Page 98 - HIV/AIDS Guidelines

Clinical Scenarios of Virologic Failure

• Low-level viremia (HIV RNA <1,000 copies/mL). Assess adherence. Consider variability in HIV RNA
assays. Patients with HIV RNA <48 copies/mL or isolated increases in HIV RNA (“blips”) do not require
a change in treatment (AII). There is no consensus regarding how to manage patients with HIV RNA
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levels >48 copies/mL and <200 copies/mL; HIV RNA levels should be followed over time to assess the
need for changes (AIII). Patients with persistent HIV RNA levels >200 copies/mL often select out drug-
resistant viral variants, particularly when HIV RNA levels are >500 copies/mL. Persistent plasma HIV
RNA levels in the 200 to 1,000 copies/mL range should be considered as possible virologic failure;
resistance testing should be attempted if the HIV RNA level is >500 copies/mL. For individuals with
sufficient therapeutic options, consider treatment change (BIII).
• Repeated detectable viremia (HIV RNA >1,000 copies/mL) and NO drug resistance identified.
Consider the timing of the drug-resistance test (e.g., was the patient off ARV for >4 weeks and/or
nonadherent?). Consider resuming the same regimen or starting a new regimen and then repeating
genotypic testing early (e.g., in 2–4 weeks) to determine whether a resistant viral strain emerges (CIII).

• Repeated detectable viremia (HIV RNA >1,000 copies/mL) and drug resistance identified. The
goals in this situation are to resuppress HIV RNA levels maximally (i.e., to <48 copies/mL) and to
prevent further selection of resistance mutations. With the availability of multiple new ARVs, including
some with new mechanisms of action, this goal is now possible in many patients, including those with
extensive treatment experience and drug resistance. With virologic failure, consider changing the
treatment regimen sooner, rather than later, to minimize continued selection of resistance mutations. In a
patient with ongoing viremia and evidence of resistance, some drugs in a regimen (e.g., NNRTI, T-20,
RAL) should be discontinued promptly to decrease the risk of selecting additional drug-resistance
mutations in order to preserve the activity of these drug classes in future regimens. A new regimen
should include at least two, and preferably three, fully active agents (AII).

• Highly drug resistant HIV. There is a subset of patients who have experienced toxicity and/or
developed resistance to all or most currently available regimens, and designing a regimen with two or
three fully active drugs is not possible. Many of these patients received suboptimal ARV regimens (i.e.,
did not have access to more than one or two of the drugs at the time they became available) or have been
unable to adhere to any regimen. If maximal virologic suppression cannot be achieved, the goals are to
preserve immunologic function and to prevent clinical progression (even with ongoing viremia). There is
no consensus on how to optimize the management of these patients. It is reasonable to observe a patient
on the same regimen, rather than changing the regimen, depending on the stage of HIV disease (BII).
Even partial virologic suppression of HIV RNA >0.5 log 10 copies/mL from baseline correlates with
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clinical benefits. There is evidence from cohort studies that continuing therapy, even in the presence of
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viremia and the absence of CD4 T-cell count increases, reduces the risk of disease progression. Other
cohort studies suggest continued immunologic and clinical benefits if the HIV RNA level is maintained
<10,000–20,000 copies/mL. 36-37 However, these potential benefits all must be balanced with the ongoing
risk of accumulating additional resistance mutations.
In general, adding a single, fully active ARV in a new regimen is not recommended because of the risk of
rapid development of resistance (BII). However, in patients with a high likelihood of clinical progression
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(e.g., CD4 cell count <100 cells/mm ) and limited drug options, adding a single drug may reduce the risk of
immediate clinical progression, because even transient decreases in HIV RNA and/or transient increases in
CD4 cell counts have been associated with clinical benefits (CI). Weighing the risks (e.g., selection of drug
resistance) and benefits (e.g., ARV activity) of using a single active drug in the heavily ART-experienced
patient is complicated, and consultation with an expert is advised.
Patients with ongoing viremia and with an insufficient number of approved treatment options to construct a

Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents H-5

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