Page 96 - HIV/AIDS Guidelines

• tolerability of medications

• concomitant medications and supplements (with consideration for adverse drug-drug interactions)
• comorbidities (including substance abuse)

In many cases, the cause(s) of virologic failure will be identified. In some cases, no obvious cause(s) may be
identified. It is important to distinguish among the reasons for virologic failure because the approaches to
subsequent therapy differ. The following potential causes of virologic failure should be explored in depth.

• Adherence. Assess the patient’s adherence to the regimen. For incomplete adherence, identify and
address the underlying cause(s) (e.g., difficulties accessing or tolerating medications, depression, active
substance abuse) and simplify the regimen if possible (e.g., decrease pill count or dosing frequency).
(See Adherence.)

• Medication Intolerance. Assess the patient’s tolerance of the current regimen and the severity and
duration of side effects, keeping in mind that even minor side effects can impact adherence. Management
strategies for intolerance in the absence of drug resistance may include:
• using symptomatic treatment (e.g., antiemetics, antidiarrheals)

• changing one ARV to another within the same drug class, if needed (e.g., change to tenofovir
[TDF] or abacavir [ABC] for zidovudine [ZDV]-related toxicities; change to nevirapine [NVP] or
etravirine [ETR] for efavirenz [EFV]-related toxicities) 4-5
• changing from one drug class to another (e.g., from a non-nucleoside reverse transcriptase
inhibitor [NNRTI] to a protease inhibitor [PI], from enfuvirtide [T-20] to raltegravir [RAL]) if
necessary and no prior drug resistance is suspected
• Pharmacokinetic Issues. Review food/fasting requirements for each medication. Review recent history
of gastrointestinal symptoms (such as vomiting or diarrhea) to assess the likelihood of short-term
malabsorption. Review concomitant medications and dietary supplements for possible adverse drug-drug
interactions (consult Drug Interactions section and tables for common interactions) and make appropriate
substitutions for ARV agents and/or concomitant medications, if possible. Therapeutic drug monitoring
(TDM) may be helpful if pharmacokinetic drug-drug interactions or impaired drug absorption leading to
decreased ARV exposure is suspected. (See also Exposure-Response Relationship and Therapeutic Drug
Monitoring.)
• Suspected Drug Resistance. Obtain resistance testing while the patient is taking the failing regimen or
within 4 weeks after regimen discontinuation if the plasma HIV RNA level is >500 copies/mL (AII).
(See Drug-Resistance Testing.) Evaluate the degree of drug resistance and consider the patient’s prior
treatment history and prior resistance test results. Drug resistance tends to be cumulative for a given
individual; thus, all prior treatment history and resistance test results should be taken into account.
Routine genotypic or phenotypic testing gives information relevant for selecting nucleoside reverse
transcriptase inhibitors (NRTIs), NNRTIs, and PIs. Additional drug-resistance tests for patients
experiencing failure on fusion inhibitors and/or integrase strand transfer inhibitors (INSTIs) and viral
tropism tests for patients experiencing failure on a CCR5 antagonist also are available. (See Drug-
Resistance Testing.)

Changing ART
There is no consensus on the optimal time to change therapy for virologic failure. The goal of ART is to
suppress HIV replication to a level where drug-resistance mutations do not emerge. However, the specific
level of viral suppression needed to achieve durable virologic suppression remains unknown. Selection of
drug resistance does not appear to occur in patients with persistent HIV RNA levels suppressed to <48
6
copies/mL, although this remains controversial. 7

Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents H-3

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