HIV Reservoirs Part 3: HIV Persistence in Anatomic Compartments
HIV reaches the central nervous system as soon as during acute infection.
At that stage, a lymphocytic meningitis is frequent, witnessing HIV invasion.
Neurons are not themselves infected but HIV reaches the brain via other cells of the monocytic lineage, taking part to the microglia.
HIV RNA levels in plasma and cerebrospinal fluid (CSF) are usually correlated.
During antiretroviral therapy (ART), HIV RNA decrease in both compartments, the decrease being a little bit delayed or slower in CSF than in plasma.
However, very low levels (around a few copies/ml) of HIV RNA can be detected in CSF in some patients, and this residual virus has been correlated to drug diffusion in the CSF.
As there is no practical way to analyze what is going on in the brain during ART, only indirect approaches are available.
There is an increased incidence of neuro-cognitive defects during effective ART, leading to the belief that therapy is only partially effective in the brain.
Furthermore, isolated cases of drug resistance selection happening first in the brain and then disseminating through the whole body, have been reported.
The brain during ART therapy therefore looks like a viral reservoir and a sanctuary site.
Another HIV reservoir resides in the gut-associated lymphoid tissue.
In fact, this is where most of the virus is located.
As most CD4+ T cells home in the gut, it is the major body HIV reservoir.
During acute HIV infection an early and profound depletion of CD4+ T cells happen in the gut, which is not reversed by ART.
Discrepancies exist according to the gut site, i.
e.
HIV and immune cells are not the same or at the same concentration in rectum, colon, or ileum.
Whether ART is equally effective in these gut cells compared to blood cells is under investigation.
The genital tract is another compartment where HIV can be genetically different, and where ART do not always have a good diffusion.
Actually, this is mainly true for Protease Inhibitors, as Nucleoside Reverse Transcriptase Inhibitors tend to concentrate in seminal fluid or cervico-vaginal secretions.
There is no clear correlation between ART drug diffusion in this compartment and HIV RNA excretion, but according to series, 5-48 percent of men with undetectable plasma HIV RNA on ART still have detectable HIV RNA in semen.
This has the potential to influence HIV transmission rates at a global level.
Other organs have been suggested to beHIV reservoirs such as the kidney, lung, thymus, but need further investigations.
At that stage, a lymphocytic meningitis is frequent, witnessing HIV invasion.
Neurons are not themselves infected but HIV reaches the brain via other cells of the monocytic lineage, taking part to the microglia.
HIV RNA levels in plasma and cerebrospinal fluid (CSF) are usually correlated.
During antiretroviral therapy (ART), HIV RNA decrease in both compartments, the decrease being a little bit delayed or slower in CSF than in plasma.
However, very low levels (around a few copies/ml) of HIV RNA can be detected in CSF in some patients, and this residual virus has been correlated to drug diffusion in the CSF.
As there is no practical way to analyze what is going on in the brain during ART, only indirect approaches are available.
There is an increased incidence of neuro-cognitive defects during effective ART, leading to the belief that therapy is only partially effective in the brain.
Furthermore, isolated cases of drug resistance selection happening first in the brain and then disseminating through the whole body, have been reported.
The brain during ART therapy therefore looks like a viral reservoir and a sanctuary site.
Another HIV reservoir resides in the gut-associated lymphoid tissue.
In fact, this is where most of the virus is located.
As most CD4+ T cells home in the gut, it is the major body HIV reservoir.
During acute HIV infection an early and profound depletion of CD4+ T cells happen in the gut, which is not reversed by ART.
Discrepancies exist according to the gut site, i.
e.
HIV and immune cells are not the same or at the same concentration in rectum, colon, or ileum.
Whether ART is equally effective in these gut cells compared to blood cells is under investigation.
The genital tract is another compartment where HIV can be genetically different, and where ART do not always have a good diffusion.
Actually, this is mainly true for Protease Inhibitors, as Nucleoside Reverse Transcriptase Inhibitors tend to concentrate in seminal fluid or cervico-vaginal secretions.
There is no clear correlation between ART drug diffusion in this compartment and HIV RNA excretion, but according to series, 5-48 percent of men with undetectable plasma HIV RNA on ART still have detectable HIV RNA in semen.
This has the potential to influence HIV transmission rates at a global level.
Other organs have been suggested to beHIV reservoirs such as the kidney, lung, thymus, but need further investigations.
Source...