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Short-course Combivir after single-dose nevirapine reduces but does not eliminate the emergence of nevirapine resistance in women.


ABSTRACT: BACKGROUND:In the Treatment Options Preservation Study (TOPS) trial, 4 or 7 days of Combivir (CBV; zidovudine/lamivudine) with maternal single-dose nevirapine (sdNVP) significantly reduced the emergence of NVP resistance as determined by virus population genotyping. To detect NVP resistance with greater sensitivity, we analysed TOPS samples by allele-specific real-time PCR (ASP). METHODS:In a random subset of women from each arm of the trial, plasma samples from before and 6 weeks after sdNVP were analysed using ASP at codons 103, 181, 184 and 190. RESULTS:Samples were analysed from 27 women in the sdNVP arm and 24 each in the CBV 4-day (sdNVP/CBV4) and 7-day (sdNVP/CBV7) arms. ASP detected NVP-resistant variants in week 6 samples from 70% of women in the sdNVP arm, 29% in the sdNVP/CBV4 arm and 33% in sdNVP/CBV7 arm (P<0.01 for sdNVP/CBV4 or sdNVP/CBV7 versus sdNVP; P=1.0 for sdNVP/CBV4 versus sdNVP/CBV7). Lamivudine resistance was detected by ASP in only 1 of 51 women who received CBV. CONCLUSIONS:Short-course CBV significantly reduced but did not eliminate the emergence of NVP resistance after sdNVP. NVP-resistant variants were detected in about one-third of women despite CBV treatment, but the duration of persistence and clinical impact of these variants in response to antiretroviral therapy is uncertain.

SUBMITTER: Palmer S 

PROVIDER: S-EPMC6752704 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Short-course Combivir after single-dose nevirapine reduces but does not eliminate the emergence of nevirapine resistance in women.

Palmer Sarah S   Boltz Valerie F VF   Chow Jeremy Y JY   Martinson Neil A NA   McIntyre James A JA   Gray Glenda E GE   Hopley Mark J MJ   Mayers Douglas D   Robinson Patrick P   Hall David B DB   Maldarelli Frank F   Coffin John M JM   Mellors John W JW  

Antiviral therapy 20111103 2


<h4>Background</h4>In the Treatment Options Preservation Study (TOPS) trial, 4 or 7 days of Combivir (CBV; zidovudine/lamivudine) with maternal single-dose nevirapine (sdNVP) significantly reduced the emergence of NVP resistance as determined by virus population genotyping. To detect NVP resistance with greater sensitivity, we analysed TOPS samples by allele-specific real-time PCR (ASP).<h4>Methods</h4>In a random subset of women from each arm of the trial, plasma samples from before and 6 weeks  ...[more]

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