Maggie L. Shaw

Despite overall survival improvements among pediatric patients living with 

 in sub-Saharan Africa (SSA) following initiation of antiretroviral therapy (ART), 20.5% do not remain engaged in care, report study findings in 

In addition, marked mortality differences are especially apparent when stratifying by income and when considering the effects of uneven access to and coverage of ART in SSA.

The authors of this retrospective cohort analysis, noting a lack of data on how the expansion of ART affected pediatric patient populations, wrote, “Several observational studies have described outcomes of children living with HIV from single cohorts and in the pre-ART era. Furthermore, we did not find any studies that compared outcomes of young children living with HIV across economic settings.”

Their primary outcomes were mortality and loss to follow-up during ART as affected by different economic settings, with patients younger than 5 years (N = 32,221) from 16 low-, lower-middle-, and upper-middle-income countries in SSA (Benin, Burundi, Côte d’Ivoire, Democratic Republic of the Congo, Ghana, Kenya, Lesotho, Malawi, Mali, Mozambique, Rwanda, South Africa, Togo, Uganda, Zambia, and Zimbabwe) who initiated ART between January 1, 2006, and December 31, 2017.

For the 3 time periods evaluated—2006 to 2010, 2011 to 2013, and 2014 to 2017—the median (interquartile range [IQR]) age when initiating ART, which the authors point out is a surrogate of earlier diagnosis, decreased from the first through the last: 20.4 (9.4-36.0) to 19.2 (8.8-33.7) months.

Patients were also almost twice as old in the low-income vs the upper-middle-income countries when starting ART, at a median (IQR) of 24.2 (13.5-39.1) vs 13.2 (4.7-26.8) months, and the rate of children starting ART before their first birthdays was more than twice as higher in upper-middle-income countries vs lower-middle- and low-income countries:

The median (IQR) CD4 percentage when starting ART jumped 25% over the study periods: from 16% (11%-22%) in 2006-2010 to 20% (13%-28%) in 2014-2017.

In addition, despite ART initiation rates nearly doubling among children younger than 3 months from 2006-2010 to 2014-2014—5.1% to 10.0%—there was a 26.1% decrease in the same measure among patients with severe immunosuppression (evaluated with CD4 percentages) between the same periods, and total children initiating ART fell from 14,943 to 7290.

Overall, by the 24-month mark after ART initiation, mortality decreased from 6.5% to 2.9% despite the aforementioned median (IQR) of 20.5% (20.1%-21.0%) who were lost to follow-up—which itself was lower in upper-middle-income (14.3%) vs low-income (21.5%) countries.

And multivariate analysis bears out drops in mortality among those who recently initiated ART (2011-2013: adjusted HR [aHR], 0.70; 95% CI, 0.63-0.79; 2014-2017: aHR, 0.53; 95% CI, 0.45-0.72 vs 2006-2010) and those living in upper-middle-income countries (aHR, 0.42; 95% CI, 0.35-0.49 vs low-income countries).

Factors identified as increasing the overall risk for mortality were living in lower-middle-income countries (aHR, 1.26; 95% CI, 1.09-1.44), severe immunosuppression at ART initiation (aHR, 1.54; 95% CI, 1.30-1.82), and being underweight (aHR, 1.72; 95% CI, 1.47-2.01).

A total of 5.1% (95% CI, 4.8%-5.3%) died during the study period, and mortality was shown to increase the older a child was at ART initiation.

“Sub-Saharan Africa is home to approximately 80% of the 1.8 million children living with HIV globally,” the authors highlight. “However, the scale-up of routine paediatric care programmes in sub-Saharan Africa continues to lag behind adult HIV care and many still present with advanced disease and remain at a high risk of early death or attrition.”

They stress that their findings showcase the immense, ever-present need for targeted efforts to buffet earlier diagnosis and treatment efforts, especially among patients younger than 3 months, mothers, and pregnant women. Also, in the final study period of 2014-2017, 25% of the children evaluated were at an advanced stage of disease when presenting for ART initiation.

“There is still a need to increase focus on sustainable approaches for improved paediatric HIV programme uptake of early infant diagnosis, early ART initiation, and engagement and retention in care for young children living with HIV,” the authors conclude. “Our findings reveal persistent loss to follow-up and considerable heterogeneity across country income groups.”

Iyun V, Technai K-G, Vinikoor M, et al. Variations in the characteristics and outcomes of children living with HIV following universal ART in sub-Saharan Africa (2006-17): a retrospective cohort study. 

 Published online April 28, 2021. doi:10.1016/S2352-3018(21)00004-7

Articles

Despite overall survival improvements among pediatric patients living with HIV, 20.5% are still lost to follow-up.

Pediatric HIV Survival Outcomes Continue to Vary in Sub-Saharan Africa

Study findings presented ahead of this year’s American College of Cardiology 70th Annual Scientific Session lay out a possible link between exposure to secondhand tobacco smoke—specifically that from cigarettes—and greater risk of 

Despite previous research bearing out a connection between worsening heart failure and secondhand smoke exposure, gaps remain in the knowledge around the potential to develop heart failure following exposure to these toxic fumes.

“It adds to overwhelming evidence that secondhand smoke is harmful,” said Travis Skipina, MD, Department of Internal Medicine, Wake Forest School of Medicine, and the study’s lead author, in a 

. “[Secondhand smoke] has been associated with stroke and heart attacks, but what really hadn’t been reported before was its association with heart failure, which is a very debilitating and costly disease."

for such heart failure–related costs as services, medicines, and days off from work.

This cross-sectional analysis by Skipina and coauthors found an overall 35% greater risk of nonsmokers developing heart failure among the close to 20% (N = 11,219 reported nonsmokers) of patients reporting secondhand smoke exposure vs those not exposed to tobacco smoke. Accounting for known risk factors of heart failure, such as high cholesterol and comorbid diabetes, did not alter these results.

For the study, secondhand smoke exposure was defined as having a 

 of at least 1 ng/mL, a level also used by the CDC.

“Serum cotinine is a metabolite of nicotine that is used to measure levels of smoke exposure and usually signifies that someone has been breathing in tobacco smoke in the environment within the last 1 to 2 days (half-life of 18-20 hours),” the authors noted.

Heart failure was defined via physician diagnosis.

The US Third National Health and Nutrition Examination Survey provided the patient data on individuals followed from 1988 through 1994. Most were women and White, at 55.9% and 70.5%, respectively, and their mean (SD) age was 48 (20.5) years.

Additionally, the elevated risk from secondhand smoke was shown to be greater in individuals with a history of myocardial infarction or stroke vs those with no history (

 < .001) and among men compared with women (

Individuals with comorbid obesity and diabetes also were shown to have a higher risk.

“Males, in general, tend to get [cardiovascular] disease at a younger age,” Skipina said, “and overall, they were younger, so that may be why they were predisposed.”

The cross-sectional nature of the study and its older data mark limitations on these findings. Still, Skipina noted that even lower levels of secondhand smoke exposure are associated with higher risk of heart failure.

“Active and secondhand smoke induces a proinflammatory state, and higher levels of inflammation affect all body tissues, and it can lead to maladaptive changes in the heart 

structure and damage to the blood vessels,” he concluded.

More research is needed, Skipina stressed, into the connection between secondhand smoke exposure and heart failure for 2 principal reasons: new methods of exposure (eg, vaping) and higher rates of tobacco use seen among lower-income communities and countries, which often have inadequate health care and less stringent health policies.

Skipina T, Upadhya B, Soliman E. Secondhand smoke is associated with prevalent heart failure: the third National Health and Nutrition Examination Survey. To be presented at: American College of Cardiology's 70th Annual Scientific Session; May 15-17, 2021.

Compared with nonsmokers who did not have recent exposure to secondhand smoke, a 35% greater chance for heart failure was seen among those with recent exposure to the toxic fumes.

Greater Potential for Heart Failure Linked to Secondhand Smoke Exposure

Previous research has shown that certain disease-modifying treatments (DMTs) can affect the immune system’s response to SARS-CoV-2, the virus that causes COVID-19, among patients with 

 can influence patient outcomes, such as 

Now research has been released that elucidates the immune system’s response among patients with MS who had asymptomatic COVID-19 infection, with B-cell depletion being a possible indicate of a less robust antibody response against SARS-CoV-2. These findings appear in a recent issue of 

“Limited information is available regarding SARS-CoV-2 antibodies in patients with MS,” the authors explained. “The objective of this study was to test for SARS-CoV-2 antibodies in a large MS cohort to evaluate asymptomatic infections and immunological responses to COVID-19.”

Overall, 23.6% of the 148 patients tested for COVID-19 via polymerase chain reaction (PCR) had positive results, and of this group, 82.6% were positive for antibodies. In addition, among the 76.4% testing negative via PCR, 18.4% had positive antibody results, and of this group, 14% had asymptomatic infection.

The most common symptom among those with positive antibody results was loss of taste and/or smell (47%).

In addition, antibody levels were less prevalent among the 74.2% of individuals who were on some sort of DMT. This part of the investigation compared injectable drugs (interferon β and glatiramer acetate) and other treatments, at 4% vs 13.1%, respectively (

The findings from this prospective cohort study cover 546 patients (mean [SD] age, 46.9 [12.1] years; median 12 years since MS diagnosis; 71.1% women) from the MS Center Amsterdam in Amsterdam, the Netherlands, who were invited to participate on July 31, 2020. Data were collected through December 18, blood samples were drawn to confirm SARS-CoV-2 antibody levels, and questionnaires were distributed to gauge demographics, current MS complaints, and COVID-19 symptoms.

In particular, analysis also shows a lowered median (interquartile [IQR]) antibody response among patients on ocrelizumab vs other patients: 0.2 (IQR, 0.1-0.4) vs 2.5 (IQR, 0.6-2.5; 

 < .001) normalized optical density (nOD) units—a finding that echoes data presented earlier this year 

 at the American Academy of Neurology annual meeting.

In the present study, an antibody measure was considered low if it ranged from 0.1 to 1.0 nOD and high if it came in above 1.0 nOD.

Limitations on findings include possible underrepresentation of patients with MS who had asymptomatic cases of COVID-19, “because patients may have been more willing to participate in this study after experiencing symptoms fitting COVID-19,” the authors noted, and the overall small percentage who were SARS-CoV-2 positive.

Still, the authors believe their findings hold merit, especially that B-cell depletion may be a risk factor for reduced SARS-CoV-2 antibody production.

“This holds important consequences for humoral immunity after COVID-19 infection and possibly vaccination,” they concluded.

van Kempen ZLE, Strijbis EMM, Al MMCT, et al. SARS-CoV-2 Antibodies in adult patients with multiple aclerosis in the Amsterdam MS cohort. 

l. Published online April 30, 2021. doi:10.1001/jamaneurol.2021.1364

New research demonstrates that patients with multiple sclerosis (MS) who were asymptomatic for COVID-19 had lower antibody levels against SARS-CoV-2, its causative virus, due to having fewer B cells.

B-Cell Depletion May Indicate Reduced COVID-19 Antibody Response Among Patients With MS

 (MS) who are younger than 60 years are not reaping maximal benefits from disease-modifying treatments (DMTs), as evidenced by their suboptimal prescription uptake, researchers concluded in a study published in 

Therapeutic Advances in Neurological Disorders

Real-world data are lacking on DMT prescribing patterns for patients with MS, and the authors proposed that younger patients should be benefiting more from these medicines due to their higher disease activity.

“With increasing age, people with MS are less likely to have clinical relapses or radiological disease activity,” they stated. “As a result, younger people with MS are more likely to derive the most documented or apparent benefits.”

Their study investigated outcomes among US veterans compared with the general population, with 2018 data supplied by North American Research Committee on Multiple Sclerosis (NARCOMS; n = 6948 patients; general population) registry and the US Department of Veterans Affairs Multiple Sclerosis Surveillance Registry (MSSR; n = 1719 patients; veteran population). NARCOMS asks its registrants to update their information every 6 months.

Their investigation revealed the following:

Fewer than half (47.9%) of NARCOMS respondents reported DMT use, and more than half (52.9%) reported no use when they took the survey.

DMT use in NARCOMS was lower among older (aged 71-80 years) vs younger (aged 40 or younger) patients: 29.5% vs 61.4%.

Just over half (54.5%) of MSSR respondents reported current prescriptions for DMTs.

DMT prescriptions in MSSR were lower among older (aged 71-80 years) vs younger (aged 40 or younger) patients: 27.2% vs 70.5%.

MSSR contained more younger patients (aged 31-40; 

 = .001) prescribed DMTs vs NARCOMS: 70.5% and 72.5% vs 61.5% and 62.7%, respectively.

For the remaining age groups (ages 21-30, 51-60, 61-70, 71-80, and 80-plus years), DMT prescriptions patterns were equivalent between the registries.

The authors highlight that their mixed results bear out that more than one-third of younger persons with MS are not using DMTs, “despite widespread recognition of the importance of early treatment in MS,” while conversely, prescriptions for them remain the norm among older patients despite greater chances of adverse effects and diminished disease activity. They attribute this latter finding to belief that “disease inactivity is due to treatment rather than the natural disease course with aging.”

“Further studies are needed to understand and address lack of treatment in young adults with MS,” the authors conclude, “as well as the reasons for persistent DMT use in the elderly.”

These studies should be randomized controlled trials, they added, and rigorous.

Limitations on their findings include that NARCOMS participation is voluntary, which could introduce responder bias compared with persons with MS not taking part in the registry, and a dearth of reasons for prescribing or not prescribing DMTs.

Zhang Y, Salter A, Jin S, et al. Disease-modifying therapy prescription patterns in people with multiple sclerosis by age. 

Published online March 31, 2021. doi:10.1177/17562864211006499

Because real-world data are lacking on disease-modifying treatment (DMT) prescribing patterns for patients with multiple sclerosis (MS), a team of investigators wanted to make sure these individuals were receiving adequate care. 

Maggie L. Shaw

Articles

Pediatric HIV Survival Outcomes Continue to Vary in Sub-Saharan Africa

Greater Potential for Heart Failure Linked to Secondhand Smoke Exposure

B-Cell Depletion May Indicate Reduced COVID-19 Antibody Response Among Patients With MS

DMT Uptake, Prescriptions Not Fitting Disease Course Among Patients With MS