Page 28 - HIV/AIDS Guidelines

the United States and Europe, recent studies suggest the risk that transmitted virus will be resistant to at least
one ARV drug is in the range of 6%–16%, 20-25 with 3%–5% of transmitted viruses exhibiting resistance to
drugs from more than one class. 16,24

If the decision is made to initiate therapy in a person with acute HIV infection, resistance testing at baseline
will provide guidance in selecting a regimen to optimize virologic response. Therefore, resistance testing in this
situation is recommended (AIII) and a genotypic assay is preferred (AIII). In this setting, treatment initiation
should not be delayed by pending resistance testing results. Once results are obtained, the treatment regimen
can be modified if warranted by the results. (See Acute HIV Infection.) In the absence of therapy, resistant
viruses may decline over time to less than the detection limit of standard resistance tests but may still increase
the risk of treatment failure when therapy is eventually initiated. 26-28 Therefore, if therapy is deferred, resistance
testing during acute HIV infection should still be performed (AIII). In this situation, the genotypic resistance
test result might be kept on record for several years before it becomes clinically useful. Because it is possible
for a patient to acquire drug-resistant virus (i.e., superinfection) between entry into care and initiation of ART,
repeat resistance testing at the time treatment is started should be considered (CIII).

Performing drug-resistance testing before ART initiation in patients with chronic HIV infection is less
straightforward. The rate at which transmitted resistance-associated mutations revert to wild-type virus has not
been completely delineated, but mutations present at the time of HIV transmission are more stable than those
selected under drug pressure, and it is often possible to detect resistance-associated mutations in viruses that
were transmitted several years earlier. 29-31 No prospective trial has addressed whether drug-resistance testing
prior to initiation of therapy confers benefit in this population. However, data from several, but not all, studies
suggest suboptimal virologic responses in persons with baseline mutations. 16-19,32-34 In addition, a cost-
effectiveness analysis of early genotypic resistance testing suggests that baseline testing in this population
35
should be performed. Therefore, resistance testing in chronically infected persons at the time of entry into
HIV care is recommended (AIII). Genotypic testing is preferred in this situation because of lower cost, more
rapid turnaround time, ability to detect mixtures of wild-type and resistant virus, and the relative ease of
interpretation (AIII). If therapy is deferred, repeat testing just prior to initiation of ART should be considered
because the patient may have acquired drug-resistant virus (i.e., superinfection) (CIII).
Standard genotypic drug-resistance testing in ARV-naive persons involves testing for mutations in the RT and
PR genes. Although transmission of INSTI-resistant virus has rarely been reported, as use of INSTIs
increases, the potential for transmission of INSTI-resistant virus may also increase. Therefore, providers may
wish to supplement standard baseline genotypic resistance testing with genotypic testing for resistance to
INSTI (CIII).

Use of Resistance Assays in the Event of Virologic Failure

Resistance assays are useful in guiding decisions for patients experiencing virologic failure while on ART.
Several prospective studies assessed the utility of resistance testing in guiding ARV drug selection in patients
with virologic failure. These studies involved genotypic assays, phenotypic assays, or both. 6, 36-42 In general,
these studies found that early virologic response to salvage regimens was improved when results of resistance
testing were available to guide changes in therapy, compared with responses observed when changes in therapy
were guided only by clinical judgment. Additionally, one observational study demonstrated improved survival
43
in patients with detectable HIV plasma RNA when drug-resistance testing was performed. Thus, resistance
testing appears to be a useful tool in selecting active drugs when changing ARV regimens for virologic failure
in persons with HIV RNA >1,000 copies/mL (AI). (See Virologic and Immunologic Failure.) In persons with
>500 but <1,000 copies/mL, testing may be unsuccessful but should still be considered (BII). Drug-resistance
testing is not usually recommended in persons with a plasma viral load <500 copies/mL because resistance
assays cannot be consistently performed given low HIV RNA levels (AIII).

Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents C-10

Downloaded from http://aidsinfo.nih.gov/guidelines on 12/8/2012 EST.