Short-course Combivir after single-dose nevirapine reduces but does not eliminate the emergence of nevirapine resistance in women. 2012

Sarah Palmer, and Valerie F Boltz, and Jeremy Y Chow, and Neil A Martinson, and James A McIntyre, and Glenda E Gray, and Mark J Hopley, and Douglas Mayers, and Patrick Robinson, and David B Hall, and Frank Maldarelli, and John M Coffin, and John W Mellors, and
HIV Drug Resistance Program, NCI, NIH, Frederick, MD, USA.

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.

UI MeSH Term Description Entries
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D011251 Pregnancy Complications, Infectious The co-occurrence of pregnancy and an INFECTION. The infection may precede or follow FERTILIZATION. Complications, Infectious Pregnancy,Infectious Pregnancy Complications,Maternal Sepsis,Pregnancy, Infectious Complications,Sepsis during Pregnancy,Sepsis in Pregnancy,Infectious Pregnancy Complication,Pregnancy Complication, Infectious,Sepsis in Pregnancies,Sepsis, Maternal
D004338 Drug Combinations Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture. Drug Combination,Combination, Drug,Combinations, Drug
D005260 Female Females
D005838 Genotype The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS. Genogroup,Genogroups,Genotypes
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012367 RNA, Viral Ribonucleic acid that makes up the genetic material of viruses. Viral RNA
D015215 Zidovudine A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia. AZT (Antiviral),Azidothymidine,3'-Azido-2',3'-Dideoxythymidine,3'-Azido-3'-deoxythymidine,AZT Antiviral,AZT, Antiviral,BW A509U,BWA-509U,Retrovir,3' Azido 2',3' Dideoxythymidine,3' Azido 3' deoxythymidine,Antiviral AZT,BWA 509U,BWA509U
D015658 HIV Infections Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS). HTLV-III Infections,HTLV-III-LAV Infections,T-Lymphotropic Virus Type III Infections, Human,HIV Coinfection,Coinfection, HIV,Coinfections, HIV,HIV Coinfections,HIV Infection,HTLV III Infections,HTLV III LAV Infections,HTLV-III Infection,HTLV-III-LAV Infection,Infection, HIV,Infection, HTLV-III,Infection, HTLV-III-LAV,Infections, HIV,Infections, HTLV-III,Infections, HTLV-III-LAV,T Lymphotropic Virus Type III Infections, Human
D018445 Infectious Disease Transmission, Vertical The transmission of infectious disease or pathogens from one generation to another. It includes transmission in utero or intrapartum by exposure to blood and secretions, and postpartum exposure via breastfeeding. Fetomaternal Infection Transmission,Infection Transmission, Fetomaternal,Infection Transmission, Maternal-Fetal,Infection Transmission, Vertical,Maternal-Fetal Infection Transmission,Mother-to-Child Transmission,Pathogen Transmission, Vertical,Vertical Infection Transmission,Vertical Infectious Disease Transmission,Vertical Transmission of Infectious Disease,Infection Transmission, Maternal Fetal,Maternal Fetal Infection Transmission,Mother to Child Transmission,Mother-to-Child Transmissions,Transmission, Fetomaternal Infection,Transmission, Maternal-Fetal Infection,Transmission, Mother-to-Child,Transmission, Vertical Infection,Transmission, Vertical Pathogen,Transmissions, Mother-to-Child,Vertical Pathogen Transmission

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