Opportunistic Infection Prophylaxis and the Impact of HAART

By Liz Highleyman

With the advent of highly effective antiretroviral therapy (HAART), the risk of opportunistic infections (OIs) has declined dramatically. However, OIs may still occur among patients who do not receive optimal antiretroviral treatment, or who respond poorly to treatment, for example due to extensive drug resistance.

Two articles in the July 1 issue of Clinical Infectious Diseases looked at the incidence of two OIs - toxoplasmosis and bacterial pneumonia - in the HAART era.

Toxoplasmosis

In the first study, J. Miro and colleagues from Spain assessed the continued need for primary and secondary prophylaxis against Toxoplasma gondii, a parasite that can cause severe brain disease (toxoplasmic encephalitis).

This non-blinded, multicenter trial included 381 patients receiving primary prophylaxis against toxoplasmic encephalitis (that is, they had never had the infection before) and 57 patients receiving secondary prophylaxis (to prevent recurrent infection). Subjects were sustained responders to combination antiretroviral therapy with CD4 counts of at least 200 cells/mm³ and HIV viral loads below 5000 copies/mL for at least three months. Participants were randomly assigned to either stop or continue Toxoplasma prophylaxis; prophylactic drugs were restarted if CD4 count fell below 200 cells/mm³.

Results

The patients receiving primary prophylaxis had a median baseline CD4 cell count of 343 cells/mm³; 318 out of 381 subjects (83%) had undetectable plasma HIV RNA.

After a median follow-up period of 25 months (409 person-years), there were no episodes of toxoplasmic encephalitis among the 196 patients who discontinued prophylaxis; at one year, the upper limit of the 95% confidence interval for the rate of infection was 2.40%.

The patients receiving secondary prophylaxis had a median baseline CD4 count of 407 cells/mm³; 49 out of 57 subjects (86%) had undetectable plasma HIV RNA.

After a median follow-up period of 30.5 months (69 person-years), there were no episodes of toxoplasmic encephalitis recurrence among the 28 patients who discontinued prophylaxis; at one year, the upper limit of the 95% confidence interval for the relapse rate was 16%.

Conclusion

The researchers concluded that in HIV-positive adult patients receiving effective HAART, primary and secondary prophylaxis against toxoplasmic encephalitis can be safely discontinued after CD4 count increases to 200 cells/mm³ or higher for at least three months.

Bacterial Pneumonia

In the second study, R. Kohli looked at the incidence of and risk factors for community-acquired bacterial pneumonia and its effect on HIV disease progression in the large HIV Epidemiology Research (HER) Study.

HER is a long-term prospective study of HIV positive women and women at risk for HIV infection. Between 1993 and 2000, the authors observed 885 HIV-infected and 425 uninfected women with a history of injection drug use or high-risk sexual behavior in four U.S. cities. Participants were interviewed and had their CD4 counts and viral loads measured twice yearly.

Results

The rate of bacterial pneumonia among the 885 HIV-positive women was 8.5 cases per 100 person-years, compared with 0.7 cases per 100 person-years among the 425 HIV-negative women (P < .001).

Looking only at data collected after January 1, 1996 (the beginning of widespread availability of protease inhibitors), HAART and use trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis were associated with a decreased risk of bacterial pneumonia.

Among women who had used TMP-SMX for 12 months, each month of HAART reduced the risk of bacterial pneumonia by 8% (adjusted hazard ratio 0.92; 95% CI 0.89-0.95).

Increments of 50 CD4 cells/mm3 also decreased the risk of bacterial pneumonia (adjusted hazard ratio 0.88; 95% CI 0.84-0.93).

Tobacco smoking doubled the risk of bacterial pneumonia (adjusted hazard ratio 2.12; 95% CI 1.26-3.55).

Having bacterial pneumonia was associated with an increased mortality rate after adjusting for CD4 count and duration of HAART and TMP-SMX use (adjusted hazard ratio 5.02; 95% CI 2.120-11.87).

Conclusion

The authors concluded that "high rates of bacterial pneumonia persist among HIV-infected women." Although use of HAART and TMP-SMX reduced the risk of infection, bacterial pneumonia was associated with accelerated progression to death. They added that, "Interventions that improve HAART utilization and promote smoking cessation among HIV-infected women are warranted."

6/16/06

References

JM Miro, JC Lopez, D Podzamczer, and others. Discontinuation of primary and secondary Toxoplasma gondii prophylaxis is safe in HIV-infected patients after immunological restoration with highly active antiretroviral therapy: results of an open, randomized, multicenter clinical trial. Clinical Infectious Diseases 43(1): 79-89. July 1, 2006.

R Kohli, Y Lo, P Homel, and others. Bacterial pneumonia, HIV therapy, and disease progression among HIV-infected women in the HIV Epidemiologic Research (HER) Study. Clinical Infectious Diseases 43(1): 90-98. July 1, 2006.