Antiretroviral-treated patients with sustained virological suppression, but a CD4 cell count below 200 cells/mm3, may be able to safely discontinue prophylaxis for pneumocystiis jiroveci pneumonia (PCP), according to the results of a small Canadian study published in the August 20th edition of AIDS.
A CD4 cell count below 200 cells/mm3, or a CD4 cell percentage of 14% or below, indicates that an HIV-positive individual has a significant risk of developing PCP pneumonia and several other AIDS-defining opportunistic infections. The incidence of PCP has declined markedly since the introduction of potent anti-HIV therapy, but PCP remains one of the most common AIDS-defining illnesses in the United Kingdom, with almost 200 cases diagnosed each year.
Prophylaxis can prevent the emergence of PCP in patients with immune suppression. It is well established that patients taking anti-HIV therapy who experience an increase in their CD4 cell count to above 200 cells/mm3 can safely discontinue PCP prophylaxis. But a number of antiretroviral-treated patients never achieve a CD4 cell count of this level, despite having sustained HIV suppression (a viral load below 50 copies/ml).
Investigators from the University of Ottawa and the Ottawa Hospital wished to see if patients taking antiretroviral therapy who had a sustained viral load below 50 copies/ml, but a plateau in their CD4 cell count below 200 cells/mm3, could safely discontinue PCP prophylaxis.
Their study included 19 patients, 15 of whom were men, with a median age of 47-years. Nadir CD4 cell count before the initiation of anti-HIV therapy was 28 cells/mm3, with median pre-treatment viral load being a little under 200,000 copies/ml. In all, 17 patients were taking primary PCP prophylaxis and one patient was taking secondary prophylaxis. The median duration of PCP prophylaxis before discontinuation was twelve months.
After initiating antiretroviral therapy, the patients had a viral load of below 50 copies/ml for a median of six months before stopping PCP prophylaxis. At the time of prophylaxis discontinuation, median CD4 cell count was 120 cells/mm3, and median CD4 cell percentage was 11%.
The investigators reported that the patients had so far been off PCP prophylaxis for a median of 13.7 months, providing a total of 261 patient-months of observation. At the most recent three-monthly follow-up, median CD4 cell count had increased to138 cells/mm3. Although one patient had two CD4 cell counts above 200 cells/mm3, these measures were not consecutive and did not meet the criteria of treatment guidelines for the discontinuation of PCP prophylaxis. Five patients had transient ‘blips’ in their viral load above 50 copies/ml.
No patient developed either laboratory confirmed PCP, presumptive PCP, or any other AIDS-defining opportunistic infection. For purposes of comparison, the investigators looked at the incidence of PCP in patients with a CD4 cell count below 200 cells/mm3 not taking potent anti-HIV therapy in the Multi Center AIDS Cohort (MACS). These patients had a PCP incidence of 20 cases per 100 patient months. The investigators write: “Our observation of no cases of PCP over a period of 261 patient-months of follow-up is significantly different from the risk of developing PCP with a CD4 T-cell count 3 in untreated HIV infection (rate difference, 9.2%; 95% CI, 5.7 – 12.8%; p
Thanks to improvements in immune function brought about by anti-HIV therapy, many patients have been able to discontinue prophylactic therapy. The investigators note that there is increasing evidence that the lower viral load achieved by HIV therapy also reduces the risk of infections, independent of CD4 cell count.
Being able to discontinue prophylaxis therapy in virologically suppressed patients with a low CD4 cell count could, the investigators suggest, have several advantages. These might include a reduction in the number of pills a patient needs to take, fewer side-effects, a lower risk of drug interactions, decreased cost of care, and possibly, improved adherence to anti-HIV therapy.
The investigators conclude that their results “would suggest that guidelines for discontinuing PCP prophylaxis not only take into account absolute CD4 numbers but virological response to antiretroviral therapy as well.”
D’Egidio GE et al. Pneumocystis jiroverci pneumonia prophylaxis is not required with a CD4+ T-cell count 3 when viral replication is suppressed. AIDS 21: 1711 – 1715, 2007.