|
The Management of Antiretroviral Therapy |
| Highly Active Antiretroviral Therapy (HAART) | |
|
Paradigm |
Multi-drug TB regimens |
|
Goal |
Reduce HIV viral load to undetectable: optimally < 20-50 copies/ml |
|
Means |
Use of highly active combinations of antiretroviral drugs in an adherent, well-monitored patient |
|
Results |
Directly stops or limits viral replication to a minimum |
| Key Principles | |
|
1 |
Monotherapy (and usually two-drug therapy ) does not work except transiently and to decrease the chance of vertical transmission. |
|
2 |
Long term success requires suppressing viral load to undetectable levels (HIV viral load < 50 copies/cc) for a long time. |
|
3 |
"Permanent" or durable success requires stopping ALL HIV replication, in plasma and all tissue compartments (it is controversial whether this can be achieved.) Viral load <20-50 copies/ml. Durable response may not be achievable in many persons. |
|
4 |
Eradication of HIV is problematic at best and probably not achievable using current antiviral therapies Decay of HIV in certain compartments may require 60 years or more under optimal conditions. |
| Criteria for Initiation of Antiretroviral Therapy | |
|
1 |
Acute HIV infection or < 6 months since acute infection |
|
2 |
Pregnancy in HIV-infected female |
| 3 | Any person with HIV infection who is ready to take antiretroviral therapy - new with 3/37/2012 DHHS Guidelines |
| 4 | Symptomatic HIV or AIDS |
|
5 |
HIV-infected partner in serodiscordant couple |
|
4 |
Postexposure prophylaxis (click PEP guidelines) after body fluid exposure |
Healthcare workers |
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Emergency or disaster workers |
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Rape victims and other "voluntary" or involuntary sexual exposures |
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| Criteria for Changing an Antiretroviral Regimen | |
|
1 |
After initially achieving complete suppression of HIV viral load, the viral load becomes detectable and rises progressively usually with loss of CD4-lymphocytes and/or clinical deterioration |
|
2 |
After incomplete suppression of viral load, the viral load rises progressively, usually with loss of CD4-lymphocytes |
|
3 |
Clinical deterioration attributed to HIV or progressive loss of CD4-lymphocytes despite stable viral load. This is not as definitive an indication for change as the other criteria. Clinical and CD4-lymphocyte changes may be driven by multiple, complex factors even in the context of excellent virologic suppression. |
| 4 | Unacceptable toxicity due to one or more components |
|
5 |
New antiretroviral therapy options become available which offer enhanced adherence or tolerance characteristics without compromising antiretroviral potency, e.g., lower pill burden and/or less frequent dosing and/or less meal dependence, etc. |
| The Logistics of Antiretroviral Therapy Change | |
|
1 |
Avoid changes of therapy within 4-6 weeks of a vaccination or intercurrent illness. |
| 2 | Strongly consider resistance testing prior to a change of therapy indicated by probable development of resistance. Perform resistance testing only when the viral load has exceeded 1000 copies/cc. |
|
3 |
Arrange clinical time for close follow-up of patient at the time of the change of therapy. If close follow-up cannot be assured, consider postponing the change until such time that such high-level follow-up is feasible. |
|
4 |
Antiretroviral therapy changes due to the development of resistance to one or more drugs should be performed as early as possible (the only mitigating factor is that resistance testing must be done when there is at least 1000 copies/cc of HIV) |
| Reason #1: To retain as much drug sensitivity as possible | |
| Reason #2: To restrict toxicity due to active or inactive drugs as much as possible | |
| Criteria for Permanent or Temporary Discontinuation of Antiretroviral Therapy | |
|
1 |
CD4-lymphocyte count increases to > 500 and patient and provider are in agreement about discontinuation. Monitor CD4 count at 2-3 intervals and reinitiate appropriately. [This strategy appears safe, but the full risk-benefit analysis awaits the completion of large clinical trials currently underway.] |
| 2 | Whenever the risk-to-benefit analysis for antiretroviral therapy is higher than is safe for the patient. Multiple drug hypersensitivities, multiple drug intolerances, unacceptable drug interactions, or severe depression as a result of therapy might be examples of this criteria. |
|
3 |
Profound nonadherence for whatever reason that cannot be quickly eliminated. Examples might include uncontrolled addiction or other significant mental health issues, poor motivation for therapy, incarceration, perception that quality of life is being diminished by drug therapy, and unstable supply of medication. Another example might be the inability to take or absorb oral medications. |
|
4 |
End-of-life or hospice care. |
| Viral Load Testing Guidelines & Considerations | |
|
1 |
Use one laboratory consistently to minimize interlaboratory variation. Attempt to perform viral load testing at the same time of the day. |
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2 |
Perform a standard sensitivity viral load measurement twice before initiation of therapy. |
|
3 |
Perform a standard sensitivity viral load measurement at approximately 15-30 days after any change in therapy including initiation. |
|
4 |
Perform an ultrasensitive viral load assay if results of the standard sensitivity test are currently nondetectable on two occasions. |
|
5 |
Perform follow-up viral load testing at 2-3 month intervals during the course of antiretroviral therapy. |
|
6 |
Avoid viral load testing for 4-6 weeks after intercurrent illness or vaccination. |
|
7 |
Significant viral load changes are greater than or equal to three-fold changes. Less than 3-fold changes are within the range of test error and the range of biologic variability. |
Branched chain DNA testing viral loads are related to RT-PCR viral load results by the following formula:
RT-PCR = b-DNA x 2
| CD4-Lymphocyte Testing Guidelines & Considerations | |
|
1 |
Perform CD4-lymphocyte quantification at baseline and at 3 month intervals for persons on therapy. |
|
2 |
Perform CD4-lymphocyte quantification at baseline and at 2-6 month intervals for those not on therapy. |
|
3 |
Avoid CD4-lymphocyte testing within 4-6 weeks of an intercurrent illness or vaccination. |
|
4 |
Changes in CD4-lymphocyte percentage of total lymphocytes are thought to more accurately represent trends of clinical significance. |
|
5 |
Perform CD4-lymphocyte counts more frequently (every 2-3 months) as they fall in the ranges indicating the need for antimicrobial prophylaxis. |
|
6 |
Persons who have undergone splenectomy or who have concomitant HTLV I/II infection may have falsely (?) elevated CD4-lymphocyte counts. |
| Resistance Testing for HIV Therapy | |
| Genotypic Assay | |
| This assay looks for specific mutations within the HIV genome (reverse transcriptase, protease, etc.) which have been associated with clinical resistance to antiviral therapy. The correct use of information from this assay combined with the clinical history of the patient and some degree of expertise in interpretation has been proven to assist in formulating a suppressive antiretroviral regimen in persons who harbor antiretroviral-resistant HIV. Cost = $200 - $400. See the lab evaluation section and/or resistance testing section for more information on interpretation. | |
| Phenotypic Assay | |
| This assay looks for inhibition of HIV by a specific drug or drugs, much like current antibacterial sensitivity testing. Done correctly this should be the gold standard; however, evidence of benefit from this type of resistance testing in persons with extensive resistance is equivocal. Cost = $400 - $1,200. | |
| Limitations of Resistance Assays | |
| 1 | Later in infection there may be multiple clones of HIV with varying resistance patterns. These assays may not pick up the drug-resistant, most significant clones reliably, especially if the patient is not on therapy. |
|
2 |
Resistant clones may be archived within memory T-cells or in remote tissue compartments where therapeutic drug concentrations are not currently reliably achievable (CNS, reproductive tracts, mesenteric lymph nodes, etc.) |
|
3 |
Resistance to specific drugs is best measured while the patient is on those drugs. |
|
4 |
Assays may not be able to provide useful information allowing for improved virologic suppression in persons who harbor the most multidrug resistant HIV. Naturally it is in these patients where this information is the most important. |
| Recommended Usage of Resistance Testing | |
|
1 |
These assays are usually performed during therapy to assist in the determination of which antiretroviral components in a failing or incompletely suppressive regimen may be losing or have lost virologic suppression due to mutationally-mediated resistance. Except for prior to initiation of therapy, the assay should be performed while the patient is on the "failing" or suboptimal regimen. This assay should be strongly considered at the earliest time that a particular regimen is found to be less than fully suppressive and other causes of virologic failure (nonadherence, etc.) have been ruled-out or are thought to be much less contributory. However, most assays require at least 1000 copies/cc of HIV to detect resistance mutations. |
|
2 |
Prior to initiation of therapy if there is epidemiologic evidence suggesting transmission of drug-resistant HIV |
| High prevalence of resistance in persons newly infected (major metropolitan areas in the US) | |
| Evidence to suggest infection was acquired from a contact with possible drug-resistance | |
| Recent infection (since 1998?) | |
| Select | NRTI | NNRTI | PI | FI | for Detailed Antiretroviral Drug Information | or HERE for a Drug Summary Table. |
2/9/2013