July 9, 2002
This poster presented some data on the magnitude of the HIV-drug resistance problem in New York State. As most of you know, resistance to HIV medications is a growing problem in the United States. Resistance is the result of multiple factors -- including transmission of drug-resistant HIV, cross resistance between drugs in the same class of HIV medications, prior sub-optimal or low potency regimens, and poor adherence to medication regimens in the presence of a detectable viral load.
This study looked at two kinds of patients, drug-naive patients who had never taken HIV medications before and HIV-drug-experienced patients, but who had been off of HIV medications for greater than six months. Patients had to have a viral load greater than 1,000. Genotypic resistance testing was performed using the Visible Genetics system.
There were 79 drug-naive patients and 114 treatment-experienced patients included in this study. Each group was almost evenly split between men and women. Over 80 percent were between the ages of 30-50. Over half were African-American. Over 50 percent of the naive patients were infected in the last two years, whereas over 75 percent of the treatment-experienced group were infected between 1990-99. The naive patients tended to have lower viral loads than the treatment experienced patients.
The results are as follows: overall 10/79 (12.7 percent) of treatment-naive patients had evidence of drug resistance mutations, compared to 38/114 (13.9 percent) of treatment-experienced patients. When drug resistance was looked at with respect to class of drugs, 6/79, 6/79, 2/79, 2/79 naive patients and 16/114, 28/114, 9/114, 14/114 treatment-experienced patients had evidence of NRTI, NNRTI, PI, or multi-drug resistance mutations respectively. The probability of drug resistance mutations in the treatment-experienced group was highly correlated with the total number of prior HIV drugs that they had taken. NNRTI-associated mutations were the most common. Despite the large number of experienced patients who had taken 3TC, only one patient had evidence of resistance.
There are a few points to emphasize from the findings in this study. First, 12 percent of newly infected, treatment-naive patients in New York State have some evidence of drug resistant virus. This is a disturbingly high number, but not inconsistent with previous national reports of drug resistance in major metropolitan areas. Whether the data presented here is directly translatable to other geographic areas requires further study. However, it does suggest that resistance testing in HIV-drug-naive patients may be an important test to obtain before starting HIV therapy for the first time.
Second, there was a high level of persistence of drug resistance mutations, even after patients stopped treatment for greater than six months. This suggests that mutant virus can be long-lived and detectable by current resistance testing assays. However, all possible drug resistance may not be detectable as evidenced by the lack of 3TC resistance, despite lots of 3TC exposure. This is explained by the fact that some mutations, particularly those associated with NNRTIs will remain present in replicating virus, even in the absence of current drug exposure, whereas mutations associated with 3TC will fade into the background in the absence of current drug exposure. It is important to know the prevalence of resistance in a given population and understand the interrelationship between drug exposure and presence or absence of mutations in order to interpret resistance test results effectively and prescribe the appropriate treatment regimen.
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