Adherence to antiretroviral therapy during pregnancy and the first year postpartum among HIV-positive women in Ukraine.

Poor adherence to antiretroviral therapy (ART) is associated with HIV disease progression and, during pregnancy, increased mother-to-child transmission risk. In Ukraine, access to combination ART is expanding but data on adherence are scarce

Effectiveness and safety of dolutegravir and raltegravir for treating children and adolescents living with HIV: a systematic review

INTRODUCTION: Globally about 1.7 million children were living with HIV in 2020. Two integrase strand transfer inhibitors, dolutegravir and raltegravir, are increasingly used in children. We conducted a systematic review to assess the effectiveness and safety of dolutegravir and raltegravir in children and adolescents living with HIV, aged 0–19 years. METHODS: Sources included MEDLINE, Embase, the Cochrane Library, clinical trial registries, abstracts from key conferences and reference list searching. Observational studies and clinical trials published January 2009–March 2021 were eligible. Outcomes included efficacy/effectiveness (CD4 counts and viral load) and/or safety outcomes (mortality, grade 3/4 adverse events and treatment discontinuation) through 6 months or more post-treatment initiation. Risk of bias was assessed using previously published tools appropriate for the study design. Narrative syntheses were conducted. RESULTS AND DISCUSSION: In total, 3626 abstracts and 371 papers were screened. Eleven studies, including 2330 children/adolescents, reported data on dolutegravir: one randomized controlled trial (RCT; low risk of bias), one single-arm trial (unclear risk of bias) and nine cohort studies (three low risk of bias, two unclear risk and four high risk). Ten studies, including 649 children/adolescents receiving raltegravir, were identified: one RCT (low risk of bias), one single-arm trial (low risk of bias) and eight cohort studies (four low risk of bias, three unclear risk and one high risk). Viral suppression levels in children/adolescents at 12 months were high (>70%) in most studies assessing dolutegravir (mostly second- or subsequent-line, or mixed treatment lines), and varied from 42% (5/12) to 83% (44/53) at 12 months in studies assessing raltegravir (mostly second- or subsequent-line). Across all studies assessing dolutegravir or raltegravir, grade 3/4 adverse events (clinical and/or laboratory) were reported in 0–50% of subjects, few resulted in discontinuation, few were drug related and no deaths were attributed to either drug. CONCLUSIONS: These reassuring findings suggest that dolutegravir and raltegravir are effective and safe as preferred regimens in children and adolescents living with HIV. With the rollout of dolutegravir in paediatric populations already underway, it is critical that data are collected on safety and effectiveness in infants, children and adolescents, including on longer-term outcomes, such as weight and metabolic changes

Using a runway paradigm to assess the relative strength of rats' motivations for enrichment objects

Laboratory animals should be provided with enrichment objects in their cages; however, it is first necessary to test whether the proposed enrichment objects provide benefits that increase the animals’ welfare. The two main paradigms currently used to assess proposed enrichment objects are the choice test, which is limited to determining relative frequency of choice, and consumer demand studies, which can indicate the strength of a preference but are complex to design. Here, we propose a third methodology: a runway paradigm, which can be used to assess the strength of an animal’s motivation for enrichment objects, is simpler to use than consumer demand studies, and is faster to complete than typical choice tests. Time spent with objects in a standard choice test was used to rank several enrichment objects in order to compare with the ranking found in our runway paradigm. The rats ran significantly more times, ran faster, and interacted longer with objects with which they had previously spent the most time. It was concluded that this simple methodology is suitable for measuring rats’ motivation to reach enrichment objects. This can be used to assess the preference for different types of enrichment objects or to measure reward system processes

Long-term Outcomes of Congenital Cytomegalovirus Infection in Sweden and the United Kingdom

Background. Congenital cytomegalovirus (CMV) is an important cause of neurological problems, particularly sensorineural hearing loss, but data on long-term sequelae and the impact of nonprimary maternal infection are limited. We report updated findings on childhood outcomes from 2 large prospective studies. Methods. Pregnant women in Malmö, Sweden, and London, United Kingdom, were included between 1977 and 1986, and newborns were screened for CMV (virus culture of urine or saliva). Cases and matched controls underwent regular, detailed developmental assessments up to at least age 5 years. Results. One hundred seventy-six congenitally infected infants were identified among >50 000 screened (Malmö: 76 [4.6/1000 births]; London: 100 [3.2/1000 births]); 214 controls were selected. Symptoms were recorded in 11% of CMV-infected neonates (19/176) and were mostly mild; only 1 neonate had neurological symptoms. At follow-up, 7% of infants (11/154) were classified as having mild, 5% (7/154) moderate, and 6% (9/154) severe neurological sequelae. Four of 161 controls (2%) had mild impairment. Among children symptomatic at birth, 42% (8/19) had sequelae, versus 14% (19/135) of the asymptomatic infants (P = .006). All moderate/severe outcomes were identified by age 1; mild sequelae were first identified at age 2-5 years in 6 children, and age 6-7 years in 3. Among the 16 children with moderate/severe outcomes, 2 had mothers with confirmed and 7 with presumed nonprimary infection. Conclusions. Moderate or severe outcomes were reported in 11% of children with congenital CMV identified through population screening, all by 1 year; all impairment detected after this age was mild. Nonprimary infections contributed substantially to the burden of childhood congenital CMV disease

Using stable isotopes of hydrogen to quantify biogenic and thermogenic atmospheric methane sources: A case study from the Colorado Front Range

Global atmospheric concentrations of methane (CH4), a powerful greenhouse gas, are increasing, but because there are many natural and anthropogenic sources of CH4, it is difficult to assess which sources may be increasing in magnitude. Here we present a data set of δ2H-CH4 measurements of individual sources and air in the Colorado Front Range, USA. We show that δ2H-CH4, but not δ13C, signatures are consistent in air sampled downwind of landfills, cattle feedlots, and oil and gas wells in the region. Applying these source signatures to air in ground and aircraft samples indicates that at least 50% of CH4 emitted in the region is biogenic, perhaps because regulatory restrictions on leaking oil and natural gas wells are helping to reduce this source of CH4. Source apportionment tracers such as δ2H may help close the gap between CH4 observations and inventories, which may underestimate biogenic as well as thermogenic sources

Impact of a hospice rapid response service on preferred place of death, and costs

Background: Many people with a terminal illness would prefer to die at home. A new palliative rapid response service (RRS) provided by a large hospice provider in South East England was evaluated (2010) to provide evidence of impact on achieving preferred place of death and costs. The RRS was delivered by a team of trained health care assistants and available 24/7. The purpose of this study was to (i) compare the characteristics of RRS users and non-users, (ii) explore differences in the proportions of users and non-users dying in the place of their choice, (iii) monitor the whole system service utilisation of users and non-users, and compare costs. Methods: All hospice patients who died with a preferred place of death recorded during an 18 month period were included. Data (demographic, preferences for place of death) were obtained from hospice records. Dying in preferred place was modelled using stepwise logistic regression analysis. Service use data (period between referral to hospice and death) were obtained from general practitioners, community providers, hospitals, social services, hospice, and costs calculated using validated national tariffs. Results: Of 688 patients referred to the hospice when the RRS was operational, 247 (35.9 %) used it. Higher proportions of RRS users than non-users lived in their own homes with a co-resident carer (40.3 % vs. 23.7 %); more non-users lived alone or in residential care (58.8 % vs. 76.3 %). Chances of dying in the preferred place were enhanced 2.1 times by being a RRS user, compared to a non-user, and 1.5 times by having a co-resident carer, compared to living at home alone or in a care home. Total service costs did not differ between users and non-users, except when referred to hospice very close to death (users had higher costs). Conclusions: Use of the RRS was associated with increased likelihood of dying in the preferred place. The RRS is cost neutral

Cell-free (RNA) and cell-associated (DNA) HIV-1 and postnatal transmission through breastfeeding

<p>Introduction - Transmission through breastfeeding remains important for mother-to-child transmission (MTCT) in resource-limited settings. We quantify the relationship between cell-free (RNA) and cell-associated (DNA) shedding of HIV-1 virus in breastmilk and the risk of postnatal HIV-1 transmission in the first 6 months postpartum.</p> <p>Materials and Methods - Thirty-six HIV-positive mothers who transmitted HIV-1 by breastfeeding were matched to 36 non-transmitting HIV-1 infected mothers in a case-control study nested in a cohort of HIV-infected women. RNA and DNA were quantified in the same breastmilk sample taken at 6 weeks and 6 months. Cox regression analysis assessed the association between cell-free and cell-associated virus levels and risk of postnatal HIV-1 transmission.</p> <p>Results - There were higher median levels of cell-free than cell-associated HIV-1 virus (per ml) in breastmilk at 6 weeks and 6 months. Multivariably, adjusting for antenatal CD4 count and maternal plasma viral load, at 6 weeks, each 10-fold increase in cell-free or cell-associated levels (per ml) was significantly associated with HIV-1 transmission but stronger for cell-associated than cell-free levels [2.47 (95% CI 1.33–4.59) vs. aHR 1.52 (95% CI, 1.17–1.96), respectively]. At 6 months, cell-free and cell-associated levels (per ml) in breastmilk remained significantly associated with HIV-1 transmission but was stronger for cell-free than cell-associated levels [aHR 2.53 (95% CI 1.64–3.92) vs. 1.73 (95% CI 0.94–3.19), respectively].</p> <p>Conclusions - The findings suggest that cell-associated virus level (per ml) is more important for early postpartum HIV-1 transmission (at 6 weeks) than cell-free virus. As cell-associated virus levels have been consistently detected in breastmilk despite antiretroviral therapy, this highlights a potential challenge for resource-limited settings to achieve the UNAIDS goal for 2015 of eliminating vertical transmission. More studies would further knowledge on mechanisms of HIV-1 transmission and help develop more effective drugs during lactation.</p&gt

Insufficient antiretroviral therapy in pregnancy: missed opportunities for prevention of mother-to-child transmission of HIV in Europe

Background: Although mother-to-child transmission (MTCT) rates are at an all-time low in Western Europe, potentially preventable transmissions continue to occur. Duration of antenatal combination antiretroviral therapy (ART) is strongly associated with MTCT risk.Methods: Data on pregnant HIV-infected women enrolled in the Western and Central European sites of the European Collaborative Study between January 2000 and July 2009 were analysed. The proportion of women receiving no antenatal ART or 1-13 days of treatment was investigated, and associated factors explored using logistic regression models.Results: Of 2,148 women, 142 (7%) received no antenatal ART, decreasing from 8% in 2000-2003 to 5% in 2004-2009 (chi(2)=8.73; P= 14 days antenatal ART and 7.4% (10/136) among those with insufficient ART.Conclusions: Over the last 10 years, around one in 11 women in this study received insufficient antenatal ART, accounting for 40% of MTCTs. One-half of these women were diagnosed before conception, suggesting disengagement from care