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Detection of HIV-1 drug resistance in women following administration of a single dose of nevirapine: comparison of plasma RNA to cellular DNA by consensus sequencing and by oligonucleotide ligation assay.
- Source :
-
Journal of clinical microbiology [J Clin Microbiol] 2010 May; Vol. 48 (5), pp. 1555-61. Date of Electronic Publication: 2010 Feb 24. - Publication Year :
- 2010
-
Abstract
- A single dose of nevirapine (sdNVP) to prevent mother-to-child transmission of HIV-1 increases the risk of failure of subsequent NVP-containing antiretroviral therapy (ART), especially when initiated within 6 months of sdNVP administration, emphasizing the importance of understanding the decay of nevirapine-resistant mutants. Nevirapine-resistant HIV-1 genotypes (with the mutations K103N, Y181C, and/or G190A) from 21 women were evaluated 10 days and 6 weeks after sdNVP administration and at the initiation of ART. Resistance was assayed by consensus sequencing and by a more sensitive assay (oligonucleotide ligation assay [OLA]) using plasma-derived HIV-1 RNA and cell-associated HIV-1 DNA. OLA detected nevirapine resistance in more specimens than consensus sequencing did (63% versus 33%, P<0.01). When resistance was detected only by OLA (n=45), the median mutant concentration was 18%, compared to 61% when detected by both sequencing and OLA (n=51) (P<0.0001). The proportion of women whose nevirapine resistance was detected by OLA 10 days after sdNVP administration was higher when we tested their HIV-1 RNA (95%) than when we tested their HIV-1 DNA (88%), whereas at 6 weeks after sdNVP therapy, the proportion was greater with DNA (85%) than with RNA (67%) and remained higher with DNA (33%) than with RNA (11%) at the initiation of antiretroviral treatment (median, 45 weeks after sdNVP therapy). Fourteen women started NVP-ART more than 6 months after sdNVP therapy; resistance was detected by OLA in 14% of the women but only in their DNA. HIV-1 resistance to NVP following sdNVP therapy persists longer in cellular DNA than in plasma RNA, as determined by a sensitive assay using sufficient copies of virus, suggesting that DNA may be superior to RNA for detecting resistance at the initiation of ART.
- Subjects :
- Adult
Chemoprevention methods
DNA Primers genetics
DNA, Viral blood
Female
HIV Infections drug therapy
HIV-1 isolation & purification
Humans
Ligase Chain Reaction methods
Microbial Sensitivity Tests methods
Oligonucleotide Probes genetics
Pregnancy
Pregnancy Complications, Infectious drug therapy
RNA, Viral blood
Sensitivity and Specificity
Sequence Analysis, DNA methods
Anti-HIV Agents therapeutic use
Drug Resistance, Viral
HIV-1 genetics
Infectious Disease Transmission, Vertical prevention & control
Nevirapine therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1098-660X
- Volume :
- 48
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of clinical microbiology
- Publication Type :
- Academic Journal
- Accession number :
- 20181911
- Full Text :
- https://doi.org/10.1128/JCM.02062-09