Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: 18-month follow-up of the HIVNET 012 randomised trial

Jackson, J. Brooks; Musoke, Philippa; Fleming, Thomas R.; Guay, Laura; Bagenda, Danstan; Allen, Melissa; Nakabiito, Clemensia; Sherman, Joseph; Bakaki, Paul M.; Owor, Maxensia; Ducar, Constance; Deseyve, Martina; Mwatha, Anthony; Emel, Lynda; Duefield, Corey; Mirochnick, Mark; Fowler, Mary Glenn; Mofenson, Lynne; Miotti, Paolo; Gigliotti, Maria; Bray, Dorothy; Mmiro, Francis

doi:10.1016/s0140-6736(03)14341-3

Cited by 437 publications

(232 citation statements)

References 29 publications

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“…2 Before treatment or interventions to prevent transmission were available, the rate of MTCT of HIV-1 in the United States was approximately 25%. 3 Major successes have been achieved in prevention of MTCT of HIV-1 in the United States; the MTCT rate has decreased to less than 2% 4 with antiretroviral treatment of HIV-1-infected pregnant women and, for women who do not yet require treatment of their HIV-1 infection, with the use of the following efficacious interventions to prevent transmission: antiretroviral prophylaxis, 3,[5][6][7][8][9][10][11] cesarean section before labor and before rupture of membranes, 12 and complete avoidance of breastfeeding. 13 The estimated annual number of perinatal HIV-1 infections in the United States has decreased from a peak of 1650 infections in 1991 14 to an estimated 111 infections in 2005.…”

Section: Introductionmentioning

confidence: 99%

Diagnosis of HIV-1 Infection in Children Younger Than 18 Months in the United States

Read¹

2007

Pediatrics

118

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The objectives of this technical report are to describe methods of diagnosis of HIV-1 infection in children younger than 18 months in the United States and to review important issues that must be considered by clinicians who care for infants and young children born to HIV-1–infected women. Appropriate HIV-1 diagnostic testing for infants and children younger than 18 months differs from that for older children, adolescents, and adults because of passively transferred maternal HIV-1 antibodies, which may be detectable in the child's bloodstream until 18 months of age. Therefore, routine serologic testing of these infants and young children is generally only informative before the age of 18 months if the test result is negative. Virologic assays, including HIV-1 DNA or RNA assays, represent the gold standard for diagnostic testing of infants and children younger than 18 months. With such testing, the diagnosis of HIV-1 infection (as well as the presumptive exclusion of HIV-1 infection) can be established within the first several weeks of life among nonbreastfed infants. Important factors that must be considered when selecting HIV-1 diagnostic assays for pediatric patients and when choosing the timing of such assays include the age of the child, potential timing of infection of the child, whether the infection status of the child's mother is known or unknown, the antiretroviral exposure history of the mother and of the child, and characteristics of the virus. If the mother's HIV-1 serostatus is unknown, rapid HIV-1 antibody testing of the newborn infant to identify HIV-1 exposure is essential so that antiretroviral prophylaxis can be initiated within the first 12 hours of life if test results are positive. For HIV-1–exposed infants (identified by positive maternal test results or positive antibody results for the infant shortly after birth), it has been recommended that diagnostic testing with HIV-1 DNA or RNA assays be performed within the first 14 days of life, at 1 to 2 months of age, and at 3 to 6 months of age. If any of these test results are positive, repeat testing is recommended to confirm the diagnosis of HIV-1 infection. A diagnosis of HIV-1 infection can be made on the basis of 2 positive HIV-1 DNA or RNA assay results. In nonbreastfeeding children younger than 18 months with no positive HIV-1 virologic test results, presumptive exclusion of HIV-1 infection can be based on 2 negative virologic test results (1 obtained at ≥2 weeks and 1 obtained at ≥4 weeks of age); 1 negative virologic test result obtained at ≥8 weeks of age; or 1 negative HIV-1 antibody test result obtained at ≥6 months of age. Alternatively, presumptive exclusion of HIV-1 infection can be based on 1 positive HIV-1 virologic test with at least 2 subsequent negative virologic test results (at least 1 of which is performed at ≥8 weeks of age) or negative HIV-1 antibody test results (at least 1 of which is performed at ≥6 months of age). Definitive exclusion of HIV-1 infection is based on 2 negative virologic test results, 1 obtained at ≥1 month of age and 1 obtained at ≥4 months of age, or 2 negative HIV-1 antibody test results from separate specimens obtained at ≥6 months of age. For both presumptive and definitive exclusion of infection, the child should have no other laboratory (eg, no positive virologic test results) or clinical (eg, no AIDS-defining conditions) evidence of HIV-1 infection. Many clinicians confirm the absence of HIV-1 infection with a negative HIV-1 antibody assay result at 12 to 18 months of age. For breastfeeding infants, a similar testing algorithm can be followed, with timing of testing starting from the date of complete cessation of breastfeeding instead of the date of birth.

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Section: Introductionmentioning

confidence: 99%

Diagnosis of HIV-1 Infection in Children Younger Than 18 Months in the United States

Read¹

2007

Pediatrics

118

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“…However, perinatal transmission of HIV-1 remains a major problem in developing countries because of limited access to antiretroviral therapy (6)(7)(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)(10)(11)(12).…”

mentioning

confidence: 99%

“…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)(10)(11)(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).…”

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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“…NVP has been used widely to prevent HIV-1 MTCT in developing countries [7][8][9][10][11]. However, a single dose of NVP is associated with the development of NVP resistant virus in mothers and their infants who become infected with HIV [56].…”

Section: Impact Of Cyp2b6 Genotype On Hiv-1 Mtct and Development Of Nmentioning

confidence: 99%

“…EFV has been included in the majority of treatment guidelines as the preferred first-line regimen for HIVinfected adults [101] and children >3 year old [102] in the United States as well as outside of the United States [103]. NVP has been used in HIV-infected infants, children and adults not only as a component of HAART [101][102][103], but also for the prevention of mother-to-child transmission (MTCT) [7][8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Effect of Host Genetic Variation on the Pharmacokinetics and Clinical Response of Nnrtis

Saitoh

Spector

2007

Future HIV Ther.

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Non-nucleoside reverse transcriptase inhibitors (NNRTIs) have been used widely for treating human immunodeficiency virus type 1 (HIV-1) infected patients as a component of highly active antiretroviral therapy (HAART) and for the prevention of mother-to-child transmission (MTCT). Cytochrome P450 (CYP) 2B6 is an important hepatic isoenzyme responsible for the metabolism of NNRTIs including efavirenz and nevirapine. Recent pharmacogenetic studies have shown that CYP2B6 genetic variants alter hepatic CYP2B6 protein expression and function, and the pharmacokinetics of several CYP2B6 substrates. In particular, the CYP2B6-G516T polymorphism in exon 4 affects the pharmacokinetics of efavirenz. Other studies have shown associations of the CYP2B6-G516T genotype with nevirapine pharmacokinetics and central nervous system adverse effects related to efavirenz use. In total, CYP2B6 genetic variants are important determinants of efavirenz and nevirapine pharmacokinetics . Further studies are needed to identify the associations of CYP2B6 genetic variants with the development of NNRTI resistant viruses.

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Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: 18-month follow-up of the HIVNET 012 randomised trial

Cited by 437 publications

References 29 publications

Diagnosis of HIV-1 Infection in Children Younger Than 18 Months in the United States

Diagnosis of HIV-1 Infection in Children Younger Than 18 Months in the United States

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

Effect of Host Genetic Variation on the Pharmacokinetics and Clinical Response of Nnrtis

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