What are the key principles in managing HIV infection?

What are the key principles in managing HIV infection?

First of all, there is no evidence that people infected with HIV can be cured by the currently available therapies. In fact, individuals who are treated for years and are repeatedly found to have no virus in their blood experience a prompt rebound in the number of viral particles when therapy is discontinued. Consequently, the decision to start therapy must balance the risk versus the benefits of treatment. The risks of therapy include the short- and long-term side effects of the drugs, described in subsequent sections, as well as the possibility that the virus will become resistant to the therapy which can limit options for future treatment.

A major reason that resistance develops is the patient's failure to correctly follow the prescribed treatment, for example, by not taking the medications at the correct time. If virus remains detectable on any given regimen, resistance eventually will develop. Indeed, with certain drugs, resistance may develop in a matter of weeks, such as with lamivudine (Epivir, 3TC), emtricitabine (Emtriva, FTC), and the drugs in the class of nonnucleoside analogue reverse transcriptase inhibitors (NNRTI) such as nevirapine (Viramune, NVP), delavirdine (Rescriptor, DLV), and efavirenz (Sustiva, EFV). Thus, if these drugs are used as part of a combination of drugs that does not suppress the viral load to undetectable levels, resistance will develop rapidly and the treatment will lose its effectiveness. In contrast, HIV becomes resistant to certain other drugs, such as zidovudine (Retrovir, AZT), stavudine (Zerit, D4T), and protease inhibitors (PIs), over months. In fact, for some PIs whose effects are enhanced by giving them in combination with the PI, ritonavir (Norvir, RTV) to delay their clearance by the body, resistance appears to be markedly delayed. These drugs are discussed in more detail in subsequent sections, but it is important to note that when resistance develops to one drug, it often results in resistance to other related drugs, so called cross-resistance. Nevertheless, HIV-infected individuals must realize that antiviral therapy can be and typically is very effective. This is the case even in those who have a low CD4 cell count and advanced disease, as long as drug resistance has not developed.

Factors to consider before starting antiviral therapy

One of the most controversial areas in the management of HIV disease is deciding the best time to start antiviral treatment. Clearly, therapy during the mildly symptomatic stage of the disease delays progression to AIDS, and treating individuals with AIDS postpones death. Consequently, most experts have long agreed that patients who have experienced complications of HIV disease, such as oral thrush (yeast infection in the mouth), chronic unexplained diarrhea, fevers, weight loss, opportunistic infections, or dementia (for example, forgetfulness) should be started on antiviral treatment even if the symptoms are mild. In patients who do not have symptoms, however, there is more uncertainty. Most recommendations for this group are based on the predictors of clinical progression, such as the number of CD4 cells. One can envision that as treatments become easier to take, better tolerated, and increasingly effective, therapy will begin to be started earlier in the course of infection.

When to start antiviral therapy

Guidelines for starting antiviral therapy have been proposed by panels of experts from several groups including the DHHS and IAS-USA. They recommend treating all patients who have symptoms and those who have CD4 cell counts of less than 350 cells per mm³. Recent data supporting even earlier initiation of therapy includes analyses of groups of patients followed over time. Although the data is imperfect, a recent study showed that those who started treatment with CD4 cells greater than 500 cells per mm³ actually were less likely to die than those who did not start treatment until their CD4 cells declined to less than 500 cells/mm³. In addition, there is increasing evidence that ongoing viral replication, even in the setting of high CD4 cells may be associated with damage to the brain, kidneys, heart, and possibly even liver. Along with these studies arguing for earlier treatment, there is growing evidence that currently used treatments are usually very well tolerated and effective in suppressing viral load. Guidelines will continue to change with time, but for now, the emphasis should be on discussing all of the potential benefits and risks of therapy and deciding when is best for each individual. Regardless, all agree that HIV is generally a slowly progressive disease, and therapy rarely needs to be started abruptly. Therefore, there usually is time for each patient to carefully consider options prior to starting treatment.

Before starting treatment, patients must be aware of the short- and long-term side effects of the drugs, including the fact that some long-term complications may not be known. Patients also need to realize that therapy is a long-term commitment and requires consistent adherence to the drugs. In addition, clinicians and patients should recognize that depression, feelings of isolation, substance abuse, and side effects of the antiviral drugs can all be associated with the failure to follow the treatment program