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Introduction: Uganda has made significant progress in expanding access to ART over the years, however, currently up to 50% of People Living with HIV still enroll into HIV care with Advanced HIV Disease (AHD). This study therefore seeks to evaluate the screening, diagnosis and treatment of AHD at a high volume not for profit health facility in an urban setting in Southwestern Uganda. Methods: A cross-sectional study utilizing secondary data from a high volume, nonprofit health facility in southwestern Uganda was conducted from April 2022 to August 2022. The analysis included patient records for 994 newly diagnosed individuals and 76 patients who were not virologically suppressed. A descriptive analysis of the data was conducted, and the two groups (newly diagnosed and non-suppressed) were compared using chi-square tests or Fisher's exact test for categorical data, as well as the Mann Whitney U test for numerical data. Results: The prevalence of AHD as defined by a CD4 + cell count below 200 cells/mm3 or WHO clinical stage 3 or 4 disease was 21.7% (216/994). The prevalence of AHD was considerably higher among males (32.5%) compared to females (13.9%) (p value < 0.001). CD4 + testing for AHD was at 74.5% (741/994) among newly enrolled patients compared to 77.6% (59/76) among virally non suppressed patients (p = 0.822). Serum CrAg testing among patients with AHD was higher among the newly enrolled HIV clients at 60.6% (131/216) compared to non-suppressed clients; 22.2% (6/27) (p < 0.001). Additionally, there was no significant difference in administration of fluconazole between the two groups (p = 0.476). Among the patients with AHD, the proportion of patient tested for TB using urine TB_LAM was higher among the newly enrolled patients (45.9%) compared to the non-suppressed clients (21.4%), and this difference was statistically significant (p = 0.010). Conclusion: This study demonstrates that the prevalence of AHD remains high, and the implementation of the AHD intervention package remains sub-optimal. The Ministry of Health and partners need to strengthen implementation strategies to improve the screening, diagnosis, and management of AHD. [ABSTRACT FROM AUTHOR]

Background: Advanced HIV disease (AHD) is still a significant problem in Uganda despite the test-and-treat strategy and the increased access to antiretroviral therapy (ART). Meningitis remains a major cause of morbidity and mortality in people with AHD. HIV counselling is essential and plays an important role in managing persons with AHD-related meningitis. We sought to describe the experiences and challenges we faced during counselling of these individuals, highlighting the strategies, gaps and how we can fill them. Methods: First, we describe our experience and major challenges in counselling people with AHD-related meningitis. Second, we describe the strategies we used to overcome each of these challenges. Third, we highlight the health system gaps and recommend solutions. Results: Major challenges include the presence of altered mental status, unknown HIV status at admission, non-disclosure of HIV status to family, insufficient ART history, caretakers-related challenges, pill burden, multiple drug side effects, invasive clinical procedures, myths about medical procedures, poverty, lack of privacy during counselling in the wards, patients/caretakers seeking alternative non-medical interventions including religious, traditional, and herbal therapies before and after initiating meningitis treatment. Conclusions: Persons with AHD-related meningitis need daily and special consideration during counselling as part of the package of care to improve treatment outcomes. Trial registrations: NCT01075152 (23 Feb 2010), NCT01802385 (28 Feb 2013), ISRCTN42218549 (24 April 2018), ISRCTN72509687 (13 July 2017), NCT04031833 (01 January 2019), ISRCTN15668391 (23 May 2019), ISRCTN18437550 (05/11/2021). [ABSTRACT FROM AUTHOR]

Background In 2022, the World Health Organization (WHO) recommended a single 10 mg/kg dose of liposomal amphotericin B in combination with 14 days of flucytosine and fluconazole (AMBITION-cm regimen) for induction therapy of human immunodeficiency virus (HIV)-associated cryptococcal meningitis, based on the results of the multisite AMBITION-cm trial. We evaluated outcomes after real-world implementation of this novel regimen in Uganda. Methods We enrolled Ugandan adults with cryptococcal meningitis into an observational cohort receiving the AMBITION-cm regimen with therapeutic lumbar punctures in routine care during 2022–2023. We compared 10-week survival and CSF early fungicidal activity with the outcomes observed in the AMBITION-cm clinical trial conducted at the same sites. Results During 2022–2023, 179 adults were treated with the AMBITION-cm regimen via routine care and compared to the 171 adults randomized to the AMBITION-cm trial interventional arm in Uganda from 2018 to 2021. No significant difference in 10-week survival occurred between the observational cohort (68.6%; 95% confidence interval [CI]: 61.6%–76.3%) and AMBITION-cm trial participants in the intervention arm (71.7%; 95% CI: 65.2%–78.8%; absolute risk difference = −3.1%; 95% CI: −13.1% to 6.9%; P =.61). Early fungicidal activity did not differ (0.42 vs 0.39 log10CFU/mL/day; P =.80) between groups. Among observational cohort participants discharged alive initially and for whom follow-up data were available, the incidence of re-hospitalizations due to persistently elevated intracranial pressure was 2.8% (4/144). Conclusions The AMBITION-cm regimen for cryptococcal meningitis resulted in similar outcomes as observed in the AMBITION-cm clinical trial when implemented in routine care. Intracranial pressure management during hospitalization and awareness after discharge are key components of optimizing outcomes. [ABSTRACT FROM AUTHOR]

Background: Under South Africa's Universal Test and Treat (UTT) policy, CD4 counts are no longer required to determine HIV treatment eligibility. However, CD4 count at presentation remains an important marker of disease progression. We assessed whether CD4 testing declined in the UTT era and, if so, by how much. Methods: We analysed CD4 count data from the National Health Laboratory Service (NHLS) National HIV Cohort and TIER.Net database for individuals in HIV care across five South African provinces. "First CD4 count" was defined as the first CD4 test recorded for each patient. In TIER.Net, "date of presentation" was the earliest date of HIV testing, CD4 measurement, or clinic visit. Trends in first CD4 testing volumes (2004–2018) were analyzed, with interrupted time-series analyses assessing the impact of UTT (September 2016). Results: Data included 5,274,218 (NHLS) and 2,265,557 (TIER.Net) individuals with a first CD4 count. In NHLS, first CD4 counts increased from 47,604 in 2004 to 383,705 in 2010 and then declined. Lower volumes were recorded in TIER.Net. Adjusting for prior trends, first CD4 counts increased slightly after UTT, by 32 individuals/day in NHLS (95% CI: − 6 to 61) and 88 individuals/day in TIER.Net (95% CI: 30 to 148). Among TIER.Net patients, the percentage with a CD4 count decreased by 4.3% (95% CI: − 5.2 to − 3.0%). Conclusions: We found no major decline in CD4 testing at presentation following UTT, contrasting findings from resource-constrained settings with greater reliance on external donors. [ABSTRACT FROM AUTHOR]

Background: The Visitect CD4 Advanced Disease test (AccuBio, Alva, United Kingdom) is a rapid, semiquantitative assay that estimates CD4 results above or below 200 cells per microliter. We evaluated the performance of the Visitect CD4 assay in semiurban laboratories in Uganda. Methods: We performed a pragmatic laboratory validation of the Visitect CD4 platform in 4 routine HIV clinics in Uganda, nested within a cluster randomized trial evaluating an enhanced package of screening and treatment for persons with advanced HIV disease (NCT05085171). As part of the clinical trial, samples processed on the Visitect CD4 platform were confirmed using another CD4 testing method. We compared the diagnostic performance of the Visitect CD4 platform against the confirmatory method by evaluating the sensitivity, specificity, and positive and negative predictive values. Results: Of 1495 venous blood samples that were processed both by the Visitect CD4 test and another confirmatory CD4 platform at clinics in Kampala, Uganda, specificity was 81% [95% confidence interval (CI): 79% to 84%] and the positive predictive value was 69% (95% CI: 66% to 73%). There were no samples for which the Visitect test was >200 cells per microliter and the confirmatory test was ≤200 cells per microliter, resulting in a sensitivity of 100%. Among Visitect CD4 tests that were read as ≤200 cells per microliter with confirmatory results >200 cells per microliter, the median confirmatory CD4 result was 397 (IQR, 281-590) cells per microliter. Specificity varied by clinic ranging from 63% to 99%. Conclusions: Given variable specificity of the Visitect CD4 Advanced Disease platform, successful implementation will require consideration of clinic context and laboratory staffing. [ABSTRACT FROM AUTHOR]

Background and Aims: Sub‐Saharan Africa drives global HIV‐related mortality, and patients continuously present with advanced HIV disease (AHD) at diagnosis. We describe prevalence, predictors, and treatment outcomes in HIV clients with AHD. Methods: We systematically reviewed PUBMED, SCOPUS, Web of Science, JSTOR, and CINAHL for relevant studies conducted in Sub‐Saharan Africa from 2010 to 2022. We used a narrative synthesis to describe included studies and a random effect meta‐analysis to determine AHD pooled prevalence. The Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) checklist guided the reporting, while the Joanna Briggs Institute's quality assessment checklist assessed the quality of included articles. Cochrane's Q and the I2 tests assessed heterogeneity between included studies. Results: We included 24 studies with a sample size of 322,676. Prevalence of AHD ranged from 11.0% to 89.7% with an overall pooled prevalence of 58.7% (95% CI: 51.3%, 66.0%): 66.1% (95% CI: 58.8%, 73.4%) between 2010 and 2016, and 51.2% (95% CI: 37.7%, 64.6%) from 2017 to 2022. Predictors of AHD include male sex, older age (≥ 35), widowed or divorced, unemployment, gap in care of ≥ 12 months before antiretroviral therapy (ART) initiation, no history of HIV testing, and seeking care from a traditional healer before presenting for HIV care. Loss to follow‐up ranged from 6.7%–58.3%, while the proportion of death ranged from 1.8%–13.1%. Predictors of death were being male, advanced age (≥ 50 years), advanced clinical stages, late ART initiation, higher mean log viral load, CD4+ cell count < 50 cells/mm3 and severe anaemia. Conclusions: The high baseline prevalence of AHD suggests the need for targeted, people‐centred HIV testing in Sub‐Saharan Africa. Country HIV programs should accelerate the implementation of comprehensive HIV services that identify clients at risk of AHD for early enrolment with systems for monitoring the WHO care package for preventing, diagnosing, and treating AHD and associated comorbid conditions. PROSPERO number: 2022 CRD42022336487. [ABSTRACT FROM AUTHOR]

Abstract Introduction Recent studies have indicated a high enduring burden of advanced HIV disease, but estimates across regions and settings are lacking. The aim of this study was to estimate the prevalence of advanced HIV disease since 2015 among those people with CD4 measured in healthcare settings, disaggregated by age group, level of healthcare and region. Methods We searched MedLine via Pubmed and Hinari for studies that reported the proportion of individuals with advanced HIV disease (defined as CD4 cell count

Histoplasmosis is a fungal disease associated with substantial mortality rates among persons with advanced HIV disease. Our systematic review synthesized data on the global prevalence of Histoplasma­-caused antigenuria in persons with HIV. We searched PubMed/Medline, Embase, and Scopus databases on January 3, 2023, to identify cross-sectional and cohort studies evaluating Histoplasma antigenuria prevalence among adults with HIV infection. We calculated point estimates and 95% CIs to summarize prevalence. Of 1,294 studies screened, we included 15. We found Histoplasma antigenuria among 581/5,096 (11%; 95% CI 11%–12%) persons with HIV and 483/3,789 persons with advanced HIV disease (13%; 95% CI 12%–14%). Among persons with HIV and symptoms consistent with histoplasmosis, Histoplasma antigenuria prevalence was 14% (95% CI 13%–15%; 502/3,631 participants). We determined that persons with advanced HIV disease, inpatients, and symptomatic persons might benefit from a systematic approach to early detection of histoplasmosis using urine antigen testing.

Abstract Background Implementation of the World Health Organization (WHO) recommended Advanced HIV Disease screening package, remains poor in most settings with limited resources. More than 50% of newly diagnosed-HIV clients are missed on screening as a result of implementation barriers. It is important to mitigate the existing barriers and leverage enablers’ inorder to maximize uptake of the advanced HIV disease screening. This study aimed to identify strategies for scaling up implementation of advanced HIV disease screening among newly HIV-diagnosed clients in pre-ART phase using a Consolidated Framework for Implementation Research-Expert Recommendation for Implementing Change (CFIR-ERIC) guiding tool. Methods A qualitative study was conducted at Rumphi district hospital in Malawi (August – September, 2023). Two sessions of Focus group discussions (FDGs) involving key stakeholders were facilitated to identify specific strategies following the initial study on exploration of barriers and facilitators of advanced HIV disease screening package. Participants comprised healthcare providers, purposively selected from key hospital departments. A deductive approach was used to analyze FDG transcripts where emerging themes were mapped with ERIC list of strategies. CFIR-ERIC Matching tool version 1.0, was used to generate an output of the most to least expert-endorsed Level 1 and Level 2 strategies. Findings About 25 key healthcare workers participated in FDGs. Overall, 6 Level 1 strategies (≥ 50% expert endorsement score) and 4 Level 2 strategies (≥ 20%, ≤ 49% expert endorsement score) were identified, targeting barriers associated with availability of resources, intervention complexity, access to knowledge and information, communication; and implementation leads. Most of the reported strategies were cross-cutting and aimed at enhancing clinical knowledge of the intervention (distributing training materials, educational meetings), developing stakeholders’ interrelations (network weaving) as well as improving clinical workflow (environmental restructuring). Use of evaluative and iterative strategies such as monthly data collection for evaluation were also recommended as part of continuous improvement while an AHD coordinator was recommended to be formally appointed inorder to spearhead coordination of AHD screening services. Conclusion Through the involvement of key stakeholders and the use of CFIR-ERIC matching tool, this study has identified cross-cutting strategies that if well implemented, can help to mitigate contextual barriers and leverage enablers for an improved delivery of AHD screening package.

Abstract Background Despite HIV's evolution to a chronic disease, the burden of advanced HIV disease (AHD, defined as a CD4 count of

Anderson Bendera,1 Deogratias Mugisha Baryomuntebe,2 Nwanna Uchechukwu Kevin,3 Miisa Nanyingi,4 Patience Bemanya Kinengyere,5 Salaam Mujeeb,6 Esther Jachi Sulle7 1Department of Radiology and Medical Imaging, Monduli District Hospital, Arusha, Tanzania; 2Faculty of Nursing, Fins Medical University, Kampala, Uganda; 3Department of Community Health, University of Rwanda, Kigali, Rwanda; 4Department of Health Sciences, Uganda Martyrs University, Kampala, Uganda; 5AiKA Health Consults, Kampala, Uganda; 6Department of Pathology, Islamic University in Uganda, Kampala, Uganda; 7Credit Department, WEDAC Microfinance Institution Ltd, Arusha, TanzaniaCorrespondence: Anderson Bendera, Department of Radiology and Medical Imaging, Monduli District Hospital, P. O. Box 12, Arusha, Tanzania, Email andybendera@gmail.comBackground: About half of people infected with Human Immunodeficiency Virus (HIV) often present late for care, resulting in higher healthcare costs, undesired treatment outcomes, and ongoing HIV transmission. This study aimed to assess the prevalence and determinants of late HIV diagnosis and advanced HIV disease (AHD) in Tanzania.Methods: Data were obtained from the 2016– 17 Tanzania HIV impact survey. We included 677 newly diagnosed people living with HIV. Late HIV diagnosis and AHD were defined as having a CD4 cell count below 350 cells/μL or 200 cells/μL at diagnosis, respectively. Bivariate and multivariable logistic regression models were fitted to identify the determinants of late HIV diagnosis or AHD.Results: The mean age of the participants was 37.8 years (SD, 12.4). About two-thirds were women (62.6%). The prevalence of late HIV diagnosis was 42.4%, whereas the prevalence of AHD was 17.7%. Factors associated with late HIV diagnosis included age 31– 40 years (adjusted odds ratio [aOR] = 1.72, 95% confidence interval [CI]: 1.14– 2.60), age ≥ 41 years (aOR = 1.79, 95% CI: 1.16– 2.76), male sex (aOR = 1.88, 95% CI: 1.29– 2.73), and active syphilis infection (aOR=2.63, 95% CI: 1.20– 5.76). Factors associated with AHD were age 31– 40 years (aOR = 2.12, 95% CI: 1.18– 3.81), age ≥ 41 years (aOR = 2.42, 95% CI: 1.32– 4.41), male sex (aOR = 1.77, 95% CI: 1.09– 2.87), formal education (aOR = 0.49, 95% CI: 0.30– 0.81) and active syphilis infection (aOR = 2.49, 95% CI: 1.07– 5.77).Conclusion: Late HIV diagnosis and AHD are prevalent among newly diagnosed people living with HIV in Tanzania. Specific subgroups are more likely to present late for HIV care, including middle-aged and older adults, men, illiterate individuals, and those with active syphilis and HIV co-infection. Therefore, we recommend expanding HIV testing services and implementing targeted interventions to improve early access and enrollment in HIV care.Keywords: advanced HIV disease, HIV/AIDS, HIV care, late presentation, Tanzania

Background Cryptococcal meningitis (CM) causes substantial mortality in African countries with a high prevalence of human immunodeficiency virus (HIV), despite advances in disease management and increasing antiretroviral therapy (ART) coverage. Reliable diagnosis of CM is cheap and more accessible than other indicators of advanced HIV disease burden such as CD4 testing or investigation for disseminated tuberculosis; therefore, monitoring CM incidence has the potential to serve as a valuable metric of HIV programmatic success. Methods Botswana national meningitis surveillance data from 2015 to 2022 were obtained from electronic health records. All electronic laboratory records from cerebrospinal fluid samples analyzed within government healthcare facilities in Botswana were extracted from a central online repository. Adjustments for missing data were made through triangulation with prospective cohort study datasets. CM case frequency was enumerated using a case definition and incidence calculated using national census data. Results A total of 1744 episodes of CM were identified; incidence declined from 15.0 (95% confidence interval [CI], 13.4–16.7) cases/100 000 person-years in 2015 to 7.4 (95% CI, 6.4–8.6) cases/100 000 person-years in 2022. However, the rate of decline slowed following the introduction of universal treatment in 2016. The highest incidence was observed in men and individuals aged 40–44 years. The proportion of cases diagnosed through cryptococcal antigen testing increased from 35.5% to 86.3%. Conclusions CM incidence has decreased in Botswana following expansion of ART coverage but persists at a stubbornly high incidence. Most cases are now diagnosed through the cheap and easy-to-use cryptococcal antigen test, highlighting the potential of using CM as key metric of program success in the Treat All era. [ABSTRACT FROM AUTHOR]

Background: Implementation of the World Health Organization (WHO) recommended Advanced HIV Disease screening package, remains poor in most settings with limited resources. More than 50% of newly diagnosed-HIV clients are missed on screening as a result of implementation barriers. It is important to mitigate the existing barriers and leverage enablers' inorder to maximize uptake of the advanced HIV disease screening. This study aimed to identify strategies for scaling up implementation of advanced HIV disease screening among newly HIV-diagnosed clients in pre-ART phase using a Consolidated Framework for Implementation Research-Expert Recommendation for Implementing Change (CFIR-ERIC) guiding tool. Methods: A qualitative study was conducted at Rumphi district hospital in Malawi (August – September, 2023). Two sessions of Focus group discussions (FDGs) involving key stakeholders were facilitated to identify specific strategies following the initial study on exploration of barriers and facilitators of advanced HIV disease screening package. Participants comprised healthcare providers, purposively selected from key hospital departments. A deductive approach was used to analyze FDG transcripts where emerging themes were mapped with ERIC list of strategies. CFIR-ERIC Matching tool version 1.0, was used to generate an output of the most to least expert-endorsed Level 1 and Level 2 strategies. Findings: About 25 key healthcare workers participated in FDGs. Overall, 6 Level 1 strategies (≥ 50% expert endorsement score) and 4 Level 2 strategies (≥ 20%, ≤ 49% expert endorsement score) were identified, targeting barriers associated with availability of resources, intervention complexity, access to knowledge and information, communication; and implementation leads. Most of the reported strategies were cross-cutting and aimed at enhancing clinical knowledge of the intervention (distributing training materials, educational meetings), developing stakeholders' interrelations (network weaving) as well as improving clinical workflow (environmental restructuring). Use of evaluative and iterative strategies such as monthly data collection for evaluation were also recommended as part of continuous improvement while an AHD coordinator was recommended to be formally appointed inorder to spearhead coordination of AHD screening services. Conclusion: Through the involvement of key stakeholders and the use of CFIR-ERIC matching tool, this study has identified cross-cutting strategies that if well implemented, can help to mitigate contextual barriers and leverage enablers for an improved delivery of AHD screening package. [ABSTRACT FROM AUTHOR]

Background: South Africa has the largest HIV epidemic globally. Despite the scale-up of antiretroviral therapy, people living with HIV are still presenting with low CD4 counts. Objectives: This study assessed CD4 trends. Method: A retrospective analysis of laboratory data from 2013 to 2023 was conducted. Annual test volumes, the median CD4, and the percentage of specimens with a count ≤ 200 cells/μL and 500 cells/μL were reported at the national and provincial levels, and by age and gender. The percentage change in both CD4 categories between 2013 and 2023 was assessed, and the CD4 counts per 100 000 population reported. Results: Data are reported for 32 154 644 specimens. The overall median CD4 increased from 396 cells/μL to 473 cells/μL. The percentage of specimens with CD4 counts 500 cells/μL increased over time but the percentage with CD4 counts ≤ 200 cells/μL remained stable. Men had lower CD4 median and higher percentage of specimens with counts ≤ 200 cells/μL than women. However, the rate of, CD4 ≤ 200 cells/μL decreased from 1411 to 700 per 100 000 population; this decrease occurred in all provinces except the Western Cape. Conclusion: This study found high percentage of specimens with CD4 counts ≤ 200 cells/μL despite an increase in median CD4 count. Men had lower CD4 counts than women.

ABSTRACT Background and Aims Sub‐Saharan Africa drives global HIV‐related mortality, and patients continuously present with advanced HIV disease (AHD) at diagnosis. We describe prevalence, predictors, and treatment outcomes in HIV clients with AHD. Methods We systematically reviewed PUBMED, SCOPUS, Web of Science, JSTOR, and CINAHL for relevant studies conducted in Sub‐Saharan Africa from 2010 to 2022. We used a narrative synthesis to describe included studies and a random effect meta‐analysis to determine AHD pooled prevalence. The Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) checklist guided the reporting, while the Joanna Briggs Institute's quality assessment checklist assessed the quality of included articles. Cochrane's Q and the I2 tests assessed heterogeneity between included studies. Results We included 24 studies with a sample size of 322,676. Prevalence of AHD ranged from 11.0% to 89.7% with an overall pooled prevalence of 58.7% (95% CI: 51.3%, 66.0%): 66.1% (95% CI: 58.8%, 73.4%) between 2010 and 2016, and 51.2% (95% CI: 37.7%, 64.6%) from 2017 to 2022. Predictors of AHD include male sex, older age (≥ 35), widowed or divorced, unemployment, gap in care of ≥ 12 months before antiretroviral therapy (ART) initiation, no history of HIV testing, and seeking care from a traditional healer before presenting for HIV care. Loss to follow‐up ranged from 6.7%–58.3%, while the proportion of death ranged from 1.8%–13.1%. Predictors of death were being male, advanced age (≥ 50 years), advanced clinical stages, late ART initiation, higher mean log viral load, CD4+ cell count

Background: Eswatini has a high HIV prevalence in adults and, despite being one of the first countries to achieve the UNAIDS 95-95-95 targets, AIDS-related deaths are still high. Objectives: This study describes the causes of death among people living with HIV (PLHIV) receiving care at five clinics in Eswatini. Method: A cross-sectional review of sociodemographic, clinical and mortality data of deceased clients who received care from 01 January 2021 to 30 June 2022, was conducted. Data were extracted from the deceased clients’ clinical records, and descriptive and comparative analysis was performed. Results: Of 257 clients, 52.5% (n = 135) were male, and the median age was 47 years (interquartile range [IQR]: 38, 59). The leading causes of death were non-communicable diseases (NCDs) (n = 59, 23.0%), malignancies (n = 37, 14.4%), COVID-19 (n = 36, 14.0%), and advanced HIV disease (AHD) (n = 24, 9.3%). Clients who had been on antiretroviral therapy (ART) for 12–60 months (OR: 0.01; 95% confidence interval [CI]: 0.0006, 0.06) and 60 months (OR: 0.006; 95% CI: 0.0003, 0.029) had lower odds of death from AHD compared to those on ART for 12 months. Clients aged ≥ 40 years had higher odds of dying from COVID-19, while female clients (OR: 2.64; 95% CI: 1.29, 5.70) had higher odds of death from malignancy. Conclusion: Most clients who died were aged 40 years and above and died from NCD-related causes, indicating a need to integrate prevention, screening, and treatment of NCDs into HIV services. Specific interventions targeting younger PLHIV will limit their risk for AHD.

Background: There is limited data on diagnoses during hospital stay among children living with HIV(CLHIV) in the antiretroviral and coronavirus disease 2019 (COVID-19) era. Objectives: The aim of this study was to describe hospital diagnoses and clinical characteristics of CLHIV before and during the COVID-19 pandemic. Method: A retrospective descriptive cross-sectional study was performed. Clinical and laboratory data were retrieved by reviewing folders and discharge summaries from January 2019 to December 2021. Period A (pre-COVID-19) was defined as the period from January 2019 to March 2020. Period B (During COVID-19) was defined as being from April 2020 to December 2021. Results: Ninety-six children contributed 215 diagnoses over the study period. The five most common diagnoses were unspecified HIV disease (47/215, 21.9%), tuberculosis (TB) (42/215, 19.5%), pneumonia (13/215, 6.0%), encephalopathy (11/215, 5.1%) and malnutrition (11/215, 5.1%). Median CD4 count was 377 cells/mm (IQR 126, 726) and 8.0% of the children were virally suppressed. Ninety-five per cent of the children had WHO Stage 3 and 4 (95%) disease and 12.5% of children required ICU admission. No child was diagnosed with COVID-19 despite universal screening. Moreover, 81.7% of the children had a social worker referral documented. Conclusion: Advanced HIV disease (AHD) remains prevalent with TB being the most common diagnosis. There were no cases of COVID-19 recorded in CLHIV. Contribution: The findings provide a description of the diagnoses of CLHIV in the South African setting prior to and during the COVID-19 pandemic. It highlights the need for more specific documentation of diagnoses to inform better prevention of AHD in children.

Abstract Background Advanced HIV disease (AHD) in young people living with HIV (PLHIV) is an increasingly pressing public health issue in sub-Saharan Africa. Despite global progress in early HIV testing and reducing HIV-related deaths, many youths experience increased rates of HIV disease progression in sub-Saharan Africa. This study describes the burden, clinical manifestations, and factors for disease progression among young PLHIV aged 15 – 24 years seeking medical services at a major public hospital in Sierra Leone. Methods We performed a cross-sectional analysis of routinely collected data for PLHIV patients aged 15 to 24 seen at Connaught Hospital in Sierra Leone between September 2022 and March 2023. We estimated the proportion of AHD in young PLHIV and performed logistic regression modelling to explore predictors of AHD. The statistical significance level was set at 0.05 for all statistical tests. Results Of the 581 PLHIV that were reported, 238 (40.9%) were between the ages of 15 and 24 years, with a median age of 22 (20—24), and 151 (63.5%) were females. On review, 178 (74.8%) has initiated antiretroviral therapy regimen (ART); 117 (65.7%) were actively on ART for ≤ 6 months, while 114 (64%) had interruptions with their ART treatment. The overall prevalence of AHD was 41.6% (99/238); 46.7% (35/68) of young PLHIV at the HIV clinic, and 39.3% (64/163) of admission. Sex—Female (OR, 0.51; 95% CI, 0.28–0.94; p = 0.030), and Tertiary Education level (OR, 0.27; 95% CI, 0.10 – 0.78; p = 0.015) have significantly lower odds of AHD in the entire study population. While for inpatients, Age (young Adults) of PLHIV (OR, 1.23; 95% CI, 1.00–1.52; p = 0.047) had 1.23 times the odds of AHD compared to adolescents, and being female (OR, 0.27; 95% CI, 0.08–0.84; p = 0.024), Overweight—Body mass index (OR, 0.10; 95% CI, 0.01–0.77; p = 0.028), Tertiary Education level (OR, 0.08; 95% CI, 0.01–0.52; p = 0.008) have significantly lower odds of AHD. Common conditions reported for the AHD group in the medical wards are tuberculosis (13.58%), hepatitis B (6.13%), Kaposi sarcoma (3.07%), and oesophagal candidiasis (2.45%). Conclusion We reported a high prevalence of advanced HIV among young patients in a tertiary Hospital in Sierra Leone. One in two young PLHIV aged 15 to 24 years reported AHD, emphasizing the need to strengthen public health measures that address access to and retention of HIV services.

Background: Advanced HIV disease (AHD) in young people living with HIV (PLHIV) is an increasingly pressing public health issue in sub-Saharan Africa. Despite global progress in early HIV testing and reducing HIV-related deaths, many youths experience increased rates of HIV disease progression in sub-Saharan Africa. This study describes the burden, clinical manifestations, and factors for disease progression among young PLHIV aged 15 – 24 years seeking medical services at a major public hospital in Sierra Leone. Methods: We performed a cross-sectional analysis of routinely collected data for PLHIV patients aged 15 to 24 seen at Connaught Hospital in Sierra Leone between September 2022 and March 2023. We estimated the proportion of AHD in young PLHIV and performed logistic regression modelling to explore predictors of AHD. The statistical significance level was set at 0.05 for all statistical tests. Results: Of the 581 PLHIV that were reported, 238 (40.9%) were between the ages of 15 and 24 years, with a median age of 22 (20—24), and 151 (63.5%) were females. On review, 178 (74.8%) has initiated antiretroviral therapy regimen (ART); 117 (65.7%) were actively on ART for ≤ 6 months, while 114 (64%) had interruptions with their ART treatment. The overall prevalence of AHD was 41.6% (99/238); 46.7% (35/68) of young PLHIV at the HIV clinic, and 39.3% (64/163) of admission. Sex—Female (OR, 0.51; 95% CI, 0.28–0.94; p = 0.030), and Tertiary Education level (OR, 0.27; 95% CI, 0.10 – 0.78; p = 0.015) have significantly lower odds of AHD in the entire study population. While for inpatients, Age (young Adults) of PLHIV (OR, 1.23; 95% CI, 1.00–1.52; p = 0.047) had 1.23 times the odds of AHD compared to adolescents, and being female (OR, 0.27; 95% CI, 0.08–0.84; p = 0.024), Overweight—Body mass index (OR, 0.10; 95% CI, 0.01–0.77; p = 0.028), Tertiary Education level (OR, 0.08; 95% CI, 0.01–0.52; p = 0.008) have significantly lower odds of AHD. Common conditions reported for the AHD group in the medical wards are tuberculosis (13.58%), hepatitis B (6.13%), Kaposi sarcoma (3.07%), and oesophagal candidiasis (2.45%). Conclusion: We reported a high prevalence of advanced HIV among young patients in a tertiary Hospital in Sierra Leone. One in two young PLHIV aged 15 to 24 years reported AHD, emphasizing the need to strengthen public health measures that address access to and retention of HIV services. [ABSTRACT FROM AUTHOR]

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Background Twenty-three percent of people with human immunodeficiency virus (HIV, PWH) die within 6 months of hospital discharge. We tested the hypothesis whether a series of structured home visits could reduce mortality. Methods We designed a disease neutral home visit package with up to 6 home visits starting 1-week post-hospitalization and every 2 weeks thereafter. The home visit team used a structured assessment algorithm to evaluate and triage social and medical needs of the participant and provide nutritional support. We compared all-cause mortality 6 months following discharge for the intervention compared to usual care in a pilot randomized trial conducted in South Africa. To inform potential scale-up we also included and separately analyzed a group of people without HIV (PWOH). Results We enrolled 125 people with HIV and randomized them 1:1 to the home visit intervention or usual care. Fourteen were late exclusions because of death prior to discharge or delayed discharge leaving 111 for analysis. The median age was 39 years, 31% were men; and 70% had advanced HIV disease. At 6 months among PWH 4 (7.3%) in the home visit arm and 10 (17.9%) in the usual care arm (P =.09) had died. Among the 70 PWOH enrolled overall 6-month mortality was 10.1%. Of those in the home visit arm, 91% received at least one home visit. Conclusions We demonstrated feasibility of delivering post-hospital home visits and demonstrated preliminary efficacy among PWH with a substantial, but not statistically significant, effect size (59% reduction in mortality). Coronavirus disease 2019 (COVID-19) related challenges resulted in under-enrollment. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. Background: Earlier antiretroviral therapy (ART) may decrease progression to advanced HIV disease (AHD) with CD4 count of <200 cells per cubic millimeter or clinical sequelae. We assessed factors associated with AHD among people living with HIV before and during the "test and treat" era. Setting: The African Cohort Study prospectively enrolls adults with and without HIV from 12 clinics in Uganda, Kenya, Tanzania, and Nigeria. Methods: Enrollment evaluations included clinical history, physical examination, and laboratory testing. Generalized estimating equations were used to estimate adjusted odds ratios and 95% confidence intervals for factors associated with CD4 count of <200 cells per cubic millimeter at study visits. Results: From 2013 to 2021, 3059 people living with HIV with available CD4 at enrollment were included; median age was 38 years [interquartile range: 30–46 years], and 41.3% were men. From 2013 to 2021, the prevalence of CD4 count of <200 cells per cubic millimeter decreased from 10.5% to 3.1%, whereas the percentage on ART increased from 76.6% to 100% (P <0.001). Factors associated with higher odds of CD4 count of <200 cells per cubic millimeter were male sex (adjusted odds ratio 1.56 [confidence interval: 1.29 to 1.89]), being 30–39 years (1.42 [1.11–1.82]) or older (compared with <30), have World Health Organization stage 2 disease (1.91 [1.48–2.49]) or higher (compared with stage 1), and HIV diagnosis eras 2013–2015 (2.19 [1.42–3.37]) or later (compared with <2006). Compared with ART-naive, unsuppressed participants, being viral load suppressed on ART, regardless of ART duration, was associated with lower odds of CD4 count of <200 cells per cubic millimeter (<6 months on ART: 0.45 [0.34–0.58]). Conclusion: With ART scale-up, AHD has declined. Efforts targeting timely initiation of suppressive ART may further reduce AHD risk. [ABSTRACT FROM AUTHOR]

Fungal infections are common in HIV-infected individuals and significantly contribute to mortality. However, a substantial number of cases are undiagnosed before death. To determine the frequency of fungal pathogens in autopsy studies of people who died with HIV in Africa. We conducted a scoping review of autopsy studies conducted in Africa. PubMed, Scopus, Web of Science, Embase, Google Scholar, and African Journal Online. The review encompasses studies published from inception to September 2023, and no language restrictions were imposed during the search process. We included studies that reported histopathological or microbiological evidence for the diagnosis of fungal infections and other pathogens. Data were summarized using descriptive statistics and no meta-analysis was performed. We examined 30 articles reporting studies conducted between 1991 and 2019, encompassing a total of 13 066 HIV-infected decedents across ten African countries. In five studies, the autopsy type was not specified. Among those studies with specified autopsy types, 20 involved complete diagnostic autopsies, whereas 5 were categorized as partial or minimally invasive autopsies. There were 2333 pathogens identified, with 946 (40.5%) being mycobacteria, 856 (36.7%) fungal, 231 (3.8%) viral, 208 (8.9%) parasitic, and 92 (3.9%) bacterial. Of the 856 fungal pathogens identified, 654 (28.0%) were Cryptococcus species, 167 (7.2%) Pneumocystis jirovecii , 16 (0.69%) Histoplasma species, 15 (0.64%) Aspergillus species, and 4 (0.17%) Candida species. Other major non-fungal pathogens identified were cytomegalovirus 172 (7.37%) and Toxoplasma gondii 173 (7.42%). Invasive fungal infections occur in over one-third of people who succumb to HIV in Africa. In addition to cryptococcosis and Pneumocystis jirovecii pneumonia, integrating other priority fungal pathogen detection and management strategies into the broader framework of HIV care in Africa is recommended. This involves increasing awareness regarding the impact of fungal infections in advanced HIV disease and strengthening diagnostic and treatment capacity. [ABSTRACT FROM AUTHOR]

Abstract Background Hospital admission outcomes for people living with HIV (PLHIV) in resource-limited settings are understudied. We describe in-hospital mortality and associated clinical-demographic factors among PLHIV admitted at a tertiary-level public hospital in Uganda. Methods We performed a cross-sectional analysis of routinely collected data for PLHIV admitted at Kiruddu National Referral Hospital between March 2020 and March 2023. We estimated the proportion of PLHIV who had died during hospitalization and performed logistic regression modelling to identify predictors of mortality. Results Of the 5,827 hospitalized PLHIV, the median age was 39 years (interquartile range [IQR] 31–49) and 3,293 (56.51%) were female. The median CD4 + cell count was 109 cells/µL (IQR 25–343). At admission, 3,710 (63.67%) were active on antiretroviral therapy (ART); 1,144 (19.63%) had interrupted ART > 3 months and 973 (16.70%) were ART naïve. In-hospital mortality was 26% (1,524) with a median time-to-death of 3 days (IQR 1–7). Factors associated with mortality (with adjusted odds ratios) included ART interruption, 1.33, 95% confidence intervals (CI) 1.13–1.57, p 0.001; CD4 + counts ≤ 200 cells/µL 1.59, 95%CI 1.33–1.91, p 20 km from hospital 1.23, 95%CI 1.04–1.46, p 0.014; hospital readmission 0.7, 95%CI 0.56–0.88, p 0.002; chronic lung disease 0.62, 95%CI 0.41–0.92, p 0.019; and neurologic disease 0.46, 95%CI 0.32–0.68, p

Abstract Background Despite tremendous progress in improving antiretroviral therapy (ART) access, advanced HIV disease (AHD) still remains a challenge globally. Reasons for delayed presentation to care and ART adherence may be affected by gender. We present qualitative study findings on gender differences in decisions for HIV testing and ART initiation/adherence in adults with AHD in Malawi. Methods We used a qualitative study design, interviewing 16 men and 16 women aged 18 years and above diagnosed with AHD in sites implementing an optimized package of AHD care, from December 2021-February 2022. We included study participants receiving AHD services for at least two months. We also interviewed 16 lay workers and 16 health care workers supporting people living with AHD. In-depths interviews (IDIs) were conducted in English or Chichewa by trained research assistants using semi-structured interview guides. A short-answer analysis was conducted, and findings were interpreted according to thematic areas. Results Both men and women reported stigma as a main barrier influencing their decision to test for HIV and to initiate and adhere to ART. Fear of side effects, insufficient food, and the need for more information were other barriers reported among men and women as well as perceived as barriers by HCWs. Men appear to have tested later for HIV and stated that they were waiting until experiencing significant symptoms before testing. According to clients and HCWs, men were also less inclined to initiate ART after a HIV diagnosis, whereas women were motivated to start treatment to remain healthy and care for the family. Both genders reported that treatment could be delayed if they were feeling healthy. Treatment fatigue was reported among all groups as the main reason to discontinue treatment. Conclusions There were similarities and differences between genders in decision-making about HIV care. Concerns about stigma were important reasons for delay in HIV care in both genders. Motivations for accessing HIV treatment and care were different among men and women, pushing the need for gender-tailored counseling services and community messaging that educate both men and women on the benefits of initiating ART early, in turn reducing the number of people presenting with AHD. Trial registration NCT05510973, first registration 22/08/2022.

Abstract Background The World Health Organization (WHO) recommends an evidence-based package of care to reduce mortality and morbidity among people with advanced HIV disease (AHD). Adoption of these recommendations by national guidelines in sub-Saharan Africa is poorly documented. We aimed to review national guidelines for AHD management across six selected countries in sub-Saharan Africa for benchmarking against the 2021 WHO recommendations. Methods We reviewed national guidelines from six countries participating in an ongoing randomized controlled trial recruiting people with AHD. We extracted information addressing 18 items of AHD diagnosis and management across the following domains: [1] Definition of AHD, [2] Screening, [3] Prophylaxis, [4] Supportive care, and [5] HIV treatment. Data from national guideline documents were compared to the 2021 WHO consolidated guidelines on HIV and an agreement score was produced to evaluate extent of guideline adoption. Results The distribution of categories of agreement varied for the national documents. Four of the six countries addressed all 18 items (Malawi, Nigeria, Sierra Leone, Uganda). Overall agreement with the WHO 2021 guidelines ranged from 9 to 15.5 out of 18 possible points: Malawi 15.5 points, Nigeria, and Sierra Leone 14.5 points, South Africa 13.5 points, Uganda 13.0 points and Botswana with 9.0 points. Most inconsistencies were reported for the delay of antiretroviral therapy (ART) in presence of opportunistic diseases. None of the six national guidelines aligned with WHO recommendations around ART timing in patients with tuberculosis. Agreement correlated with the year of publication of the national guideline. Conclusion National guidelines addressing the care of advanced HIV disease in sub-Saharan Africa are available. Besides optimal timing for start of ART in presence of tuberculosis, most national recommendations are in line with the 2021 WHO standards.

Abstract Background Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently described autoimmune inflammatory disorder of the central nervous system (CNS). There is limited data on the association between Human Immunodeficiency virus (HIV) infection and MOGAD. We report three patients with HIV infection and myelin oligodendrocyte glycoprotein (MOG) antibodies in the setting of other central nervous system infections. Case descriptions The first patient, a 44-year-old black African man, presented with acute disseminated encephalomyelitis (ADEM) with positive serum MOG antibodies. He made a significant recovery with corticosteroids but had a quick relapse and died from sepsis. The second patient, an 18-year-old black woman, presented with paraplegia and imaging revealed a longitudinally extensive transverse myelitis and had positive serum MOG antibodies. She remained paraplegic after methylprednisone and plasmapheresis treatments. Her rehabilitation was complicated by development of pulmonary embolism and tuberculosis. The third patient, a 43-year-old mixed-race woman, presented with bilateral painless visual loss. Her investigations were notable for positive MOG antibodies, positive Varicella Zoster Virus on cerebral spinal fluid (CSF) and hyperintense optic nerves on magnetic resonance imaging (MRI). Her vision did not improve with immunosuppression and eventually died from sepsis. Conclusion Our cases illustrate the diagnostic and management challenges of MOGAD in the setting of advanced HIV infection, where the risk of CNS opportunistic infections is high even without the use of immunosuppression. The atypical clinical progression and the dilemmas in the diagnosis and treatment of these cases highlight gaps in the current knowledge of MOGAD among people with HIV that need further exploration.

Background: The available few laboratory-based CD4 assay for People Living with HIV (PLHIV) experience supply stock-outs and instrument breakdowns in developing countries, affecting the ability to diagnose Advance HIV disease (AHD). We evaluated the performance of the VISITECT CD4 point of care test among healthcare workers in HIV program in Tanzania. Methods: A retrospective diagnostic accuracy study was conducted among PLHIV who received both the VISITECT CD4 and a standard-of-care. Acceptability of the VISITECT CD4 by healthcare workers was assessed using a structured questionnaire. Both FACS Count and Pima CD4 assay were considered as reference standards. Findings were summarized as proportions with 95 % confidence intervals (CI). Data were analyzed using STATA 17 (StataCorp, College Station, TX). Results: A total of 1370 PLHIV were tested using VISITECT CD4 across 20 facilities between 3 April and 14 September 2022. The median age was 37 (Interquartile range (IQR):29–46). Overall, 897 (65.5 %) were females and 449 had both VISITECT CD4 test and standard of care. The sensitivity and specificity were; 95.9 % (95 % CI: 91.8 %–98.3 %) and 78.3 % (95 % CI: 73.0 %–83.0 %) respectively. 47 healthcare workers used the VISITECT CD4, of whom 57.5 % were non-laboratory healthcare workers. Majority of the healthcare workers were of the opinion that the training was adequate and VISITECT CD4 was easy and useful in clinical decisions. Conclusion: The VISITECT CD4 test was accurate, useable and acceptable among healthcare workers in Tanzania. The scale up of VISITECT CD4 should consider development of training curriculum and the use of job aids particularly for non-laboratory healthcare workers.

Background: Hospital admission outcomes for people living with HIV (PLHIV) in resource-limited settings are understudied. We describe in-hospital mortality and associated clinical-demographic factors among PLHIV admitted at a tertiary-level public hospital in Uganda. Methods: We performed a cross-sectional analysis of routinely collected data for PLHIV admitted at Kiruddu National Referral Hospital between March 2020 and March 2023. We estimated the proportion of PLHIV who had died during hospitalization and performed logistic regression modelling to identify predictors of mortality. Results: Of the 5,827 hospitalized PLHIV, the median age was 39 years (interquartile range [IQR] 31–49) and 3,293 (56.51%) were female. The median CD4 + cell count was 109 cells/µL (IQR 25–343). At admission, 3,710 (63.67%) were active on antiretroviral therapy (ART); 1,144 (19.63%) had interrupted ART > 3 months and 973 (16.70%) were ART naïve. In-hospital mortality was 26% (1,524) with a median time-to-death of 3 days (IQR 1–7). Factors associated with mortality (with adjusted odds ratios) included ART interruption, 1.33, 95% confidence intervals (CI) 1.13–1.57, p 0.001; CD4 + counts ≤ 200 cells/µL 1.59, 95%CI 1.33–1.91, p < 0.001; undocumented CD4 + cell count status 2.08, 95%CI 1.73–2.50, p < 0.001; impaired function status 7.35, 95%CI 6.42–8.41, p < 0.001; COVID-19 1.70, 95%CI 1.22–2.37, p 0.002; liver disease 1.77, 95%CI 1.36–2.30, p < 0.001; co-infections 1.53, 95%CI 1.32–1.78, p < 0.001; home address > 20 km from hospital 1.23, 95%CI 1.04–1.46, p 0.014; hospital readmission 0.7, 95%CI 0.56–0.88, p 0.002; chronic lung disease 0.62, 95%CI 0.41–0.92, p 0.019; and neurologic disease 0.46, 95%CI 0.32–0.68, p < 0.001. Conclusion: One in four admitted PLHIV die during hospitalization. Identification of risk factors (such as ART interruption, function impairment, low/undocumented CD4 + cell count), early diagnosis and treatment of co-infections and liver disease could improve outcomes. [ABSTRACT FROM AUTHOR]

To assess the prevalence, all-cause mortality and determinants of advanced HIV disease (AHD) or severe immunosuppression (SIS) in the rural–urban communities of Southwestern China. Retrospective cohort study. Data on HIV/AIDS cases reported in 2005–20 were collected from Case Report System. A binary logistic regression model assessed the risk factors of AHD/SIS prevalence. Survival curves across rural–urban regions were compared using Kaplan–Meier estimates and log-rank tests. Determinants of all-cause mortality were identified using the Cox proportional hazard model. Among 14,533 newly diagnosed HIV/AIDS patients, 7497 (51.6%) presented with AHD and 2564 (17.6%) with SIS. Compared with urban patients, rural patients had a higher prevalence of AHD (56.7% vs 40.7%) and SIS (20.1% vs 12.4%), all-cause mortality (AHD 12.3 vs 5.6, SIS 16.3 vs 5.5, per 100 person-years). Their 5-year survival probability (AHD 59.5% vs 77.1%; SIS 54.4% vs 76.3%) and mean survival time (AHD 106.5 vs 140.6 months, SIS 95.3 vs 144.2 months, p < 0.0001) were lower. Rural patients had an increased risk of SIS prevalence (adjusted odds ratios 1.45, 95% confidence interval [CI] 1.28–1.64; p < 0.0001) and mortality of the total cohort (adjusted hazard ratios 1.41, 95% CI 1.29–1.55; p < 0.0001), AHD cohort (1.38, 1.24–1.54; p < 0.0001), and SIS cohort (1.49, 1.23–1.81; p < 0.0001). A high prevalence of AHD/SIS was a severe phenomenon that caused high mortality in rural areas. A regional point-of-care strategy targeting AHD/SIS detection and management is essential for reducing the mortality risk. [ABSTRACT FROM AUTHOR]

One mechanism of variant formation may be evolution during long-term infection in immunosuppressed people. To understand the viral phenotypes evolved during such infection, we tested SARS-CoV-2 viruses evolved from an ancestral B.1 lineage infection lasting over 190 days post-diagnosis in an advanced HIV disease immunosuppressed individual. Sequence and phylogenetic analysis showed two evolving sub-lineages, with the second sub-lineage replacing the first sub-lineage in a seeming evolutionary sweep. Each sub-lineage independently evolved escape from neutralizing antibodies. The most evolved virus for the first sub-lineage (isolated day 34) and the second sub-lineage (isolated day 190) showed similar escape from ancestral SARS-CoV-2 and Delta-variant infection elicited neutralizing immunity despite having no spike mutations in common relative to the B.1 lineage. The day 190 isolate also evolved higher cell–cell fusion and faster viral replication and caused more cell death relative to virus isolated soon after diagnosis, though cell death was similar to day 34 first sub-lineage virus. These data show that SARS-CoV-2 strains in prolonged infection in a single individual can follow independent evolutionary trajectories which lead to neutralization escape and other changes in viral properties. [ABSTRACT FROM AUTHOR]

Abstract Introduction Efficacy and safety of the attachment inhibitor fostemsavir + optimized background therapy (OBT) were evaluated through 48 and 96 weeks in the phase 3 BRIGHTE trial in heavily treatment-experienced (HTE) adults failing their current antiretroviral regimen. Here, we report 240-week efficacy and safety of fostemsavir + OBT in adults with multidrug-resistant human immunodeficiency virus (HIV)-1 in BRIGHTE. Methods Heavily treatment-experienced adults failing their current regimen entered the randomized cohort (RC; 1–2 fully active antiretrovirals available) or non-randomized cohort (NRC; no fully active antiretrovirals available) and received open-label fostemsavir + OBT (starting Day 8 in RC and Day 1 in NRC). Endpoints included proportion with virologic response (HIV-1 RNA

Abstract Background Despite the significant progress made in South Africa in getting millions of individuals living with HIV into care, many patients still present or re-enter care with Advanced HIV Disease (AHD). We aimed to estimate the prevalence of AHD among ART-naive and ART-experienced patients in South Africa using studies published between January 2010 and May 2022. Methods We searched for relevant data on PubMed, CINAHL, Scopus and other sources, with a geographical filters limited to South Africa, up to May 31, 2022. Two reviewers conducted all screening, eligibility assessment, data extraction, and critical appraisal. We synthesized the data using the inverse-variance heterogeneity model and Freeman-Tukey transformation. We assessed heterogeneity using the I2 statistic and publication bias using the Egger and Begg’s test. Results We identified 2,496 records, of which 53 met the eligibility criteria, involving 11,545,460 individuals. The pooled prevalence of AHD among ART-naive and ART-experienced patients was 43.45% (95% CI 40.1–46.8%, n = 53 studies) and 58.6% (95% CI 55.7 to 61.5%, n = 2) respectively. The time trend analysis showed a decline of 2% in the prevalence of AHD among ART-naive patients per year. However, given the high heterogeneity between studies, the pooled prevalence should be interpreted with caution. Conclusion Despite HIV’s evolution to a chronic disease, our findings show that the burden of AHD remains high among both ART-naive and ART-experienced patients in South Africa. This emphasizes the importance of regular measurement of CD4 cell count as an essential component of HIV care. In addition, providing innovative adherence support and interventions to retain ART patients in effective care is a crucial priority for those on ART.

BackgroundThe impact of the “Treat all” policy on the individual and in terms of public health is closely related to early diagnosis and retention in care. Patient-level data are scarce in Madagascar. In this study, we aimed to describe the profile of a cohort of newly diagnosed people living with HIV/AIDS (PLHIV), identify their outcomes, and assess factors associated with attrition from care and advanced HIV disease (AHD) at presentation.MethodsWe conducted a retrospective cohort study of PLHIV aged ≥15 years newly diagnosed at the University Hospital Joseph Raseta Befelatanana Antananarivo from 1 January 2010 to 31 December 2016.ResultsA total of 490 PLHIV were included in the cohort analysis. In total, 67.1% were male. The median age (interquartile range) at enrollment in care was 29 years (24-38). Overall, 36.1% of PLHIV were diagnosed with AHD at baseline. The proportion of patients with WHO stage IV at baseline increased significantly from 3.3% in 2010 to 31% in 2016 (p = 0.001 for trend). The probability of retention in care after the diagnosis at 12 months, 24 months, and 36 months was 71.8%, 65.5%, and 61.3%, respectively. Age ≥ 40 years (aHR: 1.55; 95% CI: 1.05–2.29; p = 0.026), low level of education (aHR:1.62; 95% CI: 1.11–2.36; p = 0,013), unspecified level of education (aHR:2.18; 95% CI: 1.37–3.47; p = 0.001) and unemployment (aHR:1.52; 95% CI: 1.07–2.16; p = 0.019) were independently associated with attrition from care. Factors associated with AHD at baseline were age ≥ 40 (aOR: 2.77; 95% CI: 1.38–5.57, p = 0.004), unspecified level of education (aOR: 3.80; 95% CI: 1.58–9.16, p = 0.003) and presence of clinical symptoms at baseline (aOR: 23.81; 95% CI: 10.7–52.98; p < 0.001). Sex workers were independently less likely to have an AHD at presentation (aOR: 0.23; 95% CI: 0.05–0.96, p = 0.044).ConclusionSociodemographic determinants influenced retention in care more than clinical factors. The presence of clinical symptoms and sociodemographic determinants were the main factors associated with AHD at baseline.

Background: Despite tremendous progress in improving antiretroviral therapy (ART) access, advanced HIV disease (AHD) still remains a challenge globally. Reasons for delayed presentation to care and ART adherence may be affected by gender. We present qualitative study findings on gender differences in decisions for HIV testing and ART initiation/adherence in adults with AHD in Malawi. Methods: We used a qualitative study design, interviewing 16 men and 16 women aged 18 years and above diagnosed with AHD in sites implementing an optimized package of AHD care, from December 2021-February 2022. We included study participants receiving AHD services for at least two months. We also interviewed 16 lay workers and 16 health care workers supporting people living with AHD. In-depths interviews (IDIs) were conducted in English or Chichewa by trained research assistants using semi-structured interview guides. A short-answer analysis was conducted, and findings were interpreted according to thematic areas. Results: Both men and women reported stigma as a main barrier influencing their decision to test for HIV and to initiate and adhere to ART. Fear of side effects, insufficient food, and the need for more information were other barriers reported among men and women as well as perceived as barriers by HCWs. Men appear to have tested later for HIV and stated that they were waiting until experiencing significant symptoms before testing. According to clients and HCWs, men were also less inclined to initiate ART after a HIV diagnosis, whereas women were motivated to start treatment to remain healthy and care for the family. Both genders reported that treatment could be delayed if they were feeling healthy. Treatment fatigue was reported among all groups as the main reason to discontinue treatment. Conclusions: There were similarities and differences between genders in decision-making about HIV care. Concerns about stigma were important reasons for delay in HIV care in both genders. Motivations for accessing HIV treatment and care were different among men and women, pushing the need for gender-tailored counseling services and community messaging that educate both men and women on the benefits of initiating ART early, in turn reducing the number of people presenting with AHD. Trial registration: NCT05510973, first registration 22/08/2022. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization (WHO) recommends an evidence-based package of care to reduce mortality and morbidity among people with advanced HIV disease (AHD). Adoption of these recommendations by national guidelines in sub-Saharan Africa is poorly documented. We aimed to review national guidelines for AHD management across six selected countries in sub-Saharan Africa for benchmarking against the 2021 WHO recommendations. Methods: We reviewed national guidelines from six countries participating in an ongoing randomized controlled trial recruiting people with AHD. We extracted information addressing 18 items of AHD diagnosis and management across the following domains: [1] Definition of AHD, [2] Screening, [3] Prophylaxis, [4] Supportive care, and [5] HIV treatment. Data from national guideline documents were compared to the 2021 WHO consolidated guidelines on HIV and an agreement score was produced to evaluate extent of guideline adoption. Results: The distribution of categories of agreement varied for the national documents. Four of the six countries addressed all 18 items (Malawi, Nigeria, Sierra Leone, Uganda). Overall agreement with the WHO 2021 guidelines ranged from 9 to 15.5 out of 18 possible points: Malawi 15.5 points, Nigeria, and Sierra Leone 14.5 points, South Africa 13.5 points, Uganda 13.0 points and Botswana with 9.0 points. Most inconsistencies were reported for the delay of antiretroviral therapy (ART) in presence of opportunistic diseases. None of the six national guidelines aligned with WHO recommendations around ART timing in patients with tuberculosis. Agreement correlated with the year of publication of the national guideline. Conclusion: National guidelines addressing the care of advanced HIV disease in sub-Saharan Africa are available. Besides optimal timing for start of ART in presence of tuberculosis, most national recommendations are in line with the 2021 WHO standards. [ABSTRACT FROM AUTHOR]

Background: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently described autoimmune inflammatory disorder of the central nervous system (CNS). There is limited data on the association between Human Immunodeficiency virus (HIV) infection and MOGAD. We report three patients with HIV infection and myelin oligodendrocyte glycoprotein (MOG) antibodies in the setting of other central nervous system infections. Case descriptions: The first patient, a 44-year-old black African man, presented with acute disseminated encephalomyelitis (ADEM) with positive serum MOG antibodies. He made a significant recovery with corticosteroids but had a quick relapse and died from sepsis. The second patient, an 18-year-old black woman, presented with paraplegia and imaging revealed a longitudinally extensive transverse myelitis and had positive serum MOG antibodies. She remained paraplegic after methylprednisone and plasmapheresis treatments. Her rehabilitation was complicated by development of pulmonary embolism and tuberculosis. The third patient, a 43-year-old mixed-race woman, presented with bilateral painless visual loss. Her investigations were notable for positive MOG antibodies, positive Varicella Zoster Virus on cerebral spinal fluid (CSF) and hyperintense optic nerves on magnetic resonance imaging (MRI). Her vision did not improve with immunosuppression and eventually died from sepsis. Conclusion: Our cases illustrate the diagnostic and management challenges of MOGAD in the setting of advanced HIV infection, where the risk of CNS opportunistic infections is high even without the use of immunosuppression. The atypical clinical progression and the dilemmas in the diagnosis and treatment of these cases highlight gaps in the current knowledge of MOGAD among people with HIV that need further exploration. [ABSTRACT FROM AUTHOR]

Introduction: A large proportion of the global burden of HIV-associated TB occurs in sub-Saharan Africa; including 74% of new cases of TB and 79% of deaths occurs in this area. Spontaneous pneumothorax occurs more frequently in patients with AIDS than the general population with the estimated incidence to be about 2–5% of overall total cases. Tuberculosis ARDS and septic shock are rare but carries extremely poor prognosis. Case summary: A 27 year old male with advanced HIV disease with very low CD4 count presented to Wolaita Sodo University comprehensive specialized hospital, Ethiopia on July 6, 2023. The patient diagnosed with spontaneous pneumothorax secondary to drug susceptible tuberculosis after positive urine LF-LAM and sputum gene expert. He was intubated after emergency tube thoracostomy, and subsequently treated with anti-TB, corticosteroid, broad-spectrum IV antibiotics and high dose cotrimoxazole. The patient developed ARDS due to possible tuberculosis related septic shock and died of multi-organ failure. Discussion: Spontaneous pneumothorax in the setting of HIV raises concern for PCP, though in this case it could be secondary to TB. Tuberculosis related ARDS and septic shock are rare complication but carries poor prognosis especially in setting of AHD. We had limited experience and difficulties in the management of patient with persistent pneumothorax with the concomitant ARDS requiring lung protective management, and this part remain the future area of scientific research. Conclusion: In patients with advanced HIV disease, who present with signs of respiratory failure, the likelihood of spontaneous pneumothorax, TB-ARDS and septic shock should be anticipated in the differential diagnosis and optimal management plan should be designed.

HIV-associated cryptococcal meningitis remains a key driver of AIDS-related mortality. Mortality is twice as high in those who present later to care and with severe symptoms such as confusion. We embedded a qualitative methods study within a randomised controlled trial in Gaborone, Botswana and Kampala, Uganda with the aim of understanding pathways to care. We conducted in-depth interviews with trial participants and surrogate decision makers and analysed data thematically. Between January 2020 and June 2021 we interviewed 58 individuals. Pathways to care were prolonged because headaches were disregarded by participants and healthcare workers as a common occurrence with a broad differential diagnosis of predominantly benign aetiologies. There was also a lack of awareness of cryptococcal meningitis, and it was often after HIV was diagnosed or disclosed that the pathway accelerated, resulting in hospital admission. We outline key recommendations to reduce mortality and argue for the integration of social and behavioural interventions within differentiated service delivery models for advanced HIV disease.

No abstract available.

Background Adults with HIV-associated cryptococcal meningitis have overlapping burdens of cytomegalovirus (CMV) and tuberculosis (TB) coinfections. CMV infection/reactivation is strongly associated with CMV-specific memory T-cell activation and upregulation of type 1 interferons, which may lead to increased risk of TB disease and poor outcomes. Methods We conducted a cohort study of 2-week survivors of cryptococcal meningitis during 2010–2021 to determine TB incidence and all-cause mortality over time stratified by baseline CMV status. Results We followed 497 Ugandans with HIV-associated cryptococcal meningitis for a median (interquartile range) of 4.6 (2.6–53.9) months. Overall, 42% (210/497) developed incident TB disease or died. One-fifth (98/497, 19.7%) developed incident TB disease, and 29% (142/497) of participants died during follow-up. Of 259 participants with CMV viral load measured at baseline, 37% (96/259) had concurrent CMV viremia (defined as anyone with detectable CMV DNA in plasma/serum by qualitative polymerase chain reaction [PCR] detection). Of 59 with measured CMV immunoglobulin G (IgG), 100% had positive CMV IgG antibody serology (≥10 enzyme-linked immunosorbent assay units/mL). CMV viremia was positively associated with higher HIV viral load (196 667 vs 73 295 copies/mL; P =.002) and higher cerebrospinal fluid fungal burden (68 500 vs 14 000 cfu/mL; P =.002) compared with those without. Participants with high-level CMV viremia (defined as CMV viral load ≥1000 IU/mL) had twice the risk of incident TB (subdistribution adjusted hazard ratio [aHR], 2.18; 95% CI, 1.11–4.27) and death (aHR, 1.99; 95% CI, 1.14–3.49) compared with participants with no or low-level CMV viremia. There was no association between the CMV IgG index and the incidence of TB/death (P =.75). Conclusions CMV viremia >1000 IU/mL at meningitis diagnosis was associated with increased incident TB disease and mortality during long-term follow-up. Future studies to determine the causal relationship and potential for therapeutic intervention are warranted. [ABSTRACT FROM AUTHOR]

Introduction: Efficacy and safety of the attachment inhibitor fostemsavir + optimized background therapy (OBT) were evaluated through 48 and 96 weeks in the phase 3 BRIGHTE trial in heavily treatment-experienced (HTE) adults failing their current antiretroviral regimen. Here, we report 240-week efficacy and safety of fostemsavir + OBT in adults with multidrug-resistant human immunodeficiency virus (HIV)-1 in BRIGHTE. Methods: Heavily treatment-experienced adults failing their current regimen entered the randomized cohort (RC; 1–2 fully active antiretrovirals available) or non-randomized cohort (NRC; no fully active antiretrovirals available) and received open-label fostemsavir + OBT (starting Day 8 in RC and Day 1 in NRC). Endpoints included proportion with virologic response (HIV-1 RNA < 40 copies/mL, Snapshot), immunologic efficacy, and safety. Results: At Week 240, 45% and 22% of the RC and NRC, respectively, had virologic response (Snapshot); 7% of the RC and 5% of the NRC had missing data due to coronavirus disease 2019 (COVID-19)-impacted visits. In the observed analysis, 82% of the RC and 66% of the NRC had virologic response. At Week 240, mean change from baseline in CD4+ T-cell count was 296 cells/mm3 (RC) and 240 cells/mm3 (NRC); mean CD4+/CD8+ ratio increased between Weeks 96 and 240 (RC 0.44 to 0.60; NRC 0.23 to 0.32). Between Weeks 96 and 240, four participants discontinued for adverse events, one additional participant experienced a drug-related serious adverse event, and six deaths occurred (median last available CD4+ T-cell count, 3 cells/mm3). COVID-19-related events occurred in 25 out of 371 participants; all resolved without incident. Conclusion: Through ~5 years, fostemsavir + OBT demonstrated durable virologic and immunologic responses with no new safety concerns between Weeks 96 and 240, supporting this regimen as a key therapeutic option for HTE people with multidrug-resistant HIV-1. Trial registration: ClinicalTrials.gov, NCT02362503. [ABSTRACT FROM AUTHOR]

Background: Despite the significant progress made in South Africa in getting millions of individuals living with HIV into care, many patients still present or re-enter care with Advanced HIV Disease (AHD). We aimed to estimate the prevalence of AHD among ART-naive and ART-experienced patients in South Africa using studies published between January 2010 and May 2022. Methods: We searched for relevant data on PubMed, CINAHL, Scopus and other sources, with a geographical filters limited to South Africa, up to May 31, 2022. Two reviewers conducted all screening, eligibility assessment, data extraction, and critical appraisal. We synthesized the data using the inverse-variance heterogeneity model and Freeman-Tukey transformation. We assessed heterogeneity using the I2 statistic and publication bias using the Egger and Begg's test. Results: We identified 2,496 records, of which 53 met the eligibility criteria, involving 11,545,460 individuals. The pooled prevalence of AHD among ART-naive and ART-experienced patients was 43.45% (95% CI 40.1–46.8%, n = 53 studies) and 58.6% (95% CI 55.7 to 61.5%, n = 2) respectively. The time trend analysis showed a decline of 2% in the prevalence of AHD among ART-naive patients per year. However, given the high heterogeneity between studies, the pooled prevalence should be interpreted with caution. Conclusion: Despite HIV's evolution to a chronic disease, our findings show that the burden of AHD remains high among both ART-naive and ART-experienced patients in South Africa. This emphasizes the importance of regular measurement of CD4 cell count as an essential component of HIV care. In addition, providing innovative adherence support and interventions to retain ART patients in effective care is a crucial priority for those on ART. [ABSTRACT FROM AUTHOR]

Background The burden of advanced HIV disease (AHD) and predictors of outcomes among people living with HIV (PLHIV) re-engaging in care are not well known. Methods We conducted a retrospective cohort study of PLHIV who re-engaged in care after being lost to follow-up (LFU), from 2003 to 2019, in Myanmar. We calculated the incidence rates of attrition after re-engagement and performed Cox regression to identify risk factors for attrition. Results Of 44 131 PLHIV who started antiretroviral treatment, 12 338 (28.0%) were LFU at least once: 7608 (61.6%) re-engaged in care, 4672 (61.4%) with AHD at re-engagement. The death and LFU rates were 2.21-fold (95% CI 1.82 to 2.67) and 1.46-fold (95% CI 1.33 to 1.61) higher among patients who re-engaged with AHD (p>0.001). Death in patients who re-engaged with AHD was associated with male sex (adjusted HR [aHR] 2.63; 95% CI 1.31 to 5.26; p=0.006), TB coinfection (aHR 2.26; 95% CI 1.23 to 4.14; p=0.008) and sex work (aHR 7.49, 95% CI 2.29 to 22.52; p<0.001). History of intravenous drug use was identified as a predictor of being LFU. Conclusions Re-engagement in HIV care in Myanmar is frequent and those who re-engage carry a high burden of AHD. As AHD at re-engagement is associated with higher attrition rates, implementation of differentiated interventions that enable earlier linkage to care and prompt identification and management of AHD in this population is necessary. [ABSTRACT FROM AUTHOR]

In sub-Saharan Africa, an estimated 25% of people with HIV present with advanced HIV and are at high risk of opportunistic infections. Whereas histoplasmosis has occasionally been seen in Uganda, the understanding of the local risk of acute infection is limited. We sought to determine the prevalence of Histoplasma antigenuria using an enzyme immunoassay (EIA, clarus Histoplasma GM EIA, IMMY; Norman, OK, USA) in a cohort of outpatients with advanced HIV disease in Kampala, Uganda. Among the persons with positive urine Histoplasma antigen tests, we assessed their clinical presentation and outcomes. The EIA was run on stored urine samples as per the manufacturer's instructions. Specimens ≥1 EIA units were considered positive. Among the 388 tested urine samples, 4 (1.2%) were positive for Histoplasma antigen. The histoplasmosis prevalence among participants with a CD4 < 100 cells/mcL was 2.5% (4/158). Three of the four participants with a positive Histoplasma antigen test reported systemic symptoms consistent with histoplasmosis. All four participants had a positive urine lipoarabinomannan test and were treated for tuberculosis. By the four-week follow-up visit, all participants were clinically improved, alive, and in care without antifungal therapy. In advanced HIV, the clinical presentations of tuberculosis and histoplasmosis overlap. The value of histoplasmosis screening and pre-emptive treatment is an area of future research. [ABSTRACT FROM AUTHOR]

Presentation to care with advanced HIV disease (AHD) is a significant problem in sub-Saharan Africa. We evaluated factors associated with immune recovery among individuals presenting to care with AHD in Zimbabwe. We conducted a retrospective evaluation of outcomes among adult (>18 years old) individuals with AHD (CD4 count ≤200 cells/mm3) receiving care at 18 outpatient primary care clinics in Harare, Zimbabwe. Baseline and 12-month CD4 count data were extracted from medical records. CD4 count recovery (defined as CD4 count >200 cells/mm3) after 12 months on non-nucleotide reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART) regimen was determined and factors associated with CD4 count recovery were established using logistic regression. All statistical analysis was performed on SPSS v23. A total of 1,338 participant records were included in the analysis. The median interquartile range (IQR) age was 37 (30-43) years and 52% were females. The baseline median (IQR) CD4 count was 50 (28–75) cells/mm3 and was significantly lower among patients with history of cryptococcal meningitis compared to those without [25 (10–52) vs. 52 (32–77), respectively; p = .0009]. The median (IQR) CD4 count at 12 months after ART initiation increased from 50 (28–75) at baseline to 180 (92–290) cells/mm3. Immune recovery with a CD4 count >200 cells/mm3 was observed in 181/417 (43%). Male gender and low baseline CD4 count were strong predictors of poor immunological recovery on ART. Immunological recovery following ART initiation was 43% among individuals with AHD. Male patients are most vulnerable to persistent immunological failure. Clinical Trial Registration number: NCT02434172. [ABSTRACT FROM AUTHOR]

Abstract Introduction International treatment guidelines recommend the rapid initiation of antiretroviral therapy (ART) with bictegravir (B)/emtricitabine (F)/tenofovir alafenamide (TAF) and dolutegravir (DTG)-based regimens for treatment-naïve persons living with HIV (PLWH) irrespective of their disease stage. However, we lack evidence of the virological efficacy, virological failure, and tolerability of coformulated B/F/TAF and DTG/ABC/3TC regimens in persons living with advanced HIV (PLWAH; defined as persons with a CD4+ count of

Abstract Background Information on the frequency and clinical features of advanced HIV disease (AHD) in pregnancy and its effects on maternal and perinatal outcomes is limited. The objective of this study was to describe the prevalence and clinical presentation of AHD in pregnancy, and to assess the impact of AHD in maternal and perinatal outcomes in Mozambican pregnant women. Methods This is a prospective and retrospective cohort study including HIV-infected pregnant women who attended the antenatal care (ANC) clinic at the Manhiça District Hospital between 2015 and 2020. Women were followed up for 36 months. Levels of CD4 + cell count were determined to assess AHD immune-suppressive changes. Risk factors for AHD were analyzed and the immune-suppressive changes over time and the effect of AHD on pregnancy outcomes were assessed. Results A total of 2458 HIV-infected pregnant women were enrolled. The prevalence of AHD at first ANC visit was 14.2% (349/2458). Among women with AHD at enrolment, 76.2% (260/341) were on antiretroviral therapy (ART). The proportion of women with AHD increased with age reaching 20.5% in those older than 35 years of age (p

Using data from 67 Ugandan human immunodeficiency virus (HIV) clinics (July 2019–January 2022), we report a 40% (1005/1662) reduction in the number of people with HIV presenting to care after August 2021 compared to prepandemic levels, with a greater proportion presenting with advanced HIV disease (20% vs 16% in the pre–coronavirus disease 2019 period). [ABSTRACT FROM AUTHOR]