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Troubling Persistence of Transmitted HIV Drug Resistance
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David Margolis, MD, University of Texas Southwestern Center
Shedding light on another important aspect of HIV transmission, Little (abstract 36LB) reported on the persistence of transmitted drug resistant variants in subjects with primary HIV infection who chose not to start antiretroviral therapy (ART). In 11 subjects at least one major drug-resistance mutation was identified, along with corresponding phenotypic resistance. In patients with resistance NNRTI drugs (eg. Sustiva), it took an average of nearly 200 days for resistant virus to begin to be replaced by NNRTI-sensitive HIV, but resistance persisted for 9 of 11 subjects for months with complete disappearance of transmitted NNRTI resistance in only 1 subject, nearly 3 years after infection. HIV with NRTI resistance (eg. AZT) persisted for > 300 days. Protease inhibitor resistance persisted for more than 600 days, and complete reversion of genotypic resistance was observed in only one patient at 1019 days after infection. Despite the presence of drug-resistance mutations, which often impair viral fitness or ability to replicate, the replication capacity of these transmitted drug-resistant viruses was not impaired. This is likely due to selection at transmission for viruses that can replicate well. The durability of transmitted drug resistance raised troubling questions about the likelihood of therapeutic success for these individuals.
However, Pillay and co-workers (poster abstract 685) found that of 152 persons initiating ART, 20 (13%) had one or more key mutations at seroconversion conferring resistance to therapy. Of these 132 (87%) reached HIV RNA <500 copies/mL at a median of 97 days (95% CI = 78 to 117) following ART. Pillay found no evidence to suggest that transmitted drug resistance was associated with different time to viral suppression once we adjusted for individuals without a fully active ART regimen (i.e. number of active drugs less than number of drugs in regimen). Pillay added, however, long-term follow-up is essential to assess the impact of durability of viral suppression and response to subsequent regimens. (editorial note: my recollection is that other studies have found that transmitted drug resistance can impair response to HAART).
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