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March 2003
Case Description and Question:
The following case comes from a physician in South Africa:
TI have a four-year-old patient who has received d4T/ddI/efavirenz (EFV) for nine months. Cost is a bit of an issue, and this is the most affordable regimen. Clinically, she has done very well over the past nine months. Her CD4+ lymphocyte count has increased from 75/uL ( 5.7%) to 366/uL (21.7%), and the HIV virus load has decreased from 642,000/mL to 42,400/mL. HIV resistance genotyping shows the following:
TRT mutations Y188C, G333E
PI mutations M36I, L63P, I93L
reported as low level resistance to 3TC and ZDV
susceptible to ddC, ddI, d4T, and abacavir (ABC)
high level resistance to EFV and nevirapine (NVP)
susceptible to all PIs
Ordinarily, I would just observe her because she is doing so well clinically and immunologically. However, with the benefit of genotyping, is there any point in continuing with EFV? Should we change her therapy now? Given that her virus is still susceptible to d4T and ddI (and they are the cheapest NRTIs in South Africa), could we not just switch out EFV for a PI (e.g., Kaletra), and retain d4T/ddI?
Opinion:
This is an interesting pattern of mutations. Y188L confers high-grade resistance to EFV, but it is unusual for it to appear before emergence of either the K103N or Y181C mutations. I would be reluctant to make a single drug switch, given the likelihood that there are other resistant quasispecies circulating at levels below lower limits of detection in the genotyping assay.
A change to AZT/3TC/Kaletra certainly could be justified by the incomplete virologic response to treatment. I don't know if this is affordable. If not, I don't think it would be catastrophic to continue the current regimen and check CD4+ lymphocyte count, virus load, and HIV resistance genotyping again in 2-3 months. I have no idea what implications there are, if any, of the Y188C mutation for viral fitness. If the virus load remains only moderate, and the CD4+ lymphocyte count is stable, you might opt to continue that regimen.
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