December 18, 2001
HIV drug resistance is a major emerging problem in the U.S. (see summary on abstract LB-17). Drug resistance is most frequently seen in patients who have been treated with HIV drugs, and to a lesser extent in people with acute HIV infection.
The amount of drug resistance seen in the majority of chronically infected (>6 months of infection) HIV patients is relatively small. The current guidelines available from the Department of Health and Human Services indicate that resistance testing is not generally indicated in chronically infected, drug-naive patients, because the likelihood of detecting resistance in this population is quite small. This poster examined how frequently drug resistance occurred in a chronically infected, drug-naive cohort, and additionally, compared the treatment responses between those with and those without the presence of drug resistance.
Blood was collected from a group of 88 HIV drug-naive patients in Boston in 1999, all of whom had a viral load >1,000/ml. Fifty-one percent reported heterosexual contact as their risk factor for HIV infection. Genotypic resistance testing was performed by population sequencing analysis. Patients started treatment according to standard guidelines under their own practitioners and were followed for 48 weeks. Virus with primary drug resistance mutations was found in 16 of 88 (18 percent) patients.
When studied by class of HIV drugs, twelve (14 percent) patients had viruses resistant to NRTI, four (5 percent) had resistance to NNRTI, three (3 percent) had resistance to protease inhibitors, and two (2 percent) had resistance to multiple classes. All resistant viruses were subtype B.
In patients without HIV drug resistance, 47/72 initiated HAART, and only 27/47 (57 percent) had an undetectable viral load (<50/ml) after 48 weeks. By contrast, in those patients with resistance, 12/16 initiated HAART, and 12/12 had an undetectable viral load (100 percent) after 48 weeks. In addition, those with drug resistance took significantly longer to get to undetectable levels when compared to those without drug resistance.
This small and geographically limited study found a small but significant number of patients, primarily with single-class drug resistance. The prevalence of drug resistance in chronically infected, drug-naive patients in this study is consistent with other small reports.
As stated earlier, these findings bring up the issue of whether all drug-naive patients should have resistance tests performed prior to starting HAART. The practitioners were blinded to the resistance test results, and therefore chose regimens without knowledge of whether the patients had resistant virus or not. It is interesting that patients did extremely well with respect to viral load reduction, despite having evidence of resistance.
Thus, one could argue from the results of this study, that undetectable virus was achieved in spite of drug resistance being present. The caveat in this study is that some mutations, although significant, could be overcome with potent regimens. If these patients had more complicated and serious mutations, the results might not have been as successful. An additional finding in this study was the delay in reaching an undetectable viral load when a resistant virus was present. It is important for practitioners and patients to reconsider the premature abandonment of a regimen even though the patient has not reached undetectable viral load in 4-5 months.
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