Bioinformatically designed mosaic antigens increase the breadth of HIV vaccine-elicited immunity. This study compared the safety, tolerability, and immunogenicity of a newly developed, tetravalent Ad26 vaccine with the previously tested trivalent formulation.
This randomised, parallel-group, placebo-controlled, double-blind, phase 1/2a study (TRAVERSE) was done at 11 centres in the USA and one centre in Rwanda. Eligible participants were adults aged 18 to 50 years, who were HIV-uninfected, healthy at screening based on their medical history and a physical examination including laboratory assessment and vital sign measurements, and at low risk of HIV infection in the opinion of study staff, who applied a uniform definition of low-risk guidelines that was aligned across sites. Enrolled participants were randomly assigned at a 2:1 ratio to tetravalent and trivalent groups. Participants in tetravalent and trivalent groups were then further randomly assigned at a 5:1 ratio to adenovirus 26 (Ad26)-vectored vaccine and placebo subgroups. Randomisation was stratified by region (USA and Rwanda) and based on a computer-generated schedule using randomly permuted blocks prepared under the sponsor’s supervision. We masked participants and investigators to treatment allocation throughout the study. On day 0, participants received a first injection of tetravalent vaccine (Ad26.Mos4.HIV or placebo) or trivalent vaccine (Ad26.Mos.HIV or placebo), and those injections were repeated 12 weeks later. At week 24, vaccine groups received a third dose of tetravalent or trivalent together with clade C gp140, and this was repeated at week 48, with placebos again administered to the placebo group. All study vaccines and placebo were administered by intramuscular injection in the deltoid muscle. We assessed adverse events in all participants who received at least one study injection (full analysis set) and Env-specific binding antibodies in all participants who received at least the first three vaccinations according to the protocol-specified vaccination schedule, had at least one measured post-dose blood sample collected, and were not diagnosed with HIV during the study (per-protocol set). This study is registered with Clinicaltrials.gov, NCT02788045.
Of 201 participants who were enrolled and randomly assigned, 198 received the first vaccination: 110 were in the tetravalent group, 55 in the trivalent group, and 33 in the placebo group. Overall, 185 (93%) completed two scheduled vaccinations per protocol, 180 (91%) completed three, and 164 (83%) completed four. Solicited, self-limiting local, systemic reactogenicity and unsolicited adverse events were similar in vaccine groups and higher than in placebo groups. All participants in the per-protocol set developed clade C Env binding antibodies after the second vaccination, with higher total IgG titres after the tetravalent vaccine than after the trivalent vaccine (10 413 EU/mL, 95% CI 7284-14 886 in the tetravalent group compared with 5494 EU/mL, 3759-8029 in the trivalent group). Titres further increased after the third and fourth vaccinations, persisting at least through week 72. Other immune responses were also higher with the tetravalent vaccine, including the magnitude and breadth of binding antibodies against a cross-clade panel of Env antigens, and the magnitude of IFNγ ELISPOT responses (median 521 SFU/10 peripheral blood mononuclear cells [PBMCs] in the tetravalent group and median 282 SFU/10 PBMCs in the trivalent group after the fourth vaccination) and Env-specific CD4+ T-cell response rates after the third and fourth vaccinations. No interference by pre-existing Ad26 immunity was identified.
The tetravalent vaccine regimen was generally safe, well-tolerated, and found to elicit higher immune responses than the trivalent regimen. Regimens that use this tetravalent vaccine component are being advanced into field trials to assess efficacy against HIV-1 infection.
National Institutes of Health, Henry M Jackson Foundation for Advancement of Military Medicine and the US Department of Defense, Ragon Institute of MGH, MIT, & Harvard, Bill & Melinda Gates Foundation, and Janssen Vaccines & Prevention.

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It is well-known that blood pressure measured in the doctor’s office does not reflect a person’s regular blood pressure levels.

For this reason, about half of American adults are recommended to have their blood pressure measured outside of a clinical setting, according to a new study led by Paul Muntner, Ph.D., professor of epidemiology in the School of Public Health at the University of Alabama at Birmingham. The study found that approximately 104 million Americans should routinely use a blood pressure machine at home to provide backup for—or a contrast with—the results from their visit to the doctor’s office.

According to the study, nearly 93 percent of in adults the United States who have high blood pressure when measured in their doctor’s office and do not take blood pressure medicine should be screened for “white coat hypertension,” a condition where blood pressure spikes when measured at the doctor’s office, but is normal when measured outside of a medical setting. If someone has white coat hypertension, they may not benefit from starting antihypertensive medication.

Researchers also discovered that a third of U.S. adults should be screened for “masked hypertension,” which occurs when individuals do not have high blood pressure based on readings measured in their doctor’s office but do have high blood pressure readings when measured outside of the clinic.

“For some people, a doctor’s office is a place they’re relaxed,” Muntner said. “They are away from job stress, traffic and family issues. Others get anxious they are about to get bad news about their blood pressure—or something worse. Their readings in the doctor’s office cause concern, whereas measuring in a more familiar setting would cause less stress.”

Under the American College of Cardiology and American Heart Association guidelines, people are considered to have high blood pressure if their systolic, or top number, is 130 or higher and their diastolic, or bottom number, is 80 or higher.

In order to ensure people are accurately diagnosed with hypertension, Muntner says, at-home monitoring should be used. While it may seem expensive or tedious to take one’s blood pressure at home, it does not have to be.

Many pharmacies or grocery stores have blood pressure machines customers may use free. Home versions with an electronic inflatable cuff are also available at local drug stores for less than $50.

“The most important thing is to make sure the device has been validated,” Muntner said. “You should also talk to a doctor or a nurse about buying a device and have them teach you how to accurately measure your blood pressure at home.”

Muntner says you should take your blood pressure two times in the morning and two times in the evening for a week at a time. It is best to use a device that records the readings so you do not have to write the results down, and your doctor can see the data at your next appointment.

Ultimately, the most important objective of having people measure their blood pressure at home is to make sure doctors are treating people appropriately.

“Home blood pressure monitoring will better inform the physicians, as well as the patients,” Muntner explained. “That means physicians aren’t starting a patient on medication when they may not have high blood pressure. It also ensures doctors are starting treatment on patients who do have hypertension or are at risk for cardiovascular disease.”

The study was published in Hypertension, the journal of the American Heart Association.

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Washington D.C.: A recent study discovered that vitamin D deficiency from birth to early childhood is associated with an increased risk of elevated blood pressure in later childhood and adolescence.

According to the study published in the Journal of Hypertension, researchers examined 775 children from birth to age 18. Later when they compared children who were born with adequate vitamin D levels, they found that children born with low levels of vitamin D had an approximately 60 per cent higher risk of elevated systolic blood pressure (values that determine whether your blood pressure is normal, too high or too low) between ages 6 and 18.

Secondly, the researchers discovered that children who had persistently low levels of vitamin D through early childhood had double the risk of elevated systolic blood pressure between ages 3 and 18.
And lastly, they found that high systolic blood pressure readings increase the risk of cardiovascular disease even when diastolic blood pressure, the second number in a blood pressure reading, is controlled.

“Currently, there are no recommendations from the American Academy of Pediatrics to screen all pregnant women and young children for vitamin D levels. Our findings raise the possibility that screening and treatment of vitamin D deficiency with supplementation during pregnancy and early childhood might be an effective approach to reduce high blood pressure later in life,” said Guoying Wang, the study’s lead author.

Wang added that what constitutes optimal circulating vitamin D levels during pregnancy and early childhood remains an active research question and that their study results need to be replicated in other large populations.

Vitamin D is needed for the body to absorb calcium for strong bones. It is made by our bodies when we are exposed to sunlight and found in a few foods, such as eggs, salmon and fortified milk products. It is also available as a vitamin supplement.

High blood pressure is a leading, preventable cause of cardiovascular disease worldwide. Along with an increase in obesity among children, the prevalence of high blood pressure in children has been on the rise in recent years. High blood pressure in childhood is an important risk factor for having high blood pressure and developing cardiovascular disease in adulthood.

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Some people go to the doctor and find the intake so nerve-wracking their blood pressure spikes. Others find the routine relaxing, as they’re asked to rest for a moment and breathe easy before a blood pressure cuff is wrapped around their arm.

People with borderline hypertension in both categories should confirm the readings by measuring their blood pressure outside their health care provider’s office, according to new research published Monday in the American Heart Association journal Hypertension.

Nearly 93 percent of U.S. adults who have high blood pressure when measured in their doctor’s office and don’t take blood pressure medicine meet the criteria for “white coat hypertension” because their blood pressure is in an acceptable range when re-measured outside a medical setting. Meanwhile, about a third of U.S. adults experience “masked hypertension” because their blood pressure levels measured outside of the doctor’s office are more problematic than measurements at the doctor’s office.

“For some people, a doctor’s office is a place they’re relaxed,” said Paul Muntner, an epidemiologist at the University of Alabama at Birmingham and the study’s senior author. “They are away from job stress, traffic and family issues.”

Others, he said, get anxious they are about to get bad news about their blood pressure – or something worse. Their readings in the doctor’s office cause concern whereas measuring in a more familiar setting would cause less stress.

In either case, the study used the American College of Cardiology and American Heart Association guidelines to determine that as many as 104 million Americans routinely should use a blood pressure machine at home to provide backup for – or a contrast with – the results from their visit to the doctor’s office. People are considered to have high blood pressure if their systolic, or top number, is 130 or higher and their diastolic, or bottom number, is 80 or higher.

Measuring blood pressure outside of a medical setting doesn’t have to be expensive or difficult.

Many pharmacies or grocery stores have blood pressure machines customers can use for free. Reliable home versions with an electronic inflatable cuff can be found at local drug stores for less than $50, and Muntner said the device should be one that already has been tested and validated.

Other options, such as ambulatory blood pressure machines, can be more involved. Those provide readings throughout the day and night and can flag hypertension while people are asleep.

But the sheer size of the population the study suggests should be measuring their blood pressure at home could make it a daunting task to achieve, said Dr. Raymond R. Townsend, who was not associated with the study.

“How many people would be well served by out-of-office blood pressure monitoring? My answer would be virtually anybody,” said Townsend, who heads up the high blood pressure program at the Hospital of the University of Pennsylvania in Philadelphia. “I think that’s a little ambitious.”

The study concedes there are barriers to widespread blood pressure monitoring at home: patient compliance, accuracy of the results, out-of-pocket costs of the device and the time needed to instruct patients on how to take their blood pressure.

What is not subject to debate is the importance of controlling hypertension. The consequences of unmanaged high blood pressure can include heart disease, stroke and organ damage.

And, Muntner said, the study makes a case that there is a benefit to getting more people to check their blood pressure on their own.

“For individual patients, hopefully it means people will be more engaged with their own health care and not just when they go to the doctor’s office.”

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