Advantages and Disadvantages of Class-Sparing Regimens Used in HIV-1 Therapy

Regimen Possible Advantages Possible Disadvantages Drug-Interaction Complications Impact on FutureOptions
PI-based HAARTRegimen (NNRTI- and FI-sparing) Clinical, virologic, andimmunologic efficacy well-documented
# Resistance requires multiple mutations
# Avoid NNRTI and FI-associated side effects
# Targets HIV at two steps of viral replication (RT and PI)
Some regimens are difficult to use and adhere to
¦ Long-term side effects ofteninclude lipodystrophy*, hyperlipidemia and insulin resistance
Mild to severe inhibition of cytochrome P450 pathway; Ritonavir is most potent inhibitor, (but this effect can be exploited to boost levels of other PIs) Preserves NNRTIs and FI for use intreatment failure. Resistance primes for cross-resistance with other PIs
NNRTI-basedHAART regimen (PI- and FI-sparing) Virologic, and immunologic efficacy well-documented.
Spares PI & FI-related side effects
Easier to use and adhere to, compared with most PI regimens
Resistance conferred by asingle or limited number ofmutations Fewer drug interactions compared with PIs Preserves PIs and FI for use in treatment failure
Resistance usually leads to cross-resistance across entire NNRTI class
Triple NRTI regimen(NNRTI- andPI-sparing) Generally easier to use and adhere to compared with PIs
Sparing PI, NNRTI, and FIside effects
Inferior virologic efficacy No cytochrome P450 interaction Preserves PI, NNRTI and FI classes foruse in treatment failure

* Some side effects being attributed to PI therapy, such as lipodystrophy, have not been proven to the strictly associated with the use of PI-containing regimens. Lipodystrophy has also been described among patients on NRTIs alone (especially stavudine) and in patients on no antiretroviral therapy.

Adapted from DHHS guidelines, March 23, 2004