A Nucleoside Analogue-sparing Strategy for Treatment of Chronic HIV

Nucleoside analogue-sparing combinations can serve as beneficial first-line anti-HIV drug regimens. This infrequently employed treatment approach spares the nucleoside analogue reverse transcriptase inhibitor (NRTI) drug class for future use. In addition, this strategy eliminates any immediate threat of mitochondrial toxicity though exposure to the NRTIs.

Various combinations of nucleoside analogue-sparing anti-HIV drug combinations are theoretically available and potentially useful. For example, non nucleoside reverse transcriptase inhibitors (NNRTIs) associated with protease inhibitor (PI) and boosted double-PI combinations have been used in clinical studies.

The results of these studies, although small and not comparative, suggest they are well tolerated, safe and offer potent suppression of HIV. One drawback of this approach, however, is that the NNRTIs and PIs are metabolized in the liver through the cytochrome P450 pathway, which may produce a number of unwanted drug interactions. In order to use this strategy, physicians must possess extensive knowledge of the potential interactions between NNRTIs and PIs or have access to a database on these interactions to assure use of the correct drug exposures.

In some instances, avoidance of interactions may result in the use of such a high pill burden that the regimen becomes impractical. As well, patients may experience GI side effects that limit the use of ritonavir-boosted double combination PI regimens.

New NRTI-sparing combination regimens have emerged: lopinavir/ritonavir (Kaletra) monotherapy has shown early, for instance promise. Once oral entry inhibitors become available, agents from this unique drug class might be used as part of NRTI-sparing regimens.

03/16/05

Reference
V Joly and P Yeni. Nucleoside analogue-sparing strategy for the treatment of chronic HIV infection: potential interest and clinical experience. Antiviral Therapy 1: 29–40. 2005.

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