Determinants of late presentation of HIV positive individuals: a study in Kosovo

Abstract

Background

In recent years, the global response to the HIV/AIDS pandemic has encountered significant challenges, impeding the collective aim of eliminating AIDS as a public health threat by 2030. A major concern undermining this goal is the delayed presentation (late presentation – LP) of individuals diagnosed with HIV/AIDS.

Methodology

This study includes 85 HIV positive individuals with available CD4 count and viral load (VL) data at the time of HIV diagnosis, out of 169 registered people living with HIV in Kosovo. Employing descriptive and frequency statistics, Chi-square tests, non-parametric Mann-Whitney tests, and logistic regression analyses using SPSS Version 29, we generated statistical results with 95% confidence intervals.

Results

The prevalence of LP in HIV positive individuals included in the study was 50.59%, with 30.59% classified as very late presenters (VLP). Determinants associated with LP included male gender, young adulthood, MSM mode of transmission, and a high viral load (log10 4.1–5.0 copies/mL). Comparative analysis with studies on this subject indicated similar patterns of LP in adults, males, and viral load, but different transmission mode patterns.

Conclusion

This research illuminates the specific determinants of LP in Kosovo, offering valuable insights for tailoring interventions to enhance timely diagnosis and access to care for people living with HIV/AIDS.

Keywords:

• HIV/AIDS
• late presentation
• Kosovo

Introduction

In recent years, the global response to the HIV/AIDS pandemic has faced significant challenges exacerbated by multiple crises, resource constraints, and widening inequalities. These obstacles have impeded progress toward the global goal of ending AIDS as a public health threat by 2030. As of December 2021, the international community was not on track to achieve the 2025 targets for HIV prevention, with 1.5 million people acquiring HIV infection in 2021 [1]. The 95-95-95 targets, released by UNAIDS in December 2020 and adopted by United Nations Member states in June 2021, underscore the world’s commitment to the AIDS response and achieving the 2030 sustainable development goal of ‘ending AIDS’ as a public health threat [2].

One significant concern hindering these goals is the late presentation (LP) of individuals diagnosed with HIV/AIDS. Late presentation can have adverse effects on the health and treatment outcomes of infected individuals, leading to poorer outcomes and increased healthcare costs. Late presenters, especially those age above 50, are at higher risk for developing non-infectious co-morbidities and complex multimorbidity. Moreover, late presentation can negatively impact pandemic control by increasing the risk of onward HIV transmission in individuals unaware of their HIV status and is a major contributor to virological failure [3].

Late presentation still accounts for 50% of new HIV diagnoses in Europe, with determinants including age at diagnosis, mode of transmission, region of origin, and viral load at diagnosis. Older patients (>56), heterosexual individuals, patients originating from Africa, and those presenting with a log VL >4.1 had a higher probability of being late presenters (p < 0.001). The rate of late presentation remained stable over the years, except for an increase in 2018 and 2019. Late Presenters (LP) account for 40–60% of HIV cases in Europe, 72 to 83% in Asia, 35 to 89% in Africa, and approximately 40% in Brazil [3].

According to the WHO HIV/AIDS surveillance in Europe 2022 – 2021 data, Kosovo registered 137 people living with HIV from 1999 to 2021 [4]. As of June 2023, 169 people living with HIV have been recorded in Kosovo since the discovery of the first case in 1986.

Late presentation is defined as an individual presenting with a TCD4+ count lower than 350 cells/µL or an AIDS-defining event, according to the European Late Presenter Consensus working group [5], and updated consensus definition [6].

This study aims to identify determinants of late presentation (LP) in Kosovo.

Materials and methods

This observational clinical study was conducted at the Department of Infectious Diseases, University Clinical Centre in Pristina. Among 169 registered HIV/AIDS cases in Kosovo, from 1986 when the first HIV positive individual was diagnosed until June 2023; only 85 HIV positive individuals had available data on CD4 count and viral load (VL) at the time of HIV diagnosis, and all were treatment-naive at entry.

The measurement of CD4 count and viral load (VL) for individuals diagnosed with HIV/AIDS in Kosovo commenced in 2009, aligning with the initiation of antiretroviral therapy (ART) for people living with HIV/AIDS as per the recommendations in effect at that time. Cases without this data pertain to the period before 2009.

Late presenter (LP) cases were defined as those diagnosed with HIV at a CD4 count below 350 cells/mm3. Very Late Presenter (VLP) cases constituted a subgroup of LP, with an HIV diagnosis at a CD4 count <200 cells/µL. None of the HIV positive individuals included in the study fulfils any of proposed criteria for a revision of a consensus definition.

Descriptive and frequency statistics were performed to describe the demographic and clinical characteristics of the sample. Chi-square analysis was performed to test for associations between categorical variables (gender, age groups, mode of transmission, and viral load groups) on the binary, categorical outcome of late vs. non-late presenter. Unadjusted odds ratios with 95% confidence intervals were calculated for the chi-square analyses. Non-parametric Mann-Whitney U tests were used to compare the presenter groups on the non-normal continuous outcomes of age, CD4 count, and viral load at diagnosis. Medians and interquartile ranges were interpreted for the Mann-Whitney U analyses. Logistic regression was performed to generate adjusted odds ratios with 95% confidence intervals. All analyses were performed using SPSS Version 29 (Armonk, NY: IBM Corp.) and statistical significance was assumed at an alpha value of 0.05.

Results

Patient characteristics

During the 15-year study period (2009–2023), 85 HIV positive individuals, ranging from a minimum of 2 to a maximum of 12 per year, were diagnosed with complications of advanced HIV, with an average age of 34.29 years (range 2–77, SD – standard deviation 13.243). Most of the HIV-positive individuals, 77 (90.6%), were aged 19–55. The majority of HIV-positive individuals were male, comprising 74 cases (87.1%).

LP/VLP vs. NLP

Late presenters (LP), accounted for 43 HIV positive individuals (50.6%), with 26 of them (30.6%) classified as very late presenters (VLP). All HIV positive individuals from the ≤18 age group were NLP (average CD4 747 cells/µL, range 445–1174, SD 362.03; log10 4.1 copies/mL, range 1.6–5.8, SD 2.24). Out of the 32 HIV positive individuals in the 19–30 age group, 5 (15.62%) were LP (average CD4 302 cells/µL), and 6 (18.75%) were VLP (LPAD) (average CD4 75 cells/µL); from 45 HIV positive individuals in the 31–55 age group, 11 (24.44%) were LP (average CD4 273 cells/µL), and 18 (40.0%) were VLP (LPAD) (average CD4 75 cells/µL); while out of 4 HIV positive individuals in the ≥56 age group, 1 (25.0%) was LP (average CD4 245 cells/µL), and 2 (50.0%) were VLP (LPAD) (average CD4 95 cells/µL).

Gender vs. LP/VLP

Twelve (12) male HIV positive individuals (16.21%) were LP (average CD4 277 cells/µL, range 203–311, SD 47.35), and 23 (31.08%) were VLP (average CD4 76 cells/µL, range 4–188, SD 61.35). 5 female HIV positive individuals (45.45%) were LP (average CD4 287 cells/µL, range 231–348, SD 44.21), and 3 (27.27%) were VLP (average CD4 78 cells/µL, range 7–124, SD 62.37).

Sexual transmission vs. LP/VLP

Out of the 35 HIV positive individuals identified as MSM, 5 (14.28%) of them were LP (average CD4 303 cells/µL, range 260–344, SD 33.97), and 6 (17.14%) were VLP (average CD4 78 cells/µL, range 6–183, SD 75.70). From 6 HIV positive individuals identified as bisexual, none of them was LP, and 3 (50.0%) were VLP (average CD4 67 cells/µL, range 10–144, SD 69.20). Out of 22 HIV positive individuals identified as heterosexual, 7 (31.82%) of them were LP (average CD4 288 cells/µL, range 231–3348, SD 44.70), and 8 (36.36%) were VLP (average CD4 78 cells/µL, range 7–178, SD 54.45). From 22 HIV positive individuals which did not identified their sexual orientation, 5 (15.62%) of them were LP (average CD4 245 cells/µL, range 203–303, SD 42.64), and 9 (40.91%) were VLP (average CD4 78 cells/µL, range 4–188, SD 65.03) (Table 1).

Table 1. Patient characteristics.

Patient characteristics	Total N (%)	Late Presenters N (%)	Non-Late Presenters N (%)	p-Value
Total, n (%)	85 (100.0%)	43 (50.6%)	42 (49.4%)
Sex, n (%)
Male	74 (87.1%)	35 (47.3%)	39 (52.7%)	0.20
Female	11 (12.9%)	8 (72.7%)	3 (27.3%)
Median age at diagnosis in years	33.0	40.0	27.0	<0.001
IQR, n (%)	26.0–43.0 85 (100.0%)	31.0–46.0 43 (50.6%)	23.0–35.0 42 (49.4%)
≤18	4 (4.7%)	0 (0%)	4 (100.0%)	<0.001
19–30	34 (40.0%)	11 (25.6%)	21 (50.0%)
31–55	43 (50.6%)	30 (69.8%)	13 (30.2%)
≥56	4 (4.7%)	3 (75.0%	1 (25.0%)
Mode of transmission, n (%)
Heterosexual	22 (25.9%)	15 (68.2%)	7 (31.8%)	0.025
MSM	35 (41.2%)	11 (31.4%)	24 (68.6%)
Bisexual	6 (7.1%)	3 (50.0%)	3 (50.0%)
Not declared	22 (25.9%)	14 (63.6%)	8 (36.4%)
Median CD4 count at diagnosis	348.0	126.0	509.5	<0.001
(cells/mL) IQR, n	126.0 − 508.0 85 (100%)	46.5–258.5 43 (50.6%)	442.0–656.0 42 (49.4%)
Viral Load at diagnosis	4.6	4.6	4.6	0.492
(log10 copies/mL) IQR, n	3.38–5.37, 79 (92.9%)	3.43–5.56, 38 (48.1%)	3.20–5.15, 41 (51.9%)
≤4.0	25 (31.6%)	12 (48.0%)	13 (52.0%)	0.005
4.1–5.0	27 (34.2%)	7 (25.9%)	20 (74.1%)
≥5.1	27 (34.2%)	19 (70.4%)	8 (29.6%)

Evolution of MSM mode of transmission through studied period

There was a difference in the MSM mode of transmission of HIV infection during the studied period. In the first 12 years of the 15 year studied period, 16 male individuals with HIV were identified as MSM, constituting 33% of the total of 49 HIV-positive male individuals. This figure increased dramatically in the last 3 years of the studied period (25 males, 19 MSM, 76%) (OR 4.55, 95% CI 1.49–13.92, p = 0.0079). Throughout the studied period, the proportion of male individuals identified as MSM among those with HIV/AIDS was 31.43% of the total number of male individuals.

During the first 12 years only 2 (12.5%) out of 16 HIV positive individuals identified as MSM were LP, while in the last 3 years of the studied period, out of 19 HIV positive individuals identified as MSM, 9 (47.0%) were LP (OR 6.30, 95% CI 1.112–35.672, p = 0.037).

The rate of late presentation (LP) among individuals diagnosed with HIV in the first 12 years of the studied period was 49.1% (29 non-LP, 28 LP), while the rate of LP in the last 3 years was 53.57% (13 non-LP, 15 LP) (OR 1.195, 95% CI 0.483–2.958, p = 0.7).

Determinants of late presentation

Determinants associated with late presentation are presented in Table 3. Male patients had a higher probability of being late presenters at diagnosis [AOR 6.51 (95% CI 0.49–86.90), p = 0.16] than female patients (Ref); patients less than 30 years old had a higher probability of being late presenters when compared with patients aged between 31 and 55 years old (Ref) [age group 19–30: AOR 3.49 (CI 95% 0.74–16.52), p = 0.12; age group ≥56: AOR 1.08 (95% CI 0.08–15.31), p = 0.95]. Furthermore, transmission via MSM mode had a higher probability when compared with heterosexual mode of transmission (Ref) [AOR 2.35 (95% CI 0.37–15.07), p = 0.37]. Patients presenting with a viral load from 4.1 to 5.1 had a higher probability of being LP [AOR 2.46 (95% CI 0.57–10.58), p = 0.23] than those with a viral load lower than <4.0 (Ref) (Table 2).

Table 2. Determinants associated with late presentation.

late presenters/non-late presenters
Variable	OR (95% CI)	p-value	AOR (95%CI)	p-value
Sex
Female	Ref	Ref	Ref	Ref
Male	2.97 (0.73–12.09)	0.13	6.51 (0.49–86.90)	0.16
Age groups at diagnosis
≤18	–	*	–	*
19–30	5.54 (2.07–14.8)	<0.01	3.49 (0.74–16.52)	0.12
31–55	Ref	Ref	Ref	Ref
≥56	0.77 (0.07–8.11)	0.83	1.08 (0.08–15.31)	0.95
Mode of transmission
Heterosexual	Ref	Ref	Ref	Ref
MSM	4.68 (1.49–14.71)	0.008	2.35 (0.37–15.07)	0.37
Bisexual	2.14 (0.34–13.42)	0.42	2.14 (0.24–19.03)	0.50
Not declared	1.22 (0.35–4.27)	0.75	0.53 (0.09–2.96)	0.47
Log VL groups at diagnosis
<4.0	Ref	Ref	Ref	Ref
4.1–5.0	2.64 (0.82–8.45)	0.10	2.46 (0.57–10.58)	0.23
>5.1	0.39 (0.12–1.21)	0.39	0.20 (0.04–0.90)	0.036

Discussion

We observed a 50.6% rate of late presentation (LP) among HIV positive individuals in Kosovo, with 30.6% being very late presenters (VLP). These figures are comparable with European data, where LP rates vary from 34.7 to 62.8%, and VLP from 24.0 to 39.7% [1–18]. Previous data from 34 European countries indicated LP rates ranging from 34.8% to 49.8%, depending on the region [17].

Key determinants of LP in our Kosovo cohort included male gender, young adult age, MSM transmission mode, and viral loads between 4.1 and 5.0 log10 copies/m. These factors align with trends noted in several European studies [3,7–16], highlighting the influence of stigma related to lifestyle and HIV/AIDS status on delayed diagnosis. However, our findings contrast with one European study identifying female gender as a determinant of LP [14], which was not observed in our cohort.

While injection drug use (IDU) was a determinant of LP in other studies [9,13,19,20], it was not a significant factor in our study due to the low prevalence of IDU among our participants.

Our research diverges from other European studies in that MSM was the primary mode of transmission associated with LP. This finding is consistent with studies from France, the UK, and Greece [18,21,22], but contrasts with the general European trend where non-nationals and migrants are often at higher risk due to socio-economic barriers [10]. This discrepancy highlights the unique context of Kosovo, where the majority of our cases were not non-nationals or migrants.

In terms of broader trends, studies from the USA, Brasil, Argentina, Guatemala, and Australia have identified various determinants of LP, including older age, heterosexual contacts, IDU, and socio-demographic factors [19,20,23–25]. However, these findings are more reflective of regional characteristics than directly applicable to the Kosovo context.

Lastly, studies from Asia (TAHOD), China, Ethiopia, Uganda, and South Africa offer diverse perspectives on LP determinants, ranging from socio-economic factors to healthcare access and stigma [24–34]. These studies underscore the need for context-specific approaches to addressing LP in HIV care.

Data on LP rate from different studies are presented in Table 3.

Table 3. Late presentation (LP) rates across multiple studies.

Country/Region	% LP	% VLP	Prevalent mode of transmission for LP	Ref
Europe (EIDB)	50.4	NA	Heterosexual	3
Belgium	44.0	24.0	Heterosexual	7
Spain	34.7	NA	NA	8
Spain	44.6	26.4	IDU, Heterosexual	9
Italy	55.7	37.9	Heterosexual	10
Italy	55.6	39.7	Heterosexual	11
Poland	62.9	68.7	Heterosexual, IDU	13
Poland	44.8	NA	Heterosexual	14
Turkey	47.2	23.0	NA	15
Turkey	49.4	NA	Heterosexual	16
Switzerland	49.8	NA	Heterosexual	17
France	47.7	29.3	Heterosexual	18
Greece	49.5	NA	MSM	22
US	23.3	NA	Heterosexual, IDU	19
Brazil	86.6	53.8	Heterosexual	23
Argentina	26.5	19.0	Heterosexual, IDU	20
Guatemala	81.1	NA	Heterosexual	24
Australia	18.8	NA	Heterosexual	25
Japan	61.4	36.6	Heterosexual	26
Asia (TAHOD)	72.0	NA	IDU	27
Vietnam	50.0	NA	Heterosexual	28
China	57.6	NA	Heterosexual	29
China	70.2	NA	Heterosexuals	30
Mozambique	47.0	NA	Heterosexual	31
Uganda	25.0	NA	NA	32
South Africa	60.0	NA	Heterosexual	33

Our study’s limitations include a small sample size and the absence of data on factors like education, marital status, and economic status, underscoring the need for comprehensive data collection in future research.

Conclusions

In conclusion, while the prevalence of HIV-positive individuals in Kosovo remains low, a concerning trend persists with the majority being diagnosed at a late stage. Given the heightened risk of disease progression and mortality in this scenario, it is imperative to intensify efforts aimed at HIV prevention and early detection. Specifically, targeting heterosexual groups who may not perceive themselves as a ‘risk group’ is crucial for achieving this objective. Sustained testing initiatives can play a pivotal role in reducing late-stage HIV diagnoses.

The notable shift in the identification of male HIV individuals as MSM over the past three years provides valuable insights into the evolving perspectives of this population regarding their sexual identification. However, despite this change, there has not been a corresponding improvement in the timely diagnosis of HIV infections among MSM. This highlights a significant warning for authorities and NGOs representing the interests of this population, emphasizing the urgent need for enhanced health education, particularly regarding HIV/AIDS, as well as improving the functioning and expanding the net of VCT centres in Kosovo.

In summary, timely diagnosis and effective linkage to healthcare are indispensable components of comprehensive HIV prevention and treatment strategies.

Author contributions

Ilir Tolaj, conceptualisation of the work, drafting the work, interpretation of the data for the work, critically reviewing the work for intellectual content and final approval of the version to be published; Murat Mehmeti, design of the work, acquisition, analysis and interpretation of data for the work, review, final approval of the version to be published; Hatixhe Gashi, acquisition, analysis and interpretation of data for the work, final approval of the version to be published; Arbana Kasumi, acquisition, analysis and interpretation of data for the work, final approval of the version to be published.

Institutional review board statement

This case report was reviewed and approved by the Committee of Ethics of the Kosovo Medical Association, approval number 126/23.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

All data generated or analysed during this study are included in this article. Further enquiries can be directed to the corresponding author.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.