The guidelines also make some important clarifications about which
people living with HIV should be offered a course of IPT (provided they report
none of the four TB symptoms). In short, the guidelines
recommend that everyone should receive IPT (at least in
resource-limited settings), regardless of their CD4 cell
count, whether they are on ART, have previously been treated for TB or are
pregnant women.
Guidance regarding people on
ART had previously been unclear (indeed, at the South African TB Conference, Dr
Getahun pointed out that “the quality of evidence in
support of concomitant IPT and ART is very low because there is no
study that directly addresses this question and from the
published literature the results are contrasting.”)
Meanwhile, people who previously had TB and pregnant women have often
been excluded from IPT programmes, despite reason to
believe that they may benefit.
In addition, the guidelines state a TST is not necessary before offering
IPT. The requirement to perform TST has long proven a barrier to IPT
implementation in many settings, partly because it requires maintaining a cold chain system and refrigeration to stock the
tuberculin (very difficult in some settings) and also
because reading the test requires that the patient make a repeated clinic visit just days after it is
administered. Many simply cannot return to the clinic so soon, so IPT
programmes requiring TST tend to
miss many people who might benefit from IPT.
At the same time however, the guidelines note that IPT is much more
beneficial for those who test TST positive, which becomes important when
considering how long the course of IPT should be.
The guidelines review group were absolutely clear that people should be
offered at least six months of IPT. However, one of the key findings from the BOTUSA IPT
study, mentioned earlier, was the limited durability of the short course of
IPT’s benefit in that setting — it began to wear off within six months
of completing treatment — versus the profoundly greater
benefit of 36 months of IPT, essentially, for the
purpose of that study, continuous treatment.
So the guidelines group also made a conditional recommendation that IPT
should be offered for 36 months — with small print noting that this was based
on less data, and may be specific to settings in which people with HIV are at high risk of being exposed (or
rather re-exposed) to TB.
But this recommendation presents something of a quandary for programmes
and patients. Even though a short course of isoniazid, when given consistently
with vitamin B6 (pyridoxine) to reduce the risk of peripheral neuropathy, is
‘safe’ (there are relatively few serious adverse events or deaths on treatment), the drug is not without side
effects. There are really no data at all on the
long-term safety of continuous IPT, and safety may be a particular concern for
people who have to take lifelong ART concurrently, especially given that some antiretrovirals
and isoniazid have overlapping toxicities (including neuropathy and hepatitis).
But also of concern is that the BOTUSA IPT study also showed that 36
months of IPT offered no statistically significant benefit over 6 months of IPT in people who were TST-negative at
baseline — the vast majority of people in the study.
For people who have not been exposed to TB, the risks of continuous
treatment could well outweigh the benefits. On the other hand, people may
eventually go on to be exposed to TB, especially in very high TB burden settings (in fact, someone should conduct
a study on the rate of TST conversion among people with HIV attending clinics in different
settings).
But if countries decided to require TSTs, as some do, before offering continuous IPT, it would present the same barrier to
IPT implementation that these guidelines seek to avoid, and very few people
would get IPT at all.
Ultimately, until there are more data on long-term IPT (or whether those
taking ART, or at what point after taking ART, it might be safe to discontinue
IPT), people living with HIV may have to weigh the evidence and make the choice
for themselves.
“PLHIV and AIDS, we are the people who are faced with death of TB,” said
Carol Nyirenda at this year’s Union World Conference on Lung Health. “I don’t
think some of you can actually imagine - when you are adhering to treatment;
I’ve been adhering religiously to my HIV treatment for seven years. But then TB
could come, within two weeks I’m dead. I could be speaking to you today, by the time I get home I catch TB and I’m
dead. So I don’t think you can imagine how we sit and watch our friends die and
think, ‘When is this going to happen to me?’
But with clear and accurate information - as has been with ART - we take
our treatment for life…. We should ask our governments in the South to offer us
this service of IPT. For me what I push
for is that I should be offered this service - at least on an ‘opt-out’ basis: Let ME see whether I want to take it or
not. I should be given the choice… What
we are saying is: ‘don’t close us out of the deal!’
At the same time, it is important to note that it’s highly unlikely that any person living with HIV
in a well-resourced setting with a low risk of TB would volunteer to take IPT, not to mention three or more years of
it, unless they discovered they were TST-positive. Why should people in
resource-limited settings not have the same access to information to guide their treatment decision? So activists in settings
considering continuous IPT may want to demand developing the capacity to screen
for latent TB — either with TSTs, or the gamma interferon release assays (such
as Quantiferon), or some new diagnostic tool.