A Closer Look: Phenotypic Resistance Test

Cal Cohen, M.D., M.S., Harvard Medical School

Patient: Janet H.
Doctor: Cal Cohen, M.D.
Lowest CD4 count: 10
Highest viral load: 1,208,084
Current CD4 count: 319
Current viral load: 10,000

These are the phenotypic resistance test results for Janet H. (not her real name), a 53-year-old woman living with HIV since 1985. Janet tried many treatment regimens and nearly a dozen different HIV medications; some worked well for a while, but eventually they had difficulty lowering her viral load, which hovered between 10,000 and 40,000.

By 2001, Janet's health was declining. Since starting her latest regimen -- a combination of 3TC, abacavir (Ziagen), amprenavir (Agenerase) and Kaletra -- she had developed frequent sinus infections, lipodystrophy (abnormal fat changes) around her abdomen, diarrhea and nausea. Eventually, the side effects were just too much; Janet told her doctor, Cal Cohen, M.D., that she had to stop her medications.

Before she did so, Dr. Cohen ordered two resistance tests. The first, a genotypic test, found a large number of mutations that suggested her HIV was resistant to NRTIs and protease inhibitors. The second, a phenotypic test, added more information. It found that Janet's HIV was resistant to every NRTI and protease inhibitor available in 2001, except one: AZT.

Even worse, while Janet was off her medications, her CD4 count dropped to 10 and her viral load skyrocketed to more than a million. It was time for a new regimen, and fast. But which medications to choose?

Dr. Cohen decided on a regimen of 3TC, AZT, Kaletra and two new drugs: tenofovir (which had been approved that year) and T-20 (at that time, still an experimental drug from a new class of HIV medications). His hope was that, even though Janet's HIV was resistant to some of the medications in the regimen, they would still be powerful enough to help, especially when mixed with those new medications.

Dr. Cohen was right: Janet's viral load dropped to about 10,000, where it has remained for the past two years. Her CD4 count rose from 10 to 319. Although her new regimen isn't able to completely stop HIV from reproducing, it's able to do so enough to allow her immune system to recover and her health to improve.