5 breakthroughs in medicine this week
... including the 10th person to be cured of HIV
1. The 10th patient with long-lasting HIV remission
Of the ~90 million people who’ve been infected with HIV in history, the number who have now achieved long-term remission (and possible cure) is now 10! Those patients are as follows: 2009 – Berlin patient; 2019 – London patient; 2022 – City of Hope patient; 2022 – New York patient; 2023 – Düsseldorf patient; 2023 – Geneva patient; 2024 – France patient; 2025 – Chicago patient; 2025 – Oslo patient; and, new this week, the second Berlin patient; 2025.
Most of these patients received haematopoietic stem cell transplants from donors deficient in both copies of an HIV receptor (CCR5), which are resistant to infection by most HIV strains — it’s thought that’s what led to HIV remission.
But this paper, in this week’s Nature, shifts this paradigm, reporting HIV remission following a stem cell transplant from a donor heterozygous in CCR5. The new immune cells still have one copy of CCR5, which means they can still be infected with HIV.
The patient is a 60-year old man in Berlin, who was diagnosed with HIV in 2009. In 2015, he was diagnosed with an aggressive blood cancer (acute myeloid leukaemia) which is why he had the stem cell transplant. After this he was able to stop antiretroviral therapy completely — and he’s now been in HIV remission for > 6 years.
So, how did this induce remission? There are 3 leading theories:
The donor immune cells attacked and killed HIV-infected immune cells (‘graft-versus-reservoir’)
The patient had potent HIV-specific antibodies (probably as a result of a long period when his HIV was untreated)
The conditioning chemotherapy he received (as part of the stem cell transplant) killed HIV-infected cells — which were then fully replaced by donor cells.
That a cure is feasible with a heterozygous CCR5 genotype is a biological breakthrough — but from a clinical perspective it might not make a major difference — and the approval of Lenacapavir probably remains HIV breakthrough of the year.
2. The shingles vaccine could prevent — and delay progression of — dementia
The most common types of dementia are Alzheimer’s and vascular dementia, but the best medicines we have only marginally slow progression.
Earlier this year we saw that shingles vaccination might reduce dementia risk — both for the live-attenuated vaccine and for the recombinant vaccine. This new study, in this week’s Cell, uses the same natural experiment to find that shingles vaccination also seems to prevent progression of dementia.
The Cell study finds that shingles vaccination is associated with less mild cognitive impairment in healthy people; less dementia in people with mild cognitive impairment; and less death, in people with dementia. This effect was seen both for Alzheimer’s and vascular dementia — and was actually strongest for mixed dementia (where there’s an element of both).
The data come from (very high quality) natural experiments so far, but this is a highly reproducible finding that’s now been reported many times — randomized trials are underway, too.
There may be a few reasons that this works:
1) Shingles vaccination reduces invasion of the virus that causes shingles (varicella zoster) into the brain — meaning less neuroinflammation and neuronal injury.
2) Shingles vaccination reduces the known stroke risk associated with shingles (stroke is the main cause of vascular dementia).
3) Shingles vaccination might amplify antiviral immune responses against other viruses linked to dementia.
4) Shingles vaccination prevents the pain, sleep loss, and inactivity that shingles causes (all of which contribute to increased dementia risk).
3. One HPV vaccine dose is just as good as two
The HPV vaccine is one of the most impactful in history. It’s driving down incidence of cervical cancer, and, in some cohorts, there are 0 cases of cervical cancer in those who’ve received vaccines.
New data from the New England Journal of Medicine (NEJM) this week look at the efficacy of one vs. two doses of the nonavalent HPV Vaccine (Gardasil-9) against the main carcinogenic HPV strains, 16 and 18. Efficacy of two doses was 98.5%, and of one dose was 97.0%.
So, in this population (girls aged 12 to 16 years) — one dose is just as good as two.
The world health organisation already recommends one dose of the HPV vaccine (in those aged up to 20) and >80 countries have now adopted this one-dose schedule, but still less than 30% of adolescent girls have had the vaccine globally. Adopting a one-dose schedule globally could massively ramp up access.
4. Another badly-needed target for osteoarthritis
By 2050, over a billion people will have osteoarthritis — in the knee, hips, or hands. Despite this, there are no disease-modifying treatments.
This study, published in Science this week, adds a new, exciting target. It’s a protein whose levels increase with age — previously described as a gerozyme and a hallmark of aging — called 15-PGDH, a prostaglandin-degrading enzyme that regulates inflammation.
It turns out that this protein drives osteoarthritis, too, and — in mice — its inhibition rebuilds cartilage.
Inhibition of this same protein seems to boost muscle mass and strength in aged mice, too — quite the anti-aging target!
5. The second medicine for a rare kidney disease
The best day I had in medical school, I helped out with a kidney transplant from a dad to his son. The patient had a condition called C3 glomerulopathy.
This is a very rare kidney condition that causes loss of protein in urine, swelling, and high blood pressure. It has a prevalence of ~10 per million, and the median age of diagnosis age ~21–23 years. It’s usually autoimmune or post-infectious in origin, and follows an aggressive path, with 50% of patients progressing to kidney failure in 10 years. Even after transplant it’s not cured: the disease can return to the transplanted kidney.
As the name suggests, it’s mediated by C3 complement, with C3 deposition in the glomerulus of the kidney. The first drug to be approved for this condition (in March of this year) was the complement factor B inhibitor, Iptacopan.
The second drug approved was Pegcetacoplan, in July of this year, on the basis of this trial, which was published in NEJM this week. Pegcetacoplan is an inhibitor of complement C3 and C3b — so it blocks the entire pathway:
In the trial, this reduced proteinuria (a measure of how much protein is lost in urine, and a surrogate for decline in kidney function) by almost 70% — ‘remarkable’, according to the NEJM editorial. It dramatically reversed the pathology of the disease too — as shown in these beautiful data:
We didn’t have this drug when I helped with the kidney transplant — but I wish we did.
Thank you for reading! Let me know what you think!