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Participant demographic and baseline characteristics

In this pooled analysis of 2 cohorts from 6 studies that assessed B/F/TAF in participants ≥ 50 years of age (compared with participants < 50 years of age), baseline characteristics were evaluated across both treatment-naïve and virologically suppressed cohorts (Table 1).

Among treatment-naïve participants, the median age was 55 years (quartile [Q]1, Q3: 52, 60) for those ≥ 50 years of age (n = 96) and 30 years (Q1, Q3: 25, 37) for those < 50 years of age (n = 538). This cohort included 5 participants ≥ 65 years of age, 91 participants 50 to < 65 years of age, and 538 participants < 50 years of age, for a total of 634 participants in the B/F/TAF analysis set. The majority of participants were male at birth, with 84.4% in the ≥ 50 years of age group and 90.0% in the < 50 years of age. Regionally, 58.3% of participants ≥ 50 years of age and 67.8% of those < 50 years of age were from the United States, with the remainder from other countries. Racially, 61.5% of participants ≥ 50 years of age and 56.5% of those < 50 years of age identified as White, while 31.3% and 33.7%, respectively, identified as Black. Hispanic or Latino ethnicity was reported by 11.5% of participants ≥ 50 years of age and 26.9% of those < 50 years of age. Median baseline HIV-1 RNA level was 4.48 log₁₀ copies/mL (Q1, Q3: 4.00, 4.93) for participants ≥ 50 years of age and 4.41 log₁₀ copies/mL (Q1, Q3: 4.00, 4.86) for those < 50 years of age. CD4 T-cell counts were similar, with a median of 436 cells/µL (Q1, Q3: 235, 601) in the ≥ 50 years of age group and 442 cells/µL (Q1, Q3: 299, 590) in the < 50 years of age group. Among participants ≥ 50 years of age, 16.7% had diabetes, 6.3% had cardiovascular disease, 40.6% had hyperlipidemia, and 47.9% had hypertension. Among participants < 50 years of age, 4.1% had diabetes, 1.5% had cardiovascular disease, 8.9% had hyperlipidemia, and 9.7% had hypertension (Table 1).

For the virologically suppressed cohort, the median age was 56 years (Q1, Q3: 52, 60) for participants ≥ 50 years of age (n = 450) and 39 years (Q1, Q3: 33, 45) for those < 50 years of age (n = 640). This cohort included 54 participants ≥ 65 years of age, 396 participants 50 to < 65 years of age, and 640 participants < 50 years of age, for a total of 1090 in the B/F/TAF safety analysis set. Most participants were male at birth, with 76.0% in the ≥ 50 years of age group and 61.4% in the < 50 years of age group. In terms of region, 72.7% of those ≥ 50 years of age and 45.9% of those < 50 years of age were from the United States. Among those ≥ 50 years of age, 64.7% of participants identified as White, 29.1% identified as Black, and 16.0% reported Hispanic or Latino ethnicity. In the < 50 years of age group, 57.7% of participants identified as White, 25.9% identified as Black, and 20.5% reported Hispanic or Latino ethnicity. Baseline virologic suppression was high, with 98.0% (441/450) of those ≥ 50 years of age and 98.8% (632/640) of those < 50 years of age having HIV-1 RNA < 50 copies/mL. Median CD4 T-cell counts were 640 cells/µL (Q1, Q3: 486, 852) for participants ≥ 50 years of age and 691 cells/µL (Q1, Q3: 523, 887) for those < 50 years of age. Medical history showed a notable prevalence of comorbidities among those ≥ 50 years of age: 11.1% of participants had cardiovascular disease, 16.9% had diabetes, 48.9% had hyperlipidemia, and 40.4% had hypertension. Among those < 50 years of age, 2.3% of participants had cardiovascular disease, 5.9% had diabetes, 18.9% had hyperlipidemia, and 17.3% had hypertension (Table 1).

Virologic Outcomes

In the treatment-naïve cohort, virologic suppression (HIV-1 RNA < 50 copies/mL) at Week 240 was achieved by 98.5% of participants (67/68) ≥ 50 years of age (95% CI: 92.1%−100.0%) and by 98.6% of participants (359/364) < 50 years of age (95% CI: 96.8%−99.6%), as determined by the M = E analysis (P = 0.9139; Fig. 1A). In the M = F analysis, virologic suppression at Week 240 was maintained by 69.8% of participants (67/96) ≥ 50 years of age (95% CI: 59.6%−78.7%) and by 66.7% of participants (359/538) < 50 years of age (95% CI: 62.6%−70.7%), with no significant differences observed between the 2 age groups (P = 0.50).

At Week 48 in the virologically suppressed cohort, virologic suppression (HIV-1 RNA < 50 copies/mL), as assessed by the FDA snapshot method, was achieved by 93.6% of participants, with 93.6% of participants (421/450; 95% CI: 90.9%−95.6%) ≥ 50 years of age and 93.6% of participants (599/640; 95% CI: 91.4%−95.4%) < 50 years of age achieving suppression; there were no statistically significant differences between the 2 groups (P = 1.00; Fig. 1B). The proportion of participants with HIV-1 RNA ≥ 50 copies/mL was 0.9% (4/450; 95% CI: 0.2%−2.3%) for participants ≥ 50 years of age and 1.4% (9/640; 95% CI: 0.6%−2.7%) for those < 50 years of age, with no statistically significant differences between the 2 groups (P = 0.58; Fig. 1B). At Week 48, virologic suppression (HIV-1 RNA < 50 copies/mL) was achieved by 99.3% of participants (426/429; 95% CI: 98.0%−99.9%) ≥ 50 years of age and 98.7% of participants (602/610; 95% CI: 97.4%−99.4%) < 50 years of age in the M = E analysis. The difference between the 2 age groups was not statistically significant (P = 0.54). At Week 48, virologic suppression (HIV-1 RNA < 50 copies/mL) was achieved by 94.7% of participants (426/450; 95% CI: 92.2%−96.6%) ≥ 50 years of age and 94.1% of participants (602/640; 95% CI: 91.9%−95.8%) < 50 years of age in the M = F analysis. The difference between the 2 age groups was not statistically significant (P = 0.69). No treatment-emergent resistance to B/F/TAF was observed in either age group through Week 240 in the treatment-naïve cohort or through Week 48 in the virologically suppressed cohort.

CD4 T-cell counts 

At Week 240 in the treatment-naïve cohort, CD4 T-cell counts continued to increase from baseline in both age groups (mean [SD] change from baseline: +291 [221.3] for participants ≥ 50 years of age and + 347 [238.2] for those < 50 years of age; least squares mean difference [LSMD]: − 58 [range: − 120, 4]; P = 0.07). At Week 48 in the virologically suppressed cohort, CD4 T-cell count also increased from baseline among participants ≥ 50 years of age and those < 50 years of age (mean [SD] change from baseline: +18 [162.5] and + 4 [174.9] cells/µL, respectively; LSMD: 15 [range: − 7, 36]; P = 0.18), indicating no statistically significant difference between age groups.

Adherence

Adherence to B/F/TAF through Week 240 for the treatment-naïve cohort and through Week 48 for the virologically suppressed cohort is shown in Table 2. In the treatment-naïve cohort, the median adherence rate was high in both age groups, with participants ≥ 50 years of age showing a median (Q1, Q3) adherence of 98.2% (96.7, 99.4) and those < 50 years of age at 97.0% (93.2, 98.9). A greater proportion of participants ≥ 50 years of age achieved an adherence rate of ≥ 95% compared with those < 50 years of age (82.8% vs. 66.3%, respectively; P = 0.002; Table 2). In the virologically suppressed cohort, the median adherence rate was also high for both age groups at Week 48, with a median (Q1, Q3) adherence of 98.8% (96.8, 99.7) for participants ≥ 50 years of age and 98.8% (96.8, 99.7) for those < 50 years of age. The proportion of participants with adherence rates of ≥ 95%, ≥ 85 to < 95%, and < 85% was similar between age groups, indicating consistent adherence across age categories in the virologically suppressed cohort (Table 2).

Outcomes in body weight, lipid profile, renal function, and bone health

Change from baseline in body weight through Week 240 is shown for participants ≥ 50 and < 50 years of age in the treatment-naïve cohort and through Week 48 for the virologically suppressed cohort. In the treatment-naïve cohort, there were no significant overall differences in weight change at Week 240 between participants ≥ 50 years of age and those < 50 years of age. The median (Q1, Q3) weight gain was 4.8 kg (0.7, 10.2) for participants ≥ 50 years of age and 6.4 kg (2.4, 12.0) for those < 50 years of age. At Week 48 in the virologically suppressed cohort, change in body weight was minimal, with a median (Q1, Q3) weight gain of 1.5 kg (–0.8, 3.8) for participants ≥ 50 years of age and 1.8 kg (–0.4, 4.0) for those < 50 years of age. No significant difference in weight change was observed between age groups in either cohort (Table 3 and Supplement Table 1).

Change from baseline in fasting lipid parameters, specifically the TC: HDL ratio, was assessed across both age groups. At Week 240 in the treatment-naïve cohort, the median (Q1, Q3) change from baseline in TC: HDL ratio was − 0.3 (–0.9, 0.4) for participants ≥ 50 years of age and 0.1 (–0.4, 0.6) for those < 50 years of age. At Week 48 in the virologically suppressed cohort, change in the TC: HDL ratio was minimal, with a median (Q1, Q3) change of − 0.1 (–0.5, 0.4) for participants ≥ 50 years of age and 0.0 (–0.4, 0.3) for those < 50 years of age (Table 3). Additionally, the proportion of participants who initiated lipid-modifying agents during the study was higher among those ≥ 50 years of age compared with those < 50 years of age (5.3% vs. 0.8%, respectively; P < 0.0001).

Change from baseline in eGFR was similar across age groups in both the treatment-naïve and virologically suppressed cohorts. At Week 240 in the treatment-naïve cohort, the median (Q1, Q3) change in eGFR from baseline was − 10.5 mL/min (–19.6, 2.4) for participants ≥ 50 years of age and − 7.7 mL/min (–19.4, 3.0) for those < 50 years of age, with no statistically significant difference between age groups (P = 0.30). At Week 48 in the virologically suppressed cohort, the median (Q1, Q3) change in eGFR was − 0.9 mL/min (–8.1, 5.8) for participants ≥ 50 years of age and − 1.0 mL/min (–9.6, 8.4) for those < 50 years of age (P = 0.92), indicating minimal change and no significant difference across age groups (Table 3).

Change from baseline in BMD was minimal and similar between age groups in both cohorts. At Week 240 in the treatment-naïve cohort, the mean (SD) percent change in hip BMD was 0.3% (3.26%) for participants ≥ 50 years of age and − 0.4% (5.80%) for those < 50 years of age, while mean (SD) percent change in spine BMD was 1.3% (5.64%) and − 0.9% (4.95%), respectively. At Week 48 in the virologically suppressed cohort, the mean (SD) percent change in hip BMD was 0.2% (2.43%) for participants ≥ 50 years of age and 0.1% (2.03%) for those < 50 years of age; mean percent change in spine BMD increased by 0.5% (3.52%) and 0.8% (2.78%), respectively. No significant difference was observed between age groups in either cohort (Fig. 2).

Other safety outcomes

In the treatment-naïve cohort, TEAEs were reported by 93.8% of participants ≥ 50 years of age and by 95.5% of those < 50 years of age, with study drug–related TEAEs in 26.0% and 28.4% of participants, respectively. Grade 3 or 4 TEAEs affected 31.3% of participants ≥ 50 years of age and 19.0% of those < 50 years of age, with serious TEAEs in 34.4% and 19.1% of participants, respectively. Discontinuation due to TEAEs occurred in 4.2% and 1.1% of participants in the ≥ 50 and < 50 years of age groups, respectively, with 6 deaths (6.3%) among those ≥ 50 years of age and 2 deaths (0.4%) among those < 50 years of age. In the virologically suppressed cohort, TEAEs were observed in 78.7% of participants ≥ 50 years of age and in 77.2% of those < 50 years of age, with study drug–related TEAEs in 12.9% and 12.5% of each group, respectively. Grade 3 or 4 TEAEs were seen in 7.3% and 4.7% of participants ≥ 50 and < 50 years of age, respectively, with serious TEAEs in 8.7% and 4.7%. Discontinuation due to TEAEs occurred in 1.8% of participants ≥ 50 years of age and 0.9% of those < 50 years of age, with 2 deaths reported in each age group (0.4% and 0.3%, respectively; Table 4).

Treatment-emergent diabetes and hypertension

Treatment-emergent (events that occur while on study) diabetes and hypertension through Week 240 for the treatment-naïve cohort and through Week 48 for the virologically suppressed cohort are shown in Table 5. From baseline to Week 240, treatment-emergent diabetes was observed in 5.1% of participants ≥ 50 years of age and 1.7% of those < 50 years of age (P = 0.08). Treatment-emergent hypertension was reported in 19.6% of participants ≥ 50 years of age and 12.5% of those < 50 years of age (P = 0.19). At Week 48 in the virologically suppressed cohort, the incidence of treatment-emergent diabetes was 1.1% in participants ≥ 50 years of age and 1.3% in those < 50 years of age (P = 1.00), while treatment-emergent hypertension was observed in 5.2% of participants ≥ 50 years of age and 2.6% of those < 50 years of age (P = 0.07). No significant difference in rates of treatment-emergent diabetes or hypertension was found between age groups in either cohort (Table 5).

In an effort to make personal transport more accessible, Standard Chartered Bank has launched a financing option for Yamaha motorcycles in Pakistan. The bank’s Aasan Instalment Plan allows credit card holders to purchase any Yamaha bike with 0% mark-up, spreading payments over 12 months. This initiative aims to ease the financial burden on buyers, making Yamaha motorcycles more affordable.

Offer Details:

• No interest charges during the 12-month tenure.
• Available on all Yamaha bike models.
• Flexible payment options with zero processing fee for the 0% markup.

The offer provides a budget-friendly way for individuals to buy a Yamaha motorcycle without the usual financing charges. Standard Chartered credit card holders can apply through the bank’s helpline and enjoy easy monthly payments.

Competition in the Market:

While Yamaha offers this no-interest plan, competitors like Honda and Suzuki are also stepping up with installment-based schemes. However, Yamaha’s 0% mark-up on their plan distinguishes it from others, providing a significant advantage in the budget-conscious market.

How to Apply:

Eligibility: Must be a Standard Chartered credit card holder in good standing.

Customers can reach out to Standard Chartered’s helpline at 021-111-002-002 for more details and to place orders.

This limited-time offer underscores the growing demand for affordable financing options and sets Yamaha ahead in the competitive motorcycle market.

JS Bank Limited (PSX: JSBL) reported a sharp decline in earnings for 1HFY25, with consolidated profit after tax falling 45.1% YoY to Rs5.32 bn. Earnings per share dropped to Rs1.99 from Rs3.86 a year earlier, according to the bank’s filing with the PSX.

Key Drivers:

Margin compression: Net mark-up income fell 8.3% to Rs32.45 bn, reflecting lower asset yields despite reduced funding costs.

Non-mark-up income gains: Jumped 40.8% to Rs12.51 bn, mainly due to Rs4.63 bn in securities gains (+281% YoY).

Foreign-exchange income decline: FX revenue fell 61%, reducing a historically important buffer.

Rising costs: Operating expenses surged 26.7% to Rs30.18 bn, pushing the cost-to-income ratio to ~68%.

Higher credit charges: Credit loss allowance jumped 79.8% to Rs2.28 bn, further pressuring profitability.

Pre-tax profit: Declined 36.4% to Rs11.93 bn.

The results highlight underlying pressure on core banking income, with trading gains cushioning the decline. Investors remain cautious, given the reliance on volatile income sources amid rising costs.

JS Bank 1HFY25 Consolidated Figures (vs 1HFY24)

Metric	1HFY25	1HFY24	Change
PAT	Rs5.32 bn	Rs9.70 bn	-45.1%
EPS	Rs1.99	Rs3.86	-48.4%
Net Mark-up Income	Rs32.45 bn	Rs35.38 bn	-8.3%
Non-Mark-up Income	Rs12.51 bn	Rs8.88 bn	+40.8%
Gains on Securities	Rs4.63 bn	Rs1.22 bn	+281%
Operating Expenses	Rs30.18 bn	Rs23.82 bn	+26.7%
Credit Loss Allowance	Rs2.28 bn	Rs1.27 bn	+79.8%
Pre-tax Profit	Rs11.93 bn	Rs18.75 bn	-36.4%

JS Bank’s half-year performance underscores margin pressure, rising costs, and higher credit charges. Future profitability will depend on restoring core income growth and managing expenses without over-reliance on trading gains.

 

Human epidermal growth factor receptor 2 (HER2)-positive breast cancer represents approximately 20% of breast cancer diagnoses worldwide and is historically associated with aggressive disease biology and poorer prognoses. Even as therapies like trastuzumab (Herceptin; Genentech), pertuzumab (Perjeta; Genentech), and other tyrosine kinase inhibitors have revolutionized outcomes, challenges with drug resistance and harmful effects still pose issues. This leads to a need for novel therapeutic approaches.¹

Natural products, long regarded as a source of drug discovery, are now being re-examined. A new study published in Current Research in Structural Biology explored the anti-HER2 effect of two alkaloids derived from Mitragyna speciosa (or kratom), mitragynine and 7-hydroxymitragynine (7-OH). They used tests, including molecular docking, molecular dynamics simulations, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling, to explore these possible effects.¹

The investigators reported that both mitragynine and 7-OH demonstrated stable binding affinity with the HER2 receptor. Docking analysis showed binding energies of –7.56 kcal/mol for mitragynine and –8.77 kcal/mol for 7-OH, with interactions observed at key residues such as Leu726, Val734, Ala751, Lys753, Thr798, and Asp863.¹ These results suggest that both compounds could effectively occupy HER2’s active site, potentially disrupting oncogenic signaling pathways. Molecular dynamics simulations demonstrated the stability of all 3 complexes, including mitragynine, 7-OH, and native (SYR127063), over the simulation period.¹

Further binding free energy validation using the MM-PBSA method supported these findings. SYR127063, the control variable, exhibited the strongest binding, while mitragynine and 7-OH showed moderately strong affinities. Importantly, both compounds satisfied multiple drug-likeness rules, including Lipinski, Ghose, Veber, Egan, and Muegge filters, and demonstrated favorable ADMET properties, indicating their potential as viable lead molecules for further preclinical investigation.^1,2

These results align with broader work in oncology to use natural compounds as cancer-fighting tools. Past research has shown the worth of plant-based chemicals as sources of bioactive molecules that can modulate cell signaling, apoptosis, and angiogenesis in cancer models. The chance for mitragynine and its byproduct to act as HER2 blockers is notable, given how much dependence there is on biologic treatments and the need for small-molecule alternatives that may cost less and be more accessible.

For pharmacists, these early-stage findings are important. Although the data remain strictly computational and require extensive laboratory validation, they highlight the role of computational drug discovery in oncology. Pharmacists should be aware of new natural product-based therapies, as these compounds may soon enter preclinical tests and lead to new oral HER2 inhibitors. Since mitragynine and 7-OH are main compounds of kratom, pharmacists must also keep an eye on regulatory considerations and the need to differentiate between recreational kratom use and carefully derived pharmaceutical applications.

Mitragynine and 7-OH from Mitragyna speciosa demonstrate promising early results in silico activity against HER2 and possess favorable drug traits and pharmacokinetic profiles. Although these findings are not ready for clinical recommendations, they set the base for further laboratory validation and may lead to new drug development. If these compounds work well in future clinical studies, they may represent an innovative natural product–based strategy for overcoming resistance and improving outcomes in HER2-positive breast cancer.

REFERENCES

1. Akbar NH, Suarantika F, Fakih TM, Haniffadli A, Muslimawati K, Putra AMP. Screening, docking, and molecular dynamics analysis of Mitragyna speciosa (Korth.) compounds for targeting HER2 in breast cancer. Curr Res Struct Biol. 2025;10:100171. Published 2025 Jun 20. doi:10.1016/j.crstbi.2025.100171

2. Ryan BM, Faupel-Badger JM. The hallmarks of premalignant conditions: a molecular basis for cancer prevention. Semin Oncol. 2016;43(1):22-35. doi:10.1053/j.seminoncol.2015.09.007

China’s Pop Mart says it is rolling out a mini version of its popular Labubu plush toys this month, along with a new long-fur version of the toothy little monster.

The Labubu, by artist and illustrator Kasing Lung, first appeared with pointed ears and pointy teeth, in three picture books inspired by Nordic mythology in 2015.

In 2019 Lung struck a deal with Pop Mart, a company that caters to toy connoisseurs and influencers, to sell Labubu figurines. But it wasn’t until Pop Mart started selling Labubu plush toys on key rings in 2023 that the toothy monsters suddenly seemed to be everywhere.

Pop Mart said Friday that the mini-sized Labubu vinyl plush pendant, which is part of The Monsters Pin For Love series, will be available in various colors corresponding to letters of the alphabet. They will cost $22.99 each.

The series also includes 30 letter pendant blind boxes, each with a unique pattern and Monsters charm. They will be priced at $18.99 a piece.

In addition, Pop Mart is launching the Rock the Universe vinyl plush doll, which is part of The Monsters Big Into Energy Series. The plush, which will have a pearl-and-alloy heart necklace, will be the first of the Monsters to have long fur and uses a specialized dyeing technique that ensures no two figures are exactly alike. The dolls will cost $114.99 each.

All of the new products will be available starting Aug. 29 on Pop Mart’s website either for in-store pickup or shipping. They will also be available on the company’s app and its official TikTok accounts.

Labubu has been a bonanza for Pop Mart. Its revenue more than doubled in 2024 to 13.04 billion yuan ($1.81 billion), thanks in part to its elvish monster. Revenue from Pop Mart’s plush toys soared more than 1,200% in 2024, nearly 22% of its overall revenue, according to the company’s annual report.

Earlier this week Pop Mart reported that its profit attributable to shareholders skyrocketed almost 400% for the first six months of the year. Revenue jumped more than 200% to 13.88 billion yuan ($1.93 billion). Revenue for the Asia Pacific region surged more than 250%, while revenue for the Americas soared more than 1,000%.