treated before 12 months. There was a negative linear gradient in KABC-II scores from HUU children to HEU and HIV-infected children [gradient: -6.0 (-7.7; -4.3) for nonverbal index, NVI, and -8.8 (-10.7; -6.8) for mental processing index, MPI]. After adjusting for contextual factors, scores of HEU children were not significantly different from those of HUU children (all P > 0.1) and differences between HIV-uninfected and HUU children reduced [NVI: from -11.9 (-15.3; -8.5) to -3.4 (-6.8; -0.01), MPI: from -17.6 (-21.3; -13.8) to -5.5 (-9.3; -1.7)]. Compared with uninfected children, HIV-infected children had more neurological dysfunctions and higher SDQ scores (P = 0.002). CONCLUSION: Despite early ART, perinatal-HIV infection is associated with poorer neurocognitive scores and increased behavioural difficulties during childhood. Contextual factors play an important role in this association, which emphasizes the need for early nutritional and developmental interventions targeting both HIV-affected infants and their relatives.

A review of screening strategies for cervical cancer in human immunodeficiency virus-positive women in sub-Saharan Africa.

Cervical cancer (CC) is a leading cause of cancer-related death and a major public health issue in sub-Saharan Africa. This heavy burden parallels that of the human immunodeficiency virus (HIV) infection, which increases the risk of developing CC. Despite the progressive reduction of HIV prevalence in the past decade, the CC incidence and mortality rates in sub-Saharan Africa remain high. The heterogeneity of the distribution of the two diseases in the African continent, together with the different availability of human and material resources, stands in the way of finding an appropriate screening strategy. The lack of high-quality evidence on the prevention of CC for HIV-positive women, which is necessary for the implementation of efficient screening and treatment strategies, results in the absence of a clearly defined program, which is responsible for the low screening uptake and high mortality rates in sub-Saharan Africa. By taking advantage of the HIV-positive women's frequent access to health facilities, one way to increase the CC screening coverage rates would be by providing integrated HIV and screening services within the same infrastructure. With the increasing availability of cost-effective methods, screening is becoming more and more available to women who have limited access to health care. Moreover, the introduction of point-of-care technologies for human papillomavirus testing and the subsequent implementation of screen-and-treat strategies, by reducing the number of clinical appointments and, in the long term, the loss to follow-up rates, open up new opportunities for all women, regardless of their HIV status. The purpose of this review is to provide an insight into the different screening practices for CC in order to help define one that is adapted to the resources and necessities of HIV-positive women living in middle-to-low income countries.

Detection Yield and Tolerability of String Test for Diagnosis of Childhood Intrathoracic Tuberculosis.

BACKGROUND: Difficulty to obtain sputum in children complicates diagnosis of intrathoracic tuberculosis (TB). The intragastric string test (ST) used for retrieval of enteric pathogens might be an alternative specimen collection method but requires further evaluation of its utility in TB diagnosis. We conducted a cross-sectional study comparing the TB detection yield and the tolerability of ST and sputum induction (SI) in children. METHODS: Two ST and SI procedures were performed in children (3-14 years of age) who were clinically suspected of having TB. The string was removed after a 2-hour gastric downtime, and SI was done after a maximum of 20 minutes nebulization with 5% saline solution. LED-fluorescence microscopy and mycobacterial cultures were performed on all specimens, and XpertMTB/RIF assay was performed on stored specimen sediments. Tolerability questionnaires were administered to parents of children. RESULTS: Of 137 included children (median age: 8.1 years; 33.3% with HIV infection), 14 (10.2%) were diagnosed with TB, 10 (71.4%) by ST and 12 (85.7%) by SI. Among 105 children with both ST and SI performed, 5 (4.8%) versus 4 (3.8%) were smear positive using ST and SI, respectively (McNemar P = 1.00). Nine (8.6%) in each group had positive cultures (P = 1.00). Of 64 children tested with XpertMTB/RIF, 3 (4.7%) of the ST group versus 4 (6.3%) of the SI group were TB positive (P = 1.00). No adverse serious events were reported. ST could not be performed in 22 of 137 (16.1%) children because they were unable to swallow the capsule. CONCLUSIONS: TB detection yield was comparable between ST and SI. The tolerability of ST in young children might be improved by the reduction of the size of the capsule.

The future role of CD4 cell count for monitoring antiretroviral therapy.

For more than two decades, CD4 cell count measurements have been central to understanding HIV disease progression, making important clinical decisions, and monitoring the response to antiretroviral therapy (ART). In well resourced settings, the monitoring of patients on ART has been supported by routine virological monitoring. Viral load monitoring was recommended by WHO in 2013 guidelines as the preferred way to monitor people on ART, and efforts are underway to scale up access in resource-limited settings. Recent studies suggest that in situations where viral load is available and patients are virologically suppressed, long-term CD4 monitoring adds little value and stopping CD4 monitoring will have major cost savings. CD4 cell counts will continue to play an important part in initial decisions around ART initiation and clinical management, particularly for patients presenting late to care, and for treatment monitoring where viral load monitoring is restricted. However, in settings where both CD4 cell counts and viral load testing are routinely available, countries should consider reducing the frequency of CD4 cell counts or not doing routine CD4 monitoring for patients who are stable on ART.

HIV-1 DNA concentrations and evolution among African HIV-1-infected children under antiretroviral treatment (ANRS 1244/1278).

OBJECTIVES: The objectives of this study were to describe the pretreatment HIV-1 DNA concentrations in children infected with HIV and to evaluate the impact of antiretroviral therapy (ART) on HIV-DNA concentrations. METHODS: This was a retrospective analysis of all children followed up in the 'Programme Enfant Yopougon' cohort, Abidjan, Côte d'Ivoire, from 2000 to 2004, who had cryopreserved peripheral blood mononuclear cells (PBMCs) and plasma samples. HIV-DNA was measured using a real-time PCR assay. Mixed-model analysis was used to analyse the factors associated with change in HIV-DNA concentration. RESULTS: The study included 121 children infected with HIV-1. The median age at inclusion was 6 years (IQR: 3.5-9) and children were at an advanced stage of HIV disease (46.6% and 20.3% presenting CDC stage B and CDC stage C, respectively). At baseline, the median HIV-DNA concentration was 3.4 log10 copies/10(6) PBMCs (IQR: 3.1-3.6). Fifty-four children were initiated on ART during follow-up. After 24 months of ART, HIV-DNA load decreased by 0.32 (IQR: 0.08-0.57) log10 copies/10(6) PBMCs. The only factor associated with the HIV-DNA decrease was a concomitant low HIV-RNA viral load result. Children with efficient ART had a 0.51 log10 copies (IQR: 0.40-0.86) HIV-DNA decrease per million PBMCs. CONCLUSIONS: HIV-DNA concentrations decreased following ART initiation in a large African paediatric cohort. This decline was exclusively associated with the decrease in ongoing replication level achieved. Our study points out that a strong adherence is needed for ART to be efficient on the viral reservoirs, and further reinforces that adherence support is also essential to diminish the reservoir.