The Latest on OI Prophylaxis: When to Start, When to Stop
Long before HAART, the use of medications to prevent opportunistic infections (prophylaxis) was an important component of HIV care. And while there has been a decrease in the incidence of opportunistic infections since the introduction of HAART, paying attention to prophylaxis remains crucial. Recent reports show high rates of admissions for opportunistic infections among individuals not receiving HAART in the U.S., and OIs are a serious concern in parts of the world where HAART is not available at all or available to very few people. For people who have experienced immune reconstitution with HAART, however, prophylaxis against opportunistic infections is not always necessary.
With the goals of decreasing the number of pills a person needs to take and minimizing side effects while maintaining health, researchers have examined the effects of discontinuing prophylactic regimens. The first studies showed that it is safe to discontinue primary prophylaxis (preventive treatment for someone who has never had the infection) against infections such as MAC (mycobacterium avium complex) and PCP (pneumocystis carinii pneumonia) following immune reconstitution. The positive results of early studies led researchers to look at the safety of discontinuing secondary prophylaxis (preventive treatment for someone who has already had the infection).
Several studies presented at the 13th International AIDS Conference in Durban, South Africa, indicate that it is safe to discontinue secondary prophylaxis against PCP. Swiss researchers studied 41 people with a history of PCP who had an increase in CD4 count from an average of 23 to an average of 369. All study participants discontinued PCP prophylaxis, and after a median follow up of over 5 months, no cases of PCP were observed. The results of an Italian study were similar. 124 patients on secondary prophylaxis for PCP were enrolled, and half discontinued their prophylactic medications. No PCP events were observed in either group. One of the inclusion criteria for these studies was a CD4 count greater than 200 after being on HAART, but the average count of participants in both studies was above 300. A third study, tracking over 70,000 people with HIV, identified 450 people with a history of PCP. Of the 450, about 175 never had an increase in CD4 count to above 200. Within that group, nine people discontinued their secondary PCP prophylaxis, a factor that was associated with a greater risk of PCP recurrence. PCP recurred in 18 patients overall, illustrating the importance of continuing prophylaxis in an immunocompromised state. Additional research is necessary to determine exactly when it is safe to discontinue secondary PCP prophylaxis. At present, the Centers for Disease Control and Prevention has not issued a formal recommendation.
Rates of CMV (cytomegalovirus) infection are very low, even in patients with advanced HIV disease. Primary prophylaxis against CMV infection is not generally recommended, since oral ganciclovir (Cytovene) is expensive and its efficacy as a prophylactic agent is controversial. Recognizing early signs of CMV infection, such as decreased visual clarity, is currently the best defense against CMV. An observational study from France examined the relation between CMV seroconversion and AIDS progression. 1,700 subjects enrolled in the study, 290 of whom were CMV seronegative when they enrolled. 61 of the subjects seroconverted during follow-up. The 61 subjects who seroconverted had a median CD4 cell count of 102 at the time of an AIDS-defining illness, while the seronegative individuals had a median CD4 count of 26 at the time of an AIDS-defining illness. While the difference was not statistically significant, it illustrates a trend toward more rapid HIV disease progression in CMV-positive individuals. CMV is shed in semen, cervical secretions, and saliva. Safer sex decreases the risk of CMV exposure. Basic hygienic practices such as hand washing also decrease the transmission of CMV and other germs.
Studies from the 7th Conference on Retroviruses and Opportunistic Infections in February examined the effects of discontinuing prophylactic therapies for cryptococcosis, a fungal infection, and for MAC. A team from the University of California in San Francisco followed six patients with a history of cryptococcosis to examine the effect of discontinuing antifungal prophylaxis. The group had CD4 counts greater than 150 and had been asymptomatic for cryptococcosis for at least four months after a year of fluconazole (Diflucan) therapy. Patients who discontinued therapy in April and May of 1999 were still asymptomatic when the conference abstract was submitted, leading researchers to conclude that cryptococcal infection can be "cured" in some individuals after immune reconstitution.
The recommendation for primary MAC prophylaxis is to begin prophylaxis when CD4 count falls below 50 and to stop prophylaxis when CD4 count increases to above 100. This recommendation was supported by the results of ACTG 362, an AIDS Clinical Trials Group study in which about 650 patients with immune reconstitution received either azithromycin (Zithromax) or placebo for MAC prophylaxis. There was no statistically significant difference in MAC incidence between the two groups. Other serious bacterial infections, such as pneumonia, sinusitis, and sepsis may be prevented by azithromycin, however. The patients in the ACTG 362 trial are still being followed, and the impact of discontinuing azithromycin on the rate of serious bacterial infections will be examined.
Although opportunistic infections may seem forgotten, they are certainly not gone. Any decision to discontinue prophylaxis should be done in conjunction with vigilant monitoring of immune function, and prophylactic therapies should be restarted if or when immune status changes. This way, the serious illness associated with opportunistic infections can be delayed or completely avoided.
For references, contact CRIA's Treatment Education Department or check our Web site at www.criany.org.
Anne Monroe is research associate at Cornell's Clinical Trials Unit in New York City and a writer on HIV/AIDS topics.
This article was provided by AIDS Community Research Initiative of America. It is a part of the publication CRIA Update. Visit ACRIA's website to find out more about their activities, publications and services.