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The introduction of effective multi-class ART in the mid-1990s dramatically reduced the incidence of opportunistic illnesses (OIs), or infections and malignancies that occur when the immune system is severely weakened.

Prior to the advent of combination ART -- and still today for those who are not receiving or not responding adequately to antiretroviral treatment -- people with low CD4 cell counts were advised to take prophylactic medications to prevent a first occurrence or recurrence of various opportunistic infections.

For example, people with < 200 cells/mm3 -- the threshold for an AIDS diagnosis -- were prescribed trimethoprim/sulfamethoxazole (TMP-SMX; Bactrim or Spetra) to prevent Pneumocytis pneumonia, while those with < 50 cells/mm3 received azithromycin or clarithromycin to prevent Mycobacterium avium complex (MAC).

The introduction of effective ART allowed many people with AIDS to stop taking prophylactic drugs as their CD4 cell count rose above the danger zone. But what about individuals on combination ART who have achieved full viral load suppression but still have a low CD4 counts -- a condition known as discordant response?

To explore this issue with regard to PCP, Amanda Mocroft and fellow investigators with the COHERE (Collaboration of Observational HIV Epidemiological Research) Opportunistic Infections Project Team looked at data from 23,412 HIV positive patients from 12 European cohorts who started combination ART after 1997, focusing on those with CD4 counts of 100-200 cells/mm3.

Results

·      A total of 253 Pneumocytispneumonia cases occurred during 107,016 person-years of follow-up.

·      Use of prophylaxis significantly reduced the incidence of PCP among patients with a current CD4 cell count £100 cells/mm3 (adjusted incidence rate ratio [IRR] 0.41, or a decrease of about 60%).

·      The incidence did not decrease significantly, however, among people with a current CD4 cell count of 101-200 cells/mm3 (adjusted IRR 0.63).

·      The incidence of PCP among individuals with a current CD4 cell count of 100-200 cells/mm3, viral load < 400 copies/mL, and receiving prophylaxis was 2.1 cases per 1000 person-years (7 events during 3363 person-years of follow-up).

·      In comparison, the incidence was 1.2 cases per 1000 person-years (2 events during 1614 person-years of follow-up) among people with the same CD4 count and viral load but not receiving prophylaxis (adjusted IRR 1.65).

·      Among patients who discontinued Pneumocystis prophylaxis after starting combination ART, were currently on ART, and had a current CD4 count of 101-200 cells/mm3, the incidence of primary (first occurrence) PCP was 0 cases per 1000 person-years (no events during 1363 person-years of follow-up).

Based on these findings, the researchers concluded, "The incidence of primary PCP among patients who had virologically suppressed HIV infection, were receiving combination ART, and who had CD4 cell counts > 100 cells/[mm3] was low irrespective of prophylaxis use."

"Discontinuation of prophylaxis may be safe in patients with CD4 counts of 101-200 cells/[mm3] and suppressed viral load," they added.

8/31/10

Reference

A Mocroft, P Reiss, O Kirk, and others. Is it safe to discontinue primary Pneumocystis jiroveci pneumonia prophylaxis in patients with virologically suppressed HIV infection and a CD4 cell count <200 cells/microL? Clinical Infectious Diseases 51(5): 611-619. September 15, 2010.