Study shows HIV vaccine ineffective

31st January 2023

A HIV vaccine trial has been terminated early because despite being safe it proved to be ineffective compared to placebo

A trial of a HIV vaccine has been terminated due to ineffectiveness according to a press release by Janssen pharmaceuticals who led on the study together with a global consortium.

Despite HIV having been first discovered in 1983, there are still no vaccines available against the virus. Moreover, data shows that currently, across the world, there are approximately 1.5 million peopled infected with the virus.

In 2021, findings from a phase 2b, proof of concept trial, Imbokodo, were made available. In the study, 2,637 sub-Saharan women, aged 18 to 35, received an investigational vaccine, based on mosaic immunogens, which are engineered human immunodeficiency virus type 1 (HIV-1) sequences designed to elicit clade-independent coverage against globally circulating HIV-1 strains. The vaccine used a common-cold virus (adenovirus serotype 26, Ad26) and was designed to deliver four antigens to illicit an immune response. The primary endpoint of the study was based on the difference in HIV infections between the vaccine and placebo groups, from month 7 (which was one month after the third vaccination dose) through to month 24. Unfortunately, the results showed that vaccine’s efficacy was only 25.2%, although fortunately, the study did not identify any safety concerns.

In 2019, the phase 3 Mosaico study (also referred to as HPX3002/HVTN706) was initiated and which is the trial referred to in the press release. The aim of the study was to evaluate the efficacy of a heterologous vaccine, Ad26.Mos4.HIV, a tetravalent vaccine, for the prevention of HIV-1 infection among HIV-1 seronegative cis-gender men and transgender individuals who had sex with cis-gender men and or transgender individuals. The vaccine was administered four times over 12 months and with the final two vaccine doses, individuals were also given a bivalent protein formulation containing two HIV envelope proteins, clade C gp140 and mosaic gp140, adjuvanted by aluminium phosphate to boost immune responses.

However, at a meeting of the study’s independent Data and Safety Monitoring Board, it was deemed that the regime was not effective at preventing HIV infection The study’s independent Data and Safety Monitoring Board (DSMB) determined that the regimen was not effective in preventing HIV infection compared to placebo.

Commenting on the findings in the Janssen press release, Penny Heaton, Global Therapeutics Area Head Global Therapeutic Area Head, said ‘We are disappointed with this outcome and stand in solidarity with the people and communities vulnerable to and affected by HIV‘. She added that ‘we remain steadfast in our commitment to advancing innovation in HIV, and we hope the data from Mosaico will provide insights for future efforts to develop a safe and effective vaccine. We are grateful to our Mosaico partners and the study investigators, staff and participants.’

Pomegranate juice combined with aerobic training improves type 2 diabetes risk factors

16th June 2022

Adding pomegranate juice to aerobic training could be an effective strategy for improving risk factors in patients with type 2 diabetes

Combing pomegranate juice (PJ) and aerobic training led to improvements in anthropomorphic indices and markers of insulin resistance among patients with type 2 diabetes and may therefore represent an important approach to risk modification in these patients. This was the conclusion of a trial by a team from the Department of Exercise Physiology, Faculty of Sport Sciences, Razi University, Kermanshah, Iran.

In a 2017 study it was estimated that globally, approximately 462 million individuals had type 2 diabetes, which equates to just over 6% of the world population leading to over 1 million deaths per year. In addition, elevated levels of the liver enzymes, alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyltransferase (GGT) and alkaline phosphatase (ALP) have been found to be significantly associated with an increased risk of diabetes. Lifestyle modification is an important first step in patients with type 2 diabetes with one 2019 systematic review finding that the condition is preventable by changing lifestyle and that the risk reduction is sustained for many years after the active intervention. In patients with type 2 diabetes, the hyperglycaemic state results in the production of free radicals, increasing oxidative stress and use of a dietary invention with pomegranate juice has been shown to exert a favourable effect on this oxidative stress. Pomegranate juice contains a large number of anti-oxidative poly-phenolic compounds which are assumed to have cardioprotective effects. In fact, a 2019 trial found that PJ consumption decreased systolic and diastolic blood pressure in patients with type 2 diabetes.

Since aerobic training improves insulin sensitivity and lowers insulin resistance, for the present study, the Iranian team wondered if there were additional benefits from combing aerobic training with pomegranate juice. They conducted an 8-week trial and randomised middle-aged men with type 2 diabetes into four groups: aerobic training (AT) and pomegranate juice (AT+PJ); AT and PJ alone and a control group. Those assigned to PJ drank 240 ml of pure juice once daily whereas the control group had a water-based, identical drink. Measurements of bodyweight (BW), body mass index (BMI), waist-hip ratio (WHR) and body fat percentage (BFP) were taken at baseline and at the end of trial. Other assessments included ALT, AST and GGT as well as fasting blood sugar (FBS), insulin levels and HOMA-IR – a measure of insulin resistance.

Pomegranate juice and diabetic outcomes

A total of 40 middle-aged men with a mean age of 42.2 years were randomised between the four groups.

At the end of the study there were statistically significant reductions in BW, BMI, BFP and WHR for those in the AT+PJ, AT and PJ groups compared to the control group. However, there were no significant differences between the AT+PJ, AT or PJ groups.

Reductions also occurred in FBS, HOMA-IR and insulin but this time, the reductions were significantly greater for the AT+PJ group compared to either the AT or PJ groups alone. While levels of the three liver enzymes were also significantly reduced compared to the control group, ALT and GGT levels were significantly lower in the AT+PJ compared to AT and GGT was significantly lower in the AT+PJ group compared to PJ alone.

The authors concluded that based on these findings, a combination of aerobic training and pomegranate juice could be recommended to patients with type 2 diabetes to prevent increases in the levels of liver enzymes associated with diabetes and to improve insulin resistance.

Citation
Nemati S et al. Pomegranate juice intake enhances the effects of aerobic training on insulin resistance and liver enzymes in type 2 diabetic men: a single-blind controlled trial BMC Nutr 2022

Large placebo response in subjective and objective measures in RA trials

9th October 2020

It is largely expected that in a randomised, double-blind clinical trial, individuals assigned to placebo will experience some level of improvement in relevant outcomes and this can lead to an underestimation of the effectiveness of the therapy being tested.

Consequently, researchers often use a combination of objective and subjective measures when assessing the response to treatment. For instance, it is known that subjective measures, for example, pain scores can be high, hence the need for independent, objective measures. However, in a new analysis of the placebo response among patients in trials for rheumatoid arthritis therapies, a team from the Brigham and Women’s Hospital, Boston, USA, found significant improvements in both measures. The team examined the placebo arm responses for five double-blind trials conducted internationally of at least 24 weeks duration between 2005 and 2009 among patients with rheumatoid arthritis. They extracted the individual level patient data from trials and focused on pain scores (subjective) and C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) values, both of which are objective measures. Pain scores were assessed using a standardised measure, namely a 0 to 100 mm visual analogue scale (VAS) and CPR and ESR were measured by blood testing. As some patients in the trials crossed-over to the active treatment, the researchers pre-selected 12 weeks from baseline to assess responses. Study medications included methotrexate and other disease-modifying antirheumatics.

Findings
The data set included 788 patients (82% women) with a mean age of 51 years. There was a statistically significant reduction in pain intensity (-14mm, 95% CI – 12 to 16 mm), CRP levels (-0.51mg/dl 95% CI -0.47 to -0.56) and ESR (-11mm/h, 95% CI -10 to -12), all with p values less than 0.001. Commenting on their findings, the authors were surprised by the clinically meaningful reductions in subjective and objective measures observed in placebo participants, indicating that it was more than a psychological placebo effect.

Furthermore, the cautioned that simply using objective rather than subjective measures in future trials would not necessarily lead to clearer results and that there was a need to further understand the effect of confounding factors and baseline covariates in placebo responders.

Reference
Vollett J et al. Assessment of placebo response in objective and subjective outcome measures in rheumatoid arthritis clinical trials. JAMA Netw Open 2020;3(9):e2013196. doi:10.1001/jamanetworkopen.2020.13196