Interventions to improve linkage along the HIV-tuberculosis care cascades in low- and middle-income countries: A systematic review and meta-analysis.

INTRODUCTION: In support of global targets to end HIV/AIDS and tuberculosis (TB) by 2030, we reviewed interventions aiming to improve TB case-detection and anti-TB treatment among people living with HIV (PLHIV) and HIV testing and antiretroviral treatment initiation among people with TB disease in low- and middle-income countries (LMICs). METHODS: We conducted a systematic review of comparative (quasi-)experimental interventional studies published in Medline or EMBASE between January 2003-July 2021. We performed random-effects effect meta-analyses (DerSimonian and Laird method) for interventions that were homogenous (based on intervention descriptions); for others we narratively synthesized the intervention effect. Studies were assessed using ROBINS-I, Cochrane Risk-of-Bias, and GRADE. (PROSPERO #CRD42018109629). RESULTS: Of 21,516 retrieved studies, 23 were included, contributing 53 arms and 84,884 participants from 4 continents. Five interventions were analyzed: co-location of test and/or treatment services; patient education and counselling; dedicated personnel; peer support; and financial support. A majority were implemented in primary health facilities (n = 22) and reported on HIV outcomes in people with TB (n = 18). Service co-location had the most consistent positive effect on HIV testing and treatment initiation among people with TB, and TB case-detection among PLHIV. Other interventions were heterogenous, implemented concurrent with standard-of-care strategies and/or diverse facility-level improvements, and produced mixed effects. Operational system, human resource, and/or laboratory strengthening were common within successful interventions. Most studies had a moderate to serious risk of bias. CONCLUSIONS: This review provides operational clarity on intervention models that can support early linkages between the TB and HIV care cascades. The findings have supported the World Health Organization 2020 HIV Service Delivery Guidelines update. Further research is needed to evaluate the distinct effect of education and counselling, financial support, and dedicated personnel interventions, and to explore the role of community-based, virtual, and differentiated service delivery models in addressing TB-HIV co-morbidity

Ending AIDS deaths requires improvements in clinical care for people with advanced HIV disease who are seriously ill

Over 4 million adults are living with advanced HIV disease with approximately 650 000 fatalities from HIV reported in 2021. People with advanced HIV disease have low immunity and can present to health services in two ways: those who are well but at high risk of developing severe disease, and those who are severely ill. These two groups require specific management approaches that place different demands on the health system. The first group can generally be supported in primary care settings but require differentiated care to meet their needs. The second group are at high risk of death and need focused diagnostics and clinical care, and possibly hospitalisation. Investments in high-quality clinical management of patients with advanced HIV disease who are seriously ill at primary care or hospital level (often only for a brief period of time during their acute illness) improves the likelihood that their condition will stabilise and that they will recover. Providing high-quality and safe clinical care that is accessible to these groups of people living with HIV who are at risk of severe illness and death is a key priority for reaching the global target of zero AIDS deaths

The hard part we often forget: providing care to children and adolescents with advanced HIV disease

Abstract Introduction Many children and adolescents living with HIV still present with severe immunosuppression with morbidity and mortality remaining high in those starting antiretroviral therapy (ART) when hospitalized. Discussion The major causes of morbidity and mortality in children living with HIV are pneumonia, tuberculosis, bloodstream infections, diarrhoeal disease and severe acute malnutrition. In contrast to adults, cryptococcal meningitis is rare in children under 5 years of age but increases in adolescence. In 2021, the World Health Organizations (WHO) consolidated guidelines for managing HIV disease and rapid ART included recommendations for children and adolescents. In addition, a WHO technical brief released in 2020 highlighted the various interventions that are specifically related to children and adolescents with advanced HIV disease (AHD). We discuss the common clinical presentations of children and adolescents with AHD with a focus on diagnosis, prevention and treatment, highlight some of the challenges in the implementation of the existing package of care, and emphasize the importance of additional research to address the needs of children and adolescents with AHD. Conclusions There are limited data informing these recommendations and an urgent need for further research on how to implement optimal strategies to ensure tailored approaches to prevent and treat AHD in children and adolescents. Holistic care that goes beyond a simple choice of ART regimen should be provided to all children and adolescents with AHD

The hard part we often forget: providing care to children and adolescents with advanced HIV disease

INTRODUCTION: Many children and adolescents living with HIV still present with severe immunosuppression with morbidity and mortality remaining high in those starting antiretroviral therapy (ART) when hospitalized. DISCUSSION: The major causes of morbidity and mortality in children living with HIV are pneumonia, tuberculosis, bloodstream infections, diarrhoeal disease and severe acute malnutrition. In contrast to adults, cryptococcal meningitis is rare in children under 5 years of age but increases in adolescence. In 2021, the World Health Organizations (WHO) consolidated guidelines for managing HIV disease and rapid ART included recommendations for children and adolescents. In addition, a WHO technical brief released in 2020 highlighted the various interventions that are specifically related to children and adolescents with advanced HIV disease (AHD). We discuss the common clinical presentations of children and adolescents with AHD with a focus on diagnosis, prevention and treatment, highlight some of the challenges in the implementation of the existing package of care, and emphasize the importance of additional research to address the needs of children and adolescents with AHD. CONCLUSIONS: There are limited data informing these recommendations and an urgent need for further research on how to implement optimal strategies to ensure tailored approaches to prevent and treat AHD in children and adolescents. Holistic care that goes beyond a simple choice of ART regimen should be provided to all children and adolescents with AHD

Comparative efficacy, tolerability and safety of dolutegravir and efavirenz 400mg among antiretroviral therapies for first-line HIV treatment: A systematic literature review and network meta-analysis

Background: To inform World Health Organization (WHO) global guidelines, we updated and expanded the evidence base to assess the comparative efficacy, tolerability, and safety of first-line antiretroviral therapy (ART) regimens. Methods: We searched Embase, Medline and CENTRAL on 28 February 2020 to update the systematic literature review of clinical trials comparing recommended first-line ART that informed previous WHO guidelines. Outcomes included viral suppression, change in CD4 cell counts, mortality, serious and overall adverse events (AEs), discontinuation, discontinuations due to AEs (DAEs); and new outcomes: drug-resistance, neuropsychiatric AEs, early viral suppression, weight gain and birth outcomes. Comparative effects were assessed through network meta-analyses and certainty in the evidence was assessed using the GRADE framework. Findings: We identified 156 publications pertaining to 68 trials for the primary population. Relative to efavirenz, dolutegravir had improved odds of viral suppression across all time points (odds ratio [OR]: 1·94; 95% credible interval [CrI]: 1·48-2·56 at 96 weeks); was protective of drug-resistance (OR: 0·13; 95%CrI: 0·04-0·48); and led to fewer discontinuations (OR: 0·58; 95%CrI: 0·48-0·70). Evidence supported dolutegravir use among TB-HIV co-infected persons and pregnant women. Adverse birth outcomes were observed in 33.2% of dolutegravir-managed pregnancies and 35.0% of efavirenz-managed pregnancies. Low-dose efavirenz had comparable efficacy and safety to standard-dose efavirenz, but led to fewer DAEs (OR: 0·70; 95%CrI: 0·50-0·92). Interpretation: The evidence supports choosing dolutegravir in combination with lamivudine/emtricitabine and tenofovir disoproxil fumarate as the preferred first-line regimen and low-dose efavirenz-based regimens as an alternative. Dolutegravir can be considered to be effective, safe and tolerable. Funding: WHO.</p

Acute undifferentiated febrile illness in patients presenting to a Tertiary Care Hospital in South India: clinical spectrum and outcome

Background: Acute undifferentiated febrile illness (AUFI) may have similar clinical presentation, and the etiology is varied and region specific. Materials and Methods: This prospective observational study was conducted in a tertiary hospital in South India. All adult patients presenting with AUFI of 3-14 days duration were evaluated for etiology, and the differences in presentation and outcome were analyzed. Results: The study cohort included 1258 patients. A microbiological cause was identified in 82.5% of our patients. Scrub typhus was the most common cause of AUFI (35.9%) followed by dengue (30.6%), malaria (10.4%), enteric fever (3.7%), and leptospirosis (0.6%). Both scrub typhus and dengue fever peaked during the monsoon season and the cooler months, whereas no seasonality was observed with enteric fever and malaria. The mean time to presentation was longer in enteric fever (9.9 [4.7] days) and scrub typhus (8.2 [3.2] days). Bleeding manifestations were seen in 7.7% of patients, mostly associated with dengue (14%), scrub typhus (4.2%), and malaria (4.6%). The requirement of supplemental oxygen, invasive ventilation, and inotropes was higher in scrub typhus, leptospirosis, and malaria. The overall mortality rate was 3.3% and was highest with scrub typhus (4.6%) followed by dengue fever (2.3%). Significant clinical predictors of scrub typhus were breathlessness (odds ratio [OR]: 4.96; 95% confidence interval [CI]: 3.38-7.3), total whole blood cell count >10,000 cells/mm 3 (OR: 2.31; 95% CI: 1.64-3.24), serum albumin <3.5 g % (OR: 2.32; 95% CI: 1.68-3.2). Overt bleeding manifestations (OR: 2.98; 95% CI: 1.84-4.84), and a platelet count of <150,000 cells/mm 3 (OR: 2.09; 95% CI: 1.47-2.98) were independent predictors of dengue fever. Conclusion: The similarity in clinical presentation and diversity of etiological agents demonstrates the complexity of diagnosis and treatment of AUFI in South India. The etiological profile will be of use in the development of rational guidelines for control and treatment of AUFI