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HIV Drug Resistance Testing
Table 1: Summary of Clinical Situations in Which Resistance Testing Is Recommended (IAS-USA, July 2008)
Clinical Setting Comments
Before initiation of therapy
Primary (acute and early) infection Resistance testing is recommended. Initial therapy may be altered based on resistance test results.
First evaluation of chronic HIV-1 infection Resistance testing is recommended, including in patients for whom therapy is delayed, because plasma wild-type isolates may
replace drug-resistant virus with time in the absence of treatment.
Treatment initiation for chronic HIV-1 infection Resistance testing is recommended because of a rising prevalence of baseline HIV-1 drug resistance in untreated patients with
chronic infection, unless pre-existing data or stored samples for testing are available.
In antiretroviral-treated patients
Treatment failure Resistance testing is recommended. The decision to change therapy should integrate treatment history, new and prior resistance
results (if available) and evaluation of adherence and possible drug interactions.
In specific settings
Pregnancy
a
Resistance testing is recommended before initiation of therapy to effectively treat the mother and prevent mother-to-child
transmission.
Other considerations and general recommendations
Post-exposure prophylaxis should consider treatment history and resistance data from the source, when available.
A sudden increase in HIV-1 plasma RNA may reflect superinfection, possibly with drug-resistant virus.
Plasma samples to be tested for drug resistance should contain at least 500 HIV-1 RNA copies/ml to ensure successful PCR
amplification required for all sequencing approaches.
It is preferable that the blood sample for resistance testing be obtained while the patient is receiving the failing regimen, if possible.
Resistance testing should be performed by laboratories that have appropriate operator training, certification and periodic
proficiency assurance.
Genotypic and phenotypic test results should be interpreted by individuals knowledgeable in antiretroviral therapy and drug
resistance patterns.
Inhibitory quotient testing is not recommended for clinical decision-making.
a. If resistance test results are available from before the pregnancy, clinical judgment should guide whether re-testing for resistance is necessary.
Source: Hirsch et al., 2008.
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Table 2: Recommendations of the DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents, 2008
Clinical Setting/Recommendation Rationale
Drug resistance assay recommended
In acute HIV infection: Drug resistance testing is recommended, regardless of If treatment is to be initiated, drug resistance testing will determine whether drug-resistant
whether treatment will be initiated immediately (AIII). A genotypic assay is virus was transmitted and will help in the design of initial or changed (if therapy was
generally preferred (AIII). initiated prior to test results) regimens.
If therapy is deferred, repeat resistance testing should be considered at the If treatment is deferred, testing still should be performed because of the potentially greater
time of ART initiation (CIII). likelihood that transmitted resistance-associated mutations will be detected earlier in the
course of HIV infection; results of testing may be important when treatment is eventually
initiated. Repeat testing at the time ART is initiated should be considered because of the
possibility that the patient may have acquired drug-resistant virus.
In chronic HIV infection: Drug resistance testing is recommended at the time of Transmitted HIV with baseline resistance to at least one drug may be seen in 6–16%
entry into HIV care, regardless of whether therapy will be initiated (AIII). of patients, and suboptimal virological responses may be seen in patients with baseline
A genotypic assay is generally preferred (AIII). resistant mutations.
If therapy is deferred, repeat resistance testing should be considered at the Repeat testing at the time ART is initiated should be considered because of
time ART is initiated (CIII). the possibility that the patient may have acquired drug-resistant virus.
With virological failure during combination antiretroviral therapy with Testing can help determine the role of resistance in drug failure and thus maximise
HIV RNA levels >1,000 copies/ml (AII). In persons with >500 but <1,000 copies/ml, the number of active drugs in the new regimen, if indicated. Drug resistance testing
testing may be unsuccessful but should still be considered (BII). should be performed while the patient is taking his/her antiretroviral drugs or immediately
(i.e. within four weeks) after discontinuing therapy.
With suboptimal suppression of viral load after antiretroviral therapy initiation (AIII). Testing can help determine the role of resistance and thus maximise the number of active
drugs in the new regimen, if indicated.
In HIV-infected pregnant women: Genotypic resistance testing is recommended for The goals of antiretroviral therapy in HIV-infected pregnant women are to achieve maximal
all pregnant women prior to initiation of therapy (AIII) and for those entering viral suppression for treatment of maternal HIV infection as well as for prevention of
pregnancy with detectable HIV RNA levels while on therapy (AII). perinatal HIV transmission. Genotypic resistance testing will assist the clinician in selecting
the optimal regimen for the patient.
Drug resistance assay not usually recommended
After discontinuation (>4 weeks) of drugs (BIII). Drug resistance mutations might become minor species in the absence of selective drug
pressure, and available assays might not detect minor drug-resistant species. If testing is
performed in this setting, the detection of drug resistance may be of value, but its absence
does not rule out the presence of minor drug-resistant species.
When plasma viral load <500 copies/ml (AIII). Resistance assays cannot be consistently performed because of low HIV RNA levels.
Strength of recommendation: A = Strong recommendation for the statement; B = Moderate recommendation for the statement; C = Optional recommendation. Quality of evidence for
recommendation: I = One or more randomised trials with clinical outcomes and/or validated laboratory end-points; II = One or more well designed, non-randomised trials or observational
cohort studies with long-term clinical outcomes; III = Expert opinion.
Source: Department of Health and Human Services, Panel on Antiretroviral Guidelines for Adults and Adolescents, 2008.
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