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The Body Covers: The 4th Conference on Retroviruses and Opportunistic Infections
Pneumocystis Carinii Pneumonia: What's New in the Era of Combination Antiretroviral Therapies and Protease Inhibitors?
Despite the fact that the incidence and prevalence of
pneumonia (PCP) among AIDS patients has declined over the years, due to
use of prophylaxis, it remains an important cause of morbidity and
mortality in advanced
patients with HIV infection. At a symposium held at the 4th National
Retrovirus Conference in Washington, D.C. Dr. Henry Masur from the National
Institutes of Health
reviewed the state of the art in the management and prevention of the
the era of combination antiretroviral therapies and protease inhibitors.
One of the
unanswered questions is what to do with patients whose CD4 counts rises
over 200 cells/mm3,
the threshold below which prophylaxis is usually initiated. He presented
that the repopulation of CD4 cells after indinavir therapy includes both
memory and naive cells, yet some clonal deletions of some CD4 subsets
(including some in
the TCRV beta repertoire) may result in inadequate protection against PCP
as other opportunistic infections.
The latest revision of Guidelines for the Prevention
of Opportunistic Infections in Persons with HIV Infection to be issued by
States Public Health Service and the Infectious Disease Society of America
initiating prophylaxis for PCP based on the lowest CD4 count and not
it even if the CD4 count rises over 200 cells/mm3 with antiretroviral
of PCP breakthrough episodes discussed by Dr. Masur included a prior AIDS
opportunistic infection, a CD4 count < 50 cells/mm3 and use of a
regimen other than trimethoprim/sulfamethoxazole (Bactrim or Septra). The
latter remains the prophylactic
agent of choice, yet the exact dosing schedule is still being debated.
that one single strength tablet per day, one double strength tablet per day
or one double strength tablet thrice weekly are effective, yet as the
weekly dose increases
so does the incidence of intolerability. Investigational agents which can
for prophylaxis include clindamycin/primaquine, atovaquone, malarone,
azithromycin, benzimidines and pneumocadins.
The question of whether the Pneumocystis carinii
organism becomes resistant is still being investigated. As the fungus
cannot be isolated
in culture determination of phenotypic resistance is impossible. A study
genotypic resistance among PCP breakthroughs was presented at the
showed that mutations at two nucleotide positions of the dihydropteroate
(DHPS) gene were present in 4 of 6 patients who had broken through sulfa
Due to the lack of effective prophylactic therapies for patients with sulfa
breakthroughs, Masur recommended using higher doses of
in these patients to prevent subsequent breakthroughs. Another strategy
reported was that of gradual initiation of trimethoprim/sulfamethoxazole
prophylaxis using a suspension (8 mg TMP/40 mg SMX per ml) given gradually
over two weeks.
In a randomized, double-blind , placebo-controlled study of 377 patients,
fewer subjects discontinued TMP/SMX when it was initiated gradually than
when its was initiated as a double-strength tablet.
Another researcher from the University of Oxford, Dr.Ann Wakefield presented animal
data supporting the concept that PCP is host-species specific, and unlikely
a zoonosis in humans. Genotyping of isolates of human-derived
have demonstrated various different subtypes or polymorphisms. In 4 of 7
with recurrent PCP the genetic sequences observed differed among the
at each episode. She postulated that PCP in patients with AIDS may result
from either reactivation or from reinfection with a different subtype.
Using spore traps she
was able to capture ambient air at rural sites and successfully recover
the PC spores
using PCR techniques. Whether the recovery of PC spores in ambient air from
hospitals imply that the infection is airborne and patients with AIDS and
PCP should be isolated
remains unanswered, since the infectiousness of these spores and their
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