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I Have Been Diagnosed With HIV
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Complete Prescribing Information for COMBIVIR Tablets
How COMBIVIR Works
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How COMBIVIR Works
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COMBIVIR May Help Perserve Future Treatment Options
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Resistance
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Resistance
3TC and M184V Mutation1
- 3TC retains a partial antiviral effect (0.5 log10 c/mL decline in HIV RNA at 52 weeks), even with M184V mutation
- Potential benefits of M184V
- Limited cross-resistance with other NRTIs
- Decreased viral fitness
- Restores sensitivity to ZDV/d4T resistance (pyrophosphorolysis)
- Delays TAMs (increased fidelity)
Sustained Antiviral Effect with M184V: 52-Week HIV RNA Reductions2
M184V Restores Sensitivity to ZDV in vitro3
Limited Cross-Resistance with M184V: Composite Phenotype with M184V Mutation Alone (n=1720)3
Thymidine Analogue Mutations
- Selected by ZDV and d4T (TAMs)
- 41L
- 67N
- 70R
- 210W
- 215Y/E
- 219Q/E
- Multiple TAMs are usually required to confer resistance to ZDV, d4T, ddI, ABC, and/or TDF
- Pattern and number of TAMs may predict cross-resistance to other NRTIs
Resistance Summary
- Most common mutation with COM is M184V, which confers little cross-resistance
- M184V decreases susceptibility to 3TC, but also restores sensitivity to ZDV/d4T resistance and delays development of TAMs
- TAMs are rare at the time of virologic failure with a regimen containing COMBIVIR and multiple TAMs are required to confer resistance to ZDV
- Clinical relevance of resistance data is currently being evaluated
- Varying degrees of cross-resistance among HIV NRTIs have been observed
| References |
| | 1. | Patrella M, Wainberg MA, et al. Might the M184V substitution in HIV-1 RT confer clinical benefit? AIDS Review. 2002. Oct-Dec;4:226-234. |
| | 2. | Eron JJ, Benoit SL, Jemsek J, et al for the North American HIV Working Party. Treatment with lamivudine, zidovudine, or both in HIV-positive patients with 200 to 500 CD4+ cells per cubic millimeter. N Engl J Med. 1995;333:1662-1669. |
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