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I have a new patient, age 20, CD4 261 cells/L, viral load 16,000 copies/mL. He is treatment naive and has no symptoms. Should resistance testing be done now as a guide to selection of initial therapy?

Dr. David Katzenstein responds:
Resistance testing in this setting is not likely to be useful for several reasons. First, this individual has probably been infected for at least several years (based on CD4 and RNA levels) and at this point, any "transmitted" resistance mutations, if there were any, would not be easily detected as part of the majority quasispecies. Since resistance mutations nearly always provide a selective advantage (in the presence of drug) and are selected against (due to reduced fitness) in the absence of drug, resistance testing is unlikely to be informative in a patient who has not been treated. On the other hand, a careful history could raise alarm bells if there was information on the treatment history of the source patient (i.e., that person from whom HIV infection was transmitted to the case patient). In this case, when and if you initiate ARV therapy, you should track initial response carefully (by checking 4- and 8-week RNA levels) and conducting resistance testing if there is any doubt about response (plateau or failure to see steady decline). As for PI-sparing regimens, Trizivir should be very effective virologically in this patient. While there is debate over Trizivir and nevirapine/Combivir approaches vs PI-based triple therapy in "high virus load" patients (> 100,000 copies/mL), this patient is an ideal candidate for triple NRTI therapy as CD4 cells approach <200. Combivir plus ddI or d4T, or ddI and 3TC as nucleoside combinations would likely be equally effective and could spare the "anxiety" factor associated with abacavir hypersensitivity. In the absence of symptoms and with the current lab values, one might well defer (in accordance with the patient's preference) immediate treatment. At this point, unless the patient is very anxious to begin treatment, or there is a pressing need to suppress virus (e.g., the patient is having unprotected intercourse), I would recommend measuring CD4 levels every 2-3 months and discussing need for treatment and prophylaxis with the patient. Continued RNA monitoring will be less informative than CD4 counts.

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