Measures of Longitudinal Immune Dysfunction and Risk of AIDS and Non-AIDS Defining Malignancies in Antiretroviral-Treated People With Human Immunodeficiency Virus.

BACKGROUND: Human immunodeficiency virus (HIV) infection leads to chronic immune activation/inflammation that can persist in virally suppressed persons on fully active antiretroviral therapy (ART) and increase risk of malignancies. The prognostic role of low CD4:CD8 ratio and elevated CD8 cell counts on the risk of cancer remains unclear. METHODS: We investigated the association of CD4:CD8 ratio on the hazard of non-AIDS defining malignancy (NADM), AIDS-defining malignancy (ADM) and most frequent group of cancers in ART-treated people with HIV (PWH) with a CD4 and CD8 cell counts and viral load measurements at baseline. We developed Cox proportional hazard models with adjustment for known confounders of cancer risk and time-dependent cumulative and lagged exposures of CD4:CD8 ratio to account for time-evolving risk factors and avoid reverse causality. RESULTS: CD4:CD8 ratios below 0.5, compared to above 1.0, were independently associated with a 12-month time-lagged higher risk of ADM and infection-related malignancies (adjusted hazard ratio 2.61 [95% confidence interval {CI }1.10-6.19] and 2.03 [95% CI 1.24-3.33], respectively). CD4 cell counts below 350 cells/µL were associated with an increased risk of NADMs and ADMs, as did infection, smoking, and body mass index-related malignancies. CONCLUSIONS: In ART-treated PWH low CD4:CD8 ratios were associated with ADM and infection-related cancers independently from CD4 and CD8 cell counts and may alert clinicians for cancer screening and prevention of NADM.

Association of age at antiretroviral therapy initiation with CD4 +  : CD8 + ratio recovery among virally suppressed people with HIV.

OBJECTIVE: To investigate the association of age at antiretroviral therapy (ART) initiation with CD4 +  : CD8 + T-cell ratio in virally suppressed people with HIV on long-term ART, and to characterize potential CD4 +  : CD8 + ratio recovery in this population by age. DESIGN: A longitudinal study of people attending an HIV clinic at the Royal Free Hospital NHS Trust, London, who initiated ART between 2001 and 2015, and achieved and maintained HIV-1 viral suppression (viral load <1,000 copies/ml). The association of age group at ART initiation with CD4 +  : CD8 + ratio at 5 and 10 years was assessed. METHODS: Multivariable linear regression was used to investigate the relationship between age at ART initiation and log CD4 +  : CD8 + ratio, adjusting for demographic factors (gender/HIV transmission route, ethnicity), baseline CD4 + count and calendar year. RESULTS: The sample included 1859 people aged 20-78 (75% men, 56% white ethnicity). Overall, median CD4 +  : CD8 + T-cell ratio increased from 0.24 at baseline to 0.77 at year 5 and 0.88 at year 10. Ratios increased among all age groups in unadjusted and adjusted models but increased less among older ages (baseline ages 60-69 and 70-79). Median ratios at year 5 were 0.85, 0.80, 0.72, 0.76, 0.6, and 0.44, respectively, among people aged 20-29, 30-39, 40-49, 50-59, 60-69 and 70-79 years at baseline. CONCLUSION: In a virally suppressed London population, age had a substantial impact on CD4 +  : CD8 + ratio recovery, especially for those starting ART after age 60 years. Results may indicate the level of CD4 +  : CD8 + ratio recovery possible in an HIV-positive, virally suppressed, aging population.

All-cause hospitalisation among people living with HIV according to gender, mode of HIV acquisition, ethnicity, and geographical origin in Europe and North America: findings from the ART-CC cohort collaboration.

BACKGROUND: Understanding demographic disparities in hospitalisation is crucial for the identification of vulnerable populations, interventions, and resource planning. METHODS: Data were from the Antiretroviral Therapy Cohort Collaboration (ART-CC) on people living with HIV in Europe and North America, followed up between January, 2007 and December, 2020. We investigated differences in all-cause hospitalisation according to gender and mode of HIV acquisition, ethnicity, and combined geographical origin and ethnicity, in people living with HIV on modern combination antiretroviral therapy (cART). Analyses were performed separately for European and North American cohorts. Hospitalisation rates were assessed using negative binomial multilevel regression, adjusted for age, time since cART intitiaion, and calendar year. FINDINGS: Among 23 594 people living with HIV in Europe and 9612 in North America, hospitalisation rates per 100 person-years were 16·2 (95% CI 16·0-16·4) and 13·1 (12·8-13·5). Compared with gay, bisexual, and other men who have sex with men, rates were higher for heterosexual men and women, and much higher for men and women who acquired HIV through injection drug use (adjusted incidence rate ratios ranged from 1·2 to 2·5 in Europe and from 1·2 to 3·3 in North America). In both regions, individuals with geographical origin other than the region of study generally had lower hospitalisation rates compared with those with geographical origin of the study country. In North America, Indigenous people and Black or African American individuals had higher rates than White individuals (adjusted incidence rate ratios 1·9 and 1·2), whereas Asian and Hispanic people living with HIV had somewhat lower rates. In Europe there was a lower rate in Asian individuals compared with White individuals. INTERPRETATION: Substantial disparities exist in all-cause hospitalisation between demographic groups of people living with HIV in the current cART era in high-income settings, highlighting the need for targeted support. FUNDING: Royal Free Charity and the National Institute on Alcohol Abuse and Alcoholism.

Cross-sectional study evaluating the impact of SARS-CoV-2 variants on Long COVID outcomes in UK hospital survivors.

OBJECTIVES: COVID-19 studies report on hospital admission outcomes across SARS-CoV-2 waves of infection but knowledge of the impact of SARS-CoV-2 variants on the development of Long COVID in hospital survivors is limited. We sought to investigate Long COVID outcomes, aiming to compare outcomes in adult hospitalised survivors with known variants of concern during our first and second UK COVID-19 waves, prior to widespread vaccination. DESIGN: Prospective observational cross-sectional study. SETTING: Secondary care tertiary hospital in the UK. PARTICIPANTS: This study investigated Long COVID in 673 adults with laboratory-positive SARS-CoV-2 infection or clinically suspected COVID-19, 6 weeks after hospital discharge. We compared adults with wave 1 (wildtype variant, admitted from February to April 2020) and wave 2 patients (confirmed Alpha variant on viral sequencing (B.1.1.7), admitted from December 2020 to February 2021). OUTCOME MEASURES: Associations of Long COVID presence (one or more of 14 symptoms) and total number of Long COVID symptoms with SARS-CoV-2 variant were analysed using multiple logistic and Poisson regression, respectively. RESULTS: 322/400 (wave 1) and 248/273 (wave 2) patients completed follow-up. Predictors of increased total number of Long COVID symptoms included: pre-existing lung disease (adjusted count ratio (aCR)=1.26, 95% CI 1.07, 1.48) and more COVID-19 admission symptoms (aCR=1.07, 95% CI 1.02, 1.12). Weaker associations included increased length of inpatient stay (aCR=1.02, 95% CI 1.00, 1.03) and later review after discharge (aCR=1.00, 95% CI 1.00, 1.01). SARS-CoV-2 variant was not associated with Long COVID presence (OR=0.99, 95% CI 0.24, 4.20) or total number of symptoms (aCR=1.09, 95% CI 0.82, 1.44). CONCLUSIONS: Patients with chronic lung disease or greater COVID-19 admission symptoms have higher Long COVID risk. SARS-CoV-2 variant was not predictive of Long COVID though in wave 2 we identified fewer admission symptoms, improved clinical trajectory and outcomes. Addressing modifiable factors such as length of stay and timepoint of clinical review following discharge may enable clinicians to move from Long COVID risk stratification towards improving its outcome.

Performance of SARS COV-2 IgG Anti-N as an Independent Marker of Exposure to SARS COV-2 in an Unvaccinated West African Population.

Determination of previous SARS-COV-2 infection is hampered by the absence of a standardized test. The marker used to assess previous exposure is IgG antibody to the nucleocapsid (IgG anti-N), although it is known to wane quickly from peripheral blood. The accuracies of seven antibody tests (virus neutralization test, IgG anti-N, IgG anti-spike [anti-S], IgG anti-receptor binding domain [anti-RBD], IgG anti-N + anti-RBD, IgG anti-N + anti-S, and IgG anti-S + anti-RBD), either singly or in combination, were evaluated on 502 cryopreserved serum samples collected before the COVID-19 vaccination rollout in Kumasi, Ghana. The accuracy of each index test was measured using a composite reference standard based on a combination of neutralization test and IgG anti-N antibody tests. According to the composite reference, 262 participants were previously exposed; the most sensitive test was the virus neutralization test, with 95.4% sensitivity (95% CI: 93.6-97.3), followed by 79.0% for IgG anti-N + anti-S (95% CI: 76.3-83.3). The most specific tests were virus neutralization and IgG anti-N, both with 100% specificity. Viral neutralization and IgG anti-N + anti-S were the overall most accurate tests, with specificity/sensitivity of 100/95.2% and 79.0/92.1%, respectively. Our findings indicate that IgG anti-N alone is an inadequate marker of prior exposure to SARS COV-2 in this population. Virus neutralization assay appears to be the most accurate assay in discerning prior infection. A combination of IgG anti-N and IgG anti-S is also accurate and suited for assessment of SARS COV-2 exposure in low-resource settings.

Trends in Cancer Incidence in Different Antiretroviral Treatment-Eras amongst People with HIV.

Despite cancer being a leading comorbidity amongst individuals with HIV, there are limited data assessing cancer trends across different antiretroviral therapy (ART)-eras. We calculated age-standardised cancer incidence rates (IRs) from 2006-2021 in two international cohort collaborations (D:A:D and RESPOND). Poisson regression was used to assess temporal trends, adjusted for potential confounders. Amongst 64,937 individuals (31% ART-naïve at baseline) and 490,376 total person-years of follow-up (PYFU), there were 3763 incident cancers (IR 7.7/1000 PYFU [95% CI 7.4, 7.9]): 950 AIDS-defining cancers (ADCs), 2813 non-ADCs, 1677 infection-related cancers, 1372 smoking-related cancers, and 719 BMI-related cancers (groups were not mutually exclusive). Age-standardised IRs for overall cancer remained fairly constant over time (8.22/1000 PYFU [7.52, 8.97] in 2006-2007, 7.54 [6.59, 8.59] in 2020-2021). The incidence of ADCs (3.23 [2.79, 3.72], 0.99 [0.67, 1.42]) and infection-related cancers (4.83 [4.2, 5.41], 2.43 [1.90, 3.05]) decreased over time, whilst the incidence of non-ADCs (4.99 [4.44, 5.58], 6.55 [5.67, 7.53]), smoking-related cancers (2.38 [2.01, 2.79], 3.25 [2.63-3.96]), and BMI-related cancers (1.07 [0.83, 1.37], 1.88 [1.42, 2.44]) increased. Trends were similar after adjusting for demographics, comorbidities, HIV-related factors, and ART use. These results highlight the need for better prevention strategies to reduce the incidence of NADCs, smoking-, and BMI-related cancers.

Investigation into the psychological impact of the COVID-19 pandemic for people living with HIV.

BACKGROUND: People living with HIV (PLWH) report high levels of anxiety. This study assessed the prevalence of COVID-19-related anxiety in PLWH. METHODS: Participants were recruited from two UK HIV clinics (01/03/2020 - 30/05/2022) and asked to complete the Coronavirus Anxiety Scale. The proportion with scores ≥9 (cut-off for dysfunctional pandemic-related anxiety) and ≥1 (reporting of any pandemic-related anxiety) were analysed. RESULTS: 115 PLWH were included, predominantly identifying as male (83.5%, n = 96), white (58.3%, n = 67) and reporting post-secondary education (82.6%, n = 95), with a median age of 51 years (range 22-93). Median CAS score was 0, with 4.4% scoring ≥9 (n = 5). More women scored ≥9 than men (16.7% (n = 3) and 2.1% (n = 2) respectively). Black African (13.6%, n = 3) and Other Ethnic Minority PLWH (25%, n = 2) had a greater proportion of scores ≥9 than White/Asian PLWH (both 0%). SARS-CoV-2 exposure was associated with scores greater than 1 but not greater than 9. CAS score was not associated with lower CD4 (<350 cells/mm3), detectable HIV viral load (≥50 copies/ml), or a history of pre-pandemic anxiety. CONCLUSIONS: Pandemic-related anxiety was low, but we identified a sub-population reporting dysfunctional pandemic related anxiety. Future work should further investigate the psychological impact of the pandemic on this group.

Plasma Human Immunodeficiency Virus 1 RNA and CD4+ T-Cell Counts Are Determinants of Virological Nonsuppression Outcomes With Initial Integrase Inhibitor-Based Regimens: A Prospective RESPOND Cohort Study.

BACKGROUND: There are conflicting data regarding baseline determinants of virological nonsuppression outcomes in persons with human immunodeficiency virus (HIV) starting antiretroviral treatment (ART). We evaluated the impact of different baseline variables in the RESPOND cohort. METHODS: We included treatment-naive participants aged ≥18 who initiated 3-drug ART, in 2014-2020. We assessed the odds of virological suppression (VS) at weeks 48 and 96 using logistic regression. Viral blips, low-level viremia (LLV), residual viremia (RV), and virological failure (VF) rates were assessed using Cox regression. RESULTS: Of 4310 eligible participants, 72% started integrase strand transfer inhibitor (INSTI)-based regimens. At 48 and 96 weeks, 91.0% and 93.3% achieved VS, respectively. At 48 weeks, Kaplan-Meier estimates of rates were 9.6% for viral blips, 2.1% for LLV, 22.2% for RV, and 2.1% for VF. Baseline HIV-1 RNA levels >100 000 copies/mL and CD4+ T-cell counts ≤200/µL were negatively associated with VS at weeks 48 (adjusted odds ratio, 0.51 [95% confidence interval, .39-.68] and .40 [.27-.58], respectively) and 96 and with significantly higher rates of blips, LLV, and RV. CD4+ T-cell counts ≤200/µL were associated with higher risk of VF (adjusted hazard ratio, 3.12 [95% confidence interval, 2.02-4.83]). Results were consistent in those starting INSTIs versus other regimens and those starting dolutegravir versus other INSTIs. CONCLUSIONS: Initial high HIV-1 RNA and low CD4+ T-cell counts are associated with lower rates of VS at 48 and 96 weeks and higher rates of viral blips, LLV, and RV. Low baseline CD4+ T-cell counts are associated with higher VF rates. These associations remain with INSTI-based and specifically with dolutegravir-based regimens. These findings suggest that the impact of these baseline determinants is independent of the ART regimen initiated.

Hepatitis B virus infection in general practice across England: An analysis of the Royal College of General Practitioners Research and Surveillance Centre real-world database.

OBJECTIVES: We analyzed hepatitis B surface antigen (HBsAg) screening and seropositivity within a network of 419 general practices representative of all regions of England. METHODS: Information was extracted using pseudonymized registration data. Predictors of HBsAg seropositivity were explored in models that considered age, gender, ethnicity, time at the current practice, practice location and associated deprivation index, and presence of nationally endorsed screen indicators including pregnancy, men who have sex with men (MSM), history of injecting drug use (IDU), close HBV contact or imprisonment, and diagnosis of blood-borne or sexually transmitted infections. RESULTS: Among 6,975,119 individuals, 192,639 (2.8 %) had a screening record, including 3.6-38.6 % of those with a screen indicator, and 8065 (0.12 %) had a seropositive record. The odds of seropositivity were highest in London, in the most deprived neighborhoods, among minority ethnic groups, and in people with screen indicators. Seroprevalence exceeded 1 % in people from high-prevalence countries, MSM, close HBV contacts, and people with a history of IDU or a recorded diagnosis of HIV, HCV, or syphilis. Overall, 1989/8065 (24.7 %) had a recorded referral to specialist hepatitis care. CONCLUSIONS: In England, HBV infection is associated with poverty. There are unrealized opportunities to promote access to diagnosis and care for those affected.

Coproduced resources to support parents caring for children with gastrostomies.

Objective: To describe and disseminate a package of support for parents who care for children with gastrostomies, consisting of a library of videos and resources to support families from referral for gastrostomy surgery, to long-term support at home. Methods: The resources were systematically developed and evaluated by parents, hospital and community-based nurses, paediatricians, a surgeon and researchers. Results: The videos empower families, reduce their anxiety and increase their confidence, providing support throughout the families' journey. Surveys and feedback from parents and clinicians show that the video library is seen as providing clear and comprehensive guidance and is suitable for integration into routine practice. To effectively disseminate these resources across a region, the videos need to be shared widely with relevant community and hospital-based teams, and shared through parent networks. The videos should be viewed as one part of a wider package of training and support, in combination with hands-on-practice and clinical support. Conclusions: The resources described have been developed with and for families. Critically the videos are founded in the lived-experience of families, as well as the expertise of clinicians from community and hospital services. Similar resources are needed to support families performing other types of specialist care. The resources are freely available to any parent or clinical team.

Bone Mineral Density and Vascular Calcification in Children and Young Adults With CKD 4 to 5 or on Dialysis.

Introduction: Older adults with chronic kidney disease (CKD) can have low bone mineral density (BMD) with concurrent vascular calcification. Mineral accrual by the growing skeleton may protect young people with CKD from extraosseous calcification. Our hypothesis was that children and young adults with increasing BMD do not develop vascular calcification. Methods: This was a multicenter longitudinal study in children and young people (5-30 years) with CKD stages 4 to 5 or on dialysis. BMD was assessed by tibial peripheral quantitative computed tomography (pQCT) and lumbar spine dual-energy X-ray absorptiometry (DXA). The following cardiovascular imaging tests were undertaken: cardiac computed tomography for coronary artery calcification (CAC), ultrasound for carotid intima media thickness z-score (cIMTz), pulse wave velocity z-score (PWVz), and carotid distensibility for arterial stiffness. All measures are presented as age-adjusted and sex-adjusted z-scores. Results: One hundred participants (median age 13.82 years) were assessed at baseline and 57 followed up after a median of 1.45 years. Trabecular BMD z-score (TrabBMDz) decreased (P = 0.01), and there was a nonsignificant decrease in cortical BMD z-score (CortBMDz) (P = 0.09). Median cIMTz and PWVz showed nonsignificant increase (P = 0.23 and P = 0.19, respectively). The annualized increase in TrabBMDz (ΔTrabBMDz) was an independent predictor of cIMTz increase (R 2 = 0.48, ß = 0.40, P = 0.03). Young people who demonstrated statural growth (n = 33) had lower ΔTrabBMDz and also attenuated vascular changes compared with those with static growth (n = 24). Conclusion: This hypothesis-generating study suggests that children and young adults with CKD or on dialysis may develop vascular calcification even as their BMD increases. A presumed buffering capacity of the growing skeleton may offer some protection against extraosseous calcification.

Nutritional and Anthropometric Indices in Children Receiving Haemodiafiltration vs Conventional Haemodialysis - The HDF, Heart and Height (3H) Study.

BACKGROUND: The "HDF-Heart-Height" study showed that haemodiafiltration (HDF) is associated with improved growth compared to conventional haemodialysis (HD). We report a post-hoc analysis of this study assessing the effect of extracorporeal dialysis therapies on nutritional indices. METHODS: 107 children were included in the baseline cross-sectional analysis, of whom 79 (43 HD, 36 HDF) completed the 12-month follow-up. Height (Ht), optimal 'dry' weight (Wt), and body mass index (BMI) standard deviations scores (SDS), waist-to-hip ratio, des-acyl ghrelin (DAG), adiponectin, leptin, insulin-like growth factor-1 (IGF-1)-SDS and insulin were measured. RESULTS: The levels of nutritional indices were comparable between HDF and HD patients at baseline and 12-month. On univariable analyses Wt-SDS positively correlated with leptin and IGF-1-SDS, and negatively with DAG, while Ht-SDS of the overall cohort positively correlated with IGF1-SDS and inversely with DAG and adiponectin. On multivariable analyses, higher 12-month Ht-SDS was inversely associated with baseline DAG (beta = -0.13 per 500 higher; 95%CI -0.22, -0.04; P = .004). Higher Wt-SDS at 12-month was positively associated with HDF modality (beta = 0.47 vs HD; 95%CI 0.12-0.83; P = .01) and inversely with baseline DAG (beta = -0.18 per 500 higher; 95%CI -0.32, -0.05; P = .006). Growth Hormone (GH) treated patients receiving HDF had higher annualized increase in Ht SDS compared to those on HD. CONCLUSIONS: In children on HD and HDF both Wt- and Ht-SDS independently correlated with lower baseline levels of the anorexygenic hormone DAG. HDF may attenuate the resistance to GH, but further studies are required to examine the mechanisms linking HDF to improved growth.

High-Risk Contexts for Violence Against Women: Using Latent Class Analysis to Understand Structural and Contextual Drivers of Intimate Partner Violence at the National Level.

Introduction: Intimate partner violence (IPV) affects 1 in 3 women and poses a major human rights threat and public health burden, yet there is great variation in risk globally. Whilst individual risk factors are well-studied, less research has focussed on the structural and contextual drivers of IPV and how these co-occur to create contexts of high risk. Methods: We compiled IPV drivers from freely-accessible global country-level data sources and combined gender inequality, natural disasters, conflict, colonialism, socioeconomic development and inequality, homicide and social discrimination in a latent class analysis, and identified underlying 'risk contexts' based on fit statistics and theoretical plausibility (N=5,732 country-years; 190 countries). We used multinomial regression to compare risk contexts according to: proportion of population with disability, HIV/AIDS, refugee status, and mental health disorders; proportion of men with drug use disorders; men's alcohol consumption; and population median age (N=1,654-5,725 country-years). Finally, we compared prevalence of physical and/or sexual IPV experienced by women in the past 12 months across risk contexts (N=3,175 country-years). Results: Three distinct risk contexts were identified: 1) non-patriarchal egalitarian, low rates of homicide; 2) patriarchal post-colonial, high rates of homicide; 3) patriarchal post-colonial conflict and disaster-affected. Compared to non-patriarchal egalitarian contexts, patriarchal post-colonial contexts had a younger age distribution and a higher prevalence of drug use disorders, but a lower prevalence of mental health disorders and a smaller refugee population. IPV risk was highest in the two patriarchal post-colonial contexts and associated with country income classification. Conclusions: Whilst our findings support the importance of gender norms in shaping women's risk of experiencing IPV, they also point towards an association with a history of colonialism. To effectively address IPV for women in high prevalence contexts, structural interventions and policies are needed that address not only gender norms, but also broader structural inequalities arising from colonialism.

Recent abacavir use and incident cardiovascular disease in contemporary-treated people with HIV.

OBJECTIVE: Assessing whether the previously reported association between abacavir (ABC) and cardiovascular disease (CVD) remained amongst contemporarily treated people with HIV. DESIGN: Multinational cohort collaboration. METHODS: RESPOND participants were followed from the latest of 1 January 2012 or cohort enrolment until the first of a CVD event (myocardial infarction, stroke, invasive cardiovascular procedure), last follow-up or 31 December 2019. Logistic regression examined the odds of starting ABC by 5-year CVD or chronic kidney disease (CKD) D:A:D risk score. We assessed associations between recent ABC use (use within the past 6 months) and risk of CVD with negative binomial regression models, adjusted for potential confounders. RESULTS: Of 29 340 individuals, 34% recently used ABC. Compared with those at low estimated CVD and CKD risks, the odds of starting ABC were significantly higher among individuals at high CKD risk [odds ratio 1.12 (95% confidence interval = 1.04-1.21)] and significantly lower for individuals at moderate, high or very high CVD risk [0.80 (0.72-0.88), 0.75 (0.64-0.87), 0.71 (0.56-0.90), respectively]. During 6.2 years of median follow-up (interquartile range; 3.87-7.52), there were 748 CVD events (incidence rate 4.7 of 1000 persons-years of follow up (4.3-5.0)]. The adjusted CVD incidence rate ratio was higher for individuals with recent ABC use [1.40 (1.20-1.64)] compared with individuals without, consistent across sensitivity analyses. The association did not differ according to estimated CVD (interaction P  = 0.56) or CKD ( P  = 0.98) risk strata. CONCLUSION: Within RESPOND's contemporarily treated population, a significant association between CVD incidence and recent ABC use was confirmed and not explained by preferential ABC use in individuals at increased CVD or CKD risk.

Falling treatment uptake in the hepatitis C care cascade is a growing threat to achieving elimination.

Most high-income countries are not on track to achieve the World Health Organization hepatitis C elimination targets. As elimination programmes assess growing proportions of patients in community-based pathways, rates of treatment uptake may fall. We aimed to identify factors associated with DAA treatment uptake and measure changes in their prevalence over time. We performed a time-to-treatment analysis on 2728 patients approved for hepatitis C Direct-Acting Antiviral treatment in the North Central London region between January 2016 and October 2019. We investigated the association between treatment uptake and factors including assessment/treatment setting (hospital, drug service or prison), patient age, gender, injection drug use, harmful alcohol use, cirrhosis status and previous treatment. The likelihood of treatment uptake was reduced by three independent risk factors. These included assessment setting: prison-based or drug-service pathways (aHR 0.29 or 0.81 vs. hospital outpatient pathway, 95% CI 0.21-0.40 and 0.70-0.94 respectively, p < .001); being UK-born (aHR 0.89 vs. non-UK born, 0.82-0.98, p = .01); and history of harmful alcohol use (aHR 0.84 vs. no history, 0.72-0.99, p = .04). The average number of these risk factors for not starting treatment per patient increased over time (R2  = 0.66 p < .001). Independent of these, there was an additional 5% reduction in rate of treatment initiation in each successive year of the programme (aHR 0.95, 0.91-0.99, p = .02). In conclusion, disengagement from care before treatment uptake was found to be a growing threat to elimination. Despite provision of community-based test-to-cure pathways, there are persistent barriers to treatment uptake and these are increasing over time.

Exploring the cognitive development of children born to adolescent mothers in South Africa.

This study explores the cognitive development of children born to adolescent mothers within South Africa compared to existing reference data, and explores development by child age bands to examine relative levels of development. Cross-sectional analyses present data from 954 adolescents (10-19 years) and their first-born children (0-68 months). All adolescents completed questionnaires relating to themselves and their children, and standardized child cognitive assessments (Mullen Scales of Early Learning) were undertaken. Cognitive development scores of the sample were lower than USA reference population scores and relative performance compared to the reference population was found to decline with increasing child age. When compared to children born to adult mothers in the sub-Saharan African region, children born to adolescent mothers (human immunodeficiency virus [HIV] unexposed; n = 724) were found to have lower cognitive development scores. Findings identify critical periods of development where intervention may be required to bolster outcomes for children born to adolescent mothers. Highlights: An exploration of the cognitive development of children born to adolescent mothers within South Africa utilizing the Mullen Scales of Early Learning.Cognitive development scores of children born to adolescent mothers within South Africa were lower compared to USA norm reference data and declined with child age.Previous studies utilizing the Mullen Scales of Early Learning within sub-Saharan Africa were summarized, and comparisons were made with the current sample.Findings highlight a potential risk of developmental delay among children born to adolescent mothers compared to children of adult mothers in the sub-Saharan African region.

Adolescent mothers and their children affected by HIV-An exploration of maternal mental health, and child cognitive development.

BACKGROUND: Some children born to adolescent mothers may have developmental challenges, while others do not. Research focusing on which children of adolescent mothers are at the highest risk for cognitive delay is still required. Both maternal HIV status and maternal mental health may affect child development. An examination of maternal mental health, especially in the presence of maternal HIV infection may be timely. This study explores the relationship between the mental health of adolescent mothers (comparing those living with and not living with HIV) and the cognitive development performance scores of their children. Additional possible risk and protective factors for poor child development are explored to identify those children born to adolescent mothers who may be at the greatest risk of poor cognitive development. METHODS: Cross-sectional data utilised within the analyses was drawn from a large cohort of adolescent mothers and their children residing in South Africa. Detailed study questionnaires were completed by adolescent mothers relating to their self and their child and, standardised cognitive assessments were completed by trained researchers for all children using in the Mullen Scales of Early Learning. Chi-square, t-tests (Kruskal Wallis tests, where appropriate), and ANOVA were used to explore sample characteristics and child cognitive development scores by maternal mental health status (operationalised as likely common mental disorder) and combined maternal mental health and HIV status. Multivariable linear regression models were used to explore the relationship between possible risk factors (including poor maternal mental health and HIV) and, child cognitive development scores. RESULTS: The study included 954 adolescent mothers; 24.1% (230/954) were living with HIV, 12.6% (120/954) were classified as experiencing likely common mental disorder. After adjusting for covariates, maternal HIV was found to be associated with reduced child gross motor scores (B = -2.90 [95%CI: -5.35, -0.44], p = 0.02), however, no other associations were identified between maternal likely common mental disorder, or maternal HIV status (including interaction terms), and child cognitive development scores. Sensitivity analyses exploring individual maternal mental health scales identified higher posttraumatic stress symptomology scores as being associated with lower child cognitive development scores. Sensitivity analyses exploring potential risk and protective factors for child cognitive development also identified increased maternal educational attainment as being protective of child development scores, and increased child age as a risk factor for lower development scores. CONCLUSIONS: This study addresses a critical evidence gap relating to the understanding of possible risk factors for the cognitive development of children born to adolescent mothers affected by HIV. This group of mothers experience a complex combination of risk factors, including HIV, likely common mental disorder, and structural challenges such as educational interruption. Targeting interventions to support the cognitive development of children of adolescent mothers most at risk may be of benefit. Clearly a basket of interventions needs to be considered, such as the integration of mental health provision within existing services, identifying multiple syndemics of risk, and addressing educational and structural challenges, all of which may boost positive outcomes for both the mother and the child.

Risk factors for poor mental health among adolescent mothers in South Africa.

In South Africa, high rates of adolescent pregnancy and HIV pose prominent public health challenges with potential implications for mental wellbeing. It is important to understand risk factors for mental health difficulties among adolescent mothers affected by HIV. This study aims to identify the prevalence of likely common mental disorder among adolescent mothers (both living with and not living with HIV) and explores hypothesised risk factors for likely common mental disorder. Cross-sectional data from adolescent mothers (10-19 years; n=1002) utilised within these analyses are drawn from a cohort of young mothers residing in the Eastern Cape Province, South Africa. All mothers completed a detailed questionnaire consisting of standardised measures of sociodemographic characteristics, mental health, and hypothesised risk factors. Logistic regression models were utilised to explore associations between hypothesised risk factors and likely common mental disorder. Risk factors were clustered within a hypothesised socioecological framework and entered into models using a stepwise sequential approach. Interaction effects with maternal HIV status were additionally explored. The prevalence of likely common mental disorder among adolescent mothers was 12.6%. Adolescent mothers living with HIV were more likely to report likely common mental disorder compared to adolescent mothers not living with HIV (16.2% vs 11.2%, X2=4.41, p=0.04). Factors associated with likely common mental disorder were any abuse exposure (OR=2.54 [95%CI:1.20-5.40], p=0.01), a lack of perceived social support (OR=4.09 [95%CI:2.48-6.74], p=<0.0001), and community violence exposure (OR=2.09 [95%CI:1.33-3.27], p=0.001). There was limited evidence of interaction effects between risk factors, and maternal HIV status. Violence exposure and a lack of perceived support are major risk factors for poor mental health among adolescent mothers in South Africa. Violence prevention interventions and social support may help to reduce risk. Identified risk factors spanning individual, interpersonal, and community levels have the potential to impact adolescent maternal mental health.

Liver steatosis and fibrosis in people with human immunodeficiency virus in West Africa and the relationship with hepatitis B virus coinfection.

There is a heavy burden of liver disease in West Africa. While the role of hepatitis B virus (HBV) infection is well recognized, less is known about the contributing role of liver steatosis and how the two interact in the context of human immunodeficiency virus (HIV) infection. Adults with HIV in Ghana underwent FibroScan measurements to determine prevalence of liver steatosis (expressed as controlled attenuation parameter [CAP]) and fibrosis (expressed as liver stiffness [LS]). We explored contributing factors in linear regression models, including demographics, lifestyle characteristics, medical history, HIV and HBV status, and measurements of metabolic syndrome. Among 329 adults (72.3% women; median age, 47 years), 322 (97.9%) were on antiretroviral therapy (median duration, 8.9 years). CD4 counts were preserved (median, 619 cells/mm3 ); plasma HIV RNA was fully suppressed in 162 (50.3%) of the treated participants. Cigarette smoking, excessive alcohol consumption, and use of traditional or herbal remedies were uncommon (6.1%, 1.8%, 3.3%, respectively). Largely undiagnosed metabolic syndrome was detected in 87 (26.4%) participants. We obtained readings indicative of ≥S2 steatosis and ≥F2 fibrosis in 43 (13.1%) and 55 (16.7%) participants, respectively. Higher CAP values were associated with metabolic syndrome and longer prior stavudine exposure. Higher LS values were associated with male sex, higher HIV RNA, and higher CAP values. Relative to people without HBV, those with HBV (n = 90) had a similar prevalence of ≥S2 steatosis but a higher prevalence of ≥F2 fibrosis (36.7% vs. 9.2%, p < 0.0001) and concomitant ≥S2 steatosis and ≥F2 fibrosis (9.1% vs. 1.3%, p < 0.001). Conclusion: Both HBV and liver steatosis pose a threat to long-term liver health among people with HIV in West Africa. Urgently required interventions include improving HIV suppression and diagnosing and managing determinants of the metabolic syndrome.

High burden of childhood tuberculosis in migrants: a retrospective cohort study from the Thailand-Myanmar border.

BACKGROUND: Tuberculosis (TB) is a leading cause of morbidity and mortality in children but epidemiological data are scarce, particularly for hard-to-reach populations. We aimed to identify the risk factors for unsuccessful outcome and TB mortality in migrant children at a supportive residential TB programme on the Thailand-Myanmar border. METHODS: We conducted retrospective analysis of routine programmatic data for children (aged ≤ 15 years old) with TB diagnosed either clinically or bacteriologically between 2013 and 2018. Treatment outcomes were described and risk factors for unsuccessful outcome and death were identified using multivariable logistic regression. RESULTS: Childhood TB accounted for a high proportion of all TB diagnoses at this TB programme (398/2304; 17.3%). Bacteriological testing was done on a quarter (24.9%) of the cohort and most children were diagnosed on clinical grounds (94.0%). Among those enrolled on treatment (n = 367), 90.5% completed treatment successfully. Unsuccessful treatment outcomes occurred in 42/398 (10.6%) children, comprising 26 (6.5%) lost to follow-up, one (0.3%) treatment failure and 15 (3.8%) deaths. In multivariable analysis, extra-pulmonary TB [adjusted OR (aOR) 3.56 (95% CI 1.12-10.98)], bacteriologically confirmed TB [aOR 6.07 (1.68-21.92)] and unknown HIV status [aOR 42.29 (10.00-178.78)] were independent risk factors for unsuccessful outcome. HIV-positive status [aOR 5.95 (1.67-21.22)] and bacteriological confirmation [aOR 9.31 (1.97-44.03)] were risk factors for death in the secondary analysis. CONCLUSIONS: Children bear a substantial burden of TB disease within this migrant population. Treatment success rate exceeded the WHO End TB target of 90%, suggesting that similar vulnerable populations could benefit from the enhanced social support offered by this TB programme, but better child-friendly diagnostics are needed to improve the quality of diagnoses.