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

• Published in: Antiviral therapy Vol. 17; no. 2; pp. 327 - 336
• Main Authors: PALMER, Sarah, BOLTZ, Valerie F, MALDARELLI, Frank, COFFIN, John M, MELLORS, John W, CHOW, Jeremy Y, MARTINSON, Neil A, MCLNTYRE, James A, GRAY, Glenda E, HOPLEY, Mark J, MAYERS, Douglas, ROBINSON, Patrick, HALL, David B
• Format: Journal Article
• Language: English
• Published: London International Medical Press 01.01.2012
• Subjects: Anti-HIV Agents - administration & dosage; Anti-HIV Agents - pharmacology; Anti-HIV Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; Drug Combinations; Drug Resistance, Viral - drug effects; Female; Genotype; HIV Infections - drug therapy; Humans; Infectious Disease Transmission, Vertical; Lamivudine - administration & dosage; Lamivudine - pharmacology; Lamivudine - therapeutic use; Medical sciences; Medicin och hälsovetenskap; Nevirapine - administration & dosage; Nevirapine - pharmacology; Nevirapine - therapeutic use; Pharmacology. Drug treatments; Pregnancy; Pregnancy Complications, Infectious - drug therapy; Pregnancy Complications, Infectious - virology; RNA, Viral - blood; Viral Load; Zidovudine - administration & dosage; Zidovudine - pharmacology; Zidovudine - therapeutic use; Human; Antiretroviral agent; RNA-directed DNA polymerase; Nevirapine; Enzyme; Non nucleoside compound; Transferases; Single dose; Enzyme inhibitor; Epidemiology; Resistance; Nucleotidyltransferases; Reverse transcriptase inhibitor; Antiviral; Female; Woman
• ISSN: 1359-6535; 2040-2058; 2040-2058
• DOI: 10.3851/IMP1946

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). 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. 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. 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.