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Cases and Clinician Viewpoints
20 Years of Resistance and Salvage Therapy
“Been There, Done That”
Patricia C. Kloser, MD, MPH, FACP UMDNJ-NJ Medical School and University Hospital, Newark
After 20 years of treating HIV patients, I greet the approval of new medications with both hope and caution. The new ones are much better than the old ones, for the most part. But we won't know right away how well they work for our patients, and we need to watch for longterm side effects and interactions. This is a lifelong disease, and we need to be cautious about starting patients on new medications or classes of medications, so that we get the longest and best possible benefit for the patient.
Many patients struggle with adherence and side effects, and develop resistance. Some have switched to “the newest medication” several times, with varying success. Once a patient is on a regimen that works – that keeps HIV either undetectable or at low levels, and lets the patient get on with his or her life without unbearable side effects or opportunistic infections – we will stick with that regimen until there is a problem. Then we identify their resistance patterns and find different medications, and are glad to have some new classes of medications that have not yet been tried for this patient.
I know and care for many long-term survivors, who have had HIV for 15 or 20 years. Some of them were very sick in the early days, and they have a lot of motivation to keep taking their medications every day because they have things they want to do besides take care of their HIV. I have several patients who just come in every 6 months for check-ins and support, and they are doing very well, whether they are on a long-established combination or a new medication.
Most of my patients who have developed resistance were not adherent early in treatment. It is seldom just the medication, side effects or interactions. If the patient does not have the motivation and is not adherent, then she is not ready to take on the challenge of the schedule and restrictions of the medication guidelines, and having a new regimen will not help.
We are now able to avoid some resistance by doing genotypic testing when a patient first comes in or is ready for treatment, so that we identify the mutations or resistance. Many of our patients in Newark already have resistant virus when we begin ARV treatment. We have run tropism tests on several patients but even if the results indicate Maraviroc might be appropriate, we are waiting to switch them until their current regimen fails. Sometimes patients refuse newer treatments.
CASE SCENARIO
| C.C. was a 54-year-old Hispanic woman known to me since 1985. She was found to be HIV positive at that time by way of an experimental lab test that was all that was available to us then. She had a history of substance abuse, alcohol abuse, smoking, and a “wild lifestyle” involving dancing in clubs and on cruise ships for a living. She stopped all drugs. She reluctantly started AZT in 1987 along with Bactrim. She was found to have hepatitis B and C with mild liver enzyme elevation. In 1993 she started Combivir. Over the next 13 years, I encouraged her to add an efavirenz booster, or switch to newer medicines, but she never agreed. Her husband died of AIDS in 1993 and three years later she found a new boyfriend,who was also HIV-positive. She brought him in to the clinic. He was started on Combivir and Sustiva, and does well to this day. In early 2006, after 13 years on her regimen, C.C. started to miss her Combivir doses and stopped it in early summer. At the beginning of August she developed jaundice and ascites. Her CD4+ count dropped to 123, after years of relative stability between 200 – 400. Her viral load was never undetectable, but now it increased to 98,000, after many years between 11,000 and 23,000. Her condition worsened and she started to drink again because she became depressed. Her family became discouraged, placed her on hospice care, and she died one month later. |
Discussion:
1. Why did this woman do so well for so long on dual therapy?
2. Why did she develop jaundice?
3. What would you have done when she began to decline? |
Case Input from Dr. Patricia Kloser, MD, MPH
1. Why did this woman do so well for so long on dual therapy?
She changed her lifestyle, became involved as a mentor for family and friends, conected with a clinic and provider for her long-term care.
2. Why did she develop jaundice?
She had a hepatitis flare when she stopped epivir (Combivir) and started to use alcohol and street drugs.
3. What would you have done when she began to decline?
Careful monitoring, aggressive support to stop alcohol and drugs, and started a new ARV with active hepatitis B coverage like tenofovir (Viread).
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