Perinatal Transmission of Human Immunodeficiency Virus Type 1 by Pregnant Women with RNA Virus Loads &lt;1000 Copies/mL

Ioannidis, John P. A.; Abrams, Elaine J.; Ammann, Arthur J.; Bulterys, Marc; Goedert, James J.; Gray, Linsay; Korber, Bette T.; Mayaux, Marie Jeanne; Mofenson, Lynne; Newell, Marie‐Louise; Shapiro, David E.; Teglas, Jean Paul; Wilfert, Catherine M.

doi:10.1086/318530

Cited by 334 publications

(142 citation statements)

References 39 publications

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“…he treatment of pregnant women with antiretroviral therapy, in combination with zidovudine chemoprophylaxis administered to newborns, has dramatically reduced vertical transmission of HIV in developed countries (1)(2)(3)(4)(5). However, perinatal transmission of HIV-1 remains a major problem in developing countries because of limited access to antiretroviral therapy (6)(7)(8).…”

mentioning

confidence: 99%

Persistence of nevirapine-resistant HIV-1 in women after single-dose nevirapine therapy for prevention of maternal-to-fetal HIV-1 transmission

Palmer

Boltz

Martinson

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

137

114

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Single-dose nevirapine (sdNVP) for prevention of mother-to-child transmission of HIV-1 can select nevirapine (NVP)-resistant variants, but the frequency, duration, and clinical significance of this resistance is not well defined. We used a sensitive allele-specific PCR assay to assess the emergence and persistence of NVPresistant variants in plasma samples from 22 women with HIV-1 subtype C infection who participated in a study of sdNVP for prevention of mother-to-child transmission of HIV-1. The women were categorized into three groups on the basis of detection of NVP resistance by standard genotype analysis. Group 1 (n ‫؍‬ 6) had NVP resistance detected at 2 and 6 mo after sdNVP, but not at 12 mo. Group 2 (n ‫؍‬ 9) had NVP resistance detected at 2 mo, but not 6 mo. Group 3 (n ‫؍‬ 7) had no NVP resistance detected at any time point. Allele-specific PCR analysis for the two most common NVP resistance mutations (K103N and Y181C) detected NVP-resistant variants in most (16 of 21) samples that were negative for NVP resistance by standard genotype, at levels ranging from 0.1% to 20% 1 yr after treatment. The frequency of NVP-resistant mutations decreased over time, but persisted above predose levels for more than 1 yr in >23% of the women. These findings highlight the urgent need for studies assessing the impact of sdNVP on the efficacy of subsequent antiretroviral therapy containing NVP or other nonnucleoside reverse transcriptase inhibitors.allele-specific PCR ͉ resistance ͉ low-frequency mutants T he treatment of pregnant women with antiretroviral therapy, in combination with zidovudine chemoprophylaxis administered to newborns, has dramatically reduced vertical transmission of HIV in developed countries (1-5). However, perinatal transmission of HIV-1 remains a major problem in developing countries because of limited access to antiretroviral therapy (6-8). In this latter setting, the simple regimen of maternal single-dose intrapartum nevirapine (NVP) and single-dose NVP (sdNVP) for the newborn reduces the risk of mother-to-child HIV-1 transmission (MTCT) by 41% through age 18 mo (9). Moreover, sdNVP has been demonstrated to be more effective than zidovudine chemoprophylaxis alone, and to be equivalent to NVP plus zidovudine in preventing MTCT (9-12). The efficacy of sdNVP in preventing MTCT is attributed to its potent antiviral activity, rapid absorption, placental transfer, and long half-life (13, 14). As a result, its use has been recommended by the World Health Organization as one of several options to reduce MTCT in resource-limited countries [Joint UNAIDS͞WHO press release (2000) (WHO, Geneva)].NVP is a potent nonnucleoside reverse transcriptase inhibitor (NNRTI) of HIV-1 (15-17). If administered as monotherapy, NVP selects for resistant variants within 1 wk, commonly those variants with the K103N and͞or Y181C mutations in reverse transcriptase, which confer cross-resistance to other approved drugs in the NNRTI class (18)(19)(20). The K103N mutation appears to have little effect on the replicative capacity o...

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mentioning

confidence: 99%

Persistence of nevirapine-resistant HIV-1 in women after single-dose nevirapine therapy for prevention of maternal-to-fetal HIV-1 transmission

Palmer

Boltz

Martinson

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

137

114

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“…Treatment reduced transmission even among women with low or undetectable HIV VL, suggesting that the effects of treatment were not all related to decreasing maternal viraemia but may also be related to reducing HIV in the genital tract and/or peri-exposure prophylaxis of the infant by placental transfer of zidovudine. A meta analysis of transmission outcomes in several major USA and European studies also demonstrated that an HIV VL <1000 HIV RNA copies/mL at delivery was associated with a relatively low risk of transmission and that ARV prophylaxis offered additional clinically significant protection [141]. Zidovudine has been shown to reduce cervicovaginal shedding of HIV [18] and there are no data to suggest that HAART is more effective than zidovudine at reducing cervicovaginal shedding in women with a plasma HIV VL <50 copies/mL.…”

Section: Grading: 1dmentioning

confidence: 99%

11.0 References

2012

HIV Medicine

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“…One central mechanism is by decreasing maternal viral load in the blood and genital secretions via antenatal drug administration, particularly in women with high viral loads. However, ARV drugs have been shown to reduce the risk of transmission even among women with HIV RNA levels <1,000 copies/ml (Ioannidis et al 2001). Additionally, the level of HIV RNA at delivery and receipt of antenatal ART are each independently associated with the risk of transmission, suggesting that ARV prophylaxis does not work solely through reduction in viral load (Sperling et al 1996).…”

Section: Mechanisms Of Action Of Arv Prophylaxis In Reducing Perinatamentioning

confidence: 99%

“…However, because transmission can occur even at low or undetectable HIV RNA copy numbers, HIV RNA levels should not be a determining factor when deciding whether to use ARV drugs for prevention of PT. Additionally, the efficacy of ARV drugs is not solely related to lowering viral load (Cooper et al 2002;Ioannidis et al 2001). Therefore, ARV prophylaxis should be given even to women who have a very low or undetectable viral load on no therapy.…”

Section: Perinatal Transmission Of Hiv and Maternal Viral Loadmentioning

confidence: 99%