Pneumocystis
jiroveci Pneumonia (PCP) Prophylaxis Is Not Required When Viral Load Is Suppressed
< 50 copies/ml in Patients with CD4 Cell Counts Below 200 cells/mm3
Cysts
of Pneumocystis jiroveci in AIDS.Methenamine
silver stain.
In
the HAART era, it has also been established that PCP prophylaxis can be safely
discontinued in HIV patients on HAART whose CD4 cell counts have increased and
stabilized above 200 cells/mm3.
However,
it is not clear whether prophylaxis is still needed in patients on HAART with
maximal HIV suppression (< 50 copies/mL) and CD4 cell counts below 200 cells/mm3.
There are significant
benefits for patients who are able to stop PCP prophylaxis, including reduction
of pill burden, reduced drug toxicity, fewer drug interactions, and lower costs
for therapy.
In a prospective study published in the August 20, 2007 issue
of AIDS, Gianni D'Egidio and colleagues at the University of Ottowa, Canada
evaluated a cohort of patients at a multidisciplinary HIV clinic with sustained
HIV RNA levels < 50 copies/mL and CD4 T-cell counts that plateaued below 200
cells/mm3 who discontinued PCP prophylaxis. The study objective was to determine
whether these patients could safely discontinue PCP prophylaxis.
Results
Of the 19 patients enrolled,
11 had been taking daily trimethoprim-sulfamethoxazole (Bactrim, Septra, etc),
7 were receiving monthly aerosolized pentamidine, and 1 never received PCP prophylaxis.
The median CD4 cell
count at the time of prophylaxis discontinuation and at the most recent determination
were 120 and 138 cells/mm3, respectively.
To date, patients have been off PCP prophylaxis for a mean of 13.7
+/- 10.6 months and a median of 9.0 months, for a total of 261 patient-months.
To date, no patient
has developed PCP.
This
is significantly different from the risk of developing PCP with a CD4 cell count
< 200 cells/mm3 in untreated patients (rate difference 9.2%, P < 0.05).
Conclusion
and Discussion
In
conclusion, the study authors wrote, "With sustained suppression of viral
replication, PCP prophylaxis may not be necessary, regardless of CD4 T-cell count.
This illustrates a degree of immune recovery that occurs with virologic suppression
that is not reflected in absolute CD4 T-cell count or percentage and suggests
that guidelines for P. jiroveci pneumonia prophylaxis may need to be re-evaluated."
Patients
with a CD4 cell percentage of less than 14% are at an increased risk of developing
PCP, independent of absolute CD4 T-cell count and should be considered for primary
PCP prophylaxis. In the Canadian patient cohort, the median CD4 percentage at
the time of discontinuation of prophylaxis was 10.7%, and this value remained
stable while off prophylaxis as indicated by the current median value of 10.6%.
"This further
suggests that immune function is gained independent of CD4 T-cell percentage,"
wrote the authors. "Our results support the concept that there is independent
immunologic benefit gained from suppressing viral replication."
The
authors hypothesized that the immune recovery that protects patients from PCP
is probably relevant to other opportunistic infections as well.
In
closing, the authors wrote, "The risk of specific opportunistic infections
and therefore the use of prophylactic therapies have not been related to plasma
HIV RNA levels and therefore current guidelines do not include criteria based
on plasma viral load. These data would suggest that guidelines for discontinuing
PCP prophylaxis [should] not only take into account absolute CD4 numbers but virologic
response to antiretroviral therapy as well."
08/17/07
Reference G
E D'Egidio, S Kravcik, C Cooper, and others. Pneumocystis jiroveci pneumonia prophylaxis
is not required with a CD4+ T-cell count < 200 cells/microliter when viral
replication is suppressed. AIDS 21(13): 1711-1715. August 20, 2007.