September 18, 2006 (Reuters Health)—European researchers found HIV-infected patients can develop opportunistic infections at higher-than-expected CD4+ cell counts. These findings suggest that it may be advisable to start antiretroviral therapy in patients with higher CD4+ levels than conventionally recommended, according to the report in the September 1st issue of The Journal of Infectious Diseases.

Dr. Jens D. Lundgren of Hvidovre University Hospital in Denmark was the principal investigator of the EuroSIDA study, a prospective observational study of HIV-1 infected patients from 82 medical centers across Europe, Israel and Argentina. CD4+ cell counts, HIV-1 RNA viral levels and dates of starting and stopping antiretroviral therapy (ART) were recorded.

The EuroSIDA researchers divided patients into three groups.

Group 1 consisted of 9219 patients with a CD4+ cell count threshold of at least 100 cells per microliter. Study endpoint was defined as a diagnosis of Mycobacterium avium complex (MAC), Toxoplasma gondii (cerebral toxoplasmosis) or cytomegalovirus (CMV) retinitis.

Group 2 consisted of 7934 patients with a CD4+ cell count threshold of 200 cells per microliter or higher. Endpoint was a diagnosis of Pneumocystis pneumonia (PCP) or esophageal candidiasis.

Group 3 had 7838 patient with a CD4+ cell count threshold of 300 cells per microliter or greater and a study endpoint of pulmonary or extrapulmonary tuberculosis.

Dr. Lundgren told Reuters Health that the strongest predictor of an opportunistic infection in groups 1 and 2 was CD4+ cell count. The incidence ratio for each 50% drop in CD4+ cell count for group 1 was 5.37 and for group 2 it was 4.28.

In group 3, the patients with the highest CD4+ cell count, the strongest predictor of an opportunistic infection was injection drug use.

The use of antiretroviral therapy was associated with a lower risk of opportunistic infections in all three groups, which Dr. Lundgren speculates is a result of reduced HIV-1 RNA levels.

"We got a sense that there is a threshold of CD4+ cell count alone, above which the patient is not susceptible to an opportunistic infection," Dr. Lundgren said.

"This is not a study of when to start antiretroviral therapy," Dr. Lundgren cautioned. "You need to weigh the pros and cons" of such treatment in patients with less severe HIV infection, he advised. "However, these findings help support the argument to use antiretrovirals earlier if you want to reduce the risk of opportunistic infections in a patient."



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