Human Immunodeficiency Virus (HIV, AIDS) (cont.)

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What are the key principles in managing HIV infection?

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First of all, there is no evidence that people infected with HIV can be cured by the currently available therapies, although research related to curing people of infection will be discussed later. Nevertheless, in general, those who are treated for years and are repeatedly found to have no virus in their blood by standard viral load assays will 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 the nucleoside reverse transcriptase inhibitors (NRTIs) lamivudine (Epivir, 3TC) and emtricitabine (Emtriva, FTC), the drugs in the class of nonnucleoside analogue reverse transcriptase inhibitors (NNRTI) such as nevirapine (Viramune, NVP), delavirdine (Rescriptor, DLV), efavirenz (Sustiva, EFV), and rilpivirine (Edurant, RPV), as well as the integrase strand transfer inhibitors (InSTIs) such as raltegravir (Isentress, RAL) and elvitegravir (EVG), currently only available as part of a combination with other agents (Stibild). Thus, if these drugs are used as part of a combination of agents that do 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.

What factors should be considered before starting antiviral therapy?

One of the biggest questions related to the management of HIV disease is the optimal time to start antiviral treatment. There is very strong data demonstrating that therapy is appropriate for those with CD4 cells less than 350 cells/mm3. There are also strong recommendations to treat patients with select conditions regardless of their CD4 cell count, such as during pregnancy in order to prevent transmission of HIV to the baby or those who have HIV-associated renal disease or chronic hepatitis B infection where the antiviral treatment for HIV also treats the hepatitis virus. Specific considerations related to the rationale for earlier initiation of therapy, including starting therapy in all patients regardless of CD4 cell count, are discussed below. Regardless, prior to initiating antiviral therapy, everything possible should be done to ensure that the patient is committed to the treatment, able to adhere to the regimen, and will follow up with his or her health-care professional to assess whether medications are tolerated and working.

Medically Reviewed by a Doctor on 8/5/2014

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