Mitigating Infectious morbidity and Growth deficits in HIV-exposed uninfected infanTs with human Milk Oligosaccharide (MIGH-T MO): a randomised trial protocol

Introduction
Children who are HIV-exposed uninfected (HEU), that is, children who do not acquire HIV infection despite being born to mothers with HIV, have a higher risk of mortality, infectious morbidity and growth deficits than children who are HIV-unexposed uninfected (HUU). Prior research has focused on breast feeding and has pointed to changes in human milk oligosaccharides (HMOs) associated with maternal HIV that may influence the infant microbiome and thereby lead to these adverse outcomes. However, to our knowledge, no study has attempted to intervene along this pathway to reduce the occurrence of the adverse outcomes in children HEU. We will conduct a double-blind, randomised trial of a synbiotic intervention, which combines an HMO and probiotic, in breastfed infants HEU in South Africa to evaluate whether this intervention has promise to reduce excess infectious morbidity and growth faltering compared with controls.

Methods and analysis
One hundred and forty-four breastfed infants HEU, aged 4 weeks, will be 1:1 randomised to receive either a daily synbiotic or an identical-looking placebo through age 24 weeks. Infants will be followed until age 48 weeks and outcomes of infectious morbidity, growth and biological measurements (eg, microbiota, inflammation and metabolome) will be assessed. Analyses will follow intention-to-treat principles comparing the cohorts as randomised. Infants HEU will be compared across arms with respect to the occurrence of infectious morbidity and growth outcomes through 4–24 weeks and 4–48 weeks using appropriate parametric and non-parametric statistical tests. Additionally, an observational cohort of 40 breastfed infants HUU will be recruited as a comparator group with no intervention.

Ethics and dissemination
Ethical approval for this study has been obtained from the ethics committees at Columbia University and Stellenbosch University. The findings will be disseminated in publications.

Trial registration number
ClinicalTrials.gov Identifier: NCT05282485. SANCTR ID number: DOH-27-122021-6543.

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Dicembre 2022

Cardiovascular Disease Among Persons Living With HIV: New Insights Into Pathogenesis and Clinical Manifestations in a Global Context

Circulation, Volume 147, Issue 1, Page 83-100, January 3, 2023. Widespread use of contemporary antiretroviral therapy globally has transformed HIV disease into a chronic illness associated with excess risk for disorders of the heart and circulatory system. Current clinical care and research has focused on improving HIV-related cardiovascular disease outcomes, survival, and quality of life. In high-income countries, emphasis on prevention of atherosclerotic coronary artery disease over the past decade, including aggressive management of traditional risk factors and earlier initiation of antiretroviral therapy, has reduced risk for myocardial infarction among persons living with human immunodeficiency virus-1 infection. Still, across the globe, persons living with human immunodeficiency virus-1 infection on effective antiretroviral therapy treatment remain at increased risk for ischemic outcomes such as myocardial infarction and stroke relative to the persons without HIV. Unique features of HIV-related cardiovascular disease, in part, include the pathogenesis of coronary disease characterized by remodeling ectasia and unusual plaque morphology, the relative high proportion of type 2 myocardial infarction events, abnormalities of the aorta such as aneurysms and diffuse aortic inflammation, and HIV cerebrovasculopathy as a contributor to stroke risk. Literature over the past decade has also reflected a shift in the profile and prevalence of HIV-associated heart failure, with a reduced but persistent risk of heart failure with reduced ejection fraction and a growing risk of heart failure with preserved ejection fraction. Cardiac magnetic resonance imaging and autopsy data have emphasized the central importance of intramyocardial fibrosis for the pathogenesis of both heart failure with preserved ejection fraction and the increase in risk of sudden cardiac death. Still, more research is needed to better characterize the underlying mechanisms and clinical phenotype of HIV-associated myocardial disease in the current era. Across the different cardiovascular disease manifestations, a common pathogenic feature is that HIV-associated inflammation working through different mechanisms may amplify underlying pathology because of traditional risk and other host factors. The prevalence and phenotype of individual cardiovascular disease manifestations is ultimately influenced by the degree of injury from HIV disease combined with the profile of underlying cardiometabolic factors, both of which may differ substantially by region globally.

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Dicembre 2022

Safety and efficacy of long-acting intramuscular cabotegravir and rilpivirine in adults with HIV-1 infection: a systematic review and meta-analysis protocol

Background
Current antiretroviral regimens have, for the most part, achieved optimal antiretroviral efficacy and tolerability, transforming HIV infection from a deadly disease into a manageable chronic condition. However, adherence to daily oral drug intake remains an issue, as it is the most important determinant for sustained viral suppression and prevention of the emergence of drug-resistant viral strains. The long-acting injection antiretroviral cabotegravir and rilpivirine combination, a novel drug delivery approach, is about to revolutionise the therapy for people living with HIV. In this protocol, we aim to generate a clinically useful summary of the interventions based on their efficacy.

Methods and analysis
We searched the literature for eligible studies published from inception up to 16 August 2022 through PubMed, EMBASE, Cochrane Library, Scopus and ClinicalTrials.gov. Two methodologically trained researchers will select the qualified studies for data extraction independently. Cochrane Risk of Bias tool will be used to assess the risk of bias in included studies. Statistical heterogeneity will be computed by Cochrane X2 and I2 tests. Sensitivity analysis will be conducted to evaluate the stability of the results. Publication biases will be evaluated by Begg’s and Egger’s tests. The quality of evidence will be assessed by the Grading of Recommendations Assessment, Development and Evaluation system. The RevMan V.5.3 and Stata V.14.0 software will be applied for statistical analyses.

Ethics and dissemination
Ethical approval will not be required for this systematic review because the data used are not linked to the individual patient. The results of this review will be disseminated by being published in a peer-reviewed journal.

PROSPERO registration number
CRD42022310414

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Dicembre 2022

Study protocol: A randomised trial of the effectiveness of the Common Elements Treatment Approach (CETA) for improving HIV treatment outcomes among women experiencing intimate partner violence in South Africa

Introduction
Intimate partner violence (IPV) is a barrier to consistent HIV treatment in South Africa. Previous trials have established that the Common Elements Treatment Approach (CETA), a cognitive-behavioural-based intervention, is effective in reducing mental and behavioural health problems but has not been trialled for effectiveness in improving HIV outcomes. This paper describes the protocol for a randomised trial that is testing the effectiveness of CETA in improving HIV treatment outcomes among women experiencing IPV in South Africa.

Methods and analysis
We are conducting a randomised trial among HIV-infected women on antiretroviral therapy, who have experienced sexual and/or physical IPV, to test the effect of CETA on increasing retention and viral suppression and reducing IPV. Women living with HIV who have an unsuppressed viral load or are at high risk for poor adherence and report experiencing recent IPV, defined as at least once within in the last 12 months, will be recruited from HIV clinics and randomised 1:1 to receive CETA or an active attention control (text message reminders). All participants will be followed for 24 months. Follow-up HIV data will be collected passively using routinely collected medical records. HIV outcomes will be assessed at 12 and 24 months post-baseline. Questionnaires on violence, substance use and mental health will be administered at baseline, post-CETA completion and at 12 months post-baseline. Our primary outcome is retention and viral suppression (

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Dicembre 2022

Characteristics of HIV pre-exposure prophylaxis users at first PrEP counselling visit: the CSL-PrEP cohort

Objectives
Pre-exposure prophylaxis (PrEP) is effective for HIV prevention and is mostly used by men who have sex with men (MSM). The aim of this study was to describe the characteristics of a cohort of PrEP users at first PrEP counselling visits (baseline, BL).

Design
Cross-sectional study of a cohort of MSM receiving PrEP (Centro San Luigi, CSL-PrEP Cohort).

Setting
Secondary-level sexually transmitted infections (STI) centre in Milan, Italy, from May 2017 to May 2022.

Participants
Overall, 624 MSM PrEP users were included; most users were Caucasian (97%), attended university (64%), with a median BL age of 34.5 years.

Results
Overall, 45% choose the daily-based PrEP regimen, 55% the event-based one. An increasing trend in PrEP counselling visits was observed (p=0.024). The majority had between 10 and 19 partners in the 3 months before BL and 41% were chemsex users. All had a HIV Incidence Risk Index for MSM (HIRI-MSM) >10, 54% between 20 and 29. Overall, 50% had ≥1 previous STI and 22% ≥1 BL STI. BL chlamydia (10%) was often more frequent than in the past (7%). The number of sexual partners was associated with BL chlamydia (p

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Dicembre 2022

Consent Laws for Minors Regarding Sexually Transmitted Infection and HIV Services—Reply

In Reply State laws that enable minors to consent independently to health care have important limitations, including those raised by Mr Kels. Minor consent regimes are complex and often require simultaneous application of multiple statutes, which makes the laws difficult to interpret and trust. Although these laws address the barrier of guardian consent for minors who are unable or unwilling to involve their guardian, they fail to address other hurdles that may reduce minors’ access to care. To seek care independently, minors depend on clinicians to decide that they have both the mental and legal capacity to make medical decisions without their guardians’ permission. Often, the laws also require clinicians to make a threshold judgment about whether the type of care qualifies for minors’ independent consent (eg, awaiting guardian permission would pose a threat to health). These determinations may be challenging for clinicians who are uncertain about the content of the laws or who fear that the laws will not protect them in the event of lawsuits. As Kels emphasizes, most consent laws also give clinicians separate discretion in whether to keep minors’ health information confidential from their guardians. Minors do not control these decisions; they depend on clinicians to act for their benefit.

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Dicembre 2022