Trends in mortality in people with HIV from 1999 to 2020: a multi-cohort collaboration.

BACKGROUND: Mortality among people with HIV declined with the introduction of combination antiretroviral therapy. We investigated trends over time in all-cause and cause-specific mortality in people with HIV from 1999-2020. METHODS: Data were collected from the D:A:D cohort from 1999 through January 2015 and RESPOND from October 2017 through 2020. Age-standardized all-cause and cause-specific mortality rates, classified using Coding Causes of Death in HIV (CoDe), were calculated. Poisson regression models were used to assess mortality trends over time. RESULTS: Among 55716 participants followed for a median of 6 years (IQR 3-11), 5263 participants died (crude mortality rate [MR] 13.7/1000 PYFU; 95%CI 13.4-14.1). Changing patterns of mortality were observed with AIDS as the most common cause of death between 1999- 2009 (n = 952, MR 4.2/1000 PYFU; 95%CI 4.0-4.5) and non-AIDS defining malignancy (NADM) from 2010 -2020 (n = 444, MR 2.8/1000 PYFU; 95%CI 2.5-3.1). In multivariable analysis, all-cause mortality declined over time (adjusted mortality rate ratio [aMRR] 0.97 per year; 95%CI 0.96, 0.98), mostly from 1999 through 2010 (aMRR 0.96 per year; 95%CI 0.95-0.97), and with no decline shown from 2011 through 2020 (aMRR 1·00 per year; 95%CI 0·96-1·05). Mortality due all known causes except NADM also declined over the entire follow-up period. CONCLUSION: Mortality among people with HIV in the D:A:D and/or RESPOND cohorts decreased between 1999 and 2009 and was stable over the period from 2010 through 2020. The decline in mortality rates was not fully explained by improvements in immunologic-virologic status or other risk factors.

Epigenetic aging in older people living with HIV in Eswatini: a pilot study of HIV and lifestyle factors and epigenetic aging.

BACKGROUND: People living with HIV (PLHIV) on effective antiretroviral therapy are living near-normal lives. Although they are less susceptible to AIDS-related complications, they remain highly vulnerable to non-communicable diseases. In this exploratory study of older PLHIV (OPLHIV) in Eswatini, we investigated whether epigenetic aging (i.e., the residual between regressing epigenetic age on chronological age) was associated with HIV-related parameters, and whether lifestyle factors modified these relationships. We calculated epigenetic aging focusing on the Horvath, Hannum, PhenoAge and GrimAge epigenetic clocks, and a pace of biological aging biomarker (DunedinPACE) among 44 OPLHIV in Eswatini. RESULTS: Age at HIV diagnosis was associated with Hannum epigenetic age acceleration (EAA) (ß-coefficient [95% Confidence Interval]; 0.53 [0.05, 1.00], p = 0.03) and longer duration since HIV diagnosis was associated with slower Hannum EAA (- 0.53 [- 1.00, - 0.05], p = 0.03). The average daily dietary intake of fruits and vegetables was associated with DunedinPACE (0.12 [0.03, 0.22], p = 0.01). The associations of Hannum EAA with the age at HIV diagnosis and duration of time since HIV diagnosis were attenuated when the average daily intake of fruits and vegetables or physical activity were included in our models. Diet and self-perceived quality of life measures modified the relationship between CD4+ T cell counts at participant enrollment and Hannum EAA. CONCLUSIONS: Epigenetic age is more advanced in OPLHIV in Eswatini in those diagnosed with HIV at an older age and slowed in those who have lived for a longer time with diagnosed HIV. Lifestyle and quality of life factors may differentially affect epigenetic aging in OPLHIV. To our knowledge, this is the first study to assess epigenetic aging in OPLHIV in Eswatini and one of the few in sub-Saharan Africa.

Global fight against HIV is at risk.

Will the United States remain committed to a landmark health program it started 20 years ago that saved more than 25 million lives around the world? For a younger generation of physicians, nurses, and researchers today, the depth of despair wrought by the HIV/AIDS epidemic at that time is almost unimaginable. Even more profoundly, for countries in Africa, the epidemic presented an existential threat. Without access to antiretroviral therapy or efficacious prevention tools, new infections continued unfettered, and people with HIV/ AIDS faced near-certain death. Yet, somehow out of this anguish came a ray of hope. In 2003, President George W. Bush announced the launch of the President's Emergency Plan for AIDS Relief (PEPFAR), committing billions of dollars to fight the epidemic in the poorest countries around the world. The initiative has been a shining example of global collaboration in the face of adversity. Yet, as of this September, the US Congress has yet to reauthorize PEPFAR. The Biden administration, individuals from both sides of the political divide, and former President Bush himself have urged Congress to support PEPFAR's lifesaving work. The scientific and public health communities must do the same before it is too late.

Epigenetic aging in older people living with HIV in Eswatini: a pilot study of HIV and lifestyle factors and epigenetic aging.

Background: People living with HIV (PLHIV) on effective antiretroviral therapy (ART) are living near-normal lives. Although they are less susceptible to AIDS-related complications, they remain highly vulnerable to non-communicable diseases (NCD). In this exploratory study of older PLHIV (OPLHIV) in Eswatini, we investigated whether biological aging (i.e., the difference between epigenetic age and chronological age, termed 'epigenetic age acceleration [EAA]') was associated with HIV-related parameters, and whether lifestyle factors modified these relationships. We calculated EAA focusing on the second-generation epigenetic clocks, PhenoAge and GrimAge, and a pace of aging biomarker (DunedinPACE) among 44 OPLHIV in Eswatini. Results: Among participants, the PhenoAge clock showed older epigenetic age (68 years old [63, 77]) but a younger GrimAge epigenetic age (median=56 years old [interquartile range=50, 61]) compared to the chronological age (59 years old [54, 66]). Participants diagnosed with HIV at an older age showed slower DunedinPACE (ß-coefficient [95% Confidence Interval]; -0.02 [-0.04, -0.01], p=0.002) and longer duration since HIV diagnosis was associated with faster DunedinPACE (0.02 [0.01, 0.04], p=0.002). The average daily dietary intake of fruits and vegetables was associated with faster DunedinPACE (0.12 [0.03, 0.22], p=0.01) and modified the relationship between HIV status variables (number of years living with HIV since diagnosis, age at HIV diagnosis, CD4+ T cell counts) and PhenoAge EAA, and DunedinPACE. Conclusions: Biological age is accelerated in OPLHIV in Eswatini, with those living with HIV for a longer duration at risk for faster biological aging. Lifestyle factors, especially healthier diets, may attenuate biological aging in OPLHIV. To our knowledge, this is the first study to assess biological aging in Eswatini and one of the few in sub-Saharan Africa.

Ending AIDS deaths requires improvements in clinical care for people with advanced HIV disease who are seriously ill.

Over 4 million adults are living with advanced HIV disease with approximately 650 000 fatalities from HIV reported in 2021. People with advanced HIV disease have low immunity and can present to health services in two ways: those who are well but at high risk of developing severe disease, and those who are severely ill. These two groups require specific management approaches that place different demands on the health system. The first group can generally be supported in primary care settings but require differentiated care to meet their needs. The second group are at high risk of death and need focused diagnostics and clinical care, and possibly hospitalisation. Investments in high-quality clinical management of patients with advanced HIV disease who are seriously ill at primary care or hospital level (often only for a brief period of time during their acute illness) improves the likelihood that their condition will stabilise and that they will recover. Providing high-quality and safe clinical care that is accessible to these groups of people living with HIV who are at risk of severe illness and death is a key priority for reaching the global target of zero AIDS deaths.

Comparison of Current Attitudes Toward COVID-19 Vaccination in New York City and the US Nationally.

COVID-19 vaccination has resulted in decreased hospitalization and mortality, particularly among those who have received a booster. As new effective pharmaceutical treatments are now available and requirements for non-pharmaceutical interventions (e.g. masking) are relaxed, perceptions of the risk and health consequences of SARS-CoV-2 infection have decreased, risking potential resurgence. This June 2022 cross-sectional comparative study of representative samples in New York City (NYC, n = 2500) and the United States (US, n = 1000) aimed to assess differences in reported vaccine acceptance as well as attitudes toward vaccination mandates and new COVID-19 information and treatments. NYC respondents reported higher COVID-19 vaccine acceptance and support for vaccine mandate than U.S. respondents, yet lower acceptance for the booster dose. Nearly one-third of both NYC and U.S. respondents reported paying less attention to COVID-19 vaccine information than a year earlier, suggesting health communicators may need innovation and creativity to reach those with waning attention to COVID-19-related information.

Social media use and COVID-19 vaccine status among a nationally representative population sample in Uganda.

Objectives: The effect of social media on COVID-19 vaccination behavior is sub-Saharan Africa is unclear. We conducted a study to determine social media use among a random nationally representative sample of adults in Uganda and assessed the association between recent social media use and COVID-19 vaccination uptake. Methods: We used data from the 2020 general population survey in Uganda, the Population-based HIV Impact Assessment Survey, to identify a probability sample for a mobile phone survey and included nonphone owners in the phone survey by asking phone owners to pass the phone. Results: In March 2022, of the 1022 survey participants, 213 (20%) did not own a mobile phone, 842 (80%) owned a mobile phone, of whom 199 (24%) indicated social media use, and 643 (76%) of whom did not use social media. Among all participants, the most frequent source of COVID-19 vaccine information was radio. Overall, 62% reported receiving the COVID-19 vaccination. The multivariable logistic regression model found that social media use was not associated with vaccination status. Conclusion: Social media users in this population sample from Uganda-who were mainly young, urban residents with higher educational attainment-continue to utilize TV, radio and health care workers for public health messages, thus the Government of Uganda should continue to conduct public health communication through these mediums.

Implications from COVID-19 for future pandemic global health governance.

BACKGROUND: Limitations of current global health governance revealed during the COVID-19 pandemic can inform the ongoing deliberations of an international treaty on pandemics. OBJECTIVES: To report on WHO definitions for governance and the enforcement of treaties in the context of a proposed international treaty on pandemics. SOURCES: This narrative review was based on keyword searches related to public health, global health governance, and enforcement in PubMed/Medline and Google Scholar. Snowballing for additional articles followed the keyword search review. CONTENT: WHO lacks a consistent definition of global health governance. Moreover, in its current state, the proposed international treaty on pandemics lacks articulated compliance, accountability, or enforcement mechanisms. Findings reveal that humanitarian treaties often fail to achieve their aims absent clear enforcement mechanisms. The proposed international treaty on public health is garnering a range of perspectives. Decision-makers should evaluate whether a globally aligned definition of global health governance is needed. Decision-makers should also consider whether the proposed international treaty on pandemics should be opposed if it lacks sufficiently clear compliance, accountability, and enforcement mechanisms. IMPLICATIONS: To our knowledge, this narrative review is believed to be the first of its kind to search scientific-oriented databases regarding governance and international pandemic treaties. The review includes several findings that advance the literature. These findings, in turn, reveal two key implications for decision-makers. First, whether an aligned definition for governance addressing compliance, accountability, and enforcement mechanisms is needed. Second, whether a draft treaty lacking enforcement mechanisms should be approved.

Cancer genetic mutation prevalence in sub-Saharan Africa: A review of existing data.

BACKGROUND: Cancer represents a leading cause of death worldwide. Germline mutations in several genes increase the risk of developing several cancers, including cancers of the breast, ovary, pancreas, colorectum, and melanoma. An understanding of the population prevalence of pathogenic germline variants can be helpful in the design of public health interventions, such as genetic testing, which has downstream implications for cancer screening, prevention, and treatment. While population-based studies of pathogenic germline variants exist, most such studies have been conducted in White populations. Limited data exist regarding the prevalence of germline mutations within sub-Saharan African populations. MATERIALS AND METHODS: We identified countries defined as sub-Saharan Africa by the World Bank and conducted a scoping literature review using PubMed. For each country, we identified and summarized studies that focused on the prevalence of germline genetic mutations with sample sizes >10 and in a population directly from sub-Saharan Africa, either with or without diseases associated with the relevant genetic mutations. Studies that evaluated the prevalence of somatic or likely benign variants were excluded. RESULTS: Within the 48 countries in sub-Saharan Africa, we identified 34 studies which meet the inclusion criteria. Twenty studies were conducted in South Africa, Nigeria, or Burkina Faso; four countries had more than two published papers. We found that 33 of 48 countries in sub-Saharan Africa lacked any genetic studies. Notably, there has been an increase in relevant studies starting in 2020. Importantly, of the 34 studies identified, 29 included data on BRCA1 or BRCA2. Data on the prevalence of mutations contributing to familial cancer syndromes other than BRCA1 and BRCA2 was limited. CONCLUSIONS: While some progress has been made towards understanding the prevalence of germline mutations in cancer susceptibility genes, the characterization of genetic mutations among sub-Saharan African populations remains strikingly incomplete. Given the genetic diversity in the region, there remains a great need for large-scale, population-based studies to understand the prevalence of germline pathogenic variants and adequately capture all the subpopulations in this part of the world.

MPrEP+ study protocol: a prospective cohort study assessing the feasibility and acceptability of an HIV pre-exposure prophylaxis (PrEP) strategy for male clients of female sex workers in Kisumu, Kenya.

INTRODUCTION: Male clients (MCs) are integral to sex work-driven HIV transmission dynamics as sexual partners of female sex worker (FSW). MCs contribute disproportionately to incident HIV globally and in sub-Saharan Africa, with 27% of new infections attributed to MCs of FSW and other partners of key populations. Gaps in coverage of HIV testing and prevention services for men, including MCs, are well-documented, yet research and innovative interventions to improve MC uptake of effective prevention services, including pre-exposure prophylaxis (PrEP), are scarce. METHODS AND ANALYSIS: MPrEP+ is a cohort study designed to assess the feasibility and acceptability of a PrEP-focused HIV prevention strategy providing daily oral tenofovir/emtricitabine (TDF/FTC) in combination with three adherence self-management interventions: (1) use of a validated point-of-care urine drug-level assay with real-time feedback and tailored self-management counselling; (2) frequent HIV self-testing; and (3) weekly one-way text messaging. This package of interventions is being delivered to 120 MCs enrolled in the study in Kisumu, Kenya over a 6-month period. The primary outcome is PrEP adherence at 6 months as measured by PrEP drug levels. Bivariate and multivariable regression models will be used to identify predictors of PrEP adherence. We will also explore associations of sociodemographic characteristics and PrEP beliefs with PrEP adherence. ETHICS AND DISSEMINATION: The study was approved by the Columbia University Irving Medical Center Institutional Review Board and the Maseno University Ethical Review Committee. Study enrolment was initiated in November 2021 with participant follow-up planned through August 2022. Study results will be submitted for publication in peer-reviewed journals. Summaries and infographics of study findings will be developed and distributed to MC, FSW and stakeholders working in HIV prevention and support for people who sell and buy sex, including Kenya's Ministry of Health. TRIAL REGISTRATION NUMBER: NCT04898699; Registered on 24 May 2021.

Innovations, adaptations, and accelerations in the delivery of HIV services during COVID-19.

During 2020, the COVID-19 pandemic disrupted the delivery of HIV prevention and treatment services globally. To mitigate the negative consequences of the pandemic, service providers and communities adapted and accelerated an array of HIV interventions to meet the needs of people living with HIV and people at risk of acquiring HIV in diverse geographical and epidemiological settings. As a result of these adaptations, services such as HIV treatment showed programmatic resilience and remained relatively stable in 2020 and into the first half of 2021. To review lessons learned and suggest which novel approaches to sustain, UNAIDS convened a virtual consultation on Feb 1-2, 2022, which was attended by a range of stakeholders from different areas of global HIV response.

Healthcare system responses to non-communicable diseases' needs of Syrian refugees: The cases of Jordan and Lebanon.

Introduction: Since the start of the Syrian conflict in 2011, Jordan and Lebanon have hosted large refugee populations, with a high pre-conflict burden of non-communicable diseases (NCDs). We aimed to explore NCD service provision to Syrian refugees in these two host countries and to identify lessons learned that may inform the global response to the changing health needs of refugees. Methods: Between January 2017 and June 2018, we conducted 36 in-depth interviews with stakeholders from Jordan and Lebanon, as well as global stakeholders, to understand the context, the achievements, gaps and priorities in the provision and uptake of NCD prevention, testing and treatment services to Syrian refugees. Findings: Both countries succeeded in embedding refugee health care within national health systems, yet coverage and quality of NCD health services offered to Syrian refugees in both contexts were affected by under-funding and consequent policy constraints. Changes in policies relating to cost sharing, eligibility and vulnerability criteria led to difficulties navigating the system and increased out-of-pocket payments for Syrians. Funding shortages were reported as a key barrier to NCD screening, diagnosis and management, including at the primary care level and referral from primary to secondary healthcare, particularly in Lebanon. These barriers were compounded by suboptimal implementation of NCD guidelines and high workloads for healthcare providers resulting from the large numbers of refugees. Conclusions: Despite the extraordinary efforts made by host countries, provision and continuity of high quality NCD services at scale remains a tremendous challenge given ongoing funding shortfalls and lack of prioritization of NCD care for refugees. The development of innovative, effective and sustainable solutions is necessary to counter the threat of NCDs.

Achieving the 95 95 95 targets for all: A pathway to ending AIDS.

In December 2020, UNAIDS released a new set of ambitious targets calling for 95% of all people living with HIV to know their HIV status, 95% of all people with diagnosed HIV infection to receive sustained antiretroviral therapy, and 95% of all people receiving antiretroviral therapy to have viral suppression by 2025. Adopted by United Nations Member states in June 2021 as part of the new Political Declaration on HIV and AIDS, these targets, combined with ambitious primary prevention targets and focused attention to supporting enablers, aim to bridge inequalities in treatment coverage and outcomes and accelerate HIV incidence reductions by focusing on progress in all sub-populations, age groups and geographic settings. Here we summarise the evidence and decisions underpinning the new global targets.

COVID-19 Vaccine Uptake and Factors Associated With Being Unvaccinated Among Lesbian, Gay, Bisexual, Transgender, Queer, and Other Sexual Identities (LGBTQ+) New Yorkers.

Routine data on vaccine uptake are not disaggregated by lesbian, gay, bisexual, transgender, queer, and other sexual identities (LGBTQ+) populations, despite higher risk of infection and severe disease. We found comparable vaccination uptake patterns among 1032 LGBTQ+ New Yorkers and the general population. We identified critical socioeconomic factors that were associated with vaccine hesitancy in this economically vulnerable population.

Contact Tracing: Barriers and Facilitators.

Contact tracing-the process of identifying, isolating, and managing infected persons and their contacts-is a recognized public health measure for controlling the transmission of infectious diseases. In the context of the COVID-19 pandemic, contact tracing has received intense attention. We provide a brief overview of the history of contact tracing during several major disease outbreaks in the past century: syphilis and other sexually transmitted infections, HIV infection, tuberculosis, Ebola virus disease, and COVID-19. Our discussion on the barriers to and facilitators of contact tracing offers a perspective on societal and institutional roles and dynamics, stigma as a major barrier to effective tracing efforts, and how the nature and epidemiology of the infection itself can affect its success. We explore the evolution and adaptation of contact tracing and provide insights for future programming and research. (Am J Public Health. 2022;112(7):1025-1033. https://doi.org/10.2105/AJPH.2022.306842).