Prophylaxis for PCP can be stopped safely at CD4 counts above 100 in Europe

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Prophylaxis for Pneumocystis jiroveci pneumonia (also known as PCP) can be safely stopped by patients taking HIV therapy whose CD4 cell count is as low as 101 cells/mm3, provided that they have an undetectable viral load, a team of European investigators report in the September 1st edition of Clinical Infectious Diseases.

The incidence of PCP was low amongst patients with these characteristics, and the use of prophylaxis conferred no additional advantage.

However, PCP prophylaxis was still valuable for patients taking HIV treatment whose CD4 cell count was below 100 cells/mm3, regardless of their viral load.

Glossary

Pneumocystis carinii pneumonia (PCP)

Pneumocystis carinii pneumonia is a form of pneumonia that is an AIDS defining illness.

person years

In a study “100 person years of follow-up” could mean that information was collected on 100 people for one year, or on 50 people for two years each, or on ten people over ten years. In practice, each person’s duration of follow-up is likely to be different.

pneumonia

Any lung infection that causes inflammation. The infecting organism may be bacteria (such as Streptococcus pneumoniae), a virus (such as influenza), a fungus (such as Pneumocystis pneumonia or PCP) or something else. The disease is sometimes characterised by where the infection was acquired: in the community, in hospital or in a nursing home.

epidemiology

The study of the causes of a disease, its distribution within a population, and measures for control and prevention. Epidemiology focuses on groups rather than individuals.

bias

When the estimate from a study differs systematically from the true state of affairs because of a feature of the design or conduct of the study.

“Our data support discontinuation of primary PCP prophylaxis in patients with a CD4 cell count above 100 cells/mm3 and with suppressed viral load,” comment the investigators.

They believe that “reducing the need for primary PCP prophylaxis has a number of advantages, including reducing pill burden, the potential for toxicities, inconvenience and cost”.

Pneumocystis jiroveci pneumonia, formerly known as Pneumocystis carinii pneumonia (PCP) is an AIDS-defining illness. It was a major cause of illness and death in people with HIV before effective HIV treatment became available.  Most cases occur in patients whose CD4 cell count is below 200 cells/mm3. Therefore patients with a CD4 cell count below this are recommended to take prophylaxis against the illness. The preferred drug for this treatment is cotrimoxazole (also known as trimethoprim-sulfamethoxazole, Septrin).

Patients who start HIV treatment with a low CD4 cell count are currently recommended to take cotrimoxazole for three months after their CD4 cell count increases to above 200 cells/mm3.

However, one small study found that it was safe for patients taking HIV treatment who had an undetectable viral load to stop PCP prophylaxis, even if their CD4 cell count had not increased to above 200 cells/mm3.

Investigators from the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) study group wished to gain a better understanding of when it is safe for patients taking HIV therapy to stop PCP prophylaxis.

They therefore looked at the incidence of PCP amongst 23, 412 patients who started HIV therapy in twelve European countries after 1998. The analysis excluded patients who had never taken PCP prophylaxis, or who had stopped it before starting antiretroviral therapy.

The databases did not capture the reasons why patients stopped taking prophylaxis after starting antiretroviral therapy, and one limitation of the study noted by the authors is that doctors may have encouraged patients to stop prophylaxis if they believed that they were doing well, and this may have introduced some bias into the findings.

The patients were followed for a median of 4.7 years and contributed a total of 107, 016 person years of follow-up, 11,932 of which were for patients with a CD4 cell count below 200 cells/mm3.

Overall, there were 253 cases of PCP (incidence, 2.4 cases per 1000 person-years). These patients had a median CD4 cell count of 92 cells/mm3 when they were diagnosed with PCP, at which time median viral load was 100,000 copies/ml.

Incidence of PCP was 35 cases per 1000 person years for those with a CD4 cell count below 100 cells/mm3, but 6.4 per 1000 person years for those with a CD4 cell count between 101 and 200 cells/mm3. The disease was very rare amongst patients with a CD4 cell count above this level (incidence, 0.8 per 1000 person years).

Statistical analysis showed that patients whose CD4 cell count was below 100 cells/mm3 were significantly less likely to develop PCP if they were taking prophylaxis against the infection (p < 0.001).

However, at higher CD4 cell counts the benefits were less clear. Prophylaxis reduced the risk of the infection for those with a CD4 cell count between 101 and 200 cells/mm3, but not significantly ((IRR, 0.63; 95% CI, 0.34 to 1.17, p = 0.15).

The investigators then focused their attention on patients whose current CD4 cell count was between 100 and 200 cells/mm3. These patients contributed a total of 8279 person years of follow-up.

There were seven cases of PCP during 3363 person years of follow-up amongst patients with a viral load below 400 copies/ml who were currently taking prophylaxis (incidence, 2.1 cases per 1000 person years). 

Incidence was similar amongst patients with HIV suppression who were not taking prophylaxis (1.2 per 1000 person years).

Finally the investigator looked at the risk of PCP for 4903 patients who had responded well to HIV therapy and had stopped prophylaxis a median of six months after starting to take anti-HIV drugs.

There were 24 cases of PCP amongst these patients (incidence 1.3 per 1000 person years).

The investigators estimated that twelve months after stopping prophylaxis, only 0.17% of patients would develop PCP, and after 48 months this had increased to just 0.53%.

The vast majority of cases of PCP occurred amongst patients with a CD4 cell count below 100 cells/mm3. Suppression of viral load did not significantly reduce the risk of PCP for these patients.

However, no patient taking HIV treatment with a CD4 cell count between 101 and 200 cells/mm3, and whose viral load was undetectable, developed PCP.

“The incidence of PCP among patients with CD4 cell counts of 101-200 cells/mm3 who had virologically suppressed HIV infection was sufficiently low, both overall and among patients who had stopped primary PCP prophylaxis, to merit consideration of formally revising current prophylaxis guidelines,” write the investigators.

It is important to note that these findings need to be replicated in developing country settings, where cotrimoxazole may have benefits in addition to its protective effect against PCP. Cotrimoxazole may reduce the risk of bacterial infections, and an analysis of the Home Based AIDS Care Cohort found that people on antiretroviral treatment in Uganda who stopped cotrimoxazole prophylaxis experienced a very rapid increase in the risk of developing malaria.

References

The Opportunistic Infections Project Team of the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE). Is it safe to discontinue primary Pneumocystis jiroveci pneumonia prophylaxis in patients with virologically suppressed HIV infection and a CD4 cell count < 200 cells/mm3? Clin Infect Dis 51: 611-19, 2010.