New Guidelines for Treating and Avoiding Opportunistic Infections

by David Evans
Despite the fact that HIV is now perceived as “manageable,” opportunistic infections (OIs) remain a threat, especially for those who are unaware of their HIV status and those out of HIV treatment options. In this AIDSmeds interview, National Institutes of Health (NIH) scientist Henry Masur, MD, explains the Department of Health and Human Services’ recently revised OI prevention and treatment guidelines. They help health care providers and patients steer clear of—and treat—these life-threatening illnesses.How often do we hear today that HIV is a “chronic manageable disease”?

The implication is that HIV is no longer dangerous and that it’s relatively easy to treat. But according to Dr. Masur, a lead author of the guidelines, about one-third of people who test positive for HIV in many U.S. cities do so only after they already have AIDS and require treatment for a life-threatening opportunistic infection (OI)—or are in immediate danger of experiencing one. So it can be misleading to consider HIV and its related illnesses a thing of the past.The newly revised Department of Health and Human Services’ Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents includes an entirely new section on the prevention and treatment of hepatitis B virus (HBV). The guidelines also include sections dedicated to the prevention and management of immune reconstitution inflammatory syndrome (IRIS)—a flare of potentially dangerous symptoms mimicking OIs that can occur when antiretroviral treatment is started by people with low CD4 counts and whose immunity to infections is rapidly restored. These updated guidelines will be vital for all health care providers treating people at risk for OIs, particularly those doctors who treat HIV less frequently.AIDSmeds: Rates of OIs are way down because of the widespread use of combination antiretroviral therapy. So why update the OI prevention and treatment guidelines now? Maybe a better question is: Why have these guidelines at all?Henry Masur: Yes, the incidence of OIs has declined dramatically. But it’s also true that there are an estimated 40,000 to 60,000 new cases of HIV [in the United States] per year. Those numbers haven’t changed substantially in the last two and a half decades. In most cities, 30 percent of people are diagnosed with HIV when their CD4 count is already below 200—it’s 65 percent where I live in Washington, DC—and many are finding out that they’re positive after being diagnosed with Pneumocystis pneumonia [PCP], toxoplasmosis or cytomegalovirus [CMV] in emergency rooms. So there are still a substantial number of people who develop OIs. We’re really dealing with two populations who develop OIs. One is a population that has good access to care and the other is a population that doesn’t. Even in those who have good access to care, drug resistance may develop due to poor adherence and other factors, drug options can then run out and people find themselves at risk for OIs. So [finding] strategies to prevent OIs, including immunization, and management strategies are important.Tell us about the major updates to the guidelines.In terms of diagnosis, the guidelines provide new information about the utility of new tests such as PCR or BDNA tests for Hepatitis C, Hepatitis B, CMV, and tuberculosis.We also highlight new drugs for OIs, including the antifungals voriconazole [Vfend] and posaconazole [Noxafil]. The question is, When should they be used? There are also new drugs for hepatitis B, which were not included in the 2002 version of the guidelines, so we make recommendations regarding those drugs, too.We’re seeing more and more immigrants in this country with HIV and HIV-positive U.S. citizens traveling abroad. In turn, we’re seeing more and more parasitic diseases. So there’s a new section focusing on protozoal infections and complications in the immigrant population and travelers. While I don’t think these infections are huge public health burdens in the U.S., busy health care providers will likely have to deal with them.There are a number of new sections on IRIS in the revised guidelines. How common is IRIS? What should patients and health care providers be looking for?Many HIV-positive people with low CD4 counts starting therapy for the first time experience IRIS, but it’s not always a problem. If you were to do a CT or an MRI study every two weeks in a group of people taking antiretroviral therapy for the first time, I’m sure you could find some lymph nodes that have changed in size—a sign of IRIS—but that is not usually clinically important. The question is, What is clinically important—and that clearly depends on what active diseases, or infections without symptoms, you’ve had in the past.If you’ve had cryptococcal meningitis, toxoplasmosis or even progressive multifocal leukoencephalopathy [PML] in the past, a bad flare can occur when you start antiretrovirals. People can also have a latent infection, such as Cryptococcus or Mycobacterium tuberculosis, that hasn’t caused symptoms but may cause problems once the immune system begins responding to HIV treatment.We don’t have the tools or the knowledge to predict which patients with low CD4 cell counts starting therapy will develop a severe episode of IRIS. We also don’t yet know if we should manage flares by simply monitoring our patients, prescribing steroids or stopping antiretrovirals altogether—which is usually not something you want to do.I know it’s frustrating for the people who have questions about IRIS, but unfortunately we don’t have many data-driven answers.Again, we’re talking about more and more people finding out that they’re HIV positive in emergency rooms. What is the NIH doing to make sure that health care providers, especially those in hospital emergency departments, are aware of these guidelines?We try to work with different professional societies so that they know that these guidelines exist. A major issue facing emergency medicine providers is deciding whether to deal with a health issue in the ER or elsewhere. There’s a lot of effort to make all health care providers, particularly those in emergency rooms, aware of the importance of HIV testing, the complexities of this disease and how essential it is to get infectious disease providers involved early.Any final words?We really appreciate the interest, because I think these guidelines are important. It is interesting that already 80,000 people have downloaded this document. Even without much publicity, people are looking at it and using it.The new guidelines are co-published by the NIH, the Centers for Disease Control and Prevention (CDC) and the HIV Medicine Association of the Infectious Diseases Society of America (HIVMA/IDSA). Click here to download the document.

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