This study looked at the effects of NMN and antiretroviral therapy (cART), alone or in combination, in mice infected with HIV-1.
Key Points:
- NMN did not affect NAD+ levels in HIV-1-infected mice
- Antiretroviral therapy with NMN had a greater effect on immune cell recovery than antiretroviral therapy alone
Study Evaluated Effect of NMN on Mice Infected with HIV-1
Human peripheral blood leukocyte (huPBL) were injected (i.p.) into female mice to generate a humanized mouse model.
Mice were infected with HIV-1 (10 ng p24 per mouse) via i.p. injection.
Four days after infection, mice were divided into four groups (n > 4 per group) and given their respective treatments daily:
- cART + 300 mg/kg NMN: mice received antiretroviral therapy (cART) and NMN
- cART: mice received cART only
- 300 mg/kg NMN: mice received NMN only
- PBS Ctrl: mice did not receive any treatment
Plasma viral load, peripheral CD4/CD8 ratio, and the percentage of CD4+ T cells and CCR5+CD4+ T cells were measured weekly.
Experimental Design. Four days after being infected with HIV-1, the humanized mice received their designated treatments. Their blood was drawn weekly for analysis for a period of four weeks.
NMN Did Not Change Plasma NAD+ Levels
Plasma NAD+ was measured on day 24 of the respective treatments.
The figure below illustrates the data showing there were no significant differences in plasma NAD+ in mice treated with cART + NMN (purple bar), cART (red bar), NMN (blue bar), or PBS (control, gray bar).
The researchers emphasize that the NMN dosage required to suppress HIV-1 is significantly higher than that of existing anti-HIV medications. Consequently, it was unlikely that NMN administered at the given dose could effectively suppress the virus or elevate NAD+ levels.
“In support of this notion, we did not detect any significant increase of NAD in vivo at this dose.”
Interestingly, a previous human study revealed that NMN failed to elevate NAD+ levels in certain individuals, termed “non-responders.” Further research is warranted to elucidate the factors underlying this variable response to NMN.
NMN Improved Immune Cell Recovery
Although NAD+ levels remained unchanged, the combination of NMN and the antiretroviral therapy (cART) led to better recovery of immune cells (CD4+ T cells).
“Nevertheless, a positive effect of NMN was observed when it was combined with cART for treatment in HIV-1-infected humanized mice.”
This figure depicts the CD4/CD8 ratio, where a higher ratio signifies a more robust recovery of CD4+ T cells (immune cells).
The cART + 300 mg/kg NMN group (purple line) had a higher CD4/CD8 ratio than the cART group (red line), NMN group (blue line), and PBC control group (gray line).
Conclusion
This study showed that NMN enhanced the effects of antiretroviral therapy on the immune system in mice infected with HIV-1.
“Results from the humanized mouse study demonstrated that NMN treatment could improve the therapeutic effect of cART in vivo on reconstituting CD4+ T cells and improving CD4/CD8 ratio significantly over time.”