E-drug: Antiretrovirals in developing countries
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Richard Laing raised some important questions on the
TREATMENT-ACCESS network.
1. Richard raised the question if it is reasonable to use antiretrovirals
in countries that do not have effective TB control programs.
2. Richard asks if antiretrovirals could be used without laboratory
monitoring.
1. On Richard's comparison between ARV therapy and TB treatment:
We think that ARV treatment is not reasonable where TB treatment
programs are not or only very poorly implemented. On the other hand
we should make ARV treatment as "simple" (and almost as cheap) as
TB treatment so it becomes an option for countries that can handle TB
programs reasonably well.
Although ARV's are life prolonging and TB treatment is curative the
entire concept of curative vs. life prolonging is changing in the light of
HIV. TB treatment in an HIV infected person is in a way only life
prolonging. In this sense ARV's are probably much more life
prolonging than TB treatment (not an argument against TB treatment
of course).
Compliance is an important issue with TB treatment (therefore DOTS).
Untreated TB kills and is infective. Compliance is an issue for ARV too
but an important difference is that life prolonging ARV treatment is
something every individual should decide for him/herself.
A key factor in a TB control program is universal coverage at the
community level for public health reasons (control of spread of TB).
For an ARV program, the aim is different - not control of spread, but
giving longer, more productive and better quality of life to large
numbers of people. Many of them are of working age and with young
families. We need to develop monitoring systems concentrating on
these outcomes, with simplified laboratory monitoring.
2. Richard's question on laboratory testing during ARV therapy.
We are preparing a pilot project on ARV treatment in Thailand; the
goal is to develop something that can be realistic for all of Thailand.
We have done some thinking but would appreciate input from others.
It appears to us that toxicity testing is most important. For that it
should be possible to do a CBC and probably liver transaminases and
amylase.
The usefulness of CD4 and viral load has a lot to do with the
treatment options. If only one ARV regimen is available (two or three
drugs) it does not help to detect treatment failure by CD4 or viral load
before this becomes apparent clinical (through a new opportunistic
infection).
If there are two (or more) different regimen options it would be good
to have a CD4 count to change to the second regimen before a
serious OI like TB or cryptococcal meningitis occurs (which also would
make the second ARV regimen less likely to be effective). More work
needs to be done to make CD4 measurements simpler and cheaper
(see for example: Sherman et al: CD4 T cell enumeration in HIV
infection with limited resources. J Immunol Methods 1999, 222:
209-217).
The use of total lymphocyte count instead of CD4 seems to be a
useful indicator for commencing cotrimoxazole prophylaxis (Post FA et
al: CD4 and total lymphocyte counts as predictors of HIV disease
progression. Q J Med 1996;89:505-508). Total lymphocyte count
seems far too crude to be useful for guiding ARV therapy (I don't
think this has been studied though).
Viral load is a luxury. Viral load is of course very useful especially
during protease inhibitor therapy; the earlier the treatment failure is
detected the higher the chances with a different protease inhibitor
regimen. Protease inhibitors are probably not the first choice for triple
therapy in developing countries because of the difficult dosing
schedule, the side effects and the multiple drug interactions
(particularly important with Rifampicin). NNRTI and hydroxyurea
containing regimens seem more realistic.
Tido von Schoen-Angerer, MD
David Wilson, MRCP
Medecins sans frontieres, Thailand
msfdrugs@asianet.co.th
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