Determinants of Late HIV Diagnosis and Advanced HIV Disease Among People Living with HIV in Tanzania.

Background: 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.

Mortality of cytomegalovirus infection among people living with HIV: A retrospective study from a tertiary hospital in Indonesia.

BACKGROUND: There are still many patients newly diagnosed with HIV at an advanced stage in Indonesia. We aimed to identify factors associated with 1-year mortality among cytomegalovirus (CMV)-infected people living with HIV (PLHIV). METHODS: This retrospective cohort study was carried out at a tertiary-care hospital in Jakarta, Indonesia (January 2017 to December 2022). We included PLHIV with CMV end-organ disease (EOD) and CMV syndrome. The presence of CMV infection was confirmed by fulfilling one of the following criteria: (1) positive PCR from plasma, urine, cerebrospinal fluid, or other body fluids, or associated tissue for CMV EOD; (2) positive immunoglobulin M (IgM); or (3) consistent symptoms and signs of CMV retinitis. RESULTS: Out of 1737 PLHIV, 147 (8.5%, 95% CI: 7.2 to 9.9%) were diagnosed with CMV infection. Forty (27.2%, 95% CI: 20.6 to 35.1%) patients died within 1 year of being diagnosed. Only anti-retroviral therapy (ART) defaulting (aHR 3.31, 95% CI: 1.12 to 9.73) was found to be significantly associated with 1-year mortality in multivariate analysis. CONCLUSION: Defaulted ART status is significantly associated with reduced 1-year survival after CMV infection diagnosis. Patients with low CD4 counts, especially those with <50 cells/µL, should be assessed for CMV infection, monitored, and treated accordingly.

Multidrug-Resistant Shigellosis as a Sexually Transmitted Infection in Advanced HIV: A Case Report.

Shigellosis, a significant public health concern, has increasingly been recognized as a sexually transmitted infection (STI) among men who have sex with men (MSM), particularly in those with HIV. This case report describes a 25-year-old MSM with advanced HIV who presented with recurrent multidrug-resistant (MDR) Shigella flexneri infection despite multiple hospitalizations and antibiotic courses. The patient's high-risk sexual behaviors and suboptimal HIV management likely contributed to recurrent exposure to Shigella and the selection of resistant strains. This case highlights the complex interplay of individual behaviors, immune suppression, antimicrobial resistance, and the healthcare system in the context of this emerging STI. It underscores the importance of optimized HIV care, comprehensive patient education, robust healthcare coordination, and strengthened surveillance to effectively combat MDR shigellosis in vulnerable populations.

'Not taking medications and taking medication, it was the same thing:' perspectives of antiretroviral therapy among people hospitalised with advanced HIV disease.

BACKGROUND: Despite HIV's evolution to a chronic disease, the burden of advanced HIV disease (AHD, defined as a CD4 count of < 200 cells/uL or WHO clinical Stage 3 or 4 disease), remains high among People Living with HIV (PLHIV) who have previously been prescribed antiretroviral therapy (ART). As little is known about the experiences of patients hospitalised with AHD, this study sought to discern social forces driving hospitalisation with AHD. Understanding such forces could inform strategies to reduce HIV-related morbidity and mortality. METHODS: We conducted a qualitative study with patients hospitalised with AHD who had a history of poor adherence. Semi-structured interviews were conducted between October 1 and November 30, 2023. The Patient Health Engagement and socio-ecological theoretical models were used to guide a thematic analysis of interview transcripts. RESULTS: Twenty individuals participated in the research. Most reported repeated periods of disengagement with HIV services. The major themes identified as driving disengagement included: 1) feeling physically well; 2) life circumstances and relationships; and 3) health system factors, such as clinic staff attitudes and a perceived lack of flexible care. Re-engagement with care was often driven by new physical symptoms but was mediated through life circumstances/relationships and aspects of the health care system. CONCLUSIONS: Current practices fail to address the challenges to lifelong engagement in HIV care. A bold strategy for holistic care which involves people living with advanced HIV as active members of the health care team (i.e. 'PLHIV as Partners'), could contribute to ensuring health care services are compatible with their lives, reducing periods of disengagement from care.

Strategies for scaling up pre-ART advanced HIV disease screening at a secondary referral hospital-Malawi: a qualitative study.

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.

Implementation of single high-dose liposomal amphotericin B based induction therapy for treatment of HIV-associated cryptococcal meningitis in Uganda: a comparative prospective cohort study.

BACKGROUND: In 2022, the World Health Organization (WHO) recommended a single 10mg/kg dose of liposomal amphotericin B in combination with 14 days of flucytosine and fluconazole (AMBITION-cm regimen) for induction therapy of 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 2018-2021. No significant difference in 10-week survival occurred between the observational cohort (68.6%; 95%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). CONCLUSION: 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.

Systematic Review of Prevalence of Histoplasma Antigenuria in Persons with HIV in Latin America and Africa.

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.

Advanced HIV disease and associated factors among young people aged 15-24 years at a tertiary hospital in Sierra Leone: a cross-sectional study.

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.

Causes, risks and care circumstances associated with death in older adults diagnosed with HIV in a tertiary centre in Malaysia.

BACKGROUND: A substantial number of older adults succumb soon after HIV diagnosis despite ART. We explored the causes, risk factors and circumstances before death among older adults acquring HIV. METHODS: We recruited individuals newly diagnosed at our centre from 2016-2020 and analysed data of those who died. Patients were stratified to older (≥50 years) or younger (<50 years) based on their age at diagnosis and attributes were compared. The Cox proportional multivariable model was used to identify factors associated with all-cause mortality. RESULTS: Among 75 deaths reported, the majority of deaths were AIDS-related and late presentation was common in both age groups. The majority of deaths occurred in the first 12 months after care presentation and over two-thirds in both groups disengaged from care prior to death. Older age remained an independent factor associated with death after adjusting for confounders including opportunistic infections, late presentation to care, ART initiation and chronic comorbidities at presentation. CONCLUSION: Most causes of death in our setting were AIDS-related and associated with late care presentation both in young and older individuals, although older age at diagnosis remained an independent risk factor. Our findings highlight the urgent need to encourage prompt ART initiation following diagnosis, especially in older adults.

Enhanced tuberculosis diagnosis with computer-aided chest X-ray and urine LAM in adults with HIV admitted to hospital (CASTLE study): A cluster randomised trial.

BACKGROUND: People with HIV (PHIV) admitted to hospital have high mortality, with tuberculosis (TB) being the major cause of death. Systematic use of new TB diagnostics could improve TB diagnosis and might improve outcomes. METHODS: We conducted a cluster randomised trial among adult PHIV admitted to Zomba Central Hospital, Malawi. Admission-days were randomly assigned to: enhanced TB diagnostics using urine lipoarabinomannan (LAM) antigen tests (SILVAMP-LAM, Fujifilm, Japan and Determine-LAM, Alere/Abbot, USA), digital chest X-ray with computer aided diagnosis (dCXR-CAD, CAD4TBv6, Delft, Netherlands), plus usual care ("enhanced TB diagnostics"); or usual care alone ("usual care"). The primary outcome was TB treatment initiation during admission. Secondary outcomes were 56-day mortality, TB diagnosis within 24-hours, and undiagnosed TB at discharge, ascertained by culture of one admission sputum sample. FINDINGS: Between 2 September 2020 and 15 February 2022, we recruited 419 people. Four people were excluded post-recruitment, leaving 415 adults recruited during 207 randomly assigned admission-days in modified intention-to-treat analysis. At admission, 90.8% (377/415) were taking antiretroviral therapy (ART) with median (IQR) CD4 cell count 240 cells/mm3. In the enhanced diagnostic arm, median CAD4TBv6 score was 60 (IQR: 51-71), 4.4% (9/207) had SILVAMP-LAM-positive and 14.4% (29/201) had Determine-LAM positive urine with three samples positive by both urine tests. TB treatment was initiated in 46/208 (22%) in enhanced TB diagnostics arm and 24/207 (12%) in usual care arm (risk ratio [RR] 1.92, 95% CI 1.20-3.08). There was no difference in mortality by 56 days (enhanced TB diagnosis: 54/208, 26%; usual care: 52/207, 25%; hazard ratio 1.05, 95% CI 0.72-1.53); TB treatment initiation within 24 hours (enhanced TB diagnosis: 8/207, 3.9%; usual care: 5/208, 2.4%; RR 1.61, 95% CI 0.53-4.71); or undiagnosed microbiological-confirmed TB at discharge (enhanced TB diagnosis, 0/207 (0.0%), usual care arm 2/208 (1.0%) (p = 0.50). INTERPRETATION: Urine SILVAMP-LAM/Determine-LAM plus dCXR-CAD diagnostics identified more hospitalised PHIV with TB than usual care. The increase in TB treatment appeared mainly due to greater use of Determine-LAM, rather than SILVAMP-LAM or dCXR-CAD. Poor concordance between Determine-LAM and SILVAMP-LAM urine tests requires further investigation. Inpatient mortality for adults with HIV remains unacceptability high.

Prevalence of advanced HIV disease and associated factors among antiretroviral therapy naïve adults enrolling in care at public health facilities in Kampala, Uganda.

Background: Despite adoption of the 'test-and-treat' strategy, a high proportion of antiretroviral therapy (ART) naïve people living with HIV (PLHIV) enrol in care with, and die of advanced HIV disease (AHD) in Uganda. In this study, we aimed to determine the prevalence of AHD among ART naïve adults enrolling in care and associated factors at selected public health facilities in Kampala, Uganda. Methods: From April to July 2022, we conducted a mixed-methods study at Kiswa Health Centre III, Kitebi Health Centre III, and Kawaala Health Centre IV. The study involved cross-sectional enrolment and evaluation of 581 participants, utilizing an interviewer-administered questionnaire and chart reviews. Modified Poisson regression was employed to identify factors associated with AHD, complemented by a qualitative component comprising fifteen in-depth interviews, with data analysed through thematic analysis. Results: Overall, 35.1% (204/581) of the study participants had AHD. Being male [adjusted prevalence ratio (aPR): 1.4, 95% CI: 1.04-1.88] and aged 35-50 years (aPR: 1.81, 95% CI: 1.14-2.88) were associated with AHD. Participants with no personal health perception barriers had 37% lower odds of presenting to care with AHD (aPR: 0.63, 95% CI: 0.46-0.85). Qualitative findings indicated that individual factors, such as waiting until physical health deteriorated and initially opting for alternative therapies, took precedence in contributing to enrolment in care with AHD. Conclusion: Over one in every three ART naïve adults presents to public health facilities in Uganda with AHD. Male gender, age 35-50 years, and personal health perception barriers emerged as significant factors associated with AHD; emphasizing the need for targeted interventions to address these disparities and enhance early detection and engagement in care. Routine HIV testing should be emphasized and incentivized especially for men and persons aged 35-50 years.

Health-Related Quality of Life in People with Advanced HIV Disease, from 1996 to 2021: Systematic Review and Meta-analysis.

The purpose of the study was to assess the effects of advanced HIV disease (AHD) on health-related quality of life (HRQoL) in PLHIV, the changes in HRQoL outcomes over the last 25 years, and the differences between countries according to level of economic development. We conducted a systematic review and meta-analysis. The search was conducted in PubMed and Web of Science using the terms: "health-related quality of life", "HQRoL", "HIV", "AIDS", "advanced HIV disease" and "low CD4 cells". Studies inclusion criteria were: adult population; initiated after 1996 and published before July 2021; clinical trials, cross-sectional, cohort, and case-control studies; studies analyzing the relationship between AHD and HRQoL; English or Spanish language. Standardized mean differences (d+) were calculated to estimate the effect size for the meta-analyses. Summary statistics were calculated using a random-effects model, and analyses of effect moderators, using mixed-effects models. The meta-analysis included 38 studies. The results indicated that HRQoL is worse in patients with AHD compared to those without. The main HRQoL domains affected were overall health perception and concern and physical and functional health and symptoms. We found a moderate impact for age and gender on some HRQoL domains. There were no differences in relation to socioeconomic inequities, country of residence, or time period analyzed. In conclusion, advanced HIV disease has a negative impact on health and well-being in PLHIV. Our results show that despite all the advances in antiretroviral treatments over the last 25 years, AHD persists as a source of extreme vulnerability, regardless of where PLHIV live.

RESUMEN: El objetivo del estudio fue evaluar los efectos de la enfermedad avanzada de sida (EAS) en la calidad de vida relacionada con la salud (CVRS) en personas que viven con el VIH (PVVIH), los cambios experimentados en la CVRS en los últimos 25 años y las diferencias entre países. Realizamos una revisión sistemática y metaanálisis. La búsqueda se llevó a cabo en PubMed y Web of Science utilizando los términos: "calidad de vida relacionada con la salud", "CVRS", "VIH", "SIDA", "enfermedad avanzada por VIH" y "células CD4 bajas". Los criterios de inclusión de los estudios fueron: población adulta; iniciado después de 1996 y publicado antes de julio de 2021; ensayos clínicos, estudios transversales, de cohorte y de casos y controles; estudios que analizan la relación entre EAS y CVRS; idioma inglés o español. Se calcularon diferencias de medias estandarizadas (d+) para estimar el tamaño del efecto para los metaanálisis. Los efectos promedios se calcularon utilizando un modelo de efectos aleatorios, y el análisis de moderadores utilizando modelos de efectos mixtos. El metaanálisis incluyó 38 estudios. Los resultados indicaron que la CVRS es peor en pacientes con EAS en comparación con aquellos sin EAS. Los principales dominios de CVRS afectados son la percepción de salud general y su preocupación, y la función física y de salud y los síntomas asociados. Encontramos un impacto moderado por edad y género en algunos dominios de CVRS. No encontramos diferencias en cuanto a las desigualdades socioeconómicas, país de residencia o período de tiempo analizado. En conclusión, la enfermedad avanzada por VIH tiene un impacto negativo en la salud y el bienestar en las personas con VIH. Nuestros resultados muestran que, a pesar de todos los avances en los tratamientos antirretrovirales en los últimos 25 años, el EAS persiste como una fuente de extrema vulnerabilidad, independientemente de dónde vivan las personas con VIH.

Tracking Cryptococcal Meningitis to Monitor HIV Program Success During the Treat All Era: An Analysis of National Data in Botswana.

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.

SARS-CoV-2 infection in immunosuppression evolves sub-lineages which independently accumulate neutralization escape mutations.

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.

Mortality and associated factors among people living with HIV admitted at a tertiary-care hospital in Uganda: a cross-sectional study.

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.

Evaluation of factors associated with high advanced HIV disease and mortality in Southwestern China: a retrospective cohort study, 2005-2020.

OBJECTIVES: 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. STUDY DESIGN: Retrospective cohort study. METHOD: 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. RESULTS: 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). CONCLUSIONS: 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.

Frequency of fungal pathogens in autopsy studies of people who died with HIV in Africa: a scoping review.

BACKGROUND: Fungal infections are common in HIV-infected individuals and significantly contribute to mortality. However, a substantial number of cases are undiagnosed before death. OBJECTIVE: To determine the frequency of fungal pathogens in autopsy studies of people who died with HIV in Africa. METHODS: We conducted a scoping review of autopsy studies conducted in Africa. DATA SOURCES: PubMed, Scopus, Web of Science, Embase, Google Scholar, and African Journal Online. STUDY ELIGIBILITY CRITERIA: 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 SYNTHESIS: Data were summarized using descriptive statistics and no meta-analysis was performed. RESULTS: 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%). CONCLUSIONS: 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.

Reducing HIV-associated post-hospital mortality through home-based care in South Africa: a randomized controlled trial.

BACKGROUND: Twenty-three percent of people with 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 six months among PWH 4 (7.3%) in the home visit arm and 10 (17.9%) in the usual care arm (p = 0.09) 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). COVID-19 related challenges resulted in under-enrollment.

Understanding gender differences of people with HIV newly diagnosed or returning to care with advanced HIV disease in Malawi: a qualitative study.

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.

Pathways to care with HIV-associated cryptococcal meningitis in Botswana and Uganda: Findings from a qualitative methods study.

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.