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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 up to three years and are repeatedly found to have no virus in their blood experience a prompt rebound increase in the number of viral particles when therapy is discontinued. Consequently, the decision to start therapy must balance the risk of an individual advancing to the stage of symptomatic disease against the risks associated with therapy. 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 therapy. This resistance then limits the 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. In addition, the likelihood of suppressing the virus to undetectable levels is not as good for patients with lower CD4 cell counts and higher viral loads. Finally, 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 (EpivirTM, 3TC), emtricitabine (EmtrivaTM, FTC) and the drugs in the class of nonnucleoside analogue reverse transcriptase inhibitors (NNRTI) such as nevirapine (ViramuneTM, NVP), delavirdine (RescriptorTM, DLV), and efavirenz (SustivaTM, 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 be ineffective. In contrast, HIV becomes resistant to certain other drugs, such as zidovudine (RetrovirTM, AZT), stavudine (ZeritTM, 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 (NorvirTM, RTV) to prevent 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 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.