Global and Humanitarian Medicine
RCT: Twice-Yearly Lenacapavir Reduces HIV Incidence in Men and Gender-Diverse Persons Background
28 Nov, 2024 | 12:38h | UTCBackground: 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.
Review: Chronic Low-Level Lead Poisoning
3 Nov, 2024 | 01:15h | UTCIntroduction: 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:
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
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 | UTCStudy 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.
RCT: Twice-Yearly Lenacapavir Prevents HIV Infections More Effectively Than Daily F/TAF in Women – N Engl J Med
18 Aug, 2024 | 13:56h | UTCStudy 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.
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 | UTCStudy 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.
Diagnostic Study: Enhanced prediction of TB progression with IGRAs compared to tuberculin skin test
27 Apr, 2024 | 18:53h | UTCStudy 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):
WHO report on HIV drug resistance – Rising dolutegravir resistance and implications for global care standards
27 Apr, 2024 | 16:08h | UTCThe 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 | UTCStudy 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
Commentary on Twitter
NEW #GBD study by @IHME_UW on the #anaemia burden by severity and cause, 1990–2021?https://t.co/NbiEDSkbGI
Despite a decrease in prevalence, the number of people with anaemia increased globally
In every region females had a higher #anemia YLDs than males pic.twitter.com/oFx4vHRhs1
— The Lancet Haematology (@TheLancetHaem) August 1, 2023
WHO | Seven out of 10 people protected by at least one tobacco control measure
2 Aug, 2023 | 14:14h | UTCNews Release: Seven out of 10 people protected by at least one tobacco control measure – World Health Organization
See also: MPOWER measures
Commentaries:
Expert reaction to WHO report on the global tobacco epidemic 2023 – Science Media Centre
Commentary on Twitter
The MPOWER measures include?
?-onitoring tobacco use
?-rotecting people from tobacco smoke
?-ffering support to quit smoking
?-arning about the dangers of tobacco
?-nforcing tobacco advertising, promotion & sponsorship bans
?-aising taxes on TobaccoLearn more.… pic.twitter.com/ImfGsL8in1
— World Health Organization (WHO) (@WHO) July 31, 2023
Study | Childhood deaths in high-mortality settings mostly preventable; infection, malnutrition top causes
31 Jul, 2023 | 14:05h | UTCInvited 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 | UTCNews 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
OUT TODAY: New editions of the WHO Model Lists of Essential Medicines and Essential Medicines for Children which include important new medicines for the treatment of multiple sclerosis, cancer, infectious diseases and cardiovascular conditions, among others… pic.twitter.com/RZYdgc0i65
— World Health Organization (WHO) (@WHO) July 26, 2023
WHO world drowning prevention day 2023
27 Jul, 2023 | 13:12h | UTCWorld Drowning Prevention Day 2023 – World Health Organization
Report: Hidden depths: the global investment case for drowning prevention – World Health Organization
Related:
Prevention of Drowning – Pediatrics
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)
It's #WorldDrowningPreventionDay
Every year, drowning claims at least 236,000 lives. It's one of the leading causes of death ? for children & people aged 1-24 years. We can all take action to end drowning ? https://t.co/7CSUGYBk49 pic.twitter.com/r64dbsLnHn— World Health Organization (WHO) (@WHO) July 25, 2023
Global, regional, and national burden of meningitis and its etiologies, 1990–2019
25 Jul, 2023 | 13:55h | UTC
Commentary on Twitter
Although largely preventable, meningitis still causes hundreds of thousands of deaths globally each year.
New @IHME_UW #GBDStudy in @TheLancetNeuro assesses incident cases and deaths due to acute infectious meningitis by aetiology and age from 1990–2019. https://t.co/S3KtMA7DMs pic.twitter.com/AYuSJHsNwK
— The Lancet (@TheLancet) July 20, 2023
Key factors associated with quality of postnatal care: a pooled analysis of 23 countries
25 Jul, 2023 | 13:50h | UTC
New WHO guidance on the role of HIV viral suppression in improving individual health and reducing transmission
24 Jul, 2023 | 13:17h | UTCNews 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 | UTCThe 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
People on ART with low but detectible levels of HIV viral load have almost zero risk of sexually transmitting the virus to others, in-depth review suggests #IAS2023https://t.co/wU26C8cEMK pic.twitter.com/hQHLDqPxO6
— The Lancet (@TheLancet) July 22, 2023
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
Systematic Review | Prevalence and risk factors of cardiovascular diseases in young adults across 204 countries, 1990-2019
17 Jul, 2023 | 13:47h | UTC
WHO Guideline | Policies to protect children from the harmful impact of food marketing
12 Jul, 2023 | 13:52h | UTCNews 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 | UTCNews 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, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050
26 Jun, 2023 | 01:00h | UTCSummary: 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.
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)
Today: More than 529 million people across the globe have diabetes
In the next 30 years: 1.3 billion people are projected to have diabetes
https://t.co/gh2O0K7RY0— Institute for Health Metrics and Evaluation (IHME) (@IHME_UW) June 22, 2023
WHO outlines 40 research priorities on antimicrobial resistance
26 Jun, 2023 | 00:50h | UTCNews 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 published its 1st global research agenda for the world’s scientists to address the most urgent human health priorities to combat antimicrobial resistance
It outlines 40 research topics on drug-resistant bacteria,fungi& Mycobacterium TB
H/t @paimadhuhttps://t.co/AOVObnJK5Q pic.twitter.com/owZJwMIDXK— Antibiotic Steward Bassam Ghanem?? (@ABsteward) June 22, 2023
WHO Report | Water, sanitation, hygiene, waste and electricity services in health care facilities
23 Jun, 2023 | 13:41h | UTC
Commentary on Twitter (thread – click for more)
Better access to water, sanitation, hygiene & waste services in health facilities improve quality care and help prevent millions of deaths annually.
New WHO & @UNICEF Global Progress Report 2023 outlines how:
➡️ https://t.co/moyBs6yibC pic.twitter.com/Rv0P8DjzjA— World Health Organization (WHO) (@WHO) June 13, 2023