Seroprevalence of CMV, HSV-2 and HBV among HIV-Infected Malawian Children: A Cross-sectional Survey

BACKGROUND: Little is known about viral co-infections in African human immunodeficiency virus (HIV)-infected children. We examined the prevalence of seromarkers for cytomegalovirus (CMV), herpes simplex virus type 2 (HSV-2) and hepatitis B virus (HBV) infections among HIV-infected, antiretroviral treatment (ART)-naive children in Lilongwe, Malawi. METHODS: Ninety-one serum samples were tested for IgG and IgM antibodies to CMV, and IgG antibodies to HSV-2 and hepatitis B surface antigen (HBsAg). Baseline demographic, clinical and laboratory data were abstracted from electronic records. RESULTS: CMV IgG was the most common positive result in all age groups (in 73% of children <1 year, and 100% in all other groups). Three patients were CMV IgM positive (3.3%), suggesting acute infection. HSV-2 IgG was positive in four patients (4.4%), and HBsAg in two (2.2%). CONCLUSIONS: CMV infection occurred early in life, and few children had specific signs of CMV infection at the time of ART initiation. Unrecognized HBV infection represents opportunities for testing and treatment of HIV/HBV co-infected children

Discontinuation of standard first-line antiretroviral therapy in a cohort of 1434 Malawian children

The standard first-line antiretroviral (ART) regimen in Malawi for both adults and children is a fixed-dose combination tablet containing stavudine (d4T), lamivudine (3TC) and nevirapine (NVP). This regimen has been shown to yield satisfactory virologic and immunologic outcomes in children. Published studies have described insights into discontinuation of first-line regimen and toxicities of ART in adults, but similar studies in paediatric populations are lacking

NIHAO IV: Core creation and destruction in dark matter density profiles across cosmic time

We use the NIHAO simulations to investigate the effects of baryonic physics on the time evolution of Dark Matter central density profiles. The sample is made of $\approx 70$ independent high resolution hydrodynamical simulations of galaxy formation and covers a wide mass range: 1e10< Mhalo <1e12, i.e., from dwarfs to L* . We confirm previous results on the dependence of the inner dark matter density slope, $\alpha$, on the ratio between stellar-to-halo mass. We show that this relation holds approximately at all redshifts (with an intrinsic scatter of ~0.18 in $\alpha$). This implies that in practically all haloes the shape of their inner density profile changes quite substantially over cosmic time, as they grow in stellar and total mass. Thus, depending on their final stellar-to-halo mass ratio, haloes can either form and keep a substantial density core (size~1 kpc), or form and then destroy the core and re-contract the halo, going back to a cuspy profile, which is even steeper than CDM predictions for massive galaxies (~1e12 Msun). We show that results from the NIHAO suite are in good agreement with recent observational measurements of $\alpha$ in dwarf galaxies. Overall our results suggest that the notion of a universal density profile for dark matter haloes is no longer valid in the presence of galaxy formation.Comment: 11 pages, 13 figures. Corrected typo in table 2 (middle row) with respect to the version published in MNRA

Hospital admissions from a pediatric HIV care and treatment program in Malawi

BACKGROUND: The scale up of pediatric antiretroviral treatment programs across Sub-Saharan Africa over the last decade has brought increasing numbers of children into HIV care. This patient population requiring life-long care presents new challenges in the outpatient and inpatient settings. We sought to describe hospitalizations from a large pediatric HIV treatment facility to better understand the scope of the situation and identify areas for improved care delivery. METHODS: We conducted a retrospective case series of all HIV-infected and exposed patients <18 years enrolled at Baylor College of Medicine Children’s Foundation Malawi, from October 2004-October 2010. Patients admitted to the hospital on or after the day of enrollment were included. Data were extracted from electronic clinic records. Analysis was done at the patient and admission level, as some patients had multiple admissions. RESULTS: Of 5062 patients enrolled in care, 877 (17.3 %) had 1137 admissions at median age 24 months (IQR: 12–62). 191 (21.8 %) patients had multiple admissions. A high proportion of admissions occurred in patients under two years (49.4 %), those within one month of clinic enrollment (32.9 %), those with severe immune suppression (44.0 %), and those not on ART (48.5 %). The frequency of primary admission diagnoses varied across these same variables, with malnutrition, pneumonia, and malaria being the most common. CONCLUSIONS: Illness requiring hospitalization is common in HIV-infected and exposed children and these results reinforce the need for a comprehensive care package with special attention to nutrition. Strengthened programs for malaria prevention and expanded access to pneumococcal vaccine are also needed. The high burden of admissions in children under 24 months and those newly enrolled in care suggests a need for continued improvement of early infant diagnosis and provider-initiated testing programs to link patients to care before they are symptomatic. Similarly, the high proportion of admissions in those not yet started on ART emphasizes the importance of rapid initiation of ART for eligible pediatric patients

SHCal13 Southern Hemisphere calibration, 0–50,000 years cal BP

The Southern Hemisphere SHCal04 radiocarbon calibration curve has been updated with the addition of new data sets extending measurements to 2145 cal BP and including the ANSTO Younger Dryas Huon pine data set. Outside the range of measured data, the curve is based upon the Northern Hemisphere data sets as presented in IntCal13, with an interhemispheric offset averaging 43 ± 23 yr modeled by an autoregressive process to represent the short-term correlations in the offset

Discordant retention of HIV-infected mothers and children: Evidence for a family-based approach from Southern Mozambique

It is often assumed that children and their caregivers either stay in care together or discontinue together, but data is lacking on caregiver-child retention concordance. We sought to describe the pattern of care among a cohort of human immunodeficiency virus (HIV) infected children and mothers enrolled in care at the Manhi\xC3\xA7a District Hospital (MDH).This was a retrospective review of routine HIV clinical data collected under a larger prospective HIV cohort study at MDH. Children enrolling HIV care from January 2013 to November 2016 were identified and matched to their mother's HIV clinical data. Retention in care for mothers and children was assessed at 24 months after the child's enrolment. Multinomial logistic regression was performed to evaluate variables associated with retention discordance.For the 351 mother-child pairs included in the study, only 39% of mothers had concordant care status at baseline (23% already active in care, 16% initiated care concurrently with their children). At 24-months follow up, a total of 108 (31%) mother-child pairs were concordantly retained in care, 88 (26%) pairs were concordantly lost to follow up (LTFU), and 149 (43%) had discordant retention. Pairs with concurrent registration had a higher probability of being concordantly retained in care. Children who presented with advanced clinical or immunological stage had increased probability of being concordantly LTFU.High rates of LTFU as well as high proportions of discordant retention among mother-child pairs were found. Prioritization of a family-based care model that has the potential to improve retention for children and caregivers is recommended.

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

Brief Report: Suboptimal Lopinavir Exposure in Infants on Rifampicin Treatment Receiving Double-dosed or Semisuperboosted Lopinavir/Ritonavir: Time for a Change.

BACKGROUND: Although super-boosted lopinavir/ritonavir (LPV/r; ratio 4:4 instead of 4:1) is recommended for infants living with HIV and receiving concomitant rifampicin, in clinical practice, many different LPV/r dosing strategies are applied due to poor availability of pediatric separate ritonavir formulations needed to superboost. We evaluated LPV pharmacokinetics in infants with HIV receiving LPV/r dosed according to local guidelines in various sub-Saharan African countries with or without rifampicin-based tuberculosis (TB) treatment. METHODS: This was a 2-arm pharmacokinetic substudy nested within the EMPIRICAL trial (#NCT03915366). Infants aged 1-12 months recruited into the main study were administered LPV/r according to local guidelines and drug availability either with or without rifampicin-based TB treatment; during rifampicin cotreatment, they received double-dosed (ratio 8:2) or semisuperboosted LPV/r (adding a ritonavir 100 mg crushed tablet to the evening LPV/r dose). Six blood samples were taken over 12 hours after intake of LPV/r. RESULTS: In total, 14/16 included infants had evaluable pharmacokinetic curves; 9/14 had rifampicin cotreatment (5 received double-dosed and 4 semisuperboosted LPV/r). The median (IQR) age was 6.4 months (5.4-9.8), weight 6.0 kg (5.2-6.8), and 10/14 were male. Of those receiving rifampicin, 6/9 infants (67%) had LPV Ctrough <1.0 mg/L compared with 1/5 (20%) in the control arm. LPV apparent oral clearance was 3.3-fold higher for infants receiving rifampicin. CONCLUSION: Double-dosed or semisuperboosted LPV/r for infants aged 1-12 months receiving rifampicin resulted in substantial proportions of subtherapeutic LPV levels. There is an urgent need for data on alternative antiretroviral regimens in infants with HIV/TB coinfection, including twice-daily dolutegravir

Discordant retention of HIV-infected mothers and children

It is often assumed that children and their caregivers either stay in care together or discontinue together, but data is lacking on caregiver-child retention concordance. We sought to describe the pattern of care among a cohort of human immunodeficiency virus (HIV) infected children and mothers enrolled in care at the Manhiça District Hospital (MDH).This was a retrospective review of routine HIV clinical data collected under a larger prospective HIV cohort study at MDH. Children enrolling HIV care from January 2013 to November 2016 were identified and matched to their mother's HIV clinical data. Retention in care for mothers and children was assessed at 24 months after the child's enrolment. Multinomial logistic regression was performed to evaluate variables associated with retention discordance.For the 351 mother-child pairs included in the study, only 39% of mothers had concordant care status at baseline (23% already active in care, 16% initiated care concurrently with their children). At 24-months follow up, a total of 108 (31%) mother-child pairs were concordantly retained in care, 88 (26%) pairs were concordantly lost to follow up (LTFU), and 149 (43%) had discordant retention. Pairs with concurrent registration had a higher probability of being concordantly retained in care. Children who presented with advanced clinical or immunological stage had increased probability of being concordantly LTFU.High rates of LTFU as well as high proportions of discordant retention among mother-child pairs were found. Prioritization of a family-based care model that has the potential to improve retention for children and caregivers is recommended