Virologic failure

Virologic failure refers specifically to incomplete (or lack of) HIV RNA response:

Incomplete virologic response:

After initiation of Antiretroviral therapy in a treatment-naïve patient, not achieving

  • 1 log10 copies/mL, HIV RNA decrease at 1– 4 weeks or
  • HIV RNA <400 copies/mL by 24 weeks or
  • HIV RNA <50 copies/mL by 48 weeks

Virologic rebound:

After virologic suppression, repeated detection of viremia. There is no consensus on the optimal time to change therapy for low-level viremia. The most aggressive approach would be to change for any repeated, detectable viremia (e.g., two consecutive HIV RNA >400 copies/mL after suppression to <400 copies/mL in a patient taking the regimen). Isolated episodes of viremia (“blips”, e.g. single levels of 50–1,000 copies/mL) usually are not associated with subsequent virologic failure, but rebound to higher viral load levels or more frequent episodes of viremia increase the risk of failure.

Immunologic failure

Failure to increase 25–50 cells/mm3 above the baseline CD4 cell count over the first year of therapy or experiencing a decrease to below the baseline CD4 cell count on therapy. Mean increases in CD4 cell counts in treatment-naïve patients with initial antiretroviral regimens are approximately 150 cells/mm3 over the first year.

Clinical failure

Occurrence or recurrence of HIV-related events (after at least 3 months on an antiretroviral regimen), excluding immune reconstitution syndromes.

Treatment Options

Following Virologic Failure on Initial Recommended Therapy Regimens

Regimen ClassInitial RegimenRecommended Change
NNRTI 2 nucleosides + NNRTI2 nucleosides (based on resistance testing) + PI (with or without low-dose ritonavir)
PI 2 nucleosides + PI (with or without low-dose ritonavir) 2 nucleosides (based on resistance testing) + NNRTI
Triple nucleosides3 nucleosides2 nucleosides (based on resistance testing) + NNRTI or PI (with or without low-dose ritonavir) _ NNRTI + PI (with or without low-dose ritonavir)
Nucleoside(s) (based on resistance testing) + NNRTI + PI (with or without low-dose Ritonavir)

Adapted from DHHS guidelines, April 7, 2005