Response to Antiretroviral Therapy after a Single, Peripartum Dose of Nevirapine

ArticleinNew England Journal of Medicine 356(2):135-47 · January 2007with17 Reads
DOI: 10.1056/NEJMoa062876 · Source: PubMed
A single dose of nevirapine during labor reduces perinatal transmission of human immunodeficiency virus type 1 (HIV-1) but often leads to viral nevirapine resistance mutations in mothers and infants. We studied the response to nevirapine-based antiretroviral treatment among women and infants who had previously been randomly assigned to a single, peripartum dose of nevirapine or placebo in a trial in Botswana involving the prevention of the transmission of HIV-1 from mother to child. All women were treated with antenatal zidovudine. The primary end point for mothers and infants was virologic failure by the 6-month visit after initiation of antiretroviral treatment, estimated within groups by the Kaplan-Meier method. Of 218 women who started antiretroviral treatment, 112 had received a single dose of nevirapine and 106 had received placebo. By the 6-month visit after the initiation of antiretroviral treatment, 5.0% of the women who had received placebo had virologic failure, as compared with 18.4% of those who had received a single dose of nevirapine (P=0.002). Among 60 women starting antiretroviral treatment within 6 months after receiving placebo or a single dose of nevirapine, no women in the placebo group and 41.7% in the nevirapine group had virologic failure (P<0.001). In contrast, virologic failure rates did not differ significantly between the placebo group and the nevirapine group among 158 women starting antiretroviral treatment 6 months or more post partum (7.8% and 12.0%, respectively; P=0.39). Thirty infants also began antiretroviral treatment (15 in the placebo group and 15 in the nevirapine group). Virologic failure by the 6-month visit occurred in significantly more infants who had received a single dose of nevirapine than in infants who had received placebo (P<0.001). Maternal and infant findings did not change qualitatively by 12 and 24 months after the initiation of antiretroviral treatment. Women who received a single dose of nevirapine to prevent perinatal transmission of HIV-1 had higher rates of virologic failure with subsequent nevirapine-based antiretroviral therapy than did women without previous exposure to nevirapine. However, this applied only when nevirapine-based antiretroviral therapy was initiated within 6 months after receipt of a single, peripartum dose of nevirapine. ( number, NCT00197587 [].).
    • "Though the first-line ART is potent method to fight against HIV, but the development of drug resistance could make ART less effective [24][25][26][27]. NNRTI associated drug resistance mutations could compromise the success of NNRTI-containing ART [28][29][30] . Among these mutations , K103N Y181C and G190A are the most frequent NNRTI associated drug resistance mutations. "
    [Show abstract] [Hide abstract] ABSTRACT: We built a cohort study of HIV patients taking long-term first-line Antiretroviral Therapy in 2003. In this assay, we focused on the development of primary drug resistance mutations against Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI), K103N, Y181C and G190A. The cohort study was built in Henan province, China. We used Single Genome Amplification (SGA) to analyze the frequency of K103N, Y181C and G190A in serial plasma samples of three individual patients. We also performed standard genotype HIV drug resistance assay in 204 patients of this cohort study to analyze the frequency of these mutations. In the SGA sequences, the K103N decreased and vanished, while the frequency of Y181C and G190A increased in individual patient receiving long-term Antiretroviral Therapy (ART). In the sequences of standard genotype HIV drug resistance assay, the frequency of K103N, Y181C and G190A had the similar pattern with that in SGA sequences. Among these patients, the viral suppression were still sufficient after receiving ART for 72 months, and 78.6% (160/204) patients could have their CD4 count over than 200cells/ul. In some patients, first-line ART had the possibility to provide sufficient treatment effect for over than 72 months, but in long-term treatment, the dominant NNRTI drug resistance mutation K103N could reduced, while the proportion of variants with mutation Y181C or G190A may increased. This result was not similar with that in vitro study, which state that variant with K103N or Y181C had an equal viral fitness with wild type.
    Full-text · Article · Nov 2014
    • "ART-naïve: 85.9%, adjusted Odds Ratio 3.24 [95% confidence interval 1.08-9.75], p = 0.04), however the median number of measurements recorded was the same (ZDVmexperienced: median 4 [IQR 3–5]; ART-naïve: median 42345, p = 0.83). ZDVm-experienced and ART-naïve women started therapeutic ART at similar baseline CD4 counts (ZDVmexperienced: 226 cells/mm 3 ; ART-naïve: 225 cells/mm 3 , p = 0.16) and viral load (ZDVmexperienced: 4.1 [3.2-4.5] "
    [Show abstract] [Hide abstract] ABSTRACT: Short-term zidovudine monotherapy (ZDVm) remains an option for some pregnant HIV-positive women not requiring treatment for their own health but may affect treatment responses once antiretroviral therapy (ART) is subsequently started. Data were obtained by linking two UK studies: the UK Collaborative HIV Cohort (UK CHIC) study and the National Study of HIV in Pregnancy and Childhood (NSHPC). Treatment responses were assessed for 2028 women initiating ART at least one year after HIV-diagnosis. Outcomes were compared using logistic regression, proportional hazards regression or linear regression. In adjusted analyses, ART-naive (n = 1937) and ZDVm-experienced (n = 91) women had similar increases in CD4 count and a similar proportion achieving virological suppression; both groups had a low risk of AIDS. In this setting, antenatal ZDVm exposure did not adversely impact on outcomes once ART was initiated for the woman's health.
    Full-text · Article · Mar 2014
    • "Drug resistance is another major issue. Children exposed to non-nucleoside reverse transcriptase inhibitors (NNRTIs) for PMTCT, commonly have viral resis- tance [63]; children who failed single-dose nevirapine have a high rate of virological failure when nevirapine is used for treatment in the first year of life [64]. Drug resistance may even be detectable among children who missed PMTCT [65,66]. "
    [Show abstract] [Hide abstract] ABSTRACT: The recent case report of an HIV-infected child in Mississippi with viral control post-antiretroviral therapy (ART) interruption has sparked interest in the possibility of 'functional cure' in infants if they initiate ART very soon after birth. The 'Mississippi baby' also raises many new questions around the clinical care of HIV-infected infants and young children, including when treatment should be initiated, why treatment should be initiated, what treatment should be initiated, and how to identify infants early enough to treat them adequately. Here, we review research conducted before the report of the 'Mississippi baby' highlighting the important new issues that now need to be taken into consideration.
    Article · Feb 2014
Show more