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January 2003
Case Description and Question:
The following case comes from a physician in South Africa:
A 7-year-old boy has received ZDV/3TC combination therapy for about four years and is doing well. His current CD4 count is 703 (27%) and his plasma virus load is 23,900 copies/mL. HIV genotyping was done and showed the following:
RT mutations M41L, M184V, T215Y, P236L
PI mutations L63P
Reported as:
high level resistance to 3TC and delavirdine
intermediate resistance to ddC, ZDV, ddI, abacavir
low level resistance to d4T
susceptible to efavirenz and nevirapine
susceptible to all protease inhibitors
Ordinarily, I would continue the current treatment until he fails clinically. In view of the accumulated resistance mutations, would you advise changing his treatment regimen now before he develops resistance to all nucleoside RT inhibitors, thus compromising future treatment options?
Expert Opinion:
These situations are difficult. The answer to this question may well differ from one place to another, depending on availability of alternative medications, and cost. The M184V mutation in particular confers high-grade resistance to 3TC. The M41L and T215Y mutations are thymidine analog (resistance) mutations (or TAMs), which confer resistance to ZDV, and cross-resistance to d4T and other nucleoside RT inhibitors. Mutant virus possessing the M184V mutation may be less fit than wild type virus, meaning that it replicates less efficiently. In addition, this same mutation may help reverse ZDV resistance. One could argue in this case that continued drug selection pressure is promoting the mutant (and less fit) virus as the dominant quasispecies, explaining in part the normal CD4 count and relatively low virus load. On the other hand, there is the counter argument to which you have alluded: with ongoing virus replication, additional mutations are likely to emerge. In the South African setting, where treatment options are relatively limited, you may want to continue the current therapy unless clinical evaluations and laboratory tests (CD4 count, virus load) indicate disease progression.
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