3TC Still Active Versus 3TC-Resistant Virus
3TC Still Active Versus 3TC-Resistant Virus
Subjects with 3TC-resistant virus stopped taking 3TC and sustained an increase in viral load.
A single mutation at codon 184 in the HIV genome results in high-level 3TC resistance, but it may also enhance viral sensitivity to other nucleoside drugs and decrease viral fitness. Clinically, what is the bottom line? Does the mutation completely eliminate the antiviral benefit of 3TC?
In a partially industry-supported study, researchers studied the effects of removing 3TC from combination antiretroviral therapy in six patients with the M184V mutation. All patients were clinically stable on a multidrug regimen and had detectable virus, other resistance mutations, and profound phenotypic resistance to 3TC. Baseline CD4 count ranged from 163 to 730 cells/mm, viral load from 4 to 6 log copies/mL, and replication capacity from 29% to 135%. All subjects continued taking the remaining drugs in the regimen after the 3TC was stopped.
Six weeks after 3TC withdrawal, median viral load increased to 0.5 log copies/mL above baseline; reversion of the 184 mutation was subsequently documented in four patients. CD4-cell counts remained generally unchanged in five patients and fell substantially in one. All patients dropped out of the study after 8 to 22 weeks to resume 3TC; after 3TC resumption, viral loads continued to rise in three patients and fell to baseline levels in the other three.
The results of this small study should not be overinterpreted, but they do suggest that despite genotypic and phenotypic resistance, continuing 3TC in a salvage regimen may contribute to a reduction in viral load (of about 0.5 log copies/mL) through other mechanisms. The authors point out that even this small contribution is associated with a 50% reduction in clinical events. Given 3TC's general lack of toxicity, the trade-off may be worthwhile, at least until larger studies clarify the precise processes at work.
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Subjects with 3TC-resistant virus stopped taking 3TC and sustained an increase in viral load.
A single mutation at codon 184 in the HIV genome results in high-level 3TC resistance, but it may also enhance viral sensitivity to other nucleoside drugs and decrease viral fitness. Clinically, what is the bottom line? Does the mutation completely eliminate the antiviral benefit of 3TC?
In a partially industry-supported study, researchers studied the effects of removing 3TC from combination antiretroviral therapy in six patients with the M184V mutation. All patients were clinically stable on a multidrug regimen and had detectable virus, other resistance mutations, and profound phenotypic resistance to 3TC. Baseline CD4 count ranged from 163 to 730 cells/mm, viral load from 4 to 6 log copies/mL, and replication capacity from 29% to 135%. All subjects continued taking the remaining drugs in the regimen after the 3TC was stopped.
Six weeks after 3TC withdrawal, median viral load increased to 0.5 log copies/mL above baseline; reversion of the 184 mutation was subsequently documented in four patients. CD4-cell counts remained generally unchanged in five patients and fell substantially in one. All patients dropped out of the study after 8 to 22 weeks to resume 3TC; after 3TC resumption, viral loads continued to rise in three patients and fell to baseline levels in the other three.
The results of this small study should not be overinterpreted, but they do suggest that despite genotypic and phenotypic resistance, continuing 3TC in a salvage regimen may contribute to a reduction in viral load (of about 0.5 log copies/mL) through other mechanisms. The authors point out that even this small contribution is associated with a 50% reduction in clinical events. Given 3TC's general lack of toxicity, the trade-off may be worthwhile, at least until larger studies clarify the precise processes at work.
Click here for AIDS Clinical Care subscription information.
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