Been on it for three weeks at 15-mg BID.
My question was based on your statement above of 15-mg BID several posts back. Now, should the dose be 15 mg BID or 150 mg BID? I’m not sure, but it seems to me that I saw somewhere in a RapAdmin post on Maraviroc that 15 mg BID or 30 mg daily would be appropriate.
Yes, I think it was 30mg but I’d cut 150 into four pieces and do it once per day to start and then maybe go twice per day. I wouldn’t go more than 75mg daily.
Apologies, was a typo - will correct original post. Was meant to read 150mg. My mistake 
Have you ever tried LDN 3mg-4.5mg. A lot of people seem to have good results with it. I use it and it is an excellent medication for aches and pains (but never had covid so can’t speak to that). Maybe worth a shot.
@desertshores, are you considering it? At almost 81, I’m watching this space carefully. Dose, frequency, mechanism, etc.
Not just yet, I’ve already got so many meds I’m loath to start another one.
I’ve been exploring dosing approaches to try and replicate the effects from the mouse studies. The behavior of maraviroc in humans vs. mice is so different, a compounded micro dose may be needed. For now the approach I’m going with is to split 150 mg tablet into quarters (37.5 mg) and dose every 2 weeks. Here’s the analysis of that approach from Grok:
To address your question directly: yes, dosing frequency should ideally be based on the ratio of duration of inhibition to no inhibition to maintain a similar proportion of time under CCR5 inhibition, as this could better replicate the “pulsed” exposure profile in mouse studies where transient, short-lived inhibition (followed by extended troughs) led to senotherapeutic effects like reduced senescence and improved muscle/memory outcomes. However, this ratio must be adjusted for species differences in physiology (e.g., metabolism, half-life, and aging time scales) to ensure biological relevance—direct ratio matching without scaling could result in overly extended intervals that may not align with human senescence dynamics.
Yes, thanks. I’ve been on 4.5mg LDN from Ageless RX for over a year now, unfortunately I’ve never experienced anything from it, good or bad. Staying on it just in case.
After 2 months the Maraviroc has improved my tachycardia and POTS symptoms slightly, although I still need the Metoprolol, and has also eliminated the “chirping” tinnitus that I had in my right ear, but unfortunately it hasn’t yet improved my general fatigue and weakness, exercise intolorance, or Post Exertional Malaise. I’ve one more month on it according to the current protocol, so I’m still hoping for further improvement.
Thanks for the update. If there is no improvement in the 1 month that is left, you could look into trying some new things to help fix those issues.
If your hormones are all in range, talk with your doctor about various stimulants or wakefulness-promoting agents such as:
modafinil, ritalin, vyvanse, buproprion, atomoxitine, adderall, dextroamphetamine etc.
Could also add other medications onto this if needed.
Not sure of all the supplements you take but you did mention tons and b vitamins, D3, astaxanthin, urolithin, ubiquinol etc…, but if you don’t use these other one’s already:
Could make a sport/energy protein drink with some whey (or vegan) protein powder.
Add in extra creatine around 5g. Beta alanine powder (carnosine production).
Extra tyrosine or phenylalanine for more catecholamines (dopamine, noradrenaline etc).
Use this shake with other food for a complete whole meal. Whatever you can stomach.
Other supplements to possibly take with the meal:
Omega 3 epa/dha are good. Extra vitamin b3 (niacinamide) is good (nad levels)
Multi vitamin & mineral.
Ginseng extract is decent. Coffee or caffeine pills.
Alpha gpc or citicoline for acetylcholine.
There’s more stuff but I don’t want to get too crazy.
Here’s the initial results from memory testing after a single 37.5 mg dose of maraviroc. I used the Moca Xpresso test which tests working memory. I have ADHD and therefore have baseline issues with working memory. To establish a baseline score, I did repeated testing to eliminate test familiarity gains. This resulted in a baseline score of 72. Two days after the initial dose of maraviroc, I repeated the test resulting in a score of 94. While there is the possibility of further familiarization gains, the test was noticeably easier this time, leading me to believe that there has been some improvement in working memory from the Maraviroc.
With aging the biggest decline I have noticed is in short-term working memory. I.e. remembering where did I put that tool, what I was going to do next, etc. Did you notice any improvements subjectively in your daily tasks and routines?
It’s a little too soon to say for sure, but I haven’t had any of those episodes of “what was I about to do?”
With regards to dosing, for sarcopina prevention, the dose and time extrapolated from the mouse studies is low (1/4 pill, or 37.5 mg, twice a week), but for demitia prevention, the doses currently being studied are much higher, 150 to 600 mg daily in post-stroke patients being studied in the CAMAROS and MARCH trials, whose results are expected to be published later in 2026. Perhaps lower dosing is all that’s needed for a healthy older person, but it seems likely that a minimum serum concentration will be required to pass the blood-brain barrier. Is see @fasterfour used only 37.5 mg dose. Any thoughts on dosing for the cognitive use case?
Good question. I think it might depend on your age and goals / situation. The MARCH trial is for mild cognitive impairment (MoCA Score ≤ 26), for people aged 50 to 86. Can it be helpful as a prophylactic? I think thats unknown, though it seems plausible. We have two variable to play with, frequency and dose.
While both trials use Maraviroc, they target different biological mechanisms:
| Feature | CAMAROS Trial | MARCH Trial |
|---|---|---|
| Full Name | CAnadian MAraviroc Randomized Controlled Trial to Observe Stroke Recovery | MAraviroc for Recovery of Cognitive Health (Preventing Post-Stroke Dementia) |
| Primary Focus | Motor Recovery: Augmenting physical rehabilitation (walking & arm function) in early stroke survivors. | Cognitive Protection: Preventing post-stroke cognitive impairment (PSCI) and vascular dementia in subcortical stroke patients. |
| Dosing | 300 mg twice daily (BID). | 150 mg or 600 mg once daily. |
| Duration | 8 weeks of active dosing. | 12 months (52 weeks) of active dosing. |
| Status | Active / Recruiting (Phase II). | Active / Recruiting (Phase II). |
| Feature | CAMAROS Trial | MARCH Trial |
|---|---|---|
| Age Range | 18 years and older (Adults) | 50 – 86 years (Older Adults) |
| Time Since Stroke | 5 days – 8 weeks (Sub-acute phase) | 1 month – 24 months (Chronic phase) |
| Stroke Type | Ischemic Anterior Circulation (Cortical stroke affecting motor areas) | Subcortical Ischemic Stroke (Deep brain stroke affecting white matter) |
| Baseline Status | Motor Impairment (Hemiparesis requiring rehab) | Mild Cognitive Impairment (MCI) (MoCA Score ≤ 26) |
| Key Exclusion | HIV+, Severe Kidney Disease, Seizure Meds | Dementia (MoCA < 17), Large Cortical Infarcts |
Its interesting to look at the targeted endpoints in these trials as we think about how we might measure our own progress, or lack thereof, in trying this medication.
MARCH Trial Targeted Endpoints:
CAMAROS Targeted Endpoints:
Seems like the MARCH trial tracks outcomes of interest, and I like the secondary hard endpoints. If the low-dose arm of 150 mg daily shows promise, that’s something I’d consider, although I’m wondering how low you can go and still get an impact. Seems all we can do is speculate at this point.
You raise a good point. When working through my original look at dosing I considered the dose needed to cross the blood brain barrier, but I didn’t get very deep into this aspect. Maraviroc has a transporter and readily crosses the BBB. There’s quite a bit of data from HIV studies. A 37.5mg will definitely cross the BBB and occupy receptors in brain tissue. But it’s fairly complicated, as Maraviroc is actively filtered from CSF by P-gp efflux. I need dig into this a bit more. The CAMAROS and MARCH trials are likely using the doses that they choose because those are doses that they have hard data on RO from the HIV trials. If they went with some alternate dosing scheme, then there would be some uncertainty as to how much RO they actually acheived in their trials. For the sort benefits we’re looking for in anti-aging, I don’t believe HIV dosing levels are needed. For HIV treatment to be effective, you need a near total blockade of CCR5.
True to the speculation part. I have been taking 37.5mg’s daily for over a month and I do love it’s effect especially for stamina. I literally come out of gym and then couple hours after, I feel I can go back in and do the same exercises at same intensity. Kind of hard to give an exact explanation but the best I can think of is that if someone say were able to do a certain physical activity for say one hour per day, you can easily do such activity now for 2-3 hours. As far as increasing strength it feels that way and maybe on margins, but not necessarily the case. to me what has proved effective is the fact that I don’t know what tiredness is any longer. Never tired during the day no matter how active or inactive I am.
My question @fasterfour (and others) is with regards to absorption because I read elsewhere on the web that Maraviroc should always be taken as a whole pill and never be broken. Does anyone know that splitting the pill cuts it’s absorption rate?
Thinking of going 150mgs twice per week as opposed to daily dosing of 37.5mgs.
There’s no issues with splitting Maraviroc pills. That’s just standard pharma CYA for any drug that hasn’t been explicitly tested with split dosing.
Ok, turns out the analysis of brain RO is fairly complicated. There’s not really any good way to summarize this and cover all the uncertainties, so I’m just going to post the whole analysis. The bottom line is for neurological benefit there is evidence higher dosing is likely beneficial vs. with sarcopenia, but then this gets into the potential for hepatic stress. In HIV or stroke patients, the hepatic stress risk is an easy tradeoff for the potential benefit. In someone who is healthy, the dynamic is a bit different and more caution is warranted. At any rate, here is the final analysis output from Claude Opus 4.6 extended thinking: Maraviroc CNS Pharmacokinetics: BBB Penetration, CSF Distribution, and Receptor Occupancy Analysis
Maraviroc is a confirmed P-glycoprotein (P-gp/ABCB1) substrate (FDA label). This is the dominant mechanism limiting CNS penetration. P-gp is the most abundantly expressed efflux transporter on the luminal (blood-facing) membrane of brain capillary endothelial cells and actively pumps maraviroc back into the blood compartment.
Rat IV data (Dorr et al.):
| Compartment | Concentration vs Free Plasma |
|---|---|
| CSF | ~10% of unbound plasma |
| Brain tissue | ~25% of unbound plasma |
The brain tissue > CSF gradient is consistent with P-gp dynamics: P-gp expression at the choroid plexus (blood-CSF barrier) is oriented differently from the BBB, and CSF acts as a “sink” that drug is pumped into from brain ECF via bulk flow. Brain extracellular fluid (ECF) concentrations may therefore be modestly higher than lumbar CSF measurements suggest.
No BCRP (ABCG2) or MRP involvement has been specifically characterized for maraviroc, though the BBB expresses multiple redundant efflux systems. Given maraviroc’s moderate lipophilicity and positive charge at physiological pH, P-gp is likely the dominant efflux mechanism.
CNS Penetration Effectiveness (CPE) Score: 3 (highest tier among antiretrovirals), which may seem paradoxical given low CSF concentrations — but reflects that achievable CSF levels still exceed antiviral IC₅₀/IC₉₀ targets.
| Parameter | Value |
|---|---|
| Plasma Ctrough (pre-dose) | 337 ± 74 ng/mL |
| Plasma C₄h | 842 ± 174 ng/mL |
| Plasma C₆h | 485 ± 100 ng/mL |
| CSF C₄h | 7.5 ± 1.3 ng/mL |
| CSF C₆h | 5.1 ± 1.2 ng/mL |
| CSF:plasma ratio (mean) | 1.01% (range 0.57–1.61%) |
Note: 150 mg BID dose was used because lopinavir/ritonavir (CYP3A4 inhibitor) approximately doubles maraviroc exposure. Plasma levels here are comparable to 300 mg BID without a PI booster.
After 14 days of maraviroc intensification, a 14.8% increase in right basal ganglia NAA/Cr ratio (a marker of neuronal integrity) was observed, significantly correlated with plasma Ctrough (P=0.05, r=0.61) but not with CSF concentration.
| Parameter | Value |
|---|---|
| Unbound plasma fraction | 13% (range 7–18%) (or ~24% per other studies) |
| CSF fractional penetrance vs total plasma | 2.8% |
| CSF fractional penetrance vs unbound plasma | 18.9% |
| CSF:IC₅₀ ratio (wild-type HIV) | 9.2-fold (IQR 5.6–15.4) |
Correlation between CSF and unbound plasma was statistically significant (r=0.71, p=0.03), supporting the use of unbound plasma as a CSF estimator.
The literature reports two distinct ranges for maraviroc plasma protein binding:
| Source | Protein Bound | Free Fraction (fu) |
|---|---|---|
| FDA label / DrugBank | ~76% | ~24% |
| Tiraboschi et al. clinical | 82–93% | 7–18% (median 13%) |
This discrepancy matters significantly for CSF penetration estimates. Using fu=0.24 vs fu=0.13 changes estimated CSF concentrations by nearly 2-fold. The clinical study (Tiraboschi) may better reflect conditions in HIV patients with altered α₁-acid glycoprotein levels. For conservative analysis, I’ll present both.
Using CSF penetrance ≈ 19% of unbound plasma (Tiraboschi), and approximate plasma PK from Phase I/clinical data:
Plasma PK: Cmax ~785 ng/mL, Cmin ~52 ng/mL, AUCτ ~2850 ng·h/mL, Cavg ~240 ng/mL
| Parameter | fu = 0.24 | fu = 0.13 |
|---|---|---|
| Unbound Cmax | 188 ng/mL | 102 ng/mL |
| Unbound Cmin | 12.5 ng/mL | 6.8 ng/mL |
| Est. CSF Cmax (19% of fu) | ~36 ng/mL | ~19 ng/mL |
| Est. CSF Cavg | ~8.7 ng/mL | ~5.9 ng/mL |
| Est. CSF Cmin | ~2.4 ng/mL | ~1.3 ng/mL |
Approximately half the exposure of 300 mg BID.
| Parameter | fu = 0.24 | fu = 0.13 |
|---|---|---|
| Est. CSF Cmax | ~18 ng/mL | ~10 ng/mL |
| Est. CSF Cavg | ~4.3 ng/mL | ~3.0 ng/mL |
| Est. CSF Cmin | ~1.2 ng/mL | ~0.6 ng/mL |
Similar Cmax to BID, but Cmin at 24h is much lower (~10–15 ng/mL plasma).
| Parameter | fu = 0.24 | fu = 0.13 |
|---|---|---|
| Est. CSF Cmax | ~36 ng/mL | ~19 ng/mL |
| Est. CSF at 24h trough | ~0.4 ng/mL | ~0.2 ng/mL |
Exposure increased ~4-fold. This mirrors the Garvey clinical CSF data directly.
| Parameter | Measured |
|---|---|
| CSF C₄h | 7.5 ± 1.3 ng/mL |
| CSF C₆h | 5.1 ± 1.2 ng/mL |
Important caveat: CSF concentrations lag behind plasma by hours due to slow equilibration across the blood-CSF barrier, and lumbar CSF lags behind ventricular/cortical CSF. The trough CSF estimates above likely underestimate actual brain ECF concentrations at trough, since: (a) brain tissue achieves ~2.5× higher levels than CSF in rats, and (b) the slow dissociation of maraviroc from CCR5 means RO persists independently of free drug levels.
From Rosario et al. (2008) — Phase I PK/PD analysis in healthy volunteers and HIV patients:
The KD is extraordinarily low relative to plasma concentrations. At the standard 300 mg BID dose (Cavg ~240 ng/mL), the free drug concentration (~30–60 ng/mL) exceeds the KD by ~300–700×, yielding >99.8% peripheral RO.
For antiviral efficacy, Watson et al. demonstrated a KE of ~0.012 — meaning only 1.2% of free activated CCR5 receptors are needed for 50% of the maximal infection rate. Consequently, 98.8% of CCR5 must be blocked to reduce infection rate by 50%. The in vivo antiviral IC₅₀ was ~8 ng/mL, which is ~90× higher than the binding KD.
This spare receptor dynamic is specific to HIV entry biology and does NOT apply to neuroinflammatory signaling.
Using the measured KD of 0.0894 ng/mL and the simple Emax relationship:
RO (%) = 100 × [Drug] / ([Drug] + KD)
Assuming the KD is similar for CNS CCR5 (same receptor, likely same allosteric binding pocket):
| Time Post-Dose | Est. CSF (ng/mL) | KD-Based RO | Effective RO* |
|---|---|---|---|
| 0h (trough) | 1.3–2.4 | 94–96% | ~97–98% |
| 2h (Cmax) | 19–36 | 99.5–99.8% | ~99.8% |
| 6h | 5–10 | 98–99% | ~99% |
| 12h (pre-next dose) | 1.3–2.4 | 94–96% | ~97–98% |
| Time Post-Dose | Est. CSF (ng/mL) | KD-Based RO | Effective RO* |
|---|---|---|---|
| 0h (trough) | 0.6–1.2 | 87–93% | ~93–96% |
| 2h (Cmax) | 10–18 | 99–99.5% | ~99.5% |
| 6h | 3–5 | 97–98% | ~98% |
| 12h (pre-next dose) | 0.6–1.2 | 87–93% | ~93–96% |
| Time Post-Dose | Est. CSF (ng/mL) | KD-Based RO | Effective RO* |
|---|---|---|---|
| 0h (trough, 24h) | 0.2–0.4 | 69–82% | ~85–90% |
| 2h (Cmax) | 19–36 | 99.5–99.8% | ~99.8% |
| 12h | 1.3–2.4 | 94–96% | ~97–98% |
| 18h | 0.5–1.0 | 85–92% | ~92–95% |
| 24h (pre-next dose) | 0.2–0.4 | 69–82% | ~85–90% |
| Time Post-Dose | Est. CSF (ng/mL) | KD-Based RO | Effective RO* |
|---|---|---|---|
| 0h (trough, 24h) | 0.1–0.2 | 53–69% | ~70–80% |
| 2h (Cmax) | 10–18 | 99–99.5% | ~99.5% |
| 12h | 0.6–1.2 | 87–93% | ~93–96% |
| 24h (pre-next dose) | 0.1–0.2 | 53–69% | ~70–80% |
*Effective RO accounts for maraviroc’s slow dissociation kinetics (see Section 6), which cause actual receptor occupancy to exceed what equilibrium free-drug levels would predict.
Maraviroc exhibits a two-step binding mechanism (Swinney et al., 2014):
Key kinetic parameters:
| Parameter | Value |
|---|---|
| k₋₂ (dissociation rate from R’A) | 1.2 × 10⁻³ min⁻¹ |
| Dissociation half-life (radioligand) | >6 hours (Napier et al., 2005) |
| Residence time estimate | ~10.5 hours (Cambridge MedChem) |
This means that once maraviroc occupies a CCR5 receptor and the complex isomerizes, it stays bound for many hours even after free drug concentrations drop. This has several critical implications:
CSF is produced at ~0.35 mL/min (~500 mL/day) and turns over approximately 3–4× per day (total CSF volume ~150 mL). This bulk flow dilution contributes to drug clearance from CSF independent of BBB efflux.
For maraviroc in CSF:
This further supports the concept that brain parenchymal (ECF) concentrations — and therefore actual neuronal/glial CCR5 occupancy — likely exceed what lumbar CSF measurements indicate.
Genetic evidence (CCR5Δ32):
Preclinical evidence:
Clinical evidence:
Unlike HIV entry (which requires near-complete CCR5 blockade due to spare receptors), the neurological targets of CCR5 antagonism are:
Conservative estimate: Sustained CNS RO >70–80% likely provides meaningful anti-neuroinflammatory and neuroprotective benefit. Sustained >50% RO may provide plasticity/cognitive benefits.
| Dose Regimen | Sustained CNS RO (trough estimate) | Likely Neurological Benefit |
|---|---|---|
| 300 mg BID | 94–98% (never drops below ~94%) | Maximal — near-complete CCR5 blockade throughout. Covers all proposed mechanisms. |
| 150 mg BID | 87–96% (trough ~87–93% KD-based, ~93–96% effective) | High — robust blockade with minor trough dips. Likely sufficient for all neurological targets. |
| 300 mg QD | 69–90% (trough ~69–82% KD-based, ~85–90% effective) | Moderate-to-High — Slow dissociation rescues trough significantly. Likely adequate for anti-inflammatory and plasticity benefits. Some uncertainty about sustained leukocyte trafficking inhibition. |
| 150 mg QD | 53–80% (trough ~53–69% KD-based, ~70–80% effective) | Moderate — Border zone. The slow dissociation provides critical rescue at trough, but this is the lowest regimen likely to maintain meaningful benefit. Adequate for plasticity (>50%), marginal for full anti-inflammatory effect. |
| 50 mg QD | <50% at trough (KD-based ~30–45%) | Likely insufficient — Trough RO drops below thresholds for anti-inflammatory benefit. May still provide some plasticity enhancement during peak hours. |
Do you think (or is it known) that doing intermittent dosing (i.e. once or twice per week of 150mg) is less of a risk than say daily dosing of 37.5mgs’s or the literature doesn’t get that specific?