SMITH, continued

CONCLUSION

Comparative studies have shown that monotherapy is not an effective treatment for the HIV infection (USDHHS, 2004). As summarized in Table 2 (below), no one drug alone, whether it be a reverse transcriptase inhibitor or a protease inhibitor could effectively treat the virus. This is due to the resistance that mutated forms of the virus confer to any medication when used independently. Research has shown that the best therapy for HIV is a combination of at least three drugs (Bartlett, 2001). This combination, referred to as the Highly Active Antiretroviral Therapy or ‘HAART,’ was later changed to Potent Antiretroviral Therapy upon the addition of the protease inhibitors in 1995 (USDHHS, 2004). However, the combination is still commonly recognized as HAART.

Clinical trials have devised regimens that have proven to be successful in the treatment of the virus. Today there are three different combinations that are recommended to “treatment-naïve” patients (individuals who have never taken antiretroviral
medications), which are based on the following combinations: triple NRTI-based, NNRTI-based (1 NNRTI + 2 NRTIs) and PI-based (1 or 2 PI + 2 NRTIs) regimens (USDHHS, 2004).

The triple NRTI regimens have shown many advantages that reduce the risks of adverse drug reactions, since they have fewer drug-drug interactions and a low pill burden due to the availability of a fixed dose combination drug, Trizivir (zidovudine + lamivudine + abacavir). However, triple NRTI regimens have been proven to be less potent than NNRTI-based and PI-based regimens, and to eventually become ineffective (USDHHS, 2004).

Like the triple NRTI regimens, NNRTI-based regimens also have the advantage of low pill burden. In addition, NNRTI-based regimens have the advantage of fewer adverse drug reactions than those that contain NRTI or PI, which would allow HIV-positive patients to adhere to their regimen (Project Inform, 2001). However, only a single mutation in the virus is needed to confer resistance to a NNRTI drug, which causes cross-resistance to the other two NNRTIs (USDHHS, 2004).

The introduction of the protease inhibitor to the HIV regimen dramatically enhances the treatment of the virus and allows increased patient survival (Martinez, 2000). Protease inhibitors allowed the prolonged suppression of the virus and consequently the increase in the CD4 cell count (USDHHS, 2004). In addition, the use of ritonavir to boost the concentration of other PIs allows a lower pill burden and lower drug toxicity. However, PIs are associated with side effects that sometimes outweigh their great advantages, since patients are unable to adhere to their regimens. Hence, even though PIs are successful in treating the virus, many factors have to be taken into consideration when PI-based regimens are selected due to their potential drug interactions, toxicity and metabolic abnormalities (USDHHS, 2004).

The treatment of HIV will continue to be a life-long process, since no drug has been developed that can completely eradicate the virus from the body. In addition, no one drug can effectively treat the virus due to the development of mutations. Furthermore, no one form of drug can be shown to be superior to the others, since many factors have to be considered when evaluating the efficacy of the drug. Hence, even though protease inhibitors have been shown to allow prolonged suppression of the virus, they are associated with too many fatal complications to be labeled as being superior to NRTIs and NNRTIs.

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