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.

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.

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.

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.

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.

Are the Patterns of Cytomegalovirus Viral Load Seen After Solid Organ Transplantation Affected by Circadian Rhythm?

BACKGROUND: Cytomegalovirus (CMV) is an important opportunistic pathogen after transplantation. Some virological variation in transplant recipients is explained by donor and recipient CMV serostatus, but not all. Circadian variability of herpesviruses has been described, so we investigated the effect of time of day of transplantation on posttransplant CMV viremia. METHODS: We performed a retrospective analysis of 1517 patients receiving liver or kidney allografts at a single center from 2002 to 2018. All patients were given preemptive therapy with CMV viremia monitoring after transplantation. Circulatory arrest and reperfusion time of donor organ were categorized into 4 periods. Patients were divided into serostatus groups based on previous CMV infection in donor and recipient. CMV viremia parameters were compared between time categories for each group. Factor analysis of mixed data was used to interrogate this complex data set. RESULTS: Live-donor transplant recipients were less likely to develop viremia than recipients of deceased-donor organs (48% vs 61%; P < .001). After controlling for this, there was no evidence of time of day of transplantation affecting CMV parameters in any serostatus group, by logistic regression or factor analysis of mixed data. DISCUSSION: We found no evidence for a circadian effect of transplantation on CMV viremia, but these novel results warrant confirmation by other centers.

Alcohol, smoking, recreational drug use and association with virological outcomes among people living with HIV: cross-sectional and longitudinal analyses.

OBJECTIVES: There is increasing evidence to suggest that people living with HIV (PLWH) have significant morbidity from alcohol, recreational drug use and cigarette smoking. Our aim was to report associations of these factors with antiretroviral therapy (ART) non-adherence, viral non-suppression and subsequent viral rebound in PLWH. METHODS: The Antiretroviral Sexual Transmission Risk and Attitudes (ASTRA) study recruited PLWH attending eight outpatient clinics in England between February 2011 and December 2012. Data included self-reported excessive drinking (estimated consumption of > 20 units of alcohol/week), alcohol dependency (CAGE score ≥ 2 with current alcohol consumption), recreational drug use (including injection drug use in the past 3 months), and smoking status. Among participants established on ART, cross-sectional associations with ART non-adherence [missing ≥2 consecutive days of ART on ≥2 occasions in the past three months] and viral-non suppression [viral load (VL) > 50 copies/mL] were assessed using logistic regression. In participants from one centre, longitudinal associations with subsequent viral rebound (first VL > 200 copies/mL) in those on ART with VL ≤ 50 copies/mL at baseline were assessed using Cox regression during a 7-year follow-up. RESULTS: Among 3258 PLWH, 2248 (69.0%) were men who have sex with men, 373 (11.4%) were heterosexual men, and 637 (19.6%) were women. A CAGE score ≥ 2 was found in 568 (17.6%) participants, 325 (10.1%) drank > 20 units/week, 1011 (31.5%) currently smoked, 1242 (38.1%) used recreational drugs and 74 (2.3%) reported injection drug use. In each case, prevalence was much more common among men than among women. Among 2459 people on ART who started at least 6 months previously, a CAGE score ≥ 2, drinking > 20 units per week, current smoking, injection and non-injection drug use were all associated with ART non-adherence. After adjusting for demographic and socioeconomic factors, CAGE score ≥ 2 [adjusted odds ratio (aOR) = 1.52, 95% confidence interval (CI): 1.09-2.13], current smoking (aOR = 1.58, 95% CI: 1.10-2.17) and injection drug use (aOR = 2.11, 95% CI: 1.00-4.47) were associated with viral non-suppression. During follow-up of a subset of 592 people virally suppressed at recruitment, a CAGE score ≥ 2 [adjusted hazard ratio (aHR) = 1.66, 95% CI: 1.03-2.74], use of 3 or more non-injection drugs (aHR = 1.82, 95% CI: 1.12-3.57) and injection drug use (aHR = 2.73, 95% CI: 1.08-6.89) were associated with viral rebound. CONCLUSIONS: Screening and treatment for alcohol, cigarette and drug use should be integrated into HIV outpatient clinics, while clinicians should be alert to the potential for poorer virological outcomes.

Clinical outcomes of patients with and without HIV hospitalized with COVID-19 in England during the early stages of the pandemic: a matched retrospective multi-centre analysis (RECEDE-C19 study).

BACKGROUND: The contribution of HIV to COVID-19 outcomes in hospitalized inpatients remains unclear. We conducted a multi-centre, retrospective matched cohort study of SARS-CoV-2 PCR-positive hospital inpatients analysed by HIV status. METHODS: HIV-negative patients were matched to people living with HIV (PLWH) admitted from 1 February 2020 to 31 May 2020 up to a 3:1 ratio by the following: hospital site, SARS-CoV-2 test date ± 7 days, age ± 5 years, gender, and index of multiple deprivation decile ± 1. The primary objective was clinical improvement (two-point improvement or better on a seven-point ordinal scale) or hospital discharge by day 28, whichever was earlier. RESULTS: A total of 68 PLWH and 181 HIV-negative comparators were included. In unadjusted analyses, PLWH had a reduced hazard of achieving clinical improvement or discharge [adjusted hazard ratio (aHR) = 0.57, 95% confidence interval (CI): 0.39-0.85, p = 0.005], but this association was ameliorated (aHR = 0.70, 95% CI: 0.43-1.17, p = 0.18) after additional adjustment for ethnicity, frailty, baseline hypoxaemia, duration of symptoms prior to baseline, body mass index (BMI) categories and comorbidities. Baseline frailty (aHR = 0.79, 95% CI: 0.65-0.95, p = 0.011), malignancy (aHR = 0.37, 95% CI 0.17, 0.82, p = 0.014) remained associated with poorer outcomes. The PLWH were more likely to be of black, Asian and minority ethnic background (75.0% vs 48.6%, p = 0.0002), higher median clinical frailty score [3 × interquartile range (IQR): 2-5 vs, 2 × IQR: 1-4, p = 0.0069), and to have a non-significantly higher proportion of active malignancy (14.4% vs 9.9%, p = 0.29). CONCLUSIONS: Adjusting for confounding comorbidities and demographics in a matched cohort ameliorated differences in outcomes of PLWH hospitalized with COVID-19, highlighting the importance of an appropriate comparison group when assessing outcomes of PLWH hospitalized with COVID-19.

Adolescent Motherhood and HIV in South Africa: Examining Prevalence of Common Mental Disorder.

The mental health of adolescents (10-19 years) remains an overlooked global health issue, particularly within the context of syndemic conditions such as HIV and pregnancy. Rates of pregnancy and HIV among adolescents within South Africa are some of the highest in the world. Experiencing pregnancy and living with HIV during adolescence have both been found to be associated with poor mental health within separate explorations. Yet, examinations of mental health among adolescents living with HIV who have experienced pregnancy/parenthood remain absent from the literature. As such, there exists no evidence-based policy or programming relating to mental health for this group. These analyses aim to identify the prevalence of probable common mental disorder among adolescent mothers and, among adolescents experiencing the syndemic of motherhood and HIV. Analyses utilise data from interviews undertaken with 723 female adolescents drawn from a prospective longitudinal cohort study of adolescents living with HIV (n = 1059) and a comparison group of adolescents without HIV (n = 467) undertaken within the Eastern Cape Province, South Africa. Detailed study questionnaires included validated and study specific measures relating to HIV, adolescent motherhood, and mental health. Four self-reported measures of mental health (depressive, anxiety, posttraumatic stress, and suicidality symptomology) were used to explore the concept of likely common mental disorder and mental health comorbidities (experiencing two or more common mental disorders concurrently). Chi-square tests (Fisher's exact test, where appropriate) and Kruskal Wallis tests were used to assess differences in sample characteristics (inclusive of mental health status) according to HIV status and motherhood status. Logistic regression models were used to explore the cross-sectional associations between combined motherhood and HIV status and, likely common mental disorder/mental health comorbidities. 70.5% of participants were living with HIV and 15.2% were mothers. 8.4% were mothers living with HIV. A tenth (10.9%) of the sample were classified as reporting a probable common mental disorder and 2.8% as experiencing likely mental health comorbidities. Three core findings emerge: (1) poor mental health was elevated among adolescent mothers compared to never pregnant adolescents (measures of likely common mental disorder, mental health comorbidities, depressive, anxiety and suicidality symptoms), (2) prevalence of probable common mental disorder was highest among mothers living with HIV (23.0%) compared to other groups (Range:8.5-12.8%; Χ2 = 12.54, p = 0.006) and, (3) prevalence of probable mental health comorbidities was higher among mothers, regardless of HIV status (HIV & motherhood = 8.2%, No HIV & motherhood = 8.2%, Χ2 = 14.5, p = 0.002). Results identify higher mental health burden among adolescent mothers compared to never-pregnant adolescents, an increased prevalence of mental health burden among adolescent mothers living with HIV compared to other groups, and an elevated prevalence of mental health comorbidities among adolescent mothers irrespective of HIV status. These findings address a critical evidence gap, highlighting the commonality of mental health burden within the context of adolescent motherhood and HIV within South Africa as well as the urgent need for support and further research to ensure effective evidence-based programming is made available for this group. Existing antenatal, postnatal, and HIV care may provide an opportunity for mental health screening, monitoring, and referral.

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.

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.

The Impact of Immunosuppression on Chronic Kidney Disease in People Living With Human Immunodeficiency Virus: The D:A:D Study.

BACKGROUND: Relations between different measures of human immunodeficiency virus-related immunosuppression and chronic kidney disease (CKD) remain unknown. METHODS: Immunosuppression measures included baseline, current, time-lagged and nadir CD4, years and percentage of follow-up (%FU) with CD4 ≤200 cells/µL, and CD4 recovery. CKD was defined as confirmed estimated glomerular filtration rate <60 mL/minute/1.73 m2. RESULTS: Of 33 791 persons, 2226 developed CKD. Univariably, all immunosuppression measures predicted CKD. Multivariably, the strongest predictor was %FU CD4 ≤200 cells/µL (0 vs >25%; incidence rate ratio [IRR], 0.77 [95% confidence interval [CI], .68-.88]), with highest effect in those at low D:A:D CKD risk (IRR, 0.45 [95% CI, .24-.80]) vs 0.80 [95% CI, .70-.93]). CONCLUSIONS: Longer immunosuppression duration most strongly predicts CKD and affects persons at low CKD risk more.

Decline in Hepatitis C Virus (HCV) Incidence in Men Who Have Sex With Men Living With Human Immunodeficiency Virus: Progress to HCV Microelimination in the United Kingdom?

BACKGROUND: Modeling of the London hepatitis C virus (HCV) epidemic in men who have sex with men (MSM) and are living with human immunodeficiency virus (HIV) suggested that early access to direct-acting antiviral (DAA) treatment may reduce incidence. With high rates of linkage to care, microelimination of HCV within MSM living with HIV may be realistic ahead of 2030 World Health Organization targets. We examined trends in HCV incidence in the pre- and post-DAA eras for MSM living with HIV in London and Brighton, United Kingdom. METHODS: A retrospective cohort study was conducted at 5 HIV clinics in London and Brighton between 2013 and 2018. Each site reported all acute HCV episodes during the study period. Treatment timing data were collected. Incidence rates and reinfection proportion were calculated. RESULTS: A total of.378 acute HCV infections were identified, comprising 292 first infections and 86 reinfections. Incidence rates of acute HCV in MSM living with HIV peaked at 14.57/1000 person-years of follow-up (PYFU; 95% confidence interval [CI], 10.95-18.20) in 2015. Rates fell to 4.63/1000 PYFU (95% CI, 2.60 to 6.67) by 2018. Time from diagnosis to starting treatment declined from 29.8 (2013) to 3.7 months (2018). CONCLUSIONS: We observed a 78% reduction in the incidence of first HCV episode and a 68% reduction in overall HCV incidence since the epidemic peak in 2015, which coincides with wider access to DAAs in England. Further interventions to reduce transmission, including earlier access to treatment and for reinfection, are likely needed for microelimination to be achieved in this population.

Clinical Outcomes of 2-Drug Regimens vs 3-Drug Regimens in Antiretroviral Treatment-Experienced People Living With Human Immunodeficiency Virus.

BACKGROUND: Limited data exist that compare clinical outcomes of 2-drug regimens (2DRs) and 3-drug regimens (3DRs) in people living with human immunodeficiency virus. METHODS: Antiretroviral treatment-experienced individuals in the International Cohort Consortium of Infectious Diseases (RESPOND) who switched to a new 2DR or 3DR from 1 January 2012-1 October 2018 were included. The incidence of clinical events (AIDS, non-AIDS cancer, cardiovascular disease, end-stage liver and renal disease, death) was compared between regimens using Poisson regression. RESULTS: Of 9791 individuals included, 1088 (11.1%) started 2DRs and 8703 (88.9%) started 3DRs. The most common 2DRs were dolutegravir plus lamivudine (22.8%) and raltegravir plus boosted darunavir (19.8%); the most common 3DR was dolutegravir plus 2 nucleoside reverse transcriptase inhibitors (46.9%). Individuals on 2DRs were older (median, 52.6 years [interquartile range, 46.7-59.0] vs 47.7 [39.7-54.3]), and a higher proportion had ≥1 comorbidity (81.6% vs 73.9%). There were 619 events during 27 159 person-years of follow-up (PYFU): 540 (incidence rate [IR] 22.5/1000 PYFU; 95% confidence interval [CI]: 20.7-24.5) on 3DRs and 79 (30.9/1000 PYFU; 95% CI: 24.8-38.5) on 2DRs. The most common events were death (7.5/1000 PYFU; 95% CI: 6.5-8.6) and non-AIDS cancer (5.8/1000 PYFU; 95% CI: 4.9-6.8). After adjustment for baseline demographic and clinical characteristics, there was a similar incidence of events on both regimen types (2DRs vs 3DRs IR ratio, 0.92; 95% CI: .72-1.19; P = .53). CONCLUSIONS: This is the first large, international cohort to assess clinical outcomes on 2DRs. After accounting for baseline characteristics, there was a similar incidence of events on 2DRs and 3DRs. 2DRs appear to be a viable treatment option with regard to clinical outcomes. Further research on resistance barriers and long-term durability of 2DRs is needed.

Understanding Mental Health in the Context of Adolescent Pregnancy and HIV in Sub-Saharan Africa: A Systematic Review Identifying a Critical Evidence Gap.

Adolescent (10-19 years) mental health remains an overlooked global health issue. Rates of adolescent pregnancy within sub-Saharan Africa are some of the highest in the world and occur at the epicentre of the global HIV epidemic. Both experiencing adolescent pregnancy and living with HIV have been found to be associated with adverse mental health outcomes, when investigated separately. Poor mental health may have implications for both parent and child. The literature regarding mental health within groups experiencing both HIV and adolescent pregnancy is yet to be summarised. This systematic review sought to identify (1) the prevalence/occurrence of common mental disorder amongst adolescents who are living with HIV and have experienced pregnancy, (inclusive of adolescent fathers) in sub-Saharan Africa (2) risk and protective factors for common mental disorder among this group, and (3) interventions (prevention/treatment) for common mental disorder among this group. A systematic search of electronic databases using pre-defined search terms, supplemented by hand-searching, was undertaken in September 2020. One author and an independent researcher completed a title and abstract screening of results from the search. A full-text search of all seemingly relevant manuscripts (both quantitative and qualitative) was undertaken and data extracted using pre-determined criteria. A narrative synthesis of included studies is provided. Quality and risk of bias within included studies was assessed using the Newcastle-Ottawa scale. A systematic keyword search of databases and follow-up hand searching identified 2287 unique records. Of these, thirty-eight full-text quantitative records and seven full-text qualitative records were assessed for eligibility. No qualitative records met the eligibility criteria for inclusion within the review. One quantitative record was identified for inclusion. This study reported on depressive symptomology amongst 14 pregnant adolescents living with HIV in Kenya, identifying a prevalence of 92.9%. This included study did not meet the high methodological quality of this review. No studies were identified reporting on risk and protective factors for common mental disorder, and no studies were found identifying any specific interventions for common mental disorder for this group, either for prevention or for treatment. The limited data identified within this review provides no good quality evidence relating to the prevalence of common mental disorder among adolescents living with HIV who have experienced pregnancy in sub-Saharan Africa. No data was available relating to risk and protective factors or interventions for psychological distress amongst this group. This systematic review identifies a need for rigorous evidence regarding the mental health of pregnant and parenting adolescents living with HIV, and calls for granular interrogation of existing data to further our understanding of the needs of this group. The absence of research on this topic (both quantitative and qualitative) is a critical evidence gap, limiting evidence-based policy and programming responses, as well as regional development opportunities.

Causes of hospitalisation among a cohort of people with HIV from a London centre followed from 2011 to 2018.

BACKGROUND: We describe the spectrum of ICD-10 classified causes for hospitalisations occurring between 2011 and 2018 in a cohort of people living with HIV (PLHIV). METHODS: This sub-study includes 798 PLHIV participating in the Antiretroviral, Sexual Transmission Risk and Attitudes (ASTRA) questionnaire study who were recruited from a large London centre. A medical record review identified the occurrence and causes of hospitalisation from the date of questionnaire completion (February-December 2011) until 1 June 2018. Up to five causes were classified by an HIV clinician using the ICD-10 system. RESULTS: There were 274 hospitalisations in 153 people (rate = 5.8/100 person-years; 95% CI: 5.1, 6.5). Causes were wide-ranging; the most common were circulatory (16.8%), digestive (13.1%), respiratory (11.7%), infectious diseases (11.0%), injury/poisoning (10.6%), genitourinary diseases (9.9%) and neoplasms (9.1%). A tenth (27/274) of hospitalisations were related to at least one AIDS-defining illness. Median duration of hospitalisation was 5 days (IQR 2-9). At the time of hospitalisation, median CD4 count was high (510 cells/µl; IQR: 315-739), while median CD4 nadir was relatively low (113 cells/µl; IQR: 40-239). At admission, half of individuals (51%) had a previous AIDS-defining illness and 21% had viral load > 50 copies/ml. Individuals admitted for infectious diseases were particularly likely to have unfavourable HIV-related clinical characteristics (low CD4, viral non-suppression, not on antiretroviral therapy (ART), previous AIDS). CONCLUSIONS: In the modern combination antiretroviral therapy era, the spectrum of causes of hospitalisation in PLHIV in the UK is wide-ranging, highlighting the importance of holistic care for PLHIV, including prevention, early detection and treatment of comorbidities.

Hemodiafiltration maintains a sustained improvement in blood pressure compared to conventional hemodialysis in children-the HDF, heart and height (3H) study.

BACKGROUND: Hypertension is prevalent in children on dialysis and associated with cardiovascular disease. We studied the blood pressure (BP) trends and the evolution of BP over 1 year in children on conventional hemodialysis (HD) vs. hemodiafiltration (HDF). METHODS: This is a post hoc analysis of the "3H - HDF-Hearts-Height" dataset, a multicenter, parallel-arm observational study. Seventy-eight children on HD and 55 on HDF who had three 24-h ambulatory BP monitoring (ABPM) measures over 1 year were included. Mean arterial pressure (MAP) was calculated and hypertension defined as 24-h MAP standard deviation score (SDS) ≥95th percentile. RESULTS: Poor agreement between pre-dialysis systolic BP-SDS and 24-h MAP was found (mean difference - 0.6; 95% limits of agreement -4.9-3.8). At baseline, 82% on HD and 44% on HDF were hypertensive, with uncontrolled hypertension in 88% vs. 25% respectively; p < 0.001. At 12 months, children on HDF had consistently lower MAP-SDS compared to those on HD (p < 0.001). Over 1-year follow-up, the HD group had mean MAP-SDS increase of +0.98 (95%CI 0.77-1.20; p < 0.0001), whereas the HDF group had a non-significant increase of +0.15 (95%CI -0.10-0.40; p = 0.23). Significant predictors of MAP-SDS were dialysis modality (ß = +0.83 [95%CI +0.51 - +1.15] HD vs. HDF, p < 0.0001) and higher inter-dialytic-weight-gain (IDWG)% (ß = 0.13 [95%CI 0.06-0.19]; p = 0.0003). CONCLUSIONS: Children on HD had a significant and sustained increase in BP over 1 year compared to a stable BP in those on HDF, despite an equivalent dialysis dose. Higher IDWG% was associated with higher 24-h MAP-SDS in both groups.

The impact of HIV infection on tuberculosis transmission in a country with low tuberculosis incidence: a national retrospective study using molecular epidemiology.

BACKGROUND: HIV is known to increase the likelihood of reactivation of latent tuberculosis to active TB disease; however, its impact on tuberculosis infectiousness and consequent transmission is unclear, particularly in low-incidence settings. METHODS: National surveillance data from England, Wales and Northern Ireland on tuberculosis cases in adults from 2010 to 2014, strain typed using 24-locus mycobacterial-interspersed-repetitive-units-variable-number-tandem-repeats was used retrospectively to identify clusters of tuberculosis cases, subdivided into 'first' and 'subsequent' cases. Firstly, we used zero-inflated Poisson regression models to examine the association between HIV status and the number of subsequent clustered cases (a surrogate for tuberculosis infectiousness) in a strain type cluster. Secondly, we used logistic regression to examine the association between HIV status and the likelihood of being a subsequent case in a cluster (a surrogate for recent acquisition of tuberculosis infection) compared to the first case or a non-clustered case (a surrogate for reactivation of latent infection). RESULTS: We included 18,864 strain-typed cases, 2238 were the first cases of clusters and 8471 were subsequent cases. Seven hundred and fifty-nine (4%) were HIV-positive. Outcome 1: HIV-positive pulmonary tuberculosis cases who were the first in a cluster had fewer subsequent cases associated with them (mean 0.6, multivariable incidence rate ratio [IRR] 0.75 [0.65-0.86]) than those HIV-negative (mean 1.1). Extra-pulmonary tuberculosis (EPTB) cases with HIV were less likely to be the first case in a cluster compared to HIV-negative EPTB cases. EPTB cases who were the first case had a higher mean number of subsequent cases (mean 2.5, IRR (3.62 [3.12-4.19]) than those HIV-negative (mean 0.6). Outcome 2: tuberculosis cases with HIV co-infection were less likely to be a subsequent case in a cluster (odds ratio 0.82 [0.69-0.98]), compared to being the first or a non-clustered case. CONCLUSIONS: Outcome 1: pulmonary tuberculosis-HIV patients were less infectious than those without HIV. EPTB patients with HIV who were the first case in a cluster had a higher number of subsequent cases and thus may be markers of other undetected cases, discoverable by contact investigations. Outcome 2: tuberculosis in HIV-positive individuals was more likely due to reactivation than recent infection, compared to those who were HIV-negative.

Estimation of the worldwide seroprevalence of cytomegalovirus: A systematic review and meta-analysis.

Cytomegalovirus (CMV) infection does not usually produce symptoms when it causes primary infection, reinfection, or reactivation because these three types of infection are all controlled by the normal immune system. However, CMV becomes an important pathogen in individuals whose immune system is immature or compromised, such as the unborn child. Several vaccines against CMV are currently in clinical trials that aim to induce immunity in seronegative individuals and/or to boost the immunity of those with prior natural infection (seropositives). To facilitate estimation of the burden of disease and the need for vaccines that induce de novo immune responses or that boost pre-existing immunity to CMV, we conducted a systematic survey of the published literature to describe the global seroprevalence of CMV IgG antibodies. We estimated a global CMV seroprevalence of 83% (95%UI: 78-88) in the general population, 86% (95%UI: 83-89) in women of childbearing age, and 86% (95%UI: 82-89) in donors of blood or organs. For each of these three groups, the highest seroprevalence was seen in the World Health Organisation (WHO) Eastern Mediterranean region 90% (95%UI: 85-94) and the lowest in WHO European region 66% (95%UI: 56-74). These estimates of the worldwide CMV distribution will help develop national and regional burden of disease models and inform future vaccine development efforts.

Effects of Hemodiafiltration versus Conventional Hemodialysis in Children with ESKD: The HDF, Heart and Height Study.

BACKGROUND: Hypertension and cardiovascular disease are common in children undergoing dialysis. Studies suggest that hemodiafiltration (HDF) may reduce cardiovascular mortality in adults, but data for children are scarce. METHODS: The HDF, Heart and Height study is a nonrandomized observational study comparing outcomes on conventional hemodialysis (HD) versus postdilution online HDF in children. Primary outcome measures were annualized changes in carotid intima-media thickness (cIMT) SD score and height SD score. RESULTS: We enrolled 190 children from 28 centers; 78 on HD and 55 on HDF completed 1-year follow-up. The groups were comparable for age, dialysis vintage, access type, dialysis frequency, blood flow, and residual renal function. At 1 year, cIMT SD score increased significantly in children on HD but remained static in the HDF cohort. On propensity score analysis, HD was associated with a +0.47 higher annualized cIMT SD score compared with HDF. Height SD score increased in HDF but remained static in HD. Mean arterial pressure SD score increased with HD only. Factors associated with higher cIMT and mean arterial pressure SD-scores were HD group, higher ultrafiltration rate, and higher ß2-microglobulin. The HDF cohort had lower ß2-microglobulin, parathyroid hormone, and high-sensitivity C-reactive protein at 1 year; fewer headaches, dizziness, or cramps; and shorter postdialysis recovery time. CONCLUSIONS: HDF is associated with a lack of progression in vascular measures versus progression with HD, as well as an increase in height not seen in the HD cohort. Patient-related outcomes improved among children on HDF correlating with improved BP control and clearances. Confirmation through randomized trials is required.