The human immunodeficiency virus (HIV) infects immune cells, impairing their function and eventually destroying cells over time. This gradually weakens the immune system and the body loses the ability to fight disease. While HIV is the culprit, most people who die of AIDS do not die of HIV, per se, but from the numerous infections that the body can no longer control due to the collapse of the immune system. Relatively common infections, which may cause little or no harm in a healthy person, take the opportunity provided by weakened immune defenses to cause disease. This is why they are called opportunistic infections (OIs).

A strategy to deal with OIs is an important part of a comprehensive, long-term strategy for managing HIV. The basics of an OI strategy include:

• understanding what an OI is,

• preventing infections by organisms that cause OIs,
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• using appropriate preventive treatment (sometimes called prophylaxis) against OIs,

• treating infections as they occur and using appropriate maintenance therapy to prevent recurrence of OIs.

What Is an Opportunistic Infection?

As noted above, an opportunistic infection is any infection or condition that takes the opportunity of a weakened immune system to cause disease. The Center for Disease Control (CDC) has developed a list of serious and life-threatening diseases, listed in the chart below, that in the presence of HIV infection are called Acquired Immune Deficiency Syndrome (AIDS)-defining OIs. In the presence of HIV infection, any one of these conditions results in a diagnosis of AIDS. Measures of immune health suggesting that a person is at serious risk for developing life-threatening conditions (i.e., when CD4+ cell counts are below 200 or CD4 percentages less than 14%), in the presence of HIV infection, also results in an AIDS diagnosis.

OIs can be relatively common infections, such as genital herpes. Not everyone with HIV who is having a herpes outbreak is deemed to have AIDS, however. To the contrary, herpes is deemed an opportunistic infection when it takes advantage of a severely weakened immune state to become more aggressive, persistent and less responsive to treatment. Therefore, having HIV and genital herpes isn't automatically considered AIDS, but having HIV and a herpes outbreak that persists for a month despite treatment is considered AIDS.

While there is a discrete list of AIDS-defining OIs, it's important to note that virtually any condition or disease can become opportunistic in the face of a weakened immune system. People living with HIV are not the only people at risk for OIs. Anyone with a severely weakened immune system, regardless of the cause, is at risk for OIs. For an OI to be the cause for an AIDS diagnosis, however, it must be one of the CDC AIDS-defining diseases occurring in the presence of HIV infection. People with HIV can get any number of worsening conditions that behave opportunistically and not all are on the CDC's list. Occasionally the CDC revisits this list, and over the years there have been several expansions. It's still possible, however, for people with HIV to develop opportunistic infections that are not on that list. Hepatitis C-associated disease is not AIDS-defining, though increasingly data show that people with HIV are at higher risk for more aggressive HCV-related liver disease. Most importantly virtually any condition or disease can behave in an opportunistic manner and the first line of defense is prevention.

Preventing Infections in the First Place

OIs are often caused by infections and some of them are preventable. For people never exposed to herpes, for example, practicing safer sex reduces the risk of genital herpes infection. If you are not infected with herpes simplex virus, there is no worry of herpes becoming opportunistic or life threatening. Project Inform has a publication called "Sex and Prevention Concerns for Positive People." This publication contains information on how you can prevent infections by many of the organisms that can cause opportunistic infections. Some of these are sexually transmitted, and you can reduce your risk of infection by practicing safer sex. Others are preventable with vaccines. Still others can be avoided through safer food handling and preparation and/or by being aware of and avoiding (when possible) disease-causing organisms. This might include being aware of diseases that birds carry and not handling birds, even those kept as pets. It may also include using gloves when changing cat litter boxes, or even better, having someone else deal with the cat litter box and/or keeping only indoor cats.

Recently there have been outbreaks of drug-resistant staph skin infections. The infection can be spread through casual contact, and some speculate that in urban areas staph infections may be spread through something as simple as sharing equipment at the gym. Because the organisms are drug resistant, treatment might require intravenous therapy. Doing something as simple as putting a towel down on shared gym equipment before use, and not using that towel to wipe sweat from your body, might help to prevent staph infection.

Preventing exposure to organisms is a great way to reduce your risk of particular OIs. In some cases, however, the organisms that can cause OIs are in our environment, unavoidable and/or exposures may have already occurred. People living with HIV should receive screening for many OIs upon first finding out that they are HIV-positive, as part of early lab screenings. This allows people to know, in some instances, if they are already exposed to an organism and enables people to learn about prevention for infections they don't already have. For more information on what's generally looked for on these lab tests, call the Project Inform hotline. In the case of Pneumocystis carinii pneumonia (PCP), however, it's simply not known how the organism is spread and it is assumed that most people are infected with it. In that case, preventive treatment is routinely used as the immune system weakens and the risk for PCP increases. PCP remains the leading cause of death of people with AIDS in the United States and is largely preventable.

Preventive Treatment for OIs

OIs are generally not a problem for people whose CD4+ cell counts remain stable above 200. It is extremely rare for a person living with HIV to die of AIDS when CD4+ cell counts are above 200. As CD4+ cell counts decline, however, a person's risk for developing opportunistic conditions increases. Perhaps the best strategy for preventing OIs is to not let CD4+ cell counts fall close to the 200 threshold. Therefore the Federal Guidelines for the use of anti-HIV therapy recommend that people consider starting anti-HIV therapy when CD4+ cell counts are 350 or below. Moreover the Guidelines strongly recommend treatment for anyone experiencing symptoms of HIV disease (regardless of CD4+ cell counts) and for anyone with CD4+ cell counts of 200 or below. This is because anti-HIV therapy has been shown to stop the destruction of immune cells by HIV, preventing the further decline in immune defenses.

There are Federal Guidelines for the prevention and treatment of HIV-related opportunistic infections. A summary of these guidelines is available in Project Inform's "Opportunistic Infections Chart."

In general, if CD4+ cell counts fall to 200 or below (or CD4 percentage falls below 14), people are at increased risk for PCP and preventive therapy is indicated. For people experiencing other symptoms of HIV infection, particularly recurrent fungal (candida) infections, PCP preventive therapy is often initiated when CD4+ cell counts are higher, around 300. If CD4+ cell counts fall to between 150 and 100, preventive therapy for toxoplasmosis is recommended for people who are toxo-positive. If CD4+ cell counts fall to 50 or below, preventive therapy for MAC and CMV is recommended. For people who have suspected exposure to tuberculosis, preventive therapy is warranted.

Treating Infections as They Occur

As noted previously, Project Inform's OI chart summarizes Federal Guidelines for the treatment of the major OIs. Because HIV replicates more when the immune system is actively battling an infection, treating infections as they occur is critical not only to dealing with the infection, but also curbing further destruction of the immune system by HIV. This is true whether or not the infection is an opportunistic infection. When it comes to OIs, however, and many issues in later-stage HIV disease, diagnosing some infections can be difficult.

One of the biggest challenges of OI treatment is early diagnosis, before it has been able to take hold in many different organ systems (e.g., the lungs, colon, brain, bone marrow, etc.). The earlier something is diagnosed and treated, the more likely treatment will be successful and result in full recovery. This means regular monitoring by a doctor (at least quarterly) and talking to a doctor about symptoms. If you experience any new or unusual symptoms and are between doctor visits, make an appointment -- don't wait for three months to have something looked at. Keep a health journal or diary, or merely write on a calendar when a new or unusual symptom occurs and record how long the symptom remains. This might help a doctor figure out if a symptom is a drug side effect, sign of an OI or something else.

Many OIs have the same symptoms and some infections may be masking others -- thus initial treatment may deal with part of a problem, but not the whole problem. Dealing successfully with multiple infections may take diligence and persistence when dealing with multiple doctors and specialists. It's ideal to have your primary doctor leading the charge, talking with all of your other doctors and specialists and making sure that they're talking to one another. The most difficult part of dealing with multiple conditions is that doctors often aren't very good about talking to each other. It easily can become a full time job trying to juggle doctor appointments and many different doctors ordering many different laboratory tests. It's your primary doctor's job to coordinate all of this, even when they're busy. Especially in cases where many problems may be rearing their heads at once, preparing for your appointments, writing down your questions beforehand and having an advocate with you to record answers to your questions is strongly encouraged.

Once a condition is diagnosed, following a course of recommended treatment through to completion is vital. Drugs to treat some opportunistic infections may interact with anti-HIV medications. Any time a new treatment is being added to your regimen an assessment should be done to make sure it's safe to use with the other medications you are taking and to make any necessary dose adjustments to compensate for drug interactions.

Maintenance Therapy

After treating an OI, sometimes life-long medications are required to prevent the recurrence of the disease. This is called maintenance therapy. In some instances maintenance therapy may be stopped if a person is able to see sufficient and sustained immune recovery and control of HIV with the use of anti-HIV therapy. The guidelines around maintenance therapy, and stopping maintenance therapy, are outlined in Project Inform's OI chart.

Some people with recurrent herpes infections will take long-term anti-herpes therapies to prevent recurrences. Similarly, some people who have had trouble with recurrent fungal infections will take long-term anti-fungal drugs to prevent recurrences. In both of these cases, maintenance therapy is somewhat controversial. This is because the organisms can develop resistance to the drugs, leaving few viable options for treatment if or when a serious infection occurs. When herpes or fungal infections become recurrent, however, it may come down to a quality of life issue and long-term therapy may be the only viable option for a person. Weighing the risks and benefits of these approaches carefully is critical to making the right choice. Some will choose to risk losing viable treatment options to alleviate the problems of recurrent infections. Others will choose to simply treat the recurrent infections when they happen in hopes of preserving the benefits of therapy.

Discussion

Regardless of where someone is at in the spectrum of HIV disease, there are things that can be done to prevent and/or treat opportunistic infections. Prevention of OIs is relevant to people at all stages of HIV infection. Prevention includes:

• maintaining good immune health,

• using anti-HIV therapies as appropriate to preserve the immune system from destruction by HIV and allow for immune recovery,

• preventing infections by the organisms that can cause OIs when possible,

• using treatments to prevent OIs when indicated, and

• using treatments to prevent recurrences of OIs when indicated.

A plan for treating OIs includes:

• Seeing a doctor regularly (generally quarterly, but it might be twice annually for people who have good measures of immune health or monthly for people dealing with complications from HIV or medications) who specializes in HIV disease, is informed about HIV and has treated other people living with HIV. (An experienced doctor is better able to recognize symptoms of OIs and will be more familiar with preventive OI medicine and how to treat OIs.)

• Telling your doctor about all symptoms you are experiencing so that they can diagnose problems early.

• Treating infections as they occur, aggressively, following through on a course of treatment to completion and using maintenance therapy as indicated. This might include the need for life-long maintenance therapy to prevent recurrence.

Back to the Project Inform Perspective January 2004 contents page.