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2012-02-23Zeitschriftenartikel DOI: 10.1371/journal.pone.0032055
Emergence of Minor Drug-Resistant HIV-1 Variants after Triple Antiretroviral Prophylaxis for Prevention of Vertical HIV-1 Transmission
dc.contributor.authorHauser, Andrea
dc.contributor.authorSewangi, Julius
dc.contributor.authorMbezi, Paulina
dc.contributor.authorDugange, Festo
dc.contributor.authorLau, Inga
dc.contributor.authorZiske, Judith
dc.contributor.authorTheuring, Stefanie
dc.contributor.authorKücherer, Claudia
dc.contributor.authorHarms, Gundel
dc.contributor.authorKunz, Andrea
dc.date.accessioned2018-05-07T15:28:27Z
dc.date.available2018-05-07T15:28:27Z
dc.date.created2012-03-19
dc.date.issued2012-02-23none
dc.identifier.otherhttp://edoc.rki.de/oa/articles/rewBC21I1pNbc/PDF/28KMGIAR2EyiU.pdf
dc.identifier.urihttp://edoc.rki.de/176904/1159
dc.description.abstractBackground: WHO-guidelines for prevention of mother-to-child transmission of HIV-1 in resource-limited settings recommend complex maternal antiretroviral prophylaxis comprising antenatal zidovudine (AZT), nevirapine single-dose (NVP-SD) at labor onset and AZT/lamivudine (3TC) during labor and one week postpartum. Data on resistance development selected by this regimen is not available. We therefore analyzed the emergence of minor drug-resistant HIV-1 variants in Tanzanian women following complex prophylaxis. Method: 1395 pregnant women were tested for HIV-1 at Kyela District Hospital, Tanzania. 87/202 HIV-positive women started complex prophylaxis. Blood samples were collected before start of prophylaxis, at birth and 1–2, 4–6 and 12–16 weeks postpartum. Allele-specific real-time PCR assays specific for HIV-1 subtypes A, C and D were developed and applied on samples of mothers and their vertically infected infants to quantify key resistance mutations of AZT (K70R/T215Y/T215F), NVP (K103N/Y181C) and 3TC (M184V) at detection limits of ,1%. Results: 50/87 HIV-infected women having started complex prophylaxis were eligible for the study. All women took AZT with a median duration of 53 days (IQR 39–64); all women ingested NVP-SD, 86% took 3TC. HIV-1 resistance mutations were detected in 20/50 (40%) women, of which 70% displayed minority species. Variants with AZT-resistance mutations were found in 11/50 (22%), NVP-resistant variants in 9/50 (18%) and 3TC-resistant variants in 4/50 women (8%). Three women harbored resistant HIV-1 against more than one drug. 49/50 infants, including the seven vertically HIV-infected were breastfed, 3/7 infants exhibited drug-resistant virus. Conclusion: Complex prophylaxis resulted in lower levels of NVP-selected resistance as compared to NVP-SD, but AZTresistant HIV-1 emerged in a substantial proportion of women. Starting AZT in pregnancy week 14 instead of 28 as recommended by the current WHO-guidelines may further increase the frequency of AZT-resistance mutations. Given its impact on HIV-transmission rate and drug-resistance development, HAART for all HIV-positive pregnant women should be considered.eng
dc.language.isoeng
dc.publisherRobert Koch-Institut, Infektionskrankheiten / Erreger
dc.subject.ddc610 Medizin
dc.titleEmergence of Minor Drug-Resistant HIV-1 Variants after Triple Antiretroviral Prophylaxis for Prevention of Vertical HIV-1 Transmission
dc.typeperiodicalPart
dc.identifier.urnurn:nbn:de:0257-10021943
dc.identifier.doi10.1371/journal.pone.0032055
dc.identifier.doihttp://dx.doi.org/10.25646/1084
local.edoc.container-titlePLoS ONE
local.edoc.container-textHauser A , Sewangi J , Mbezi P , Dugange F , Lau I , et al. (2012) Emergence of Minor Drug-Resistant HIV-1 Variants after Triple Antiretroviral Prophylaxis for Prevention of Vertical HIV-1 Transmission. PLoS ONE 7(2): e32055.
local.edoc.fp-subtypeArtikel
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-urlhttp://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0032055
local.edoc.container-publisher-namePublic Library of Science
local.edoc.container-volume7
local.edoc.container-issue2
local.edoc.container-year2012

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