TB risk and CD4 cell
There is no CD4 cell
count where a person living with HIV is safe
from developing active TB.
The risk of TB in
people with CD4 cell counts above 500 is dramatically higher than in the
general public. In the Cascade Study at least, the risk of TB increased a
little more, but not significantly, for people with CD4 cell counts between
The risk of TB grows
much greater when CD4 cell counts fall below 350 and especially below 200 CD4
cells. In the CASCADE study, the risk of TB doubled at CD4 cell counts between
350 and 200, then it shot through the roof when CD4 cell counts fell below 200. But the CD4 cell count does not appear to be the only factor
increasing the risk of TB in people living with HIV.
Time since HIV
The risk of TB jumps very
soon after becoming HIV-infected and continues climbing sharply over the next
year, according to the CASCADE study.
After that, though the risk in the HIV-infected participants
of the CASCADE study fell by about half and stayed more or less the same for
two or three years. Then it began to grow again, with TB becoming more and more
common the longer someone had been infected — until starting antiretroviral
Notably, this mirrors how the level of HIV in the blood is
very high soon after infection, and then a massive response from the body’s
immune system knocks it down and keeps it low for a few years in many people.
Then, viral load begins to rise again — and at that point, CD4 cell counts
That doesn’t mean that TB prevention becomes less important
during this stage, because the risk of TB is still far greater than when
someone is not HIV-infected. But it may tell us something about TB and HIV —
either the high HIV levels, or the immune system reaction to it, are partly
responsible for the high risk of TB in people living with HIV.
HIV infection seems to enable TB to break free from the
places where it is walled up in the lungs. When someone is infected by HIV, their immune
system tries to mount a defence against it, and some of the weapons the immune
system uses accidentally break down the granuloma prison walls, wake up the
sleeping TB bacilli, which then escape, and while HIV keeps the immune system
busy or distracted, TB colonies spring up in lungs, and the bacteria may be
free to spread to other parts of the body, causing extrapulmonary TB.
Another way of looking at it is that when a person has
latent TB, the immune system can’t wipe the TB out, but it can contain it —
there is a sort of balance. HIV disturbs the balance. This might also explain the gradual decline in the risk of TB when
someone living with HIV is put on ART.
The risk of TB on ART
ART dramatically reduces the risk of TB in people living
with HIV in people who qualify for treatment (with CD4 cell counts below 350) according
to data from CASCADE and several other studies.
However, during the early weeks after starting treatment,
there is a jump in TB diagnoses
shortly after starting ART in people, especially those who come to the clinic
with very low CD4 cell counts (below 50).
These TB cases are most common in the first three to six
months after going onto ART. Some of the cases are due to the immune system
belatedly recognising previously undetected TB, and reacting quite violently. However, other cases may actually be
triggered by changes in the balance of the immune system, now that it no longer
has to contend with so much HIV. The
first several months on ART are a time to monitor patients very closely.
People on ART continue to have a
significantly higher risk of TB than the general population
In the CASCADE study, after people had been on effective
ART for about two years, and from then onward, the risk of TB was lower than at
any point since HIV infection — but it was still higher than among the general
This could be because the immune system never fully
recovers after HIV — or takes years to do so.
Another possibility is that people living with HIV are at
greater risk of being exposed to TB, either in their communities, or their
health facilities or other congregate settings.
Starting ART earlier,
when CD4 cell counts are above 350, has not been shown to have much effect upon
the risk of TB
Many researchers believe that earlier treatment, at CD4
counts above 350, could be expected to reduce the risk of TB — and indeed
this makes sense if it prevents people’s CD4 cell counts from falling to where
they are at greater risk of TB.
However, findings from a randomised study of earlier treatment
in couples where one partner has HIV and the other does not — this was the
famous study that showed ART could prevent HIV transmission between theses
couples — also looked at whether earlier treatment reduced the risk of
pulmonary TB. It did not reduce the risk of TB over the relatively limited
course of follow-up in the study, though there was some change reported in
extrapulmonary TB, mostly at sites in India.
Other studies have shown that sustaining CD4 cell counts
above 500 is associated with less risk of TB. People who start treatment with
higher CD4 cell counts have a better chance of keeping them high. So over the
long run, this may be a good strategy.
Nevertheless, when someone starts to
take ART, reducing the amount of HIV in the body could temporarily disturb the
balance in the immune system, and activate TB, or, people attending the clinic
routinely to receive ART might also be exposed to TB in the health facility.