Quantitative Analysis of HIV-1 Variants With the K103N Resistance Mutation After Single-Dose Nevirapine in Women With HIV-1 Subtypes A, C, and D

Flys, Tamara; Chen, Shu; Jones, Donna; Hoover, Donald R.; Church, Jessica D.; Fiscus, Susan A.; Mwatha, Anthony; Guay, Laura; Mmiro, Francis; Musoke, Philippa; Kumwenda, Newton; Taha, Taha E.; Jackson, J. Brooks; Eshleman, Susan H.

doi:10.1097/01.qai.0000221686.67810.20

Cited by 80 publications

(53 citation statements)

References 13 publications

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“…Lee et al [14] found drug-resistant virus in 65% of breast milk samples of women infected with HIV-1 subtype C 8 weeks after NVP-SD exposure using a population-based approach. Similarly, drug-resistant viruses in plasma have been shown to emerge at higher frequencies in subtype C as compared with subtype A and D [4,11], which also appears to be true for breast milk.…”

Section: Discussionmentioning

confidence: 99%

“…Nevirapine single-dose (NVP-SD) is still widely used to reduce the transmission of HIV type-1 (HIV-1) from the mother to the child in resource-limited settings, although it is associated with a high incidence of NVP-resistant HIV-1 [2][3][4][5][6][7][8][9][10][11]. To date, most studies have focused on the development of NVP-resistant virus in plasma, and it has been shown that 19-75% of women exposed to NVP-SD harbour NVP-resistant HIV-1 variants in their blood [3][4][5][6][7][8][9][10][11]. Although the proportion of resistant virus in plasma fades over time, minor drug-resistant populations can persist for long periods in this compartment [5,8,9].…”

Section: Introductionmentioning

confidence: 99%

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Minor Drug-Resistant HIV Type-1 Variants in Breast Milk and Plasma of HIV Type-1-Infected Ugandan Women after Nevirapine Single-Dose Prophylaxis

et al. 2011

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Minor Drug-Resistant HIV Type-1 Variants in Breast Milk and Plasma of HIV Type-1-Infected Ugandan Women after Nevirapine Single-Dose Prophylaxis

et al. 2011

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“…143 Around half the women who received one dose of nevirapine to prevent mother-to-child transmission harbour viruses resistant to non-nucleoside reverse transcriptase inhibitors (NNRTI). 144,145 These resistant viruses replicate efficiently and can be transmitted by breast milk, 146 and minor resistant populations present long after the intervention can possibly decrease the effectiveness of subsequent NNRTI-based treatment regimens. 147 The combination of short-course zidovudine, lamivudine, and nevirapine prevents peripartum transmission while reducing the risk of nevirapine resistant viruses.…”

Section: Drug Resistancementioning

confidence: 99%

HIV/AIDS epidemiology, pathogenesis, prevention, and treatment

2006

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The HIV-1 pandemic is a complex mix of diverse epidemics within and between countries and regions of the world, and is undoubtedly the defining public-health crisis of our time. Research has deepened our understanding of how the virus replicates, manipulates, and hides in an infected person. Although our understanding of pathogenesis and transmission dynamics has become more nuanced and prevention options have expanded, a cure or protective vaccine remains elusive. Antiretroviral treatment has transformed AIDS from an inevitably fatal condition to a chronic, manageable disease in some settings. This transformation has yet to be realised in those parts of the world that continue to bear a disproportionate burden of new HIV-1 infections and are most a % ected by increasing morbidity and mortality. This Seminar provides an update on epidemiology, pathogenesis, treatment, and prevention interventions pertinent to HIV-1. HIV pandemicAn estimated 38·6 (33·4-46·0) million people live with HIV-1 worldwide, while about 25 million have died already. 1 In 2005 alone, there were 4·1 million new HIV-1 infections and 2·8 million AIDS deaths. 1 These estimates mask the dynamic nature of this evolving epidemic in relation to temporal changes, geographic distribution, magnitude, viral diversity, and mode of transmission. Today, there is no region of the world untouched by this pandemic (figure 1). 2 Heterosexual transmission remains the dominant mode of transmission and accounts for about 85% of all HIV-1 infections. Southern Africa remains the epicentre of the pandemic and continues to have high rates of new HIV-1 infections. 3 Although overall HIV-1 prevalence remains low in the emerging epidemics in China and India, the absolute numbers, which are fast approaching those seen in southern Africa, are of concern. 1 Outside of sub-Saharan Africa, a third of all HIV-1 infections are acquired through injecting drug use, most (an estimated 8·8 million) of which are in eastern Europe and central and southeast Asia. 1 The rapid spread of HIV-1 in these regions through injecting drug use is of importance, since it is a bridge for rapid establishment of more generalised epidemics. NIH-PA Author ManuscriptA defining feature of the pandemic in the current decade is the increasing burden of HIV-1 infections in women, 4 which has additional implications for mother-to-child transmission. Women now make up about 42% of those infected worldwide; over 70% of whom live in sub-Saharan Africa. 1 Overall, a quarter of all new HIV-1 infections are in adults aged younger than 25 years. 1 HIV-1 infection rates are three to six times higher in female adolescents than in their male counterparts, 1,5-7 and this difference is attributed to sexual coupling patterns of young women with older men. Population prevalence of HIV-1 infection, concurrent sexual relationships, partner change, sexual practices, the presence of other sexually transmitted diseases, [8][9][10][11] and population mobility patterns 12-14 for economic and other reasons (eg, natu...

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“…More sensitive assays detect NNRTI resistance mutations in 51 to 87% of postpartum sdNVPexposed mothers (9,22), and these mutations remain detectable in 8 to 33% of women after a year (5,8,10). Comparative analyses of the decay of NVP resistance in HIV-1 DNA and RNA in blood using sensitive methods found a lower proportion of women with resistance in their HIV-1 DNA (5,22), although the input of HIV-1 DNA was not directly determined in these studies, precluding estimations of the sensitivity limits of the assays.…”

mentioning

confidence: 99%

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

et al. 2010

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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.A single dose of nevirapine (sdNVP) reduces mother-tochild transmission (MTCT) of HIV-1 by 47% to 58% (12,17) but is associated with the selection of mutant viruses resistant to nonnucleoside reverse transcriptase inhibitors (NNRTI) (7,15) and may jeopardize the effectiveness of subsequent nevirapine (NVP)-based antiretroviral treatment (ART) (5, 15, 21). However, the adverse impact of sdNVP therapy on NVP-ART efficacy seems to decrease with longer time intervals between the administration of sdNVP and the initiation of NVP-ART (ART start) (21, 29).In 21 to 32% of sdNVP-treated mothers, consensus sequencing of HIV-1 RNA detects NNRTI mutations, which decay to undetectable levels over 1 year (7,8,15). More sensitive assays detect NNRTI resistance mutations in 51 to 87% of postpartum sdNVPexposed mothers (9,22), and these mutations remain detectable in 8 to 33% of women after a year (5,8,10). Comparative analyses of the decay of NVP resistance in HIV-1 DNA and RNA in blood using sensitive methods found a lower proportion of women with resistance in their HIV-1 DNA (5, 22), although the input of HIV-1 DNA was not directly determined in these studies, precluding estimations of the sensitivity limits of the assays.We inv...

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Quantitative Analysis of HIV-1 Variants With the K103N Resistance Mutation After Single-Dose Nevirapine in Women With HIV-1 Subtypes A, C, and D

Abstract: After administration of single-dose NVP, K103N was detected more frequently and at higher levels in women with subtypes C and D than A. Further studies are needed to evaluate the clinical significance of NVP-resistant variants in this setting.

Cited by 80 publications

References 13 publications

Minor Drug-Resistant HIV Type-1 Variants in Breast Milk and Plasma of HIV Type-1-Infected Ugandan Women after Nevirapine Single-Dose Prophylaxis

Minor Drug-Resistant HIV Type-1 Variants in Breast Milk and Plasma of HIV Type-1-Infected Ugandan Women after Nevirapine Single-Dose Prophylaxis

HIV/AIDS epidemiology, pathogenesis, prevention, and treatment

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

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