Can Maintenance Therapy for Opportunistic Infections in HIV-Infected People Be Stopped Safely?

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The summary below is from the full report titled "Safe Interruption of Maintenance Therapy against Previous Infection with Four Common HIV-Associated Opportunistic Pathogens during Potent Antiretroviral Therapy." It is in the 20 August 2002 issue of Annals of Internal Medicine (volume 137, pages 239-250). The authors are O Kirk, P Reiss, C Uberti-Foppa, M Bickel, J Gerstoft, C Pradier, FW Wit, B Ledergerber, JD Lundgren, and H Furrer, for Seven European HIV Cohorts.

What is the problem and what is known about it so far?

HIV infection damages the body's ability to resist all types of infection, even by organisms that do not usually cause disease in healthy people (opportunistic infections). Because of increased susceptibility to infection, HIV-positive patients are often advised to take preventive antibiotics on a long-term basis to ward off opportunistic infections. Doctors estimate an individual's level of susceptibility to infection by measuring how many of a particular kind of white blood cell (CD4 lymphocytes) are present in the blood. More CD4 lymphocytes in the blood produce a lower susceptibility to infection. Modern combinations of medications used to treat HIV infection can raise the number of CD4 lymphocytes in the blood. Researchers have already proven that preventive antibiotic therapy can be safely discontinued when the CD4 count rises to protective levels. On the other hand, it is not known whether antibiotic therapy can ever be stopped safely in HIV-positive patients who have already been infected with these opportunistic organisms.

Why did the researchers do this particular study?

To find out whether it is safe to stop antibiotic treatment of established opportunistic infections in patients who are receiving potent anti-HIV therapy.

Who was studied?

358 HIV-positive patients receiving potent anti-HIV therapy whose active treatment for at least one of four common opportunistic infections (cytomegalovirus, cryptococcosis, Mycobacterium avium complex, or toxoplasmosis) had been interrupted. Patients were included only if CD4 lymphocyte counts were available within 6 months before interruption of antibiotic therapy.

How was the study done?

Data were analyzed from seven different groups of European patients receiving anti-HIV therapy. Patients were followed by observing CD4 lymphocyte counts and evidence of relapse of opportunistic infection following interruption of antibiotic therapy. Reports of relapse, death, or restarting maintenance therapy were confirmed by reviewing each patient's medical chart.

What did the researchers find?

Among the 358 patients (in whom maintenance therapy for opportunistic infections was interrupted 379 times), relapses occurred 5 times (in 2 patients with very low CD4 lymphocyte counts, 2 patients with moderately low counts, and 1 patient with a CD4 count that many doctors consider protective against opportunistic infections). Incidence rates were very low for each type of opportunistic infection studied.

What were the limitations of the study?

There was no advance requirement for specific evaluation of early signs of relapse of infection, so some cases of relapse may have been missed. Furthermore, the anti-HIV therapy used in these patients did not consistently follow current U.S. standards for HIV treatment.

What are the implications of the study?

The very low incidence of relapse in patients treated with potent anti-HIV medications suggests that maintenance therapy for previous infection with opportunistic organisms can be safely interrupted when the CD4 lymphocyte count rises to acceptable levels.