E-drug: Unintended ARV treatment interruptions (cont'd)
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Dr Tim Read, HIV specialist clinician from the Burnet Institute and
Melbourne Sexual Health Clinic, has provided the following
contribution in the discussion on unintended ARV treatment
interruptions.
First, if the third drug is temporarily interrupted then stopping all
drugs is a good idea because plenty of evidence exists that
attempting to maintain patients on two drugs has a significantly
greater risk of virologic failure (see Cochrane review below).
Similarly in the early 1990s we were using two-drug combination
therapy only with much worse results than with three drugs.
There is some evidence that four drugs are even better, but the
trade-off with side-effects and cost is not so favourable. BUT
people on two drugs do significantly better with fewer opportunistic
infections than people on one drug (one drug is no better than
none after a few months). So if the third drug is PERMANENTLY
unavailable (eg because of side-effects) then for sicker patients
who cannot wait, perhaps staying on two is sensible.
I think that if you know that you are about to stop someone's drugs
you should stop the longest half-life drug a few days early (often
nevirapine) so that levels all drop to zero at around the same time.
Cochrane review
Three- or four- versus two-drug antiretroviral maintenance
regimens for HIV infection.
Rutherford GW, Feldman KA, Kennedy GE.
University of California, San Francisco, Prevention Sciences Group
San Francisco, California 94105-3444, USA.
grutherford@psg.ucsf.edu
BACKGROUND: Combination antiretroviral therapy administered to
HIV-infected individuals has been shown to improve immunologic
function and delay the progression of HIV infection. However,
because patient adherence to complicated combination-therapy
antiretroviral regimens is difficult and because of concerns
regarding cumulative toxicity of antiretroviral drugs, regimens that
utilize fewer antiretroviral agents are desirable.
OBJECTIVES: To compare the use three- or four- versus two-drug
antiretroviral maintenance regimens following successful induction
therapy for HIV infection.
SELECTION CRITERIA: Randomized controlled trials in which
HIV-infected adults who had successfully completed three- or
four-drug antiretroviral induction therapy were randomized to
maintenance therapy with three or four drugs or maintenance
therapy with two drugs. Successful induction therapy was defined
by a plasma viral load of less than 500 copies/ml.
DATA COLLECTION AND ANALYSIS: Two reviewers assessed
eligibility and trial quality. Attempts were made to contact the
authors of the included abstract. Data on the number of patients
experiencing loss of viral suppression were abstracted by two
reviewers. The data were pooled, where appropriate, to yield odds
ratios, using random effects models.
MAIN RESULTS: Four trials were identified including three
published studies and one abstract. Compared to three- or
four-drug maintenance therapy, maintenance therapies including
fewer drugs were associated with a higher risk of virologic failure
(loss of HIV suppression to non-detectable levels). Combining the
results of all four studies yielded an odds ratio of 5.55 (95%
confidence interval, 3.14 - 9.80). Similar results were obtained
when the one abstract was excluded (odds ratio, 5.48; 95%
confidence interval, 2.82 - 10.65). Performing subgroup analyses of
studies using the same induction and maintenance regimens gave
similar results. Maintenance regimens of zidovudine and
lamivudine compared to maintenance regimens with zidovuine,
lamivudine and indinavir, were associated with significantly higher
rates of virologic failure (odds ratio, 4.57; 95% confidence interval,
1.80 - 11.58). Similarly, maintenance regimens that discontinued
one or more protease inhibitor after including them in induction
therapy were also associated with a significantly higher risk of
virologic failure (odds ratio, 6.15; 95% confidence interval, 3.40
-11.10).
Beverley Snell
Centre for International Health
Macfarlane Burnet Institute for Medical Research & Public Health
GPO Box 2284, Melbourne 3001 Australia
Telephone 613 9282 2115 / 9282 2275
Fax 61 3 9282 2144 or 9282 2100
Time zone: 10 hours ahead of GMT.
email <bev@burnet.edu.au>
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