Praziquantel for the treatment of schistosomiasis during human pregnancy.

In 2014, an estimated 40 million women of reproductive age were infected with Schistosoma haematobium, S. japonicum and/or S. mansoni. In both 2003 and 2006, the World Health Organization (WHO) recommended that all schistosome-infected pregnant and breastfeeding women be offered treatment, with praziquantel, either individually or during treatment campaigns. In 2006, WHO also stated the need for randomized controlled trials to assess the safety and efficacy of such treatment. Some countries have yet to follow the recommendation on treatment and many programme managers and pregnant women in other countries remain reluctant to follow the recommended approach. Since 2006, two randomized controlled trials on the use of praziquantel during pregnancy have been conducted: one against S. mansoni in Uganda and the other against S. japonicum in the Philippines. In these trials, praziquantel treatment of pregnant women had no significant effect on birth weight, appeared safe and caused minimal side-effects that were similar to those seen in treated non-pregnant subjects. Having summarized the encouraging data, on efficacy, pharmacokinetics and safety, from these two trials and reviewed the safety data from non-interventional human studies, we recommend that all countries include pregnant women in praziquantel treatment campaigns. We identify the barriers to the treatment of pregnant women, in countries that already include such women in individual treatments and mass drug administration campaigns, and discuss ways to address these barriers

From pediatric covariate model to semiphysiological function for maturation: part I-extrapolation of a covariate model from morphine to Zidovudine

Pharmacolog

HIV-1 Drug Resistance Emergence among Breastfeeding Infants Born to HIV-Infected Mothers during a Single-Arm Trial of Triple-Antiretroviral Prophylaxis for Prevention of Mother-To-Child Transmission: A Secondary Analysis

Analysis of a substudy of the Kisumu breastfeeding trial by Clement Zeh and colleagues reveals the emergence of HIV drug resistance in HIV-positive infants born to HIV-infected mothers treated with antiretroviral drugs

From pediatric covariate model to semiphysiological function for maturation: Part I-extrapolation of a covariate model from morphine to zidovudine

New approaches to expedite the development of safe and effective pediatric dosing regimens and first-in-child doses are urgently needed. Model-based approaches require quantitative functions on the maturation of different metabolic pathways. In this study, we directly incorporated a pediatric covariate model for the glucuronidation of morphine into a pediatric population model for zidovudine glucuronidation. This model was compared with a reference model that gave the statistically best description of the data. Both models had adequate goodness-of-fit plots and normalized prediction distribution errors (NPDE), similar population clearance values for each individual, and a Δobjective function value of 13 points (Δ2df). This supports our hypothesis that pediatric pharmacokinetic covariate models contain system-specific information that can be used as semiphysiological functions in pediatric population models. Further research should explore the validity of the semiphysiological function for other UDP-glucuronosyltransferase 2B7 substrates and patient populations and reveal how this function can be used for pediatric physiologically based pharmacokinetic models

Toward Earlier Inclusion of Pregnant and Postpartum Women in Tuberculosis Drug Trials: Consensus Statements From an International Expert Panel

Tuberculosis is a major cause of morbidity and mortality in women of childbearing age (15–44 years). Despite increased tuberculosis risk during pregnancy, optimal clinical treatment remains unclear: safety, tolerability, and pharmacokinetic data for many tuberculosis drugs are lacking, and trials of promising new tuberculosis drugs exclude pregnant women. To advance inclusion of pregnant and postpartum women in tuberculosis drug trials, the US National Institutes of Health convened an international expert panel. Discussions generated consensus statements (>75% agreement among panelists) identifying high-priority research areas during pregnancy, including: (1) preventing progression of latent tuberculosis infection, especially in women coinfected with human immunodeficiency virus; (2) evaluating new agents/regimens for treatment of multidrug-resistant tuberculosis; and (3) evaluating safety, tolerability and pharmacokinetics of tuberculosis drugs already in use during pregnancy and postpartum. Incorporating pregnant women into clinical trials would extend evidence-based tuberculosis prevention and treatment standards to this special population

Combined evaluation of sexually transmitted infections in HIV-infected pregnant women and infant HIV transmission

Background Sexually transmitted infections (STIs) including Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Treponema pallidum (TP), and cytomegalovirus (CMV) may lead to adverse pregnancy and infant outcomes. The role of combined maternal STIs in HIV mother-to-child transmission (MTCT) was evaluated in mother-infant pairs from NICHD HPTN 040. Methodology Urine samples from HIV-infected pregnant women during labor were tested by polymerase chain reaction (PCR) for CT, NG, and CMV. Infant HIV infection was determined by serial HIV DNA PCR testing. Maternal syphilis was tested by VDRL and confirmatory treponemal antibodies. Results A total of 899 mother-infant pairs were evaluated. Over 30% had at least one of the following infections (TP, CT, NG, and/or CMV) detected at the time of delivery. High rates of TP (8.7%), CT (17.8%), NG (4%), and CMV (6.3%) were observed. HIV MTCT was 9.1% (n = 82 infants). HIV MTCT was 12.5%, 10.3%, 11.1%, and 26.3% among infants born to women with CT, TP, NG or CMV respectively. Forty-two percent of HIV-infected infants were born to women with at least one of these 4 infections. Women with these infections were nearly twice as likely to have an HIV-infected infant (aOR 1.9, 95% CI 1.1-3.0), particularly those with 2 STIs (aOR 3.4, 95% CI 1.5-7.7). Individually, maternal CMV (aOR 4.4 1.5-13.0) and infant congenital CMV (OR 4.1, 95% CI 2.2-7.8) but not other STIs (TP, CT, or NG) were associated with an increased risk of HIV MTCT. Conclusion HIV-infected pregnant women identified during labor are at high risk for STIs. Co-infection with STIs including CMV nearly doubles HIV MTCT risk. CMV infection appears to confer the largest risk of HIV MTCT.NICHD (NICHD)(Brazilian AIDS Prevention Trials International Network), NIAID/ NIHNational Institute of Allergy and Infectious Diseases (NIAID)Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)National Institute of Mental Health (NIMH)Boehringer Ingelheim Pharmaceuticals Inc. (BIPI)GlaxoSmithKline, on behalf of ViiV HealthcareCepheid for the testing of CTNG in a prior HPTNUCLA Children's Discovery and Innovation Institute (CDI) through the Harry Winston Fellowship AwardUCLA AIDS InstituteUCLA Center for AIDS Research (CFAR) NIH/ NIAIDUCLA Pediatric AIDS Coalition, and WestatNIH/NICHDDavid Geffen UCLA Sch Med, Los Angeles, CA 90095 USAWestat Corp, Rockville, MD USAFundacao Oswaldo Cruz FIOCRUZ, Rio De Janeiro, RJ, BrazilUS Dept State, Off Global AIDS Coordinator, Washington, DC 20520 USAElizabeth Glaser Pediat AIDS Fdn, Washington, DC USAHosp Geral Nova Iguacu, Nova Iguacu, RJ, BrazilHosp Fed Servidores Estado, Rio De Janeiro, RJ, BrazilUniv Witwatersrand, SAMRC & Perinatal HIV Res Unit, Johannesburg, South AfricaStellenbosch Univ, Tygerberg Hosp, Cape Town, South AfricaHosp Conceicao, Porto Alegre, RS, BrazilHosp Femina, Porto Alegre, RS, BrazilIrmandade Santa Casa Misericordia Porto Alegre, Porto Alegre, RS, BrazilUniv Fed Minas Gerais, Belo Horizonte, MG, BrazilUniv Sao Paulo, Ribeirao Preto Med Sch, Sao Paulo, BrazilFdn Maternal & Infant Hlth FUNDASAMIN, Buenos Aires, DF, ArgentinaUniv Fed Sao Paulo, Escola Paulista Med, Sao Paulo, SP, BrazilEunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USAUCLA, Fielding Sch Publ Hlth, Los Angeles, CA USAUCSD Sch Med, La Jolla, CA USAUC Davis Sch Med, Davis, CA USABoston Univ, Sch Med, Boston, MA 02118 USAUniv Fed Sao Paulo, Escola Paulista Med, Sao Paulo, SP, BrazilNICHD (NICHD): HHSN267200800001C, N01-HD-8-0001Brazilian AIDS Prevention Trials International Network: NIAID/ NIH [U01 AI047986National Institute of Allergy and Infectious Diseases (NIAID): U01 AI068632, UM1AI068632, UM1AI068616, UM1AI106716NIMH: AI068632NG in a prior HPTN :040UCLA Center for AIDS Research (CFAR) NIH/ NIAID: AI02869, AI28697NIH/NICHD: HHSN275201300003CWeb of Scienc

Non-adherence to the single dose nevirapine regimen for the prevention of mother-to-child transmission of HIV in Bindura town, Zimbabwe: a cross-sectional analytic study

<p>Abstract</p> <p>Background</p> <p>The Prevention of Mother to Child Transmission of HIV (PMTCT) programme was introduced at Bindura Hospital in 2003. Seven additional satellite PMTCT clinics were set up in the district to increase service coverage but uptake of PMTCT interventions remained unsatisfactory. In this study we determined the prevalence of and factors associated with non-adherence to the single dose nevirapine (SD-NVP) regimen for PMTCT in Bindura town.</p> <p>Methods</p> <p>An analytic cross-sectional study was conducted in four health institutions in Bindura town. Participants were mother-baby pairs on the PMTCT programme attending routine six weeks post natal visits in the participating health institutions from March to July 2008. We interviewed 212 mothers using a structured questionnaire.</p> <p>Results</p> <p>The non-adherence rate to the maternal nevirapine dose was 30.7%, while non-adherence to the newborn nevirapine dose was 26.9%. The combined mother-baby pair nevirapine non-adherence was 42.9%. Non-adherence to the maternal dose of nevirapine was associated with lack of maternal secondary education (POR = 2.38; 95%CI: 1.05-3.39) and multi-parity (POR = 2.66; 95%CI: 1.05-6.72), while previous maternal exposure to the PMTCT programme (POR = 0.22; 95%CI: 0.08-0.57) and giving the mother a NVP tablet to take home during antenatal care (POR = 0.03; 95%CI: 0.01-0.09) were associated with improved maternal adherence to nevirapine. Non-adherence to the infant dose of nevirapine was associated with maternal non-disclosure of HIV results to sexual partner (POR = 2.75; 95%CI: 1.04-7.32) and home deliveries (POR = 48.76; 95%CI: 17.51-135.82).</p> <p>Conclusions</p> <p>Non-adherence to nevirapine prophylaxis for PMTCT was high in Bindura. Ensuring institutional deliveries, encouraging self-disclosure of HIV results by the mothers to their partners and giving HIV positive mothers nevirapine doses to take home early in pregnancy all play significant roles in improving adherence to PMTCT prophylaxis.</p

Prioritising the most needed paediatric antiretroviral formulations: the PADO4 list

Despite considerable progress in paediatric HIV treatment and timely revision of global policies recommending the use of more effective and tolerable antiretroviral regimens, optimal antiretroviral formulations for infants, children, and adolescents remain limited. The Paediatric Antiretroviral Drug Optimization group reviews medium-term and long-term priorities for antiretroviral drug development to guide industry and other stakeholders on formulations most needed for low-income and middle-income countries. The group convened in December, 2018, to assess progress since the previous meeting and update the list of priority formulations. Issues relating to drug optimisation for neonatal prophylaxis and paediatric treatment, and those relating to the investigation of novel antiretrovirals in adolescents and pregnant and lactating women were also discussed. Continued focus on identifying, prioritising, and providing access to optimal antiretroviral formulations suitable for infants, children, and adolescents is key to ensuring that global HIV treatment targets can be met

Population Pharmacokinetics of Praziquantel in Pregnant and Lactating Filipino Women Infected with Schistosoma japonicum.

An estimated 40 million women of reproductive age are infected with one of three species of the waterborne parasite Schistosoma spp. Treatment with praziquantel (PZQ) via mass drug administration (MDA) campaigns is the mainstay of schistosomiasis control for populations living in areas of endemicity. The World Health Organization recommends that pregnant and lactating women be included in schistosomiasis MDA programs, and several recent studies have evaluated the safety and efficacy of PZQ use during pregnancy. To date, there are no data describing PZQ pharmacokinetics (PK) during pregnancy or among lactating postpartum women. As part of a randomized controlled trial investigating the safety and efficacy of PZQ during human pregnancy, we examined the PK of this therapeutic drug among three distinct cohorts of women infected with S. japonicum in Leyte, Philippines. Specifically, we studied the PK properties of PZQ among early- and late-gestation pregnant women (n = 15 each) and lactating postpartum women (n = 15) with schistosomiasis. We found that women in early pregnancy had increased apparent clearance and lower area-under-the-curve (AUC0-24) values that may be related to physiological changes in drug clearance and/or changes in oral bioavailability. There was no relationship between body weight and apparent clearance. The mean ± standard deviation partition ratio of plasma to breast milk was 0.36. ± 0.13. The estimated median infant PZQ daily dose would be 0.037 mg/kg of body weight ingested from breast milk, which is significantly lower than the dosage required for antischistosomal activity and not known to be harmful to the infant. Our PK data do not support the suggestion to delay breastfeeding 72 h after taking PZQ. Results can help inform future drug efficacy studies in pregnant and lactating women with schistosomiasis