Evolving Trends in Late HIV Diagnosis: Increasing Frequency but Improved Survival and Reduced Opportunistic Infections in a 10-Year Hospital-Based Cohort

Abstract

Introduction

Late HIV diagnosis increases hospitalization and mortality, but evidence from Latin America remains limited. This study assessed the frequency of late HIV diagnosis among hospitalized patients and described temporal trends in clinical characteristics, opportunistic infections, and short-term outcomes in the Colombian Caribbean.

Methods

A retrospective cohort study was conducted at a tertiary referral hospital (2014-2023), including adults with late HIV diagnosis defined as CD4⁺ T-cell counts <350 cells/µL or an AIDS-defining illness. Data was obtained from medical records, and 6-month mortality was verified through the national health insurance database. Multivariable logistic regression assessed predictors of 6-month mortality, and temporal trends were evaluated (chi-square for trend).

Results

Eighty-one patients met the criteria for late HIV diagnosis. Most were male (74.1%) with a median age of 42 years (interquartile range [IQR] 32-50), low socioeconomic status, and limited education. Opportunistic infections were frequent, particularly infectious diarrhea (46.9%), Pneumocystis jirovecii pneumonia (24.7%), and tuberculosis (16%). Median CD4⁺ T-cell count was 46 cells/µL (IQR 21–112). Intensive care unit (ICU) admission occurred in 27.2%, with in-hospital and 6-month mortality of 13.5% and 32.1%, respectively. CD4⁺ T-cell count <100 cells/µL independently predicted 6-month mortality (OR 7.9, 95% CI 1.48-42.8; p=0.01). Over time, patients with late HIV diagnosis increased, while opportunistic infections (p=0.009), severe immunosuppression (p=0.02), and in-hospital (p=0.02) and 6-month mortality (p=0.003) declined significantly.

Conclusions

These findings underscore the substantial burden and evolving pattern of late HIV diagnosis, with increasing cases but improved short-term outcomes. Early detection and targeted interventions remain essential in this population.

Keywords

human immunodeficiency virus opportunistic infections trends delayed diagnosis mortality

Introduction

Human immunodeficiency virus (HIV) infection remains a major global public health challenge, generating substantial clinical, social, and economic consequences through its impact on healthcare systems, households, and the working-age population.¹ Late HIV diagnosis is consistently associated with increased morbidity and mortality, and higher healthcare expenditures. In addition, late HIV diagnosis is related with suboptimal immunologic recovery, poorer virologic response to antiretroviral therapy, and an elevated risk of onward transmission.^2,3 Mortality during the first year after diagnosis can be up to ten-fold higher among patients presenting with advanced immunosuppression. These patients also more frequently experience opportunistic infections and severe clinical deterioration. For surveillance and research purposes, late HIV diagnosis is commonly defined as HIV detection in individuals with a CD4⁺ T-cell count <350 cells/µL or the presence of an AIDS-defining condition at diagnosis.⁴

Globally, a substantial proportion of people living with HIV remain unaware of their infection, contributing to delayed diagnosis and ongoing transmission.^5,6 According to the Pan American Health Organization (PAHO), approximately one-third of individuals in the region are diagnosed late with advanced immunosuppression.⁶ In many countries across the Americas, barriers to early diagnosis include limited access to HIV testing services, persistent stigma, and low perceived risk among key populations.⁷ In Colombia, national surveillance data indicate that 58.3% of individuals diagnosed in 2024 presented with CD4⁺ T cells <350 cells/µL at the time of diagnosis.⁸ Although population-level estimates of late diagnosis are available in Latin America, relatively few studies have examined the detailed clinical and prognostic evolution of patients with late HIV diagnosis over time.

The aim of this study was to estimate the frequency of late HIV diagnosis and to characterize the clinical, epidemiologic, laboratory profile, co-infections and outcomes among patients admitted to a tertiary referral center in the Colombian Caribbean. Additionally, we performed a 10-year temporal trend analysis (2014-2023) to identify clinically meaningful shifts in immune status, co-infection patterns, and prognosis.

Materials and Methods

Population and Study Design

An observational, retrospective cohort study was conducted at the Hospital Universidad del Norte, located in Soledad, Atlántico, Colombia, between January 1, 2014, and December 31, 2023. The hospital primarily serves patients with limited economic resources, as it is located in a city where approximately 79% of the population live in low-income conditions (socioeconomic strata 1 and 2). Individuals aged 18 years or older who were hospitalized and diagnosed with late-stage HIV infection were included. Late HIV diagnosis was defined according to the European Centre for Disease Prevention and Control/World Health Organization (ECDC/WHO) consensus as a newly diagnosed HIV-positive individual with a CD4 T-cell count of <350 cells/μL or with an AIDS-defining condition, regardless of the CD4 count.³ Patients with previous HIV diagnosis were excluded.

The study was approved by the Research Committee of the Universidad del Norte Hospital and the Ethics Committee of the Universidad del Norte (Record No. 334, File No. 2503-8113 - 2025). In accordance with Resolution 8430 of 1993 of the Colombian Ministry of Health, the study was classified as low-risk research. No individual identifiers were extracted for analysis. This study was conducted and reported in accordance with the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines.⁹

Data Collection and Variable Definition

Data were collected from clinical records, including sociodemographic information, viral load, CD4+ T-cell count, comorbidities defined according to the Charlson Comorbidity Index, and opportunistic infections. Tuberculosis was diagnosed based on clinical signs and microbiological confirmation (Ziehl-Neelsen stain, molecular tests, or culture). Diarrhea was defined as an increase in stool frequency (≥3 per day) and changes in consistency with or without blood in feces. Pneumocystis jirovecii pneumonia was diagnosed with subacute respiratory symptoms and advanced immunosuppression, confirmed by histopathology, antigen detection, polymerase chain reaction (PCR), or clinical response to empirical treatment. Syphilis was confirmed with non-treponemal (e.g., VDRL, RPR) and treponemal (e.g., FTA-ABS, TPHA) serological tests. Cerebral toxoplasmosis was defined by subacute headache and focal neurological deficits in patients with CD4 T lymphocyte <200 cells/μL, identified by imaging and clinical response to empirical treatment. Esophageal candidiasis was diagnosed with retrosternal pain and white plaques observed via endoscopy. Cryptococcal meningitis was confirmed by antigen detection or positive PCR in cerebrospinal fluid (CSF). Other infections (e.g., hepatitis B, hepatitis C, histoplasmosis, herpes viruses, and Kaposi’s sarcoma) were defined according to NIH guidelines for HIV-related opportunistic infections.¹⁰

Additional data collected included intensive care unit (ICU) admission, in-hospital complications, and mortality during hospital admission and six months after discharge. Six-month mortality was ascertained through the Single Database of Affiliates of the National Health System, queried up to December 2024. Deaths occurring during hospitalization were also counted toward the 6-month mortality denominator.

Statistical Analysis

Categorical variables were expressed as frequencies and percentages, while quantitative variables were summarized using medians and interquartile ranges (IQR). To assess significant differences between study subgroups (6-months survivors vs. non-survivors), the Mann-Whitney U test was used for continuous variables, and the chi-square or Fisher’s exact test for proportions. A multivariate model was used to identify factors associated with 6-month mortality, including variables with p < 0.10 in bivariate analysis and clinically relevant factors. The model discriminatory ability was assessed by the area under the receiver operating characteristic (ROC) curve, based on the predicted probabilities generated by the model. The optimal cut-off point of area under ROC curve was determined using the Youden index. The goodness-of-fit of the model was evaluated using the Hosmer-Lemeshow test. Trends over the years of clinical characteristics, opportunistic infections, and prognosis were analyzed with the chi-square test for trend (qualitative variables) and Kruskal-Wallis (quantitative variables). A p-value ≤ 0.05 was considered statistically significant. Data processing and analysis were performed using IBM SPSS Statistics for Windows, Version 20.0.

Results

In this retrospective cohort study, 87 patients with de novo HIV diagnosis requiring hospitalization through the emergency department were identified. Of these, 81 patients (93.1%) met the criteria for late HIV diagnosis and were analyzed. The clinical and laboratory characteristics, as well as opportunistic infections and prognosis of the late HIV diagnosis cohort, along with comparative outcomes between 6-month survivors and non-survivors, are summarized in Table 1.

Table 1.

Main Characteristics of Patients With Late HIV Diagnosis as Well as Comparisons Between Patients Who Survived and Died After Six Months of Hospital Admission

	All patients	6-month mortality^a		P-value
		Survivors	Non-survivors
		(N = 81)	(N = 53)	(N = 26)
Demographic data
Age (years), median (IQR)	42 (32-50)	42 (32-49)	48 (39-54)	.05
Male sex	60 (74.1)	40 (75.5)	19 (73.1)	.81
Low socioeconomic status	46 (56.8)	32 (65.3)	14 (58.3)	.56
Completed secondary education or higher	19 (24.4)	12 (23.1)	7 (29.2)	.56
Comorbidities	24 (29.6)	12 (22.6)	11 (42.3)	.07
Laboratory parameters
CD4 T-cell count (cells/µL), median (IQR)	46 (21-112)	68 (32-201)	29 (11-75)	.006
CD4 T-cell count <100 cells/µL	55 (69.6)	31 (58.5)	24 (92.3)	.002
HIV viral load (copies/mL), median (IQR)	269153 (94860-744491)	260664 (66544-744491)	323576 (120965-8256929	.29
Opportunistic infections	57 (70.4)	33 (62.3)	22 (84.6)	.04
Suspected infectious diarrhea	38 (46.9)	22 (41.5)	14 (53.8)	.30
P. jirovecii pneumonia	20 (24.7)	11 (20.8)	9 (34.6)	.18
Cerebral toxoplasmosis	12 (14.8)	6 (11.3)	6 (23.1)	.19
Tuberculosis	13 (16)	8 (15.4)	4 (15.4)	1
Esophageal candidiasis	11 (13.6)	10 (18.9)	1 (3.8)	.09
Cryptococcosis	6 (7.4)	3 (5.7)	3 (11.5)	.38
Community-acquired infections at admission
Syphilis	20 (24.7)	14 (26.4)	6 (23.1)	.74
Community-acquired pneumonia	12 (14.8)	8 (15.1)	3 (11.5)	1
Urinary tract infection	6 (7.4)	3 (5.7)	3 (11.5)	.38
Clinical outcomes
ICU admission	22 (27.8)	10 (18.9)	12 (46.2)	.01
In-hospital mortality	11 (13.5)

Note. Data are presented as n (%), unless otherwise specified. ^aSix-month mortality was unavailable for 2 cases. Abbreviations: HIV, human immunodeficiency virus; ICU, intensive care unit; IQR, interquartile range.

Most patients with late HIV diagnosis were male (74.1%), with a median age of 42 years (IQR 32–50). More than half were classified within low socioeconomic strata (1–2; 56.8%), and only one patient (1.2%) belonged to a high stratum (≥4). The majority had no formal education or completed only primary school (75.6%). Chronic non–HIV comorbidities were infrequent (11.1%), most commonly chronic liver disease (eight cases of hepatitis B and one of hepatitis C), followed by chronic pulmonary disease (three cases) and diabetes mellitus (two cases). Infectious diseases were the leading driver of hospitalization. Non-opportunistic infections accounted for 28.5% of diagnoses, most commonly syphilis, community-acquired pneumonia, and urinary tract infections. Among opportunistic infections, presumptive infectious diarrhea was the most frequent presentation (46.9%), followed by P. jirovecii pneumonia (24.7%), tuberculosis (16.0%), cerebral toxoplasmosis (14.8%), esophageal candidiasis (13.6%), and Cryptococcus neoformans infection (7.4%). At admission, patients showed severe immunosuppression, with a median CD4⁺ T lymphocytes of 46 cells/µL (IQR 21–112). ICU care was required for 22 patients (27.2%). Eleven patients (13.5%) died during the hospitalization, and cumulative 6-month mortality reached 32.1% (26 patients).

When comparing 6-month survivors and non-survivors after hospital admission, no significant differences were identified in sociodemographic characteristics or in the occurrence of opportunistic or non-opportunistic infections. In contrast, patients who died presented with significantly lower CD4⁺ levels and had higher rates of ICU admission and invasive mechanical ventilation during the hospitalization. Among the 22 patients requiring ICU care, 6-month mortality was 54.5% (12 patients), with 6 deaths occurring in-hospital and 6 additional deaths within six months of admission.

Temporal Trend Analysis Across Biennial Periods

Temporal trends in sociodemographic characteristics, opportunistic infections, and prognostic indicators are summarized in Figure 1. Hospitalized patients with late HIV diagnosis increased from 6 cases in 2014-2015 to 36 cases in 2022-2023. No significant differences in age, sex, or chronic comorbidities were observed across study periods. Although median CD4⁺ levels remained relatively stable, the proportion of patients presenting with CD4⁺ T lymphocytes <100 cells/µL declined significantly over time, from 83.3% in 2014-2015 to 61.1% in 2022-2023 (p = 0.02). Among infectious diagnoses, syphilis exhibited a progressive upward trend (p = 0.07), while tuberculosis (p = 0.05) and P. jirovecii pneumonia (p = 0.08) showed downward trends. The overall proportion of patients with documented opportunistic infections, including diarrhea, cryptococcosis, P. jirovecii pneumonia, cerebral toxoplasmosis, esophageal candidiasis, or tuberculosis, decreased significantly from 83.3% in 2014-2015 to 41.7% in 2022-2023 (p = 0.009). Both in-hospital mortality and cumulative 6-month mortality declined significantly over the study period (p = 0.02 and p = 0.003, respectively).

Figure 1.

Temporal trends across biennial periods in hospitalized patients with late HIV diagnosis who presented with (A) opportunistic infections, and (B) low CD4⁺ T lymphocyte counts and clinical outcomes. Percentages represent the proportion of patients within each biennial period

Independent Factor Associated With 6-month Mortality: Multivariate Analysis

Table 2 summarizes the multivariable analysis of factors associated with 6-month mortality after hospital admission. After adjustment for potential confounders, a CD4⁺ level <100 cells/µL was independently associated with increased 6-month mortality (OR 7.9, 95% CI 1.48-42.8; p = 0.01). The multivariable logistic regression model showed acceptable discrimination, with an area under the ROC curve of 0.78 (95% CI 0.68–0.89). At the optimal cut-off, determined by the Youden index, sensitivity was 80.8% and specificity was 50.9%

Table 2.

Factors Associated With 6-Month Mortality in Patients With Late HIV Diagnosis: Multivariate Analysis

Characteristics	aOR	95% CI	P-value
Age	2.12	(0.69 - 6.51)	.18
Comorbidities	1.97	(0.60 – 6.40)	.25
CD4 T-cell count <100 cells/µL	7.97	(1.48 – 42.8)	.01
Opportunistic infections	1.11	(0.34 – 3.64)	.85
ICU admission	2.97	(0.91 – 9.64)	.06

Note. Abbreviations: aOR, adjusted odds ratio; CI, confidence interval; HIV, human immunodeficiency virus; ICU, intensive care unit. Area under the receiver operating characteristic (ROC) curve 0.78 (95% CI 0.68-0.89), and the Hosmer-Lemeshow test 0.30.

Discussion

In this study, late HIV diagnosis was highly prevalent among hospitalized patients, with opportunistic infections as the main cause of admission. Although sociodemographic characteristics remained stable over time, we observed temporal changes in immune status, opportunistic infections, and mortality. Severe immunosuppression remained a key predictor of mortality.

This study identified a recent rise in hospital admissions involving patients with late HIV diagnosis. A temporary decline in late HIV diagnoses occurred in 2020-2021, aligned with the COVID-19 pandemic. This was followed by a pronounced rebound from 2022 onward, surpassing pre-pandemic case numbers. Similar disruptions were reported globally. Multiple countries experienced reductions in HIV testing and continuity of care due to healthcare resource reallocation and prioritization of the pandemic response. In Germany and Brazil, similar post-pandemic increases in late HIV diagnosis were documented.^11,12 Evidence from international cohorts further illustrates the high and heterogeneous burden of late HIV diagnosis. In Latin America, a multicenter study including 9,229 cases across Argentina, Brazil, Chile, Haiti, Honduras, Mexico, and Peru reported a late diagnosis prevalence of 56%.⁷ National surveillance data from Colombia documented a late HIV diagnosis rate of 58.3% in 2024, with 33.9% of cases presenting with <200 CD4 T lymphocytes.⁸ In Spain, late diagnosis reached 44.6%,¹³ while in southeastern Africa (Malawi, Zambia, Zimbabwe), a prevalence of 49% has been reported.¹⁴ In Asia, estimates of late HIV diagnosis ranged from 28.5% to 71%, with most countries exceeding 50% prevalence.¹⁵ These findings reinforce the global scope of late HIV diagnosis and its marked inter-country variability. Our analysis was restricted to hospitalized patients, which may explain the higher prevalence of late HIV diagnosis compared with studies including outpatient populations. This may have contributed to an overestimation relative to broader epidemiologic reports.

Opportunistic infections remain a major and largely preventable cause of morbidity and mortality among people living with HIV. Combination antiretroviral therapy has markedly improved quality of life and extended survival. However, universal achievement and durable maintenance of viral suppression continue to present significant clinical and health-system challenges. A considerable fraction of HIV infections remains undiagnosed. Among those diagnosed, many individuals already exhibit advanced immunosuppression, limiting the timely prevention of opportunistic infections. In our cohort, 70.4% of patients with late HIV diagnosis presented with at least one opportunistic infection at admission. This finding is consistent with diagnoses made during emergency department encounters triggered by symptomatic complications. Despite expanded access to modern diagnostics in recent years, including molecular assays and antigen detection platforms, the proportion of opportunistic infections declined steadily over the study period. This trend paralleled an increase in baseline immune status, reflected by a reduction in patients presenting with CD4⁺ levels <100 cells/µL.

The distribution of specific opportunistic infections, including diarrhea, P. jirovecii pneumonia, tuberculosis, and cryptococcosis, varies widely across regions and study populations.^16-18 This variability highlights the influence of epidemiologic context on clinical presentation. Diarrhea persisted as a frequent and debilitating opportunistic complication, affecting nearly half of patients at the time of HIV diagnosis. Moreover, syphilis co-infection was identified in 24.7% of our cohort and increased progressively over time. This aligns with reports from multiple international studies documenting a sustained high burden of syphilis among patients living with HIV.^19,20 Although a recent U.S. analysis observed a decline in syphilis incidence between 2017 and 2024 among high-burden groups,²⁰ syphilis continues to pose a substantial public health challenge. These findings reinforce the importance of systematic and active syphilis screening at the time of HIV diagnosis, alongside early linkage to care. This approach may help mitigate downstream complications and transmission.

Prognosis among patients with late HIV diagnosis continues to represent a critical global health challenge. Delayed detection is consistently linked to elevated mortality risk.^2,21 In the present study, both in-hospital and 6-month mortality were high and exceeded estimates reported in other cohorts.^2,22 Notably, mortality rates declined progressively over the 10-year study period. In multivariable model, advanced immunosuppression was independently associated with mortality, reaffirming immune status as a central prognostic determinant. Interestingly, the proportion of patients presenting with CD4⁺ T lymphocytes <100 cells/µL decreased over time. This improvement may partially explain the observed increase in survival, alongside the decline in opportunistic infections. Because data on outpatient antiretroviral initiation, long-term adherence, and retention in care were unavailable, their potential contribution to mortality trends could not be evaluated. International studies have similarly described clinical predictors of death among people presenting with advanced or late-diagnosed HIV. In a systematic review and meta-analysis from Sub-Saharan Africa, the strongest predictors of mortality included male sex, age ≥50 years, advanced clinical stage, and delayed antiretroviral initiation. Additional predictors were higher viral load, CD4⁺ levels <50 cells/mm³, and severe anemia.²³ In Brazil, advanced HIV cohorts have also identified mortality-associated features, including antiretroviral-naïve status, altered mental status, anemia, elevated creatinine, histoplasmosis, and cryptococcosis. In contrast, demographic factors such as gender, race, education level, and sexual orientation were not associated with mortality in adjusted analyses.²⁴ Collectively, these data emphasize the persistent clinical burden and survival impact of delayed HIV diagnosis. Accordingly, strengthening early detection strategies and expanding access to testing are essential. Ensuring rapid antiretroviral availability and timely linkage to care is also critical to reduce avoidable mortality in this population.

This study has inherent limitations related to its retrospective, single-center design. The sample size and limited number of mortality events may have reduced statistical power, contributing to the absence of significant associations for some analyses. Similarly, this may increase the risk of overfitting and reduce the stability of adjusted estimates in the multivariable modeling. Moreover, specific causes of death were not systematically recorded, preventing cause-specific mortality assessment. Similarly, we did not distinguish acute from chronic diarrhea, which may affect associations with opportunistic infections. The study setting and exclusive focus on hospitalized patients further limit generalizability to the broader population of individuals with late HIV diagnosis. Despite these constraints, the study provides clinically meaningful evidence from a geographically underexplored region. Additionally, it applies a structured analytical framework to characterize temporal trends in case frequency, opportunistic infections, and immune-status–associated mortality risk. Importantly, during the study period there were no changes in the hospital HIV testing policy.

Conclusion

Late HIV diagnosis remains common and continues to impose a substantial clinical burden, with high rates of opportunistic infections, ICU admission, and mortality. Low CD4⁺ T-cell counts were independently associated with mortality, reaffirming immune status as a key determinant of short-term survival. Across the study period, opportunistic infections declined, and prognosis improved, likely due to fewer patients presenting with severe immunosuppression. However, additional non-immunological factors not evaluated in this study should also be considered, such as earlier initiation of antiretroviral therapy and improvements in the diagnosis and management of opportunistic infections. These findings highlight the importance of early HIV detection, timely linkage to care, and systematic screening for co-infections. Future studies should assess targeted interventions to further improve outcomes among late presenters.

Footnotes

ORCID iD

Diego Viasus

Ethical Considerations

The study was approved by the Research Committee of the Hospital Universidad del Norte and the Ethics Committee of the Universidad del Norte (Record No. 334, File No. 2503-8113 - 2025).

Consent to Participate

The requirement for written informed consent was waived by the Ethics Committee.

Author Contributions

Sandra Teran: Conceptualization, Data Curation, Investigation, Validation, Formal Analysis, Writing – Original Draft; Juan Espitia: Formal Analysis, Methodology, Writing – Original Draft; Geraldine Chávez: Data Curation, Investigation, Writing – Original Draft; Marcela Hernández: Data Curation, Investigation, Writing – Review & Editing; Vanessa Sarmiento: Investigation, Resources, Writing – Review & Editing; Sharon Quintero: Investigation, Resources, Writing – Review & Editing; Julio Insignares: Data Curation, Investigation, Writing – Review & Editing; Luis Fernando Marin Ortega: Formal Analysis, Visualization, Writing – Review & Editing; Sofia Abuchaibe: Data Curation, Investigation, Writing – Review & Editing; Diego Viasus: Conceptualization, Formal Analysis, Methodology, Supervision, Writing – Review & Editing.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Data Availability Statement

Data will be made available on request.*

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