Severity of Respiratory Syncytial Virus vs COVID-19 and Influenza Among Hospitalized US Adults.

Importance: On June 21, 2023, the Centers for Disease Control and Prevention recommended the first respiratory syncytial virus (RSV) vaccines for adults aged 60 years and older using shared clinical decision-making. Understanding the severity of RSV disease in adults can help guide this clinical decision-making. Objective: To describe disease severity among adults hospitalized with RSV and compare it with the severity of COVID-19 and influenza disease by vaccination status. Design, Setting, and Participants: In this cohort study, adults aged 18 years and older admitted to the hospital with acute respiratory illness and laboratory-confirmed RSV, SARS-CoV-2, or influenza infection were prospectively enrolled from 25 hospitals in 20 US states from February 1, 2022, to May 31, 2023. Clinical data during each patient's hospitalization were collected using standardized forms. Data were analyzed from August to October 2023. Exposures: RSV, SARS-CoV-2, or influenza infection. Main Outcomes and Measures: Using multivariable logistic regression, severity of RSV disease was compared with COVID-19 and influenza severity, by COVID-19 and influenza vaccination status, for a range of clinical outcomes, including the composite of invasive mechanical ventilation (IMV) and in-hospital death. Results: Of 7998 adults (median [IQR] age, 67 [54-78] years; 4047 [50.6%] female) included, 484 (6.1%) were hospitalized with RSV, 6422 (80.3%) were hospitalized with COVID-19, and 1092 (13.7%) were hospitalized with influenza. Among patients with RSV, 58 (12.0%) experienced IMV or death, compared with 201 of 1422 unvaccinated patients with COVID-19 (14.1%) and 458 of 5000 vaccinated patients with COVID-19 (9.2%), as well as 72 of 699 unvaccinated patients with influenza (10.3%) and 20 of 393 vaccinated patients with influenza (5.1%). In adjusted analyses, the odds of IMV or in-hospital death were not significantly different among patients hospitalized with RSV and unvaccinated patients hospitalized with COVID-19 (adjusted odds ratio [aOR], 0.82; 95% CI, 0.59-1.13; P = .22) or influenza (aOR, 1.20; 95% CI, 0.82-1.76; P = .35); however, the odds of IMV or death were significantly higher among patients hospitalized with RSV compared with vaccinated patients hospitalized with COVID-19 (aOR, 1.38; 95% CI, 1.02-1.86; P = .03) or influenza disease (aOR, 2.81; 95% CI, 1.62-4.86; P < .001). Conclusions and Relevance: Among adults hospitalized in this US cohort during the 16 months before the first RSV vaccine recommendations, RSV disease was less common but similar in severity compared with COVID-19 or influenza disease among unvaccinated patients and more severe than COVID-19 or influenza disease among vaccinated patients for the most serious outcomes of IMV or death.

Disease Severity of Respiratory Syncytial Virus Compared with COVID-19 and Influenza Among Hospitalized Adults Aged ≥60 Years - IVY Network, 20 U.S. States, February 2022-May 2023.

On June 21, 2023, CDC's Advisory Committee on Immunization Practices recommended respiratory syncytial virus (RSV) vaccination for adults aged ≥60 years, offered to individual adults using shared clinical decision-making. Informed use of these vaccines requires an understanding of RSV disease severity. To characterize RSV-associated severity, 5,784 adults aged ≥60 years hospitalized with acute respiratory illness and laboratory-confirmed RSV, SARS-CoV-2, or influenza infection were prospectively enrolled from 25 hospitals in 20 U.S. states during February 1, 2022-May 31, 2023. Multivariable logistic regression was used to compare RSV disease severity with COVID-19 and influenza severity on the basis of the following outcomes: 1) standard flow (<30 L/minute) oxygen therapy, 2) high-flow nasal cannula (HFNC) or noninvasive ventilation (NIV), 3) intensive care unit (ICU) admission, and 4) invasive mechanical ventilation (IMV) or death. Overall, 304 (5.3%) enrolled adults were hospitalized with RSV, 4,734 (81.8%) with COVID-19 and 746 (12.9%) with influenza. Patients hospitalized with RSV were more likely to receive standard flow oxygen, HFNC or NIV, and ICU admission than were those hospitalized with COVID-19 or influenza. Patients hospitalized with RSV were more likely to receive IMV or die compared with patients hospitalized with influenza (adjusted odds ratio = 2.08; 95% CI = 1.33-3.26). Among hospitalized older adults, RSV was less common, but was associated with more severe disease than COVID-19 or influenza. High disease severity in older adults hospitalized with RSV is important to consider in shared clinical decision-making regarding RSV vaccination.

Contraception and intersection with HIV services in 11 high HIV burden sub-Saharan African countries: Results from the population-based HIV Impact Assessment cross-sectional studies conducted from 2015 to 2018.

OBJECTIVE: The United Nations' Sustainable Development Goal 3.7.1 addresses the importance of family planning. The objective of this paper is to provide information on family planning to policymakers to help increase access to contraceptive methods to women in sub-Saharan Africa. METHODS: We analyzed data from the Population-based HIV Impact Assessment studies conducted in 11 sub-Saharan African countries from 2015 to 2018 to assess the relationship between HIV services and family planning. Analyses were restricted to women aged 15-49 years who reported being sexually active within the past 12 months and had data on contraceptive use. RESULTS: Approximately 46.4% of participants reported using any form of contraception; 93.6% of whom used modern contraceptives. Women with a positive HIV status were more likely to use contraceptives (P < 0.0001) than HIV-negative women. Unmet need was higher among women who were confirmed to be HIV-negative in Namibia, Uganda, and Zambia than confirmed to be positive. Women aged 15-19 years used contraception less than 40% of the time. CONCLUSION: This analysis highlights crucial gaps in progress among HIV-negative and young women (aged 15-19 years). To provide access to modern contraception for all women, programs and governments need to focus on women who desire but do not have access to these family planning resources.

Tuberculosis care models for children and adolescents: a scoping review.

Objective: To map which tuberculosis care models are best suited for children and adolescents. Methods: We conducted a scoping review to assess the impact of decentralized, integrated and family-centred care on child and adolescent tuberculosis-related outcomes, describe approaches for these care models and identify key knowledge gaps. We searched seven literature databases on 5 February 2021 (updated 16 February 2022), searched the references of 18 published reviews and requested data from ongoing studies. We included studies from countries with a high tuberculosis burden that used a care model of interest and reported tuberculosis diagnostic, treatment or prevention outcomes for an age group < 20 years old. Findings: We identified 28 studies with a comparator group for the impact assessment and added 19 non-comparative studies to a qualitative analysis of care delivery approaches. Approaches included strengthening capacity in primary-level facilities, providing services in communities, screening for tuberculosis in other health services, co-locating tuberculosis and human immunodeficiency virus treatment, offering a choice of treatment location and providing social or economic support. Strengthening both decentralized diagnostic services and community linkages led to one-to-sevenfold increases in case detection across nine studies and improved prevention outcomes. We identified only five comparative studies on integrated or family-centred care, but 11 non-comparative studies reported successful treatment outcomes for at least 71% of children and adolescents. Conclusion: Strengthening decentralized services in facilities and communities can improve tuberculosis outcomes for children and adolescents. Further research is needed to identify optimal integrated and family-centred care approaches.

Growth and Metabolic Changes After Antiretroviral Initiation in South African Children.

BACKGROUND: Poor growth and metabolic disturbances remain concerns for children living with HIV (CLHIV). We describe the impact of viral load (VL) on growth and lipid outcomes in South African CLHIV <12 years initiating World Health Organization recommended first-line antiretroviral therapy (ART) from 2012 to 2015. METHODS: Z scores for length-for-age (LAZ), weight-for-age (WAZ) and body mass index-for-age were calculated. Lipids (total cholesterol, low-density lipoprotein and high-density lipoprotein) were measured. Hemoglobin A1C ≥5.8 was defined as at risk for type 2 diabetes. Mixed effects models were used to assess the association of VL at ART initiation with Z scores and lipids over time. RESULTS: Of 241 CLHIV, 151 (63%) were <3 years initiating LPV/r-based ART and 90 (37%) were ≥3 years initiating EFV-based ART. Among CLHIV <3 years, higher VL at ART initiation was associated with lower mean LAZ (ß: -0.30, P=0.03), WAZ (ß: -0.32, P=0.01) and low-density lipoprotein (ß: -6.45, P=0.03) over time. Among CLHIV ≥3, a log 10 increase in pretreatment VL was associated with lower mean LAZ (ß: -0.29, P=0.07) trending towards significance and lower WAZ (ß: -0.32, P=0.05) as well as with more rapid increases in LAZ (ß: 0.14 per year, P=0.01) and WAZ (ß: 0.19 per year, P=0.04). Thirty percent of CLHIV were at risk for type 2 diabetes at ART initiation. CONCLUSIONS: CLHIV initiating ART <3 years exhibited positive gains in growth and lipids, though high viremia at ART initiation was associated with persistently low growth and lipids, underscoring the need for early diagnosis and rapid treatment initiation. Future studies assessing the long-term cardiometabolic impact of these findings are warranted.

Expansion and scale-up of HIV care and treatment services in four countries over ten years.

BACKGROUND: Scale-up and expansion of antiretroviral therapy (ART) for people living with HIV (PLHIV) have been a global priority for more than 15 years. METHODS: We describe PLHIV at enrollment in care and ART initiation in Ethiopia, Kenya, Mozambique and Tanzania from 2005-2014 and report on enrollment location, CD4 count and loss to follow-up (LTF), death, and combined attrition (LTF and death) pre- and post-ART initiation over time. Pre-ART outcomes were estimated using competing risk and post-ART using Kaplan-Meier estimators; LTF defined as no visit within six months pre-ART and 12 months after ART start. RESULTS: From 2005-2014, 884,328 PLHIV enrolled in care at 350 health facilities, median age was 32.0 years (interquartile range [IQR] 26.0-42.0), and majority were female (66.5%). The proportion of PLHIV enrolled at primary and rural facilities increased from 12.9% and 15.3% in 2005-2006 to 43.5% and 41.7% in 2013-2014 (p<0.0001). Median CD4+ cell count at enrollment increased from 171 cell/mm3 in 2005-2006 (IQR 71-339) to 289 cell/mm3 in 2013-2014 (IQR 133-485) (p<0.0001). A total of 460,758 (57.4%) PLHIV initiated treatment. Cumulative risk of LTF for PLHIV prior to ART initiation 12 months after enrollment was 33.5% (95%CI 33.36-33.58) and 21.98% (95%CI 21.9-22.1) after ART initiation. Pregnant women and the youngest PLHIV group had the highest attrition after ART initiation, at 24 months 40.8% (95%CI 40.1-41.6) of pregnant women and 47.4% (95%CI 46.4-48.4) of PLHIV 15-19 years were not retained. Attrition at 12 months after enrollment among PLHIV regardless of ART status was 38.5% (95%CI 38.4-38.6). CONCLUSION: Over 10 years of HIV scale-up in four sub-Saharan African countries, close to a million PLHIV were enrolled in care increasingly at rural and primary facilities with increasing CD4 count. Loss to follow-up from HIV care remains alarmingly high, particularly among pregnant women and younger PLHIV.

Delays in fast track antiretroviral therapy initiation and reasons for not starting treatment among eligible children in Eastern Cape, South Africa.

: We report data from an observational cohort of South African children living with HIV less than 12 years of age eligible for fast track antiretroviral therapy (rapid) initiation. We found that less than half of children eligible for rapid antiretroviral therapy initiation based on immunologic and disease status started treatment within 1 week.

Effect of Antiretroviral Therapy on Treatment Outcomes in a Prospective Study of Extensively Drug-Resistant Tuberculosis (XDR-TB) HIV Coinfection Treatment in KwaZulu-Natal, South Africa.

BACKGROUND: Extensively drug-resistant tuberculosis (XDR-TB)/HIV coinfection has been associated with high mortality and poor TB outcomes. We performed a prospective study to comprehensively characterize a cohort of patients with XDR-TB. METHODS: Adult patients with XDR-TB were enrolled at treatment initiation at a TB referral hospital in KwaZulu-Natal Province, South Africa, and followed through the end of treatment. Clinical data, questionnaires, adherence data, and sputum were collected monthly. Whole genome sequencing was performed on baseline Mycobacterium tuberculosis (MTB) isolates. Treatment outcomes were defined using standard definitions. RESULTS: One hundred five patients with XDR-TB (76.1% HIV-infected) were enrolled from August 2009 to July 2011. Among HIV-coinfected patients, 82.5% were on antiretroviral therapy initially and 93.8% cumulatively over the study period. At 24 months, 31.4% had a successful outcome and 68.6% had an unsuccessful outcome with 41% mortality. Antiretroviral therapy was associated with improved mortality in HIV-coinfected patients (P = 0.05), as was TB culture conversion (P < 0.0001). On whole genome sequencing, most strains were LAM4/KZN lineage (68%), with few single nucleotide polymorphism differences. CONCLUSIONS: Despite improved HIV care, treatment outcomes and mortality were only modestly improved compared with previous South African XDR-TB/HIV treatment cohorts. Of note, this study was completed before the introduction of new antimycobacterial agents (eg, bedaquiline and delamanid). As new TB drugs and regimens become available, it is important to monitor treatment to ensure that benefits seen in clinical trials are reproduced in high-burden, low-resource settings.

HIV viral suppression and longevity among a cohort of children initiating antiretroviral therapy in Eastern Cape, South Africa.

INTRODUCTION: There are limited data on viral suppression (VS) in children with HIV receiving antiretroviral therapy (ART) in routine care in low-resource settings. We examined VS in a cohort of children initiating ART in routine HIV care in Eastern Cape Province, South Africa. METHODS: The Pediatric Enhanced Surveillance Study enrolled HIV-infected ART eligibility children zero to twelve years at five health facilities from 2012 to 2014. All children received routine HIV care and treatment services and attended quarterly study visits for up to 24 months. Time to VS among those starting treatment was measured from ART start date to first viral load (VL) result <1000 and VL <50 copies/mL using competing risk estimators (death as competing risk). Multivariable sub-distributional hazards models examined characteristics associated with VS and VL rebound following suppression among those with a VL >30 days after the VS date. RESULTS: Of 397 children enrolled, 349 (87.9%) started ART: 118 (33.8%) children age <12 months, 122 (35.0%) one to five years and 109 (31.2%) six to twelve years. At study enrolment, median weight-for-age z-score (WAZ) was -1.7 (interquartile range (IQR):-3.1 to -0.4) and median log VL was 5.6 (IQR: 5.0 to 6.2). Cumulative incidence of VS <1000 copies/mL at six, twelve and twenty-four months was 57.6% (95% CI 52.1 to 62.7), 78.7% (95% CI 73.7 to 82.9) and 84.0% (95% CI 78.9 to 87.9); for VS <50 copies/mL: 40.3% (95% CI 35.0 to 45.5), 63.9% (95% CI 58.2 to 69.0) and 72.9% (95% CI 66.9 to 78.0). At 12 months only 46.6% (95% CI 36.6 to 56.0) of children <12 months had achieved VS <50 copies/mL compared to 76.9% (95% CI 67.9 to 83.7) of children six to twelve years (p < 0.001). In multivariable models, children with VL >1 million copies/mL at ART initiation were half as likely to achieve VS <50 copies/mL (adjusted sub-distributional hazards 0.50; 95% CI 0.36 to 0.71). Among children achieving VS <50 copies/mL, 37 (19.7%) had VL 50 to 1000 copies/mL and 31 (16.5%) had a VL >1000 copies/mL. Children <12 months had twofold increased risk of VL rebound to VL >1000 copies/mL (adjusted relative risk 2.03, 95% CI: 1.10 to 3.74) compared with six to twelve year olds. CONCLUSIONS: We found suboptimal VS among South African children initiating treatment and high proportions experiencing VL rebound, particularly among younger children. Greater efforts are needed to ensure that all children achieve optimal outcomes.

High risk of loss to follow-up among South African children on ART during transfer, a retrospective cohort analysis with community tracing.

INTRODUCTION: Decentralization of HIV care for children has been recommended to improve paediatric outcomes by making antiretroviral treatment (ART) more accessible. We documented outcomes of children transferred after initiating ART at a large tertiary hospital in the Eastern Cape of South Africa. METHODS: Electronic medical records for all children 0-15 years initiating ART at Dora Nginza Hospital (DNH) in Port Elizabeth, South Africa January 2004 to September 2015 were examined. Records for children transferred to primary and community clinics were searched at 16 health facilities to identify children with successful (at least one recorded visit) and unsuccessful transfer (no visits). We identified all children lost to follow-up (LTF) after ART initiation: those LTF at DNH (no visit >6 months), children with unsuccessful transfer, and children LTF after successful transfer (no visit >6 months). Community tracing was conducted to locate caregivers of children LTF and electronic laboratory data were searched to measure reengagement in care, including silent transfers. RESULTS: 1,582 children initiated ART at median age of 4 years [interquartile range (IQR): 1-8] and median CD4+ of 278 cells/mm3 [IQR: 119-526]. A total of 901 (57.0%) children were transferred, 644 (71.5%) to study facilities; 433 (67.2%) children had successful transfer and 211 (32.8%) had unsuccessful transfer. In total, 399 children were LTF: 105 (26.3%) from DNH, 211 (52.9%) through unsuccessful transfer and 83 (20.8%) following successful transfer. Community tracing was conducted for 120 (30.1%) of 399 children LTF and 66 (55.0%) caregivers were located and interviewed. Four children had died. Among 62 children still alive, 8 (12.9%) were reported to not be in care or taking ART and 18 (29.0%) were also not taking ART. Overall, 65 (16.3%) of 399 children LTF had a laboratory result within 18 months of their last visit indicating silent transfer and 112 (28.1%) had lab results from 2015 to 2016 indicating current care. CONCLUSION: We found that only two-thirds of children on ART transferred to primary and community health clinics had successful transfer. These findings suggest that transfer is a particularly vulnerable step in the paediatric HIV care cascade.

Using mHealth for HIV/TB Treatment Support in Lesotho: Enhancing Patient-Provider Communication in the START Study.

BACKGROUND: mHealth is a promising means of supporting adherence to treatment. The Start TB patients on ART and Retain on Treatment (START) study included real-time adherence support using short-text messaging service (SMS) text messaging and trained village health workers (VHWs). We describe the use and acceptability of mHealth by patients with HIV/tuberculosis and health care providers. METHODS: Patients and treatment supporters received automated, coded medication and appointment reminders at their preferred time and frequency, using their own phones, and $3.70 in monthly airtime. Facility-based VHWs were trained to log patient information and text message preferences into a mobile application and were given a password-protected mobile phone and airtime to communicate with community-based VHWs. The use of mHealth tools was analyzed from process data over the study course. Acceptability was evaluated during monthly follow-up interviews with all participants and during qualitative interviews with a subset of 30 patients and 30 health care providers at intervention sites. Use and acceptability were contextualized by monthly adherence data. FINDINGS: From April 2013 to August 2015, the automated SMS system successfully delivered 39,528 messages to 835 individuals, including 633 patients and 202 treatment supporters. Uptake of the SMS intervention was high, with 92.1% of 713 eligible patients choosing to receive SMS messages. Patient and provider interviews yielded insight into barriers and facilitators to mHealth utilization. The intervention improved the quality of health communication between patients, treatment supporters, and providers. HIV-related stigma and technical challenges were identified as potential barriers. CONCLUSIONS: The mHealth intervention for HIV/tuberculosis treatment support in Lesotho was found to be a low-tech, user-friendly intervention, which was acceptable to patients and health care providers.