Maraviroc Fights Middle-Aged Memory Loss

News
#31

This study demonstrated some significant neuro-cognitive benefits of Maraviroc in humans (albeit in an HIV-infected population):

Background & Rationale

  • HIV-associated neurocognitive disorders (HAND): Despite effective combined antiretroviral therapy (cART), 20–50% of HIV patients continue to show cognitive impairment, especially in psychomotor speed, working memory, learning, and executive function.
  • Challenges: HAND persists due to chronic inflammation, low-level CNS viral replication, and variable CNS penetration of drugs.
  • CCR5 role: HIV replication in the brain heavily depends on CCR5. The CCR5 antagonist maraviroc (already approved for HIV treatment) has:
    • Good CNS penetration.
    • Anti-inflammatory effects.
    • Shown neuroprotective potential in animal and early human studies.
  • Objective: Test whether maraviroc-intensified cART improves neurocognition in virally suppressed HAND patients

Results

  • Participants:
    • 17 randomized (9 maraviroc, 8 control).
    • 14 completed study (9 maraviroc, 5 control).
    • Mostly middle-aged White males (~55 years), moderate education, long-term HIV with stable suppression.
  • Primary Outcome (Neurocognition):
    • Improvement in maraviroc arm:
      • 6 months: large effect size (d = 0.77).
      • 12 months: moderate effect size (d = 0.55).
    • No baseline differences between groups.
    • Suggests sustained cognitive benefit from maraviroc intensification.
  • Secondary Outcomes:
    • MRS brain metabolites: No significant treatment-related changes.
    • CSF biomarkers: No treatment-related changes in neopterin or β2-microglobulin.
    • Indicates clinical improvement occurred without measurable biomarker/metabolite changes

Abstract:

https://journals.lww.com/aidsonline/abstract/2016/02200/maraviroc_intensified_combined_antiretroviral.7.aspx

Full paper on Sci-hub

https://sci-hub.ru/10.1097/QAD.0000000000000951

3 Likes
#32

Is anyone trying / using this?

#33

I would try it, if I could get the medications. Given that India and most other countries shipping medications are shut down right now, its very difficult I think.

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#34

"C-C chemokine receptor type 5, also known as CCR5 or CD195, is a protein on the surface of white blood cells that is involved in the immune system as it acts as a receptor for chemokines.[5] " (CCR5 - Wikipedia)

“In addition to playing a major role in the activation of host immune responses, chemokines are important for biological processes, including morphogenesis and wound healing, as well as in the pathogenesis of diseases like cancers.[1][3]” (Chemokine - Wikipedia)

Seems like its main systemic functions point to the same direction as growth (aka displacement) signals. So, blocking another one abnormal growth signal reverses some aging and senescence outcomes.
But rapamycin also does the similar thing (blocks abnormal growth signal).
Are rapamycin effects on cognitive function less effective?

1 Like
#35

One of the primary regulators of CCL5 expression is TLR4 signaling (e.g by bacterial LPS), which can induce >800-fold expression in macrophages. This regulation is quite stringent compared to other TLR4-induced genes (requiring both NF-κB and IRF3 for promoter remodeling), which suggests that CCR5 (and/or other activities of CCL5) signaling must be precisely regulated.

There’s also evidence that TLR4 variants govern longevity, although of course this doesn’t prove a CCL5-dependent mechanism.

The role of lipopolysaccaride receptor TLR4 is paradigmatic. It initiates the innate immune response against gram-negative bacteria; and TLR4 polymorphisms, as ASP299GLY, suggested to attenuate receptor signaling, have been described. We demonstrated that TLR4 ASP299GLY polymorphism shows a significantly lower frequency in patients affected by myocardial infarction compared to controls, whereas centenarians show a higher frequency.

#36

Interesting to see this self-report on Maraviroc helping in CFS below. Note that it seems that Maravoc was one of the best treatments…

G01qjOOawAAvKZw
G01qjOOawAAvKZw1920×1509 236 KB

Source:

Patient-reported treatment outcomes in ME/CFS and long COVID

https://www.pnas.org/doi/10.1073/pnas.2426874122

Related:

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#37

This is looking like a “No Brainer”.

And at a reasonable{in my view] cost at Walgreens with the discount code below, a prescription is required

U.S. Prescription Discount Coupon _ PharmacyChecker.com.pdf (282.8 KB)

1 Like
#38

The challenge would be to get a prescription… perhaps via Push? Or if you have a very open minded doctor.

1 Like
#39

Hire a physician that work for You, not the other way.

This is not that difficult to locate{a physician]

#40

As it appears this is going to be the Maravircoc Thread…

Review

My view…

Cost{out of pocket in the US]is less the $10.00 per day.

This is not unreasonable to try for several months.

Review the following ;

“Potential application of maraviroc in the therapy of neuropathic pain”.

Sojka P 1, Właszczuk A 1, Olakowska E 1

Author information

Polski Merkuriusz Lekarski : Organ Polskiego Towarzystwa Lekarskiego, 01 Oct 2021, 49(293):379-381Language:pol
PMID: 34800029

Abstract

According to International Association for the Study of Pain (IASP) neuropathic pain is defined as a pain caused by a lesion or disease of the somatosensory nervous system. In general population 7-8% adults suffer from chronic pain with neuropathic characteristic. The most common causes include: lumbar radiculopathy, postherpetic neuropathy, HIV infection, autoimmune diseases (multiple sclerosis), metabolic diseases (diabetic neuropathy), stroke or spinal cord injury. Current pharmacotherapy of neuropathic pain has insufficient effectiveness, so comprehension of neuropathic pain mechanism is necessary for research of new therapeutic methods. In the study we verify the analgesic effect of maraviroc (antagonist of the chemokine receptor - CCR5) and its potential role in the treatment of neuropathic pain. In the study we focused on dependency between opioid and chemokine receptors, because of similar structure between this receptors occurs cross-desensitization phenomenon. Chemokine antagonist maraviroc belongs to a group of entry inhibitors, antiretroviral drug. It enhances analgesic properties of opioids by inhibition of crossdesensitization of opioid’s receptor. Application of maraviroc with morphine can reduce effective dosage of morphine 2,3 fold. Moreover, research show that prophylactic administration of maraviroc without opioid analgesics suppresses development of neuropathic pain symptoms. It has influence on glial phenotype, decreases secretion of proinflammatory cytokines and increases anti-inflammatory cytokine secretion. Furthermore it decreases expression of chemikine receptor mRNA and chemikine ligand’s secreted by microglia and astrocytes as a result of nerve injury. We conclude that maraviroc has immunomodulatory properties, potentiates opioid analgesics effect, and can be used in neuropathic pain therapy as a potential co-analgesic.

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Li SL, Li J, Xu HC, Liu YC, Yang TT, Yuan H

Ibrain, 8(1):23-36, 02 Mar 2022

Cited by: 8 articles | PMID: 37786421 | PMCID: PMC10529196

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Above from:

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#41

I have not done a deep dive into the infection-fighting drugs with regard to their impact on memory and brain function - so I can’t comment on that.

  1. We are still in the very earliest days with regard to possible uses of these antiviral type drugs in longevity protocols. I’m open to trying these, given the good safety data I could find (and taking Dr. Fraser’s perspective that you want to be careful with drug/drug interactions, so may want to pause rapamycin while initiating any trials). But so far I’ve seen nobody even trying these drugs in longevity applications yet. I think it would be interesting to do a battery of pre-testing of cognitive function, such as done via the NeuroAge app: Predicting Alzheimers & Dementia (and minimizing risk) - #313 by RapAdmin , and then retesting after a week or a month of using Maraviroc.

I’ve seen no studies that link drugs like Maraviroc to increased lifespan, so I think the data so far is limited to specific areas, though broadly of course inflammation is an issue in aging, so there could be some systemic benefits.

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#42

Right on, thanks for the reply. Glad to hear all that. Had no idea.
Hopefully you can trial Maraviroc one day and share your review on it.
You bring up a good point about it being limited to specific areas, and it appears to be only available in a few continents.
Might be a while before seeing any results for increased lifespan from the data.

Though would be cool to have people who use (or can get) these medications and do various testing such as the cognitive tests, or other types of testing such as rate of aging, blood testing etc - to see if there is anything good or bad with the testing.

#43

I just started Maraviroc a few days ago, 300mg BID, for Long COVID. I became interested in it based on the Patient-reported treatment outcomes study that @RapAdmin posted earlier. I had already been taking Sirolimus, 6mg weekly, also for Long COVID, for the past 6 months with little discernable improvements. I discussed with my prescribing Doctor and he thinks there is no significant interactions between the two, despite both being metabolized by the CYP3A4 enzyme. However I’m planning to decrease the Sirolimus dose to 4mg weekly.

I’m also currently taking 180mg ER Mestinon and 12mg Metoprolol, both of which improve POTS symptoms, and 10mg Rosevestatin, to reduce fractalkine and LDL, which came back high after my acute COVID infection. Also tons of supplements, including most B vitamins, D3, astaxanthin, urolithin, ubiquinol, etc.

I used the free new Long COVID AI platform at RTHM.com to analyze this drug combination, and it judged theese to be a synergistic drug combination that that targets multiple pathways identified in the current Long COVID research. I’m hopeful, but generally take AI with a grain of salt.

I had a liver panel done before taking and will have another in 2 weeks. So far no noticible effects or side-effects. We expect it’ll be 3-4 weeks before anything becomes evident and 2 months before any full effect. Brain fog and memery issues have been an issue since my acute infection, so I’m hoping Maraviroc will help. I used nicotine patches with great cognitive and memory improvements earlier this year, but stopped patching when I started Mestinon so as to avoid overloading the cholinergic system.

The current thought is to take Maraviroc for 3 months, but I’m open to longer if it seems helpful. HIV patients are documented to have taking Maraviroc for 5 years with no ill effects. Both Polybio and HealthBio are running Maraviroc clinical trials for Long COVID now with results coming out early next year.

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#44

Please do some pre and post measurement of memory abilities, and report back if you see any signal in the data. Some options:

Here’s a structured table of ~10 memory/cognition-measurement and training tools, along with validation status, pros/cons, ideal user profiles—tailored for your systems-thinking, longitudinal-monitoring mindset.

# Tool Category Validation / Scientific Basis Pros Cons Best For
1 Lila (by Cogstate) Measurement / screening Described as “science-backed, reliable … episode memory” test. (Cogstate) Well-designed for memory/episodic domain; repeatable baseline option More screening-oriented (early Alzheimer’s risk) than peak performance; cost/licensing may apply High-signal baseline & periodic assessment in a longevity stack
2 XpressO (by Montreal Cognitive Assessment (MoCA)) Measurement Digital self-assessment from MoCA platform. (Moca Cognition) From well-known cognitive screening source; quick, easy Still screening/impairment focus, less optimized for high-performer tracking A convenient “check-in” tool for periodic monitoring
3 BrainTest Measurement Promotes itself as clinically validated (sensitivity/specificity stats) for MCI/dementia screening. (Apple) Good for establishing a baseline and historical change tracking Geared to impairment detection; less about fine-grained high-function cognition For users concerned about early decline and wanting baseline data
4 CANTAB Digital Cognitive Assessments (by Cambridge Cognition) Measurement / professional Marketed as “most validated cognitive assessment software available”. (Cambridge Cognition) Very high-fidelity, used in research/clinical contexts; good depth Higher cost, less consumer-friendly; may require more time/effort For someone doing serious longitudinal cognitive tracking as part of a health/longevity stack
5 CogniFit Hybrid (Measurement + some training) Popular consumer app; claims many abilities. (Google Play) Easy to access; offers both measures and “games” Consumer-grade; training effects transfer to real-world cognition remain uncertain (see notes) Good for casual use and tracking but treat training gains cautiously
6 Peak (with game “Decoder” developed at University of Cambridge) Training / practice “Decoder” game shows improved attention in one study. (University of Cambridge) Evidence-based game integrated; more fun/engaging Still primarily training specific tasks; broad transfer is unclear For practice/engagement, not sole strategy for cognitive improvement
7 Elevate Training / practice Common commercial brain-training app; limited strong external validation Gamified, easy to deploy daily Evidence for broad real-world benefits is weak. (Harvard Health) As a daily stimulation tool, but not a primary intervention
8 NeuroNation Training / practice Commercial brain-training app. Review shows limited evidence of broad transfer. (Wikipedia) Wide user base; accessible training modules Again: gains may stay task-specific; everyday effects uncertain For supplemental use and cognitive variety
9 Cogmed Training (working memory) Developed in academic context; meta-analysis shows only near-transfer effects and no strong durability. (Wikipedia) Specific focus (working memory); research pedigree Doesn’t broadly generalize; target population often children/clinical If you want focused working memory training, under supervision
10 Miscellaneous mobile cognitive training apps (various) Training / practice Reviews show variable quality; many apps lack rigorous evidence. (JMIR mHealth and Uhealth) Many choices, low entry cost Hard to know which are good; risk of wasted time Use with caution, pick ones with credibility & evidence base

:mag: Meta-Takeaways for Your Use-Case

Given your interest in tracking, biomarker integration, and high-fidelity monitoring, here are some recommendations and caveats:

  • Use measurement tools as baseline + periodic check-ins: Tools #1-#4 are better suited for your stack (baseline cognitive/episodic memory status, tracking change over time).
  • Treat training apps as supplemental: Tools #5-#10 can be part of your lifestyle “cognitive hygiene” stack (like sleep, exercise, nutrition) but should not be over-interpreted as major drivers of cognitive change. This is because the evidence for broad transfer (i.e., “get better at game → big improvement in daily memory tasks”) remains weak. (Stanford Center on Longevity)
  • Document intervals and context: Like you do for biomarkers, track measurement results over consistent intervals (6-12 months maybe), note intervening variables (sleep, stress, illness, medication, lifestyle changes) so you can correlate memory/cognition performance with those external variables.
  • Beware of practice effects and ceiling/floor effects: If you use the same tool repeatedly, some improvement may reflect “you know the test now” rather than true cognitive gain. Especially if you’re already high-performing, marginal gains may be small.
  • Complement with lifestyle & other biomarkers: The evidence suggests that physical activity, social engagement, sleep quality, medical risk factors (vascular, metabolic) are more robust for cognitive health than brain-training apps alone. (Harvard Health)
  • Interpret changes thoughtfully: If you see decline, use it as an early flag—not panic—but consider further work-up (medical/neurology) especially given the screening-oriented nature of some tools (#1-#3).
  • Choose tools suited to your performance level and objectives: For example, if you are a high-cognitive-performer tracking subtle changes, measurement tools with high sensitivity (like CANTAB) will serve better than casual training apps. If you’re older or worried about early decline, those screening tools become more valuable.

If you like, I can pull downloadable links, cost/price tiers, platform (iOS/Android/web), and a summary score (based on criteria: scientific validation, user experience, suitability for high-performer tracking vs. aging/impairment risk) for each of the above tools, so you can decide which to integrate into your monitoring stack. Would you like me to build that?

Also…

My CGPT5 prompt:

Identify the best, most scientifically validated memory measurement and practice websites and apps

Response:

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#45

Just downloaded the ExpressO by MoCA and scored a 93. I’ll try again in a few weeks to see if I’ve improved. But as the “Cons” column said, this is geared towards detecting impairment, not measuring high-functioning cognition, so I’m not sure how useful it’ll be. I have a cognitively demanding job and I can tell when I’m off my game, although I know that’s a subjective measurement.

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#46

Has anyone found a source for maraviroc? My Indian supplier says it’s not produced in India and is therefore not available. Would be interesting to try for the memory improvement benefit.

#47

In this link I posted the image from a search on Indiamart.com of a bunch of resellers listing Maraviroc for sale… Maraviroc Fights Middle-Aged Memory Loss - #3 by RapAdmin

You might try contacting some of the companies listed in this thread: Buy Rapamycin Online - List of Reliable Pharmacies

Or try contacting some of the ones listing it on Indiamart: https://export.indiamart.com/search.php?ss=maraviroc&prdsrc=1&tags=qr_nm:splt-gd|cs:12597|res:RC3|com-cf:nl|ptrs:na|ktp:N0|mc:446143|cat:571|mtp:S|qry_typ:P|lang:en|wc:1|rtn:0-0-0-0-0-10-1|qrd:251203|mrd:251203|prdt:251204|qcr:1

#48

FWIW, my sis in law was looking for something that I found on the Indiamart website.

I contacted 3 well known vendors and they all confirmed it was not actually available in India.

This one might be available, but I learned they do post things as click bait.

1 Like
#49

There is a pharma company in India producing it, but it looks to be a smaller company. I’m suspicious / leery of smaller Indian Pharma companies as their quality control tends to be worse than the major International Pharma. Another approach might be to contact a doctor through something like Push Health and try to get a US-based prescription and source.

From Gemini: Based on your request, the manufacturer and company details for Axentri 150mg Maraviroc Tablets are listed below.

Manufacturer Identification

  • Manufacturer: Emcure Pharmaceuticals Ltd.1
  • Headquarters: Pune, India2
  • Therapeutic Class: CCR5 co-receptor antagonist (Antiretroviral)3

Company Website

Product Context

Axentri is a branded generic version of Maraviroc , an entry inhibitor used in the treatment of CCR5-tropic HIV-1 infection.4 Unlike other antiretrovirals that target viral replication after cell entry, Maraviroc blocks the CCR5 receptor on the CD4 cell surface to prevent viral entry.5 As a prescription pharmaceutical, specific product pages may be restricted depending on regional compliance laws; however, the manufacturer’s corporate site provides general portfolio information.

#50

Just a note : Rosuvastatin in some patients is associated with decreased cognition that mimics long covid. I certainly found that was the case for me. By switching to Atorvastatin (or Pitavastatin) for 7 days and then switching back to Rosuvastatin for 7 days (try it a few times) you can quickly determine if you someone who is sensitive to the effects.