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Trimethoprim-sulfamethoxazole continues to be the best
choice for preventing PCP in AIDS patients
Pneumocystis carinii pneumonia (PCP) remains one of the most
common life-threatening complications of AIDS. Of the three
regimens most often used for PCP prophylaxis,
trimethoprim-sulfamethoxazole (TMP-SMX) is superior to prevent
initial and second-time PCP (primary and secondary prophylaxis)
and most cost-effective for secondary prophylaxis, according to
two studies supported in part by the Agency for Health Care
Policy and Research (HS07782 and HS06694).
A meta-analysis of 35 randomized trials (conducted between 1991
and 1995 and involving 6,583 patients) led by Joseph Lau, M.D.,
of New England Medical Center Hospitals, compared three different
treatment regimens: TMP-SMX, dapsone, (both are oral
medications), and aerosolized pentamidine (AP) with each other or
placebo. AP was well tolerated regardless of the dose used (usual
recommended dose is 300 mg per month via nebulizer), but
prophylaxis failure might be halved if the dose were doubled.
Oral medications were five times more likely than AP to be
discontinued because of toxic reactions.
Regardless of dose, TMP-SMX was almost universally effective for
patients who tolerated it. The risk of discontinuation because of
side effects decreased 43 percent if one double-strength tablet
(160 mg TMP, 800 mg SMX) was given three times per week instead
of daily (usual recommended dose). For dapsone, in 100 patients
given 100 mg per day instead of twice per week for 1 year
(primary prophylaxis), 7 fewer patients would develop PCP, but 17
more would have significant toxic reactions.
The second study shows that TMP-SMX also is more cost-effective
than AP for preventing recurring PCP. Investigators at Dartmouth
Medical School developed a model of secondary PCP prophylaxis
based on the medical literature and then used efficacy and
toxicity data from a controlled clinical trial to validate the
model. They compared three clinical strategies in a hypothetical
group of patients who had completed 21 days of therapy for PCP:
no prophylaxis (control group), prophylaxis with TMP-SMX (one
double-strength tablet per day), and prophylaxis with AP (300 mg
per month).
In the literature-based model, yearly prophylaxis costs for
TMP-SMX and AP were $468 and $1,577, respectively. Assuming equal
efficacy for the two agents, the incremental cost-effectiveness
ratio for TMP-SMX was $350 compared with no prophylaxis; for AP
it was $110,880 compared with TMP-SMX, since AP was associated
with only a minimal increase in life expectancy and a substantial
increase in cost. Data from the randomized trial indicated annual
costs of $656 per person for TMP-SMX and $1,573 per person for
AP. This translates into annual savings of over $17.4 million for
the 19,039 patients newly diagnosed as having PCP in 1993, if
they were started on TMP-SMX rather than AP to prevent
reinfection with PCP.
More details of the first study are in "Meta-analysis of the
relative efficacy and toxicity of Pneumocystis carinii prophylactic regimens," by John P. Ioannidis, M.D., Joseph C.
Cappeleri, Ph.D., M.P.H., Paul R. Skolnik, M.D., and others, in
the January 22, 1996 Archives of Internal Medicine 156,
pp. 177-188.
For the second study, see "Validating
literature-based models with direct clinical trial results," by
Kenneth A Freedberg, M.D., M.Sc., W. David Hardy, M.D., Robert S.
Holzman, M.D., and others, in the January 1996 issue of Medical Decision Making 16(1), pp. 29-35.
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