TMP-SMX
Remains the Therapeutic Drug of Choice for HIV-related PCP in First- and Second-line
Settings By
Ronald Baker, PhD Pneumocystis
jirovecii, formerly Pneumocystis carinii (PCP) is a well-recognized
cause of a life-threatening pneumonia in individuals with advanced HIV disease.
PCP remains one of the most frequent opportunistic infections (OIs) in people
with AIDS despite the availability of specific prophylaxis (preventive treatment)
and HAART.  The
drug of choice for first-line treatment of PCP is TMP-SMX, a combination of two
antibiotic drugs, trimethoprim and sulfamethoxazole. TMP-SMX is also known as
cotrimoxazole and is marketed in the U.S. as Bactrim (by Roche) or Septra
(by Monarch Pharmaceuticals). TMP-SMX is sold under many other names in different
parts of the world.
If
a patient with PCP fails on initial treatment with TMP-SMX, therapeutic alternatives
include intravenous pentamidine, clindamycin with primaquine, dapsone with trimethoprim,
atovaquone, and trimetrexate with folinic acid.  | | X-ray
of Pneumocystis jirovecii pneumonia There is increased white (opacity)
in the lower lungs on both sides, characteristic of Pneumocystis pneumonia. |
|
Clinical
trial results have demonstrated comparable first-line efficacy for these agents
in mild to moderate PCP, but inferior efficacy of atovaquone and trimetrexate
compared with TMP-SMX in moderate to severe PCP. Clinical trial data for clindamycin
with primaquine, or dapsone with TMP compared with TMP-SMX as treatment for moderate
to severe PCP have not been reported. Clinical
evidence to support second-line treatment options for patients who fail or do
not tolerate their first-line treatment is scarce. Because controlled clinical
trials of second-line salvage treatment are neither available nor being conducted,
systematic reviews of observational studies have become a powerful tool to evaluate
alternative treatment options. In
the present study, summarized here and published in the March 20, 2008 online
edition of the Journal of Acquired Immune Deficiency Syndromes (JAIDS),
Danish, Italian and British researchers performed a systematic search of MEDLINE
for all randomized and observational studies of PCP treatment published up to
August 2007 and included individual treatment data of AIDS-associated PCP from
a tri-center study. The
study presents a thorough updated review of second-line salvage treatment that
includes additional clinical case data and 14 published studies that were not
included in an earlier systematic review. The
investigators calculated pooled estimates of reported outcome of second-line treatment
using averaged odds ratios (ORs).  Results
•
A total of 1188 episodes of HIV-associated
PCP among 1122 patients were analyzed; 17 patients (1.5%) were lost to follow-up.
•
207 (17%) patients switched drugs because
of toxicity and were not included in this analysis.
•
104 (8.8%) patients switched from first-line
to second-line treatment because of suspected treatment failure.
•
Of these, 22 patients changed after 4 or more
days of treatment and were excluded from the present analysis.
•
29 studies with sufficient detail about second-line
treatment and outcomes, including data from 82 individual cases from the tri-center
study, yielded a total of 468 PCP second-line treatment episodes.
•
Response rates to second-line treatment were
comparable for trimethoprim-sulfamethoxazole (TMP-SMX; 68%) and clindamycin-primaquine
(73%), but were considerably lower for intravenous pentamidine (44%).
Conclusion In
conclusion, the authors wrote, "Here, we show that clindamycin-primaquine
is associated with a better outcome of second-line treatment compared with pentamidine
after treatment failure." Further,
they noted, "TMP-SMX is associated with a favorable outcome of second-line
treatment for those failing first-line treatments with regimens other than TMP-SMX." Finally,
they stated, "TMP-SMX remains the therapeutic drug of choice for HIV-associated
PCP in first-line and subsequent-line settings unless the patient is intolerant
of TMP-SMX." Department
of Infectious Diseases, Hvidovre University Hospital, University of Copenhagen,
Copenhagen, Denmark; Department of Infectious Diseases, Luigi Sacco Hospital,
Milan, Italy; Centre for Sexual Health and HIV Research, University College London,
UK; and the Department of Infectious Diseases, Copenhagen University Hospital,
University of Copenhagen, Copenhagen, Denmark. 4/01/08 Reference
T Benfield, C Atzori, RF Miller, and J Helweg-Larsen. Second-Line Salvage
Treatment of AIDS-Associated Pneumocystis jirovecii Pneumonia: A Case Series and
Systematic Review. J Acquired Immune Deficiency Syndromes. March 20, 2008
[Epub ahead of print]. | 
