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.
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.
Authors: Valerie F Boltz; Yajing Bao; Shahin Lockman; Elias K Halvas; Mary F Kearney; James A McIntyre; Robert T Schooley; Michael D Hughes; John M Coffin; John W Mellors Journal: J Infect Dis Date: 2014-01-16 Impact factor: 5.226
Authors: Randall G Fisher; Davey M Smith; Ben Murrell; Ruhan Slabbert; Bronwyn M Kirby; Clair Edson; Mark F Cotton; Richard H Haubrich; Sergei L Kosakovsky Pond; Gert U Van Zyl Journal: J Clin Virol Date: 2014-11-20 Impact factor: 3.168
Authors: Deborah K McMahon; Lu Zheng; Jane Hitti; Ellen S Chan; Elias K Halvas; Feiyu Hong; Joseph Kabanda; Frank Taulo; Nagalingeswaran Kumarasamy; Jerry Bonhomme; Carole L Wallis; Karin L Klingman; Michael D Hughes; John W Mellors Journal: Clin Infect Dis Date: 2013-01-08 Impact factor: 9.079
Authors: Jane Hitti; Elias K Halvas; Lu Zheng; Constantinos G Panousis; Joseph Kabanda; Frank Taulo; Nagalingeswaran Kumarasamy; Jean William Pape; Umesh Lalloo; Heather Sprenger; Karin L Klingman; Ellen S Chan; Deborah McMahon; John W Mellors Journal: J AIDS Clin Res Date: 2014-11-09