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

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].