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Global and Humanitarian Medicine

RCT: Twice-Yearly Lenacapavir Reduces HIV Incidence in Men and Gender-Diverse Persons Background

28 Nov, 2024 | 12:38h | UTC

Background: Although preexposure prophylaxis (PrEP) effectively reduces HIV transmission, adherence to daily oral regimens is suboptimal among high-risk populations. Lenacapavir, a long-acting HIV-1 capsid inhibitor administered subcutaneously every six months, has shown efficacy in cisgender women, but its efficacy in men and gender-diverse individuals remains unclear.

Objective: To evaluate the safety and efficacy of twice-yearly subcutaneous lenacapavir compared to background HIV incidence and daily oral emtricitabine–tenofovir disoproxil fumarate (F/TDF) in preventing HIV infection among men and gender-diverse persons.

Methods: In this phase 3, double-blind, randomized trial, 3,271 HIV-negative participants were assigned in a 2:1 ratio to receive subcutaneous lenacapavir every 26 weeks or daily oral F/TDF, with matching placebos. Participants were cisgender men, transgender women and men, and gender-nonbinary persons aged 16 or older who have sex with male-assigned partners. The primary endpoint compared HIV incidence in the lenacapavir group to background incidence; secondary analysis compared lenacapavir to F/TDF.

Results: In the modified intention-to-treat analysis (n=3,265), HIV infections occurred in 2 participants in the lenacapavir group (0.10 per 100 person-years) and 9 in the F/TDF group (0.93 per 100 person-years). The background HIV incidence was 2.37 per 100 person-years. Lenacapavir significantly reduced HIV incidence compared to background (incidence rate ratio [IRR], 0.04; 95% CI, 0.01–0.18; P<0.001) and F/TDF (IRR, 0.11; 95% CI, 0.02–0.51; P=0.002). No significant safety concerns emerged. Injection-site reactions led to discontinuation in 1.2% of lenacapavir recipients and 0.3% of F/TDF recipients.

Conclusions: Twice-yearly subcutaneous lenacapavir significantly reduced HIV incidence compared to both the background incidence and daily oral F/TDF among men and gender-diverse persons. These findings support lenacapavir as an effective PrEP option in this population.

Implications for Practice: The introduction of a long-acting, twice-yearly injectable PrEP option like lenacapavir could improve adherence and uptake among populations challenged by daily oral regimens.

Study Strengths and Limitations: Strengths include a large, diverse participant population with significant representation of transgender and gender-nonbinary persons, and the use of an active comparator. The novel counterfactual design estimating background HIV incidence avoided ethical issues of placebo controls but may have limitations in accuracy. Limitations include a relatively short follow-up and potential impact of injection-site reactions on adherence. The emergence of resistance mutations in participants who acquired HIV while on lenacapavir is a concern needing further investigation.

Future Research: Further studies should assess the long-term safety, efficacy, and resistance patterns associated with lenacapavir use. Research into optimizing injection techniques to minimize injection-site reactions and exploring lenacapavir’s applicability in other at-risk populations is recommended.

Reference: Kelley CF, et al. Twice-Yearly Lenacapavir for HIV Prevention in Men and Gender-Diverse Persons. New England Journal of Medicine. Published November 27, 2024. DOI: http://doi.org/10.1056/NEJMoa2411858

 

Review: Chronic Low-Level Lead Poisoning

3 Nov, 2024 | 01:15h | UTC

Introduction: Lead poisoning, historically known as plumbism, remains a significant health concern despite reductions in lead use. Chronic low-level lead exposure has been identified as a critical risk factor for cardiovascular disease in adults and cognitive deficits in children, even at blood lead concentrations previously deemed safe. This review by Lanphear et al. explores the multifaceted effects of chronic, low-level lead poisoning, emphasizing its impact on neurodevelopment, kidney function, and cardiovascular health, and underscores the urgent need for effective prevention strategies.

Key Findings:

  1. Exposure and Absorption: Lead exposure occurs primarily through ingestion and inhalation, with children absorbing lead more readily than adults. Absorption is enhanced in the presence of iron or calcium deficiency. Once absorbed, lead is predominantly stored in the skeleton, and factors altering bone metabolism can mobilize lead back into the bloodstream.
  2. Neurodevelopmental Effects: Lead exposure is linked to preterm birth, cognitive deficits, attention deficit–hyperactivity disorder (ADHD), and behavioral disorders in children. Notably, cognitive deficits are proportionately larger at lower blood lead levels, with significant IQ reductions observed even at the lowest measurable concentrations.
  3. Kidney Disease: Chronic lead exposure is a risk factor for chronic kidney disease. Higher blood lead levels are associated with reduced glomerular filtration rates and an increased risk of developing chronic kidney conditions.
  4. Cardiovascular Disease: Lead induces hypertension and atherosclerosis through mechanisms such as oxidative stress and endothelial dysfunction. It is a leading risk factor for mortality from cardiovascular disease, with substantial risk increases even at low blood lead concentrations. Studies indicate that lead exposure may have contributed to historical trends in coronary heart disease mortality.
  5. Global Burden: In 2019, lead exposure accounted for approximately 5.5 million deaths from cardiovascular disease and the loss of 765 million IQ points in children globally. The economic cost associated with lead-related health outcomes is estimated at $6 trillion annually, representing about 7% of the global gross domestic product.
  6. Screening and Treatment: Screening high-risk populations is recommended, including children in older housing and workers in certain industries. While chelation therapy can reduce body lead burden, its effects on health outcomes are inconsistent, highlighting the importance of primary prevention.
  7. Prevention Strategies: Eliminating environmental sources of lead through government-funded population strategies is essential. This includes replacing lead-containing infrastructure like water service lines, banning leaded aviation fuel, reducing lead in consumer products, and remediating contaminated soils and older housing with lead-based paints.

Conclusion: Chronic low-level lead poisoning continues to pose a significant global health threat, contributing to cardiovascular disease and neurodevelopmental deficits. The disproportionate effects at even the lowest exposure levels underscore the necessity for robust, population-wide prevention strategies. Implementing stringent regulatory actions to eliminate sources of lead exposure is imperative to reduce the substantial morbidity, mortality, and economic burdens associated with lead poisoning.

Reference: Lanphear B, Navas-Acien A, Bellinger DC. Lead Poisoning. New England Journal of Medicine. 2024;391(17):1621–1631. DOI: http://doi.org/10.1056/NEJMra2402527

 

Cluster-Randomized Trial: Twice-Yearly Azithromycin Reduces Mortality in Children Aged 1 to 59 Months in Niger – New England Journal of Medicine

24 Aug, 2024 | 19:44h | UTC

Study Design and Population: This adaptive cluster-randomized trial evaluated the impact of twice-yearly azithromycin distribution on childhood mortality in rural communities in Niger. A total of 1273 communities were assigned to three groups: children aged 1 to 59 months receiving azithromycin, infants aged 1 to 11 months receiving azithromycin and placebo for older children, and a placebo group. The study included 382,586 children and followed mortality over 419,440 person-years.

Main Findings: The study found a significant 14% reduction in mortality among children aged 1 to 59 months in the azithromycin group compared to placebo (11.9 vs. 13.9 deaths per 1000 person-years; P<0.001). However, azithromycin did not significantly reduce mortality in infants aged 1 to 11 months when compared to placebo (22.3 vs. 23.9 deaths per 1000 person-years).

Implications for Practice: Azithromycin distribution to children aged 1 to 59 months effectively reduces mortality in rural sub-Saharan Africa. However, targeting only infants may not yield significant benefits. Continuous monitoring for antimicrobial resistance is essential.

Reference: O’Brien KS, Arzika AM, Amza A, et al. (2024). Azithromycin to reduce mortality — an adaptive cluster-randomized trial. N Engl J Med, 391(8), 699-709. DOI: https://doi.org/10.1056/NEJMoa2312093

 

RCT: Twice-Yearly Lenacapavir Prevents HIV Infections More Effectively Than Daily F/TAF in Women – N Engl J Med

18 Aug, 2024 | 13:56h | UTC

Study Design and Population: This phase 3, double-blind, randomized controlled trial included 5,338 adolescent girls and young women in South Africa and Uganda. Participants were assigned to receive either twice-yearly subcutaneous lenacapavir, daily oral emtricitabine–tenofovir alafenamide (F/TAF), or daily oral emtricitabine–tenofovir disoproxil fumarate (F/TDF) as an active control, with corresponding placebos.

Main Findings: Lenacapavir demonstrated superior efficacy in HIV prevention, with zero infections observed among its recipients. In contrast, the F/TAF group experienced 39 HIV infections (2.02 per 100 person-years), while the F/TDF group had 16 infections (1.69 per 100 person-years). HIV incidence was significantly lower with lenacapavir compared to background incidence and F/TDF, while no significant difference was observed between F/TAF and F/TDF.

Implications for Practice: Twice-yearly lenacapavir could be a more effective and potentially easier-to-adopt HIV prevention strategy than daily oral F/TAF in cisgender women, though considerations of injection-site reactions are necessary. This approach could improve adherence and outcomes in populations with low persistence in daily PrEP use.

Reference: Bekker, L.-G., Das, M., Abdool Karim, Q., Ahmed, K., Batting, J., Brumskine, W., Gill, K., et al. (2024). Twice-yearly lenacapavir or daily F/TAF for HIV prevention in cisgender women. New England Journal of Medicine, 391(7), 648-659. DOI: 10.1056/NEJMoa2407001.

 

Phase 3 RCT: Butantan-DV Dengue Vaccine is Safe and Shows 67.3% Efficacy Over 3.7 Years in Participants Aged 2–59 Years – Lancet Infect Dis

10 Aug, 2024 | 20:23h | UTC

Study Design and Population: This double-blind, randomized, placebo-controlled, phase 3 trial conducted in Brazil evaluated the efficacy and safety of the Butantan-dengue vaccine (Butantan-DV) in 16,235 healthy participants aged 2–59 years. Participants, who had not previously received a dengue vaccine, were randomly assigned to receive either a single dose of Butantan-DV or a placebo and were followed up for an average of 3.7 years.

Main Findings: The study found that Butantan-DV demonstrated 67.3% efficacy against virologically confirmed dengue (VCD) caused by any dengue virus serotype, with no cases of VCD caused by DENV-3 or DENV-4. The proportions of serious adverse events were similar between the vaccine and placebo groups, indicating that the vaccine was generally well tolerated.

Implications for Practice: The results support the potential of the Butantan-DV vaccine as an effective intervention for preventing symptomatic dengue, particularly from DENV-1 and DENV-2, across a broad age range regardless of dengue serostatus. Continued development and monitoring are warranted to confirm long-term efficacy and safety.

Reference: Nogueira, M. L., et al. (2024). Efficacy and safety of Butantan-DV in participants aged 2–59 years through an extended follow-up: results from a double-blind, randomised, placebo-controlled, phase 3, multicentre trial in Brazil. The Lancet Infectious Diseases. DOI: https://doi.org/10.1016/S1473-3099(24)00376-1.

 

Diagnostic Study: Enhanced prediction of TB progression with IGRAs compared to tuberculin skin test

27 Apr, 2024 | 18:53h | UTC

Study Design and Population:

This prospective diagnostic study analyzed the predictive accuracy of tuberculosis (TB) tests among 22,020 high-risk participants across 10 US sites from 2012 to 2020. Participants included individuals with close contacts to infectious TB cases, those born in or travelers to high-incidence countries, individuals living with HIV, or belonging to locally prevalent high-risk groups. Testing included two interferon-γ release assays (IGRAs), QuantiFERON-TB Gold In-Tube (QFT-GIT) and SPOT.TB (TSPOT), alongside the traditional tuberculin skin test (TST).

 

Main Findings:

The study found that both IGRAs, TSPOT and QFT-GIT, showed significantly superior positive predictive value (PPV) for predicting TB disease progression compared to the TST, with PPV ratios of 1.65 (95% CI, 1.35-2.02) and 1.47 (95% CI, 1.22-1.77) respectively. Additionally, when considering a positive TST result, further positive results from either IGRA significantly increased the PPV, emphasizing the enhanced predictive capability of IGRAs over TST alone.

 

Implications for Practice:

The superior predictive performance of Interferon-γ Release Assays (IGRAs) suggests they should be considered in clinical settings for high-risk populations, if available and feasible, to better identify individuals at increased risk of progressing to active tuberculosis (TB). This enhanced detection capability could guide more targeted preventive treatments, ultimately supporting global efforts toward TB elimination. Clinicians should assess the accessibility and cost-effectiveness of IGRAs to refine decision-making processes in TB prevention strategies, ensuring that the benefits of these advanced diagnostics are balanced against their costs.

 

Reference (free full-text):

Ayers, T. et al. (2024). Comparison of Tuberculin Skin Testing and Interferon-γ Release Assays in Predicting Tuberculosis Disease. JAMA Network Open, 7(4), e244769. DOI: https://doi.org/10.1001/jamanetworkopen.2024.4769.

WHO report on HIV drug resistance – Rising dolutegravir resistance and implications for global care standards

27 Apr, 2024 | 16:08h | UTC

The World Health Organization’s latest HIV Drug Resistance Report highlights both the effectiveness and emerging challenges with dolutegravir (DTG)-based therapies. While there is significant suppression of HIV viral loads in populations treated with DTG, data reveals increasing resistance levels, particularly among those with high viral loads and prior treatment experiences. The report calls for enhanced surveillance and management strategies to address these resistance patterns and maintain treatment efficacy. It also underscores the necessity of robust data systems and proactive healthcare policies to improve the overall quality of HIV treatment and prevent the transmission of resistant HIV strains, aligning with global efforts to combat antimicrobial resistance.

 

Source:

New report documents increase in HIV drug resistance to dolutegravir – World Health Organization

Systematic Analysis: Global Burden and Trends of Nervous System Disorders, 1990–2021

21 Mar, 2024 | 11:10h | UTC

Study Design and Population

This study, a systematic analysis conducted by the Global Burden of Disease Study 2021, aimed to estimate the global, regional, and national health loss attributable to 37 unique nervous system conditions from 1990 to 2021. The researchers estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life years (DALYs) across 204 countries. The analysis included morbidity and deaths directly resulting from damage to the central or peripheral nervous system, as well as neurological health loss from conditions where nervous system morbidity is a secondary outcome.

Main Findings

The collective global burden of these nervous system conditions emerged as the leading cause of DALYs in 2021, affecting approximately 3.40 billion individuals (43.1% of the global population) and resulting in 443 million DALYs. Although global DALY counts for these conditions increased by 18.2% from 1990 to 2021, there was a notable decrease in the age-standardised rates of deaths and DALYs by 33.6% and 27.0%, respectively. The conditions contributing most significantly to the age-standardised DALYs were stroke, neonatal encephalopathy, migraine, and Alzheimer’s disease among others.

Implications for Practice

This analysis underscores the critical need for effective prevention, treatment, and rehabilitation strategies for nervous system disorders, which now lead the global disease burden. Highlighting an 18.2% increase in DALY counts over the study period, it calls for heightened public health attention and resource allocation towards these conditions. The findings support the prioritization of nervous system health on the global health agenda and stress the importance of further research into modifiable risk factors and equitable access to care.

Reference

GBD 2021 Nervous System Disorders Collaborators (2024). Systematic Analysis: Global Burden and Trends of Nervous System Disorders, 1990–2021. The Lancet Neurology, Volume(issue), Pages. DOI: https://doi.org/10.1016/S1474-4422(24)00038-3. Access the study here: Link

Global prevalence, years lived with disability, and trends in anemia burden by severity and cause, 1990–2021

3 Aug, 2023 | 13:43h | UTC

Prevalence, years lived with disability, and trends in anaemia burden by severity and cause, 1990–2021: findings from the Global Burden of Disease Study 2021 – The Lancet Haematology

News Release: New study reveals global anemia cases remain persistently high among women and children. Anemia rates decline for men – Institute for Health Metrics and Evaluation

 

Commentary on Twitter

 

WHO | Seven out of 10 people protected by at least one tobacco control measure

2 Aug, 2023 | 14:14h | UTC

News Release: Seven out of 10 people protected by at least one tobacco control measure – World Health Organization

See also: MPOWER measures

Report: WHO report on the global tobacco epidemic, 2023: protect people from tobacco smoke – World Health Organization

Commentaries:

While Anti-Smoking Policies Cover 70% of Global Population, Taxation is Under-Utilised – Health Policy Watch

Expert reaction to WHO report on the global tobacco epidemic 2023 – Science Media Centre

 

Commentary on Twitter

 

Study | Childhood deaths in high-mortality settings mostly preventable; infection, malnutrition top causes

31 Jul, 2023 | 14:05h | UTC

Causes of Death Among Infants and Children in the Child Health and Mortality Prevention Surveillance (CHAMPS) Network – JAMA Network Open

Invited Commentary: Need for a Structural Approach to Promote Child Survival – JAMA Network Open

News Release: Eight out of ten child deaths in low-income countries could be prevented – Barcelona Institute for Global Health

 

New WHO lists of essential medicines

28 Jul, 2023 | 14:23h | UTC

News Release: WHO endorses landmark public health decisions on Essential Medicines for Multiple Sclerosis – World Health Organization

Lists of Essential Medicines

Model Lists of Essential Medicines – World Health Organization

Model Lists of Essential Medicines for Children – World Health Organization

 

Commentary on Twitter

 

WHO world drowning prevention day 2023

27 Jul, 2023 | 13:12h | UTC

World Drowning Prevention Day 2023 – World Health Organization

Report: Hidden depths: the global investment case for drowning prevention – World Health Organization

Related:

Wilderness Medical Society Clinical Practice Guidelines for the Treatment and Prevention of Drowning: 2019 Update

Tracing the emergence of drowning prevention on the global health and development agenda: a policy analysis – The Lancet Global Health

WHO Guideline on the prevention of drowning through provision of day-care and basic swimming and water safety skills – World health Organization

Wilderness Medical Society Clinical Practice Guidelines for the Treatment and Prevention of Drowning: 2019 Update

Prevention of Drowning – Pediatrics

The burden of unintentional drowning: global, regional and national estimates of mortality from the Global Burden of Disease 2017 Study – Injury Prevention

Preventing drowning: an implementation guide – World Health Organization

Global report on drowning: preventing a leading killer – World Health Organization

Hidden Hazards: An Exploration of Open Water Drowning and Risks for Children – Safe Kids Worldwide

 

Commentary on Twitter (thread – click for more)

 

Global, regional, and national burden of meningitis and its etiologies, 1990–2019

25 Jul, 2023 | 13:55h | UTC

Global, regional, and national burden of meningitis and its aetiologies, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019 – The Lancet Neurology

 

Commentary on Twitter

 

Key factors associated with quality of postnatal care: a pooled analysis of 23 countries

25 Jul, 2023 | 13:50h | UTC

Key factors associated with quality of postnatal care: a pooled analysis of 23 countries – eClinicalMedicine

 

New WHO guidance on the role of HIV viral suppression in improving individual health and reducing transmission

24 Jul, 2023 | 13:17h | UTC

News Release: New WHO guidance on HIV viral suppression and scientific updates released at IAS 2023 – World Health Organization

WHO Guidance: The role of HIV viral suppression in improving individual health and reducing transmission – Word Health Organization

Related WHO Guidelines:

WHO recommends optimizing HIV testing services – World Health Organization

Primary health care and HIV: convergent actions – World Health Organization

 

Systematic Review | Low-level HIV viremia (below 1000 copies/mL) linked to minimal sexual transmission risk

24 Jul, 2023 | 13:15h | UTC

The risk of sexual transmission of HIV in individuals with low-level HIV viraemia – The Lancet

Editorial: HIV is sexually untransmittable when viral load is undetectable – The Lancet

Related: Study: Growing Acceptability of “Undetectable = Untransmittable” but Widespread Misunderstanding of HIV Transmission Risk Persists (several texts on the subject)

 

Commentary on Twitter

 

M-A | Exposure to smoke, overcrowding, poor living conditions, and contact with TB cases identified as risk conditions for pediatric TB

24 Jul, 2023 | 12:43h | UTC

Risk factors for the development of tuberculosis among the pediatric population: a systematic review and meta-analysis – European Journal of Pediatrics

 

Systematic Review | Prevalence and risk factors of cardiovascular diseases in young adults across 204 countries, 1990-2019

17 Jul, 2023 | 13:47h | UTC

Global, regional, and national burden of cardiovascular diseases in youths and young adults aged 15–39 years in 204 countries/territories, 1990–2019: a systematic analysis of Global Burden of Disease Study 2019 – BMC Medicine

 

WHO Guideline | Policies to protect children from the harmful impact of food marketing

12 Jul, 2023 | 13:52h | UTC

Policies to protect children from the harmful impact of food marketing: WHO guideline – World Health Organization

News Release: WHO recommends stronger policies to protect children from the harmful impact of food marketing – World Health Organization

Commentary: WHO Launches New Guideline for Protecting Children from Unhealthy Food Marketing – Health Policy Watch

 

Global Burden of Disease Study | Understanding global trends of infectious diseases in younger population, 1990-2019

10 Jul, 2023 | 13:54h | UTC

The unfinished agenda of communicable diseases among children and adolescents before the COVID-19 pandemic, 1990–2019: a systematic analysis of the Global Burden of Disease Study 2019 – The Lancet

News Release: Global efforts to reduce infectious diseases must extend beyond early childhood – Murdoch Children’s Research Institute

Commentary: Global infectious disease burden shifting from younger to older youth – CIDRAP

 

Global incidence in hospital-associated infections resistant to antibiotics: an analysis of point prevalence surveys from 99 countries

30 Jun, 2023 | 14:33h | UTC

Global incidence in hospital-associated infections resistant to antibiotics: An analysis of point prevalence surveys from 99 countries – PLOS Medicine

 

Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050

26 Jun, 2023 | 01:00h | UTC

Summary: This systematic review analyzed the global burden of diabetes, including trends, projections, and attributions to risk factors. It considered data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), covering 204 countries and territories.

In 2021, an estimated 529 million people worldwide were living with diabetes. Regionally, the highest rates were observed in North Africa, the Middle East, and Oceania. Type 2 diabetes accounted for 96% of diabetes cases and 95.4% of diabetes DALYs (disability-adjusted life-years). More than half of global type 2 diabetes DALYs were attributable to high body mass index (BMI).

Predictions suggest that more than 1.31 billion people will have diabetes by 2050, with high prevalence rates in North Africa, the Middle East, and Latin America. The study notes the ongoing challenge of preventing and controlling type 2 diabetes, largely driven by increasing obesity. An understanding of disparities in risk profiles and disease burdens can inform strategies to control diabetes risk factors.

Article: Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021 – The Lancet

Editorial: Diabetes: a defining disease of the 21st century – The Lancet

News Release: Global diabetes cases to soar from 529 million to 1.3 billion by 2050 – Institute for Health Metrics and Evaluation

 

Commentary on Twitter (thread – click for more)

 

WHO outlines 40 research priorities on antimicrobial resistance

26 Jun, 2023 | 00:50h | UTC

News release: WHO outlines 40 research priorities on antimicrobial resistance – World Health Organization

Report: Global research agenda for antimicrobial resistance in human health – World Health Organization

 

Commentary on Twitter

 

WHO Report | Water, sanitation, hygiene, waste and electricity services in health care facilities

23 Jun, 2023 | 13:41h | UTC

Water, sanitation, hygiene, waste and electricity services in health care facilities: progress on the fundamentals – World Health Organization

News Release: Frontline health facilities faltering without water, sanitation, hygiene and electricity – WHO, UNICEF new report – World Health Organization

 

Commentary on Twitter (thread – click for more)

 

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