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INTRODUCTION
In New Jersey and other areas of high HIV/AIDS prevalence, many HIV patients have taken multiple treatment regimens, and their HIV has become resistant to multiple classes of HIV medications. Drug interactions and toxicity have also led to the need for changes from the first-line and available salvage therapies for people with HIV/AIDS who have become “treatment experienced” or resistant to more than one medication or class of medications.
In 2007, two new agents in two new antiretroviral classes were approved by the FDA for use with treatment-experienced HIV patients. Maraviroc is an entry inhibitor, which was FDA approved on August 6, 2007 for treatment experienced HIV adults infected with only CCR5-tropic HIV-1 strains resistant to multiple antiretroviral agents. Raltegravir, an integrase inhibitor, was FDA approved on October 12, 2007 for the treatment of HIV-1 infection in treatment-experienced adult patients who have HIV-1 strains that are resistant to multiple antiretroviral agents.
New antiretroviral agents can only be prescribed once there is laboratory confirmation, through genotypic/phenotypic tests, that the patient’s HIV strain will respond to these specific treatments.
One of the greatest challenges for clinicians providing HIV care is managing treatment-experienced patients, who have developed resistance to multiple classes of antiretroviral medications. The clinician must know the history of treatment, resistance patterns identified through testing, and when and how to use new drugs for salvage therapy. Cross-resistance within the currently available antiretroviral classes has driven the development of agents from novel drug classes. The availability of new agents for treatment-experienced patients offers options for replacing existing agents which are no longer working.
Treatment Goals
According to the December 1, 2007, U.S. Department of Health & Human Services guidelines for antiretroviral therapy in adults, the goal of treatment for all patients, regardless of their level of treatment experience and drug resistance, is to maximally suppress the HIV-1 RNA level.1 The International AIDS Society-US guidelines from August 2006, state that the goal of achieving HIV-1 RNA <50 copies/ml should be achievable for most patients if newer antiretroviral agents are employed.2
| UPDATED GUIDELINES:
Management of the Treatment-Experienced Patient
PANEL’S RECOMMENDATIONS:
- In treatment-experienced patients with suppressed viremia, assess adherence
frequently and simplify the regimen as much as possible. Change individual
antiretroviral drugs to reduce or manage toxicity, as needed.
- Evaluation of antiretroviral treatment failure in a patient should include an
assessment of the severity of HIV disease of the patient; the antiretroviral
treatment history, including the duration, drugs used, antiretroviral potency,
adherence history, and drug intolerance/toxicity; HIV RNA and CD4 T-cell
count trends over time; and the results of prior drug resistance testing.
- Virologic failure on treatment can be defined as a confirmed HIV RNA level >400
copies/mL after 24 weeks, >50 copies/mL after 48 weeks, or a repeated detectable
HIV RNA level after prior suppression of viremia.
- Drug resistance testing should be obtained while the patient is taking the failing
antiretroviral regimen (or within 4 weeks of treatment discontinuation) (AI).
- The goal of treatment for patients with prior drug exposure and drug resistance
is to re-establish maximal virologic suppression, HIV RNA <50 copies/mL (AI).
- Use the treatment history and the past and current resistance test results to
identify fully active agents to design a new regimen (AII). A fully active agent is
one that is likely to demonstrate antiretroviral activity on the basis of both the
treatment history and susceptibility on drug resistance testing. Adding at least
two, and preferably three, fully active agents to an optimized background
antiretroviral regimen can provide significant antiretroviral activity (BII).
- Immunologic failure can be defined as a failure to achieve and maintain an
adequate CD4 response despite virologic suppression.
- For immunologic failure, current medications, untreated coinfection, and
serious medical conditions should be assessed.
- There is no consensus for when and how to treat immunologic failure.
- Assessing and managing a patient who has antiretroviral experience, who
exhibits drug resistance, and who is experiencing treatment failure is complex
and expert advice is critical.
1 USDHSS. Guidelines for the use of antiretroviral agents in HIV-1 infected adults and
adolescents.December 1, 2007. |
Indications for Changing ARV Regimens
There are generally four indications for changing the antiretroviral regimen, which are reflected in the USDHHS guidelines in the table on this page.
- Drug-drug toxicity (accounts for half of all regimen changes),
- Virologic failure (defined as the failure to achieve a viral load <50 copies/ml by 24 weeks after initiation of antiretroviral regimen or any sustained return of the viral load to >50copies/ml),
- Difficulty adhering to the regimen, and
- Sub-optimal current antiretroviral regimen.
The most common causes of virologic failure with the recommended regimens are the development of resistance and inadequate adherence. The development of resistance to the current antiretroviral regimen is documented through the use of genotypic or phenotypic tests. Commercially available resistance tests generally require a viral load of at least 1000 copies/ ml. In patients who are experiencing failure of an antiretroviral (ART) regimen, the goal is to select a regimen with at least three active ART medications. Patients with resistance to an NNRTI-based regimen will usually be resistant to all NNRTIs. In contrast, it may be possible to use alternate PIs or NRTIs in patients resistant to some members of those classes.3
Virologic failure often leads to the impression of non-adherence. If there is actual non-adherence, the clinician must determine if the patient is ready to adhere to an antiretroviral regimen, and what barriers may have contributed to inconsistent treatment in the past.
In patients who are experiencing failure of an antiretroviral regimen because of viral resistance, the goal is to select a regimen with preferably three, or minimally, two active antiretroviral medications.2 Use of a single active agent usually leads to resistance to that particular drug and limits future treatment options. |
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