Intrapartum transmission after mucosal exposure to HIV was not observed with single-dose nevirapine for mother and child

BACKGROUND: Intrapartum transmission of HIV has been reported to be associated with HIV in oropharyngeal secretions (OPSs) of the child. In this study, we analyze the frequency of intrapartum transmission after mucosal exposure to HIV after administration of single-dose nevirapine. METHODS: Eighty mothers and their children participating in a prevention of mother-to-child transmission of HIV program in Uganda who took a single dose of nevirapine according to the HIVNET012 protocol participated in the study. HIV-1 was quantified by polymerase chain reaction (PCR) in the mothers' and children's plasma, in cervicovaginal secretions (CVSs), and in the children's OPSs. Intrapartum transmission was defined as a positive HIV-1 RNA PCR result at week 1 or 2 after birth and a previously negative PCR result. RESULTS: Ninety-seven percent of children had detectable nevirapine in their OPS (median = 592 ng/mL). Fifty-seven (81%) children had HIV-negative OPSs, and 13 (19%) had HIV-positive OPSs. All children of mothers with HIV-negative CVSs had HIV-negative OPSs. HIV-1 levels of OPSs and CVSs correlated (r = 0.33, P = 0.027). None of the babies with detectable HIV-1 in the OPSs became infected by means of intrapartum transmission. CONCLUSION: Intrapartum HIV infection was not observed after mucosal exposure to HIV-1 after administration of a single dose of nevirapine to the mother and child.     

Likely stakeholders in the prevention of mother to child transmission of HIV/AIDS in Blantyre, Malawi

Objectives

To determine potential partners for pregnant women in the prevention of mother to child transmission of HIV and to determine pregnant women''s perceptions towards selected potential HIV prevention efforts

Design

Cross sectional, questionnaire-administered study

Setting

Ante-natal clinics of eleven public health centers and the major referral and university teaching hospital of Queen Elizabeth Central Hospital (QECH) in Blantyre, Malawi

Subjects

A total of 321 pregnant women attending ante-natal clinics

Results

Antenatal women in Blantyre, Malawi obtain health information on HIV/AIDS from the radio (96.3%), health workers (82.2%), religious gatherings (66.7%), friends (54.8%) and newspapers (39.3%). The majority intend to be accompanied by own mother and sister for delivery (52.4% and 15.4% respectively). Almost all (99%) planned to breast feed with 91.8% reporting an intended breastfeeding period of at least 6 months. About 97% of married women reported desire to tell spouse in case of HIV sero-positive results while only 65.1% had ever discussed about HIV with spouse, and only 5.2% had ever attended antenatal clinic with spouse. Whether woman had ever discussed about HIV/AIDS with spouse or not did not influence desire to disclose HIV status to spouse.

Conclusion

Close relatives, spouse and the media are important stakeholders in the health of pregnant women. Programs aimed at prevention of mother to child transmission of HIV should give serious consideration to these partners.     

Emergence of HIV-1 drug-resistant variants in women following antiretroviral prophylaxis for the prevention of mother to child transmission

Purpose: Emergence of drug resistance following HIV prophylaxis has an important impact on ART program. Objective: To investigate the emergence of drug resistance in HIV-1 infected pregnant women. Materials and Methods: Fifty-three HIV-1 infected pregnant women who had received 4-12 weeks of antenatal AZT followed by Nevirapine during delivery and Combivir [AZT + 3TC] for 1 week postpartum (group-1, n = 48) or who come at the time of delivery and received Nevirapine followed by Combivir for 1 week (group-2, n = 5) were recruited. Samples were collected prior to the start of the prophylaxis and 5-8 weeks postpartum. In addition, a third sample was collected between 26-65 weeks postpartum from 7 women. Amplification of HIV-1 pol gene and drug resistance analysis was done. Result: Two (3.8%) women in group-1 showed transmitted drug resistance and they continued to show this even at 6 weeks postpartum. One (2%) woman from group-1 showed a mutation after 6-8 weeks of prophylaxis. Among the samples collected between 26-65 weeks postpartum, 3/7 (43%) showed mutations and all these women belong to group-1. Women belonging to group-2 didn’t show mutation prior to or following prophylaxis. Conclusion: In contrast to the available data among pregnant women with ART prophylaxis, our data showed reduced frequency of mutations following 5-8 weeks of postpartum but an emergence of mutation later (26-65 weeks). The addition of Combivir with the single dose Nevirapine during delivery and the early stage of the disease with higher CD4 counts could be the reasons for this.     

Missed opportunities for diabetes prevention: post-pregnancy follow-up of women with gestational diabetes mellitus in England

Background

Women with gestational diabetes mellitus (GDM) should be followed-up to exclude ongoing diabetes and for prevention of type 2 diabetes. The National Institute for Health and Clinical Excellence (NICE) diabetes in pregnancy guideline recommends checking fasting plasma glucose (FPG) at 6 weeks postpartum (short term), and annually thereafter (long term).

Aim

To examine the reported practice regarding GDM follow-up.

Design and setting

Nationwide postal survey in England 2008-2009.

Method

Questionnaires were distributed to a consultant diabetologist and obstetrician in all maternity units, and to a random sample of general practices (approximately 1 in 5).

Results

Response rates were: 60% (915/1532) GPs, 93% (342/368) specialists; 80% of GPs and 98% of specialists reported women with GDM had short-term follow-up. More GPs (55%) than specialists (13%) used a FPG test to exclude ongoing diabetes; 26% of GPs versus 89% of specialists thought the hospital was responsible for ordering the test. Twenty per cent of GPs had difficulty in discovering women had been diagnosed with GDM in secondary care. Seventy-three per cent of specialists recommended long-term follow-up; only 39% of GPs recalled women with GDM for this. A minority of GPs and specialists had joint follow-up protocols

Conclusion

Follow-up of GDM in England diverged from national guidance. Despite consensus that short-term follow-up occurred, primary and secondary care doctors disagreed about the tests and responsibility for follow-up. There was lack of long-term follow-up. Agreement about the NICE guideline, its promotion and effective implementation by primary and secondary care, and the systematic recall of women with GDM for long-term follow-up is required.     

Perspectives of older people engaging in nurse-led cardiovascular prevention programmes: a qualitative study in primary care in the Netherlands

BackgroundCardiovascular prevention programmes are increasingly being offered to older people. To achieve the proposed benefits, adherence is crucial. Understanding the reasons for adherence and non-adherence can improve preventive care.AimTo gain insight into what motivates older people living in the community to partake in a cardiovascular prevention programme, and reasons for subsequent continuation or withdrawal.MethodSemi-structured interviews were conducted with a purposive sample of 15 participants (aged 76–82 years). Interviews were audiorecorded and analysed by two independent researchers using a thematic approach. Participants were asked about their motivation for participating in the programme, along with the facilitators and barriers to continue doing so.ResultsResponders reported that regular check-ups offered a feeling of safety, control, or being looked after, and were an important motivator for participation. For successful continuation, a personal relationship with the nurse and a coaching approach were both essential; the lack of these, along with frequent changes of nursing staff, were considered to be barriers. Participants considered general preventive advice unnecessary or patronising, but practical support was appreciated.ConclusionTo successfully engage older people in long-term, preventive consultations, the approach of the healthcare provider is crucial. Key elements are to offer regular check-ups, use a coaching approach and to build a personal relationship with the patient.     

Persistence of nevirapine exposure during the postpartum period after intrapartum single-dose nevirapine in addition to zidovudine prophylaxis for the prevention of mother-to-child transmission of HIV-1

OBJECTIVE: To determine nevirapine (NVP) plasma levels during the postpartum period after a single intrapartum NVP dose for the prevention of mother-to-child transmission. METHODS: Plasma samples at delivery and during days 8 to 45 postpartum were obtained from HIV-infected Thai women who received an intrapartum NVP dose in the Perinatal HIV Prevention Clinical Trial-2 (PHPT-2) for the prevention of perinatal HIV transmission. These data were combined with NVP concentration data from 2 phase 1 studies of NVP for a population analysis. RESULTS: The median NVP level fell to 68 ng/mL (range: <50-228, n = 43) 8 to 14 days after dosing and to 51 ng/mL (range: <50-166, n = 25) between 15 and 21 days. During the second and third weeks postpartum, NVP levels were below the limit of quantitation in 23% and 44% of samples, respectively. Between 21 and 45 days, no sample had a quantifiable NVP concentration. A simulation derived from the population analysis predicts that NVP concentration falls to less than 10 ng/mL in 5% of women by 11 days, in 50% of women by 17.5 days, and in 95% of women by 28 days. CONCLUSIONS: Significant NVP concentrations remained for up to 20 days in these Thai women. To ensure that coverage is maintained until NVP concentrations fall to nonsuppressive levels, 1 month of additional antiretroviral treatment after delivery should be considered to prevent the emergence of resistant viruses.     

A cluster randomized controlled trial of lay health worker support for prevention of mother to child transmission of HIV (PMTCT) in South Africa

Background

We evaluate the impact of clinic-based PMTCT community support by trained lay health workers in addition to standard clinical care on PMTCT infant outcomes.

Methods

In a cluster randomized controlled trial, twelve community health centers (CHCs) in Mpumalanga Province, South Africa, were randomized to have pregnant women living with HIV receive either: a standard care (SC) condition plus time-equivalent attention-control on disease prevention (SC; 6 CHCs; n? = 357), or an enhanced intervention (EI) condition of SC PMTCT plus the “Protect Your Family” intervention (EI; 6 CHCs; n? = 342). HIV-infected pregnant women in the SC attended four antenatal and two postnatal video sessions and those in the EI, four antenatal and two postnatal PMTCT plus “Protect Your Family” sessions led by trained lay health workers. Maternal PMTCT and HIV knowledge were assessed. Infant HIV status at 6 weeks postnatal was drawn from clinic PCR records; at 12 months, HIV status was assessed by study administered DNA PCR. Maternal adherence was assessed by dried blood spot at 32 weeks, and infant adherence was assessed by maternal report at 6 weeks. The impact of the EI was ascertained on primary outcomes (infant HIV status at 6 weeks and 12 months and ART adherence for mothers and infants), and secondary outcomes (HIV and PMTCT knowledge and HIV transmission related behaviours). A series of logistic regression and latent growth curve models were developed to test the impact of the intervention on study outcomes.

Results

In all, 699 women living with HIV were recruited during pregnancy (8–24 weeks), and assessments were completed at baseline, at 32 weeks pregnant (61.7%), and at 6 weeks (47.6%), 6 months (50.6%) and 12 months (59.5%) postnatally. Infants were tested for HIV at 6 weeks and 12 months, 73.5% living infants were tested at 6 weeks and 56.7% at 12 months. There were no significant differences between SC and EI on infant HIV status at 6 weeks and at 12 months, and no differences in maternal adherence at 32 weeks, reported infant adherence at 6 weeks, or PMTCT and HIV knowledge by study condition over time.

Conclusion

The enhanced intervention administered by trained lay health workers did not have any salutary impact on HIV infant status, ART adherence, HIV and PMTCT knowledge. Trial registration clinicaltrials.gov: number NCT02085356

     

Osmotic-hypertensive opening of the blood-brain barrier in rats does not necessarily provide access for potassium to cerebral interstitial fluid

The blood-brain barrier was breached in urethane anaesthetized rats by infusing hypertonic mannitol or NaCl at high rate under high pressure into one internal carotid artery. Opening of the blood-brain barrier was confirmed by staining of the perfused hemisphere by intravenous Evans Blue dye. Orthodromic-evoked potentials in CA1 region of hippocampus were transiently extinguished, and the extracellular potential in hippocampus and neocortex shifted in the positive direction during hypertonic infusion. After the hypertonic infusion, the permeability of the barrier to K+ was tested by infusing into the internal carotid artery artificial cerebrospinal fluid in which K+ replaced most of the Na+, raising the concentration of K+ in the blood plasma in the superior sagittal sinus to 13-17 mM. Extracellular potential and interstitial potassium concentration ([K+]O) in hippocampus and neocortex, and evoked potentials in hippocampus, remained unchanged during prolonged infusion of high K+, unless and until spreading depression occurred. After a wave of spreading depression, [K+]O returned to baseline in spite of continued high K+ infusion. We conclude that [K+]O in brain tissue is effectively regulated even when colloidal dye can penetrate the blood-brain barrier, but excess K+ may have entered the cerebral interstitial space in scattered patches outside the region sensed by the ion-selective microelectrodes, triggering spreading depression.     

Effectiveness of nevirapine and zidovudine in a pilot program for the prevention of mother-to-child transmission of HIV-1 in Uganda

Background

Single dose nevirapine and a short course of zidovudine (AZT) are now administered in most hospitals in Uganda to prevent mother-to-child transmission (MTCT) of HIV. The effectiveness of these antiretroviral (ARV) regimens has been shown in the clinical trials but has not been demonstrated outside the clinical trials setting in this country.

Objectives

The study evaluated the effectiveness of short course ARV regimens in a pilot program to prevent mother-to-child transmission of HIV and determined the risk factors for perinatal transmission.

Methods

Cross-sectional study design was used to compare perinatal transmission rates of HIV in two sets of mothers: ARV-treated mothers and ARV-untreated mothers.

Results

109 treated and 90 naïve mother-infant pairs were recruited. HIV transmission rates were similar in the nevirapine (10/61) and AZT (8/48) groups (16.4% vs. 16.7%) respectively but higher in the naïve group (43/90 48%, p= 0.0001). ARV therapy offers a protective effect against MTCT of HIV (Adjusted Odds Ratio 0.22 95%CI 0.09, 0.54) but mothers in Stage 1 and 2 of disease were more likely to benefit from this intervention than mothers in Stage 3 and 4.

Conclusion

In this community-based observational study, ARV reduces the risk of perinatal transmission of HIV but does not eliminate the risk completely. Early screening of asymptomatic pregnant women will identify a group of mothers more likely to benefit from the intervention.     

Using new media to build social capital for health: a qualitative process evaluation study of participation in the CityNet project

The present article presents an exploratory qualitative process evaluation study of 'Ambassador' participation in CityNet, an innovative information-communication technology-based (ICT) project that aims to build aspects of social capital and improve access to information and services among disadvantaged groups in Nottingham, UK. A purposive sample of 40 'Ambassadors' interviewees was gathered in three waves of data collection. The two emergent analytic themes highlighted how improvements in confidence, self-esteem and social networks produced via participation were mitigated by structural problems in devolving power within the project. This illustrates how concepts of power are important for understanding the process of health promotion interventions using new media.     

Comparison of two strategies for administering nevirapine to prevent perinatal HIV transmission in high-prevalence,resource-poor settings

Universal nevirapine (NVP) therapy (provision of the drug without HIV testing) has been suggested as potentially superior to targeted NVP therapy (provision of the drug to seropositive patients identified through voluntary HIV counseling and testing [VCT]) for perinatal HIV prevention in low-resource, high-prevalence settings. The authors postulated that uptake (the proportion of women who accept the strategy when offered) may be higher for universal therapy, since it does not require a woman to learn her serostatus; they further postulated that adherence (the proportion of women who actually ingest the NVP tablet at labor onset) may be higher for targeted therapy, since knowledge of serostatus could motivate better adherence. Two clinics in Lusaka, Zambia were assigned to provide either the targeted or universal strategy. Halfway through the study period, the approach offered at each clinic was crossed over. Adherence was assessed by liquid chromatographic assay for NVP of cord blood. Regarding uptake, 1524 pregnant women were offered participation, and 1025 (67%) accepted. Of 694 women offered enrollment in the universal strategy, 496 (71%) accepted; of 830 women offered enrollment in the targeted strategy, 529 (64%) accepted (p <.01). Uptake was similar at both clinics for the universal strategy: 250 of 339 (74%) at clinic A and 246 of 355 (69%) at clinic B (p =.2), but differed significantly between clinics for the targeted strategy: 229 of 316 (72%) at clinic A and 300 of 514 (58%) at clinic B (RR, 1.51; 95% CI, 1.23, 1.86). Increased uptake correlated with having been offered the universal rather than the targeted strategy (AOR, 1.5; 95% CI, 1.1, 2.1), attendance at clinic A (AOR, 1.4; 95% CI, 1.01, 2.0), and maternal report of a prior fetal or infant death (AOR, 1.6; 95% CI, 1.1, 2.5). Regarding adherence, in the universal strategy, 40 of 103 women (39%) were nonadherent compared with 25 of 98 women (26%) in the targeted strategy (RR, 1.5; 95% CI, 1.004, 2.3). Failure to adhere correlated with participation in the universal strategy (AOR, 2.0; 95% CI, 1.04, 4.2) and illiteracy (AOR, 2.6; 95% CI, 1.2, 5.3). In high-prevalence settings with adequate VCT services, uptake of NVP using the universal or targeted approach appears comparable. However, the universal strategy may result in better uptake in clinics with less well-functioning VCT services (as with clinic B). Adherence to the single-dose NVP intervention was lower among women who did not learn their HIV status. Programs that seek to save the greatest possible number of infants from perinatal HIV acquisition should consider a combination approach, in which women who desire HIV testing can access NVP through a targeted strategy, and women who do not desire testing can access NVP through a universal strategy.     

Contributions of parental alcoholism, prenatal substance exposure, and genetic transmission to child ADHD risk: a female twin study

BACKGROUND: Genetic influences have been shown to play a major role in determining the risk of attention-deficit hyperactivity disorder (ADHD). In addition, prenatal exposure to nicotine and/or alcohol has also been suggested to increase risk of the disorder. Little attention, however, has been directed to investigating the roles of genetic transmission and prenatal exposure simultaneously. METHOD: Diagnostic telephone interview data from parents of Missouri adolescent female twin pairs born during 1975-1985 were analyzed. Logistic regression models were fitted to interview data from a total of 1936 twin pairs (1091 MZ and 845 DZ pairs) to determine the relative contributions of parental smoking and drinking behavior (both during and outside of pregnancy) as risk factors for DSM-IV ADHD. Structural equation models were fitted to determine the extent of residual genetic and environmental influences on ADHD risk while controlling for effects of prenatal and parental predictors on risk. RESULTS: ADHD was more likely to be diagnosed in girls whose mothers or fathers were alcohol dependent, whose mothers reported heavy alcohol use during pregnancy, and in those with low birth weight. Controlling for other risk factors, risk was not significantly increased in those whose mothers smoked during pregnancy. After allowing for effects of prenatal and childhood predictors, 86% of the residual variance in ADHD risk was attributable to genetic effects and 14% to non-shared environmental influences. CONCLUSIONS: Prenatal and parental risk factors may not be important mediators of influences on risk with much of the association between these variables and ADHD appearing to be indirect.     

Homozygosity for a CHEK2*1100delC mutation identified in familial colorectal cancer does not lead to a severe clinical phenotype

It has recently been suggested that the frequency of the germline CHEK2*1100delC mutation is higher among breast cancer families with colorectal cancer, although the mutation does not seem to be significantly associated with familial colorectal cancer. Five hundred and sixty-four familial colorectal tumours were studied for expression of CHEK2 using tissue microarrays and an antibody against the NH2-terminal SQ regulatory domain of the CHEK2 protein. Normal colonic tissue from patients whose tumours showed loss of CHEK2 expression was investigated further using fragment and sequence analysis for the presence of a CHEK2*1100delC mutation and five other (R117G, R137Q, R145W, I157T, and R180H) known germline variants in CHEK2. Twenty-nine tumours demonstrated loss of expression for CHEK2. Analysis of matched normal colonic tissue from these patients revealed germline CHEK2*1100delC mutation in three cases. In two of these, the mutation was heterozygous but, interestingly, the third patient proved to be homozygous for the deletion, using six different primer pair combinations. None of the other tested germline variants were identified. No CHEK2*1100delC mutations were found in patients whose tumours stained positive. Homozygosity for the CHEK2*1100delC mutation appears not to be lethal in humans. No severe clinical phenotype was apparent, although the patient died from colonic carcinoma at age 52 years. This observation is in line with recent knockout mouse models, although in the latter, cellular defects in apoptosis and increased resistance to irradiation seem to exist. It is also concluded that CHEK2 protein abrogation is not caused by the CHEK2 germline variants R117G, R137Q, R145W, I157T, and R180H in familial colorectal cancer.     

Leveraging progress in prevention of mother-to-child transmission of HIV for improved maternal, neonatal, and child health services

Finding ways to leverage the substantial investment in prevention of mother-to-child transmission of HIV to address other maternal, neonatal, and child health threats is a priority. With increased emphasis on health systems strengthening and the integration of disease-specific initiatives within primary care, we propose three areas for consideration: 1) increased integration of service delivery; 2) adaptation of successful implementation models; and 3) a reconceptualization of the care continuums for prevention of mother-to-child HIV transmission and maternal, neonatal, and child health.