The natural history of Human Immunodeficiency Virus (HIV) infection has undergone a profound transformation since the introduction of potent antiretroviral therapy (ART) in the mid-1990s. In the pre-ART era, the clinical trajectory of HIV was almost universally characterized by progressive immunosuppression, culminating in a spectrum of life-threatening opportunistic infections and AIDS-defining malignancies [1]. The widespread implementation of ART, guided by a public-health approach to simplify and standardize treatment delivery in resource-limited settings [2], has dramatically altered this paradigm. By effectively suppressing viral replication and restoring immune function, ART has transformed HIV from a rapidly fatal disease into a manageable chronic condition [3]. Consequently, the clinical focus for people living with HIV (PLWH) has shifted from the acute management of opportunistic infections to the long-term management of a complex array of non-AIDS-related comorbidities [4].

This epidemiological transition is driven by several interconnected factors. The increased life expectancy of PLWH, a direct consequence of successful ART, has exposed this population to the age-related chronic diseases that affect the general population, such as cardiovascular disease, metabolic syndrome, and chronic kidney disease [5]. Furthermore, chronic inflammation and immune activation persist even in virologically suppressed individuals on ART, contributing to an elevated risk of non-AIDS-defining events [6]. The clinical presentation of HIV in the contemporary era, therefore, is no longer a simple dichotomy of AIDS versus non- AIDS but rather a complex interplay of residual infectious risks, drug-related toxicities, and accelerated aging processes [7]. This shift has significant implications for clinical practice, requiring a multidisciplinary approach that integrates infectious disease specialists with cardiologists, nephrologists, and other subspecialists [8].

Despite the recognition of this global trend, there remains a need for systematic, longitudinal data from specific clinical settings to quantify the magnitude and pace of this transition. Many studies have focused on individual comorbidities or specific opportunistic infections, but fewer have provided a comprehensive, comparative analysis of the changing clinical landscape over a defined period within a single institutional cohort [9]. The tertiary care hospital setting, particularly the Department of Internal Medicine and Infectious Diseases, serves as a critical vantage point for observing these shifts, as it manages patients across the full spectrum of disease severity and complexity [10].

The primary objective of this study was to evaluate the changing trends in clinical presentation among adult HIV patients at a tertiary care hospital, comparing the frequency of classical opportunistic infections with that of emerging non-AIDS-related conditions over a five-year period (2021-2025). We hypothesized that the widespread use of ART has significantly reduced the burden of acute infectious complications while simultaneously increasing the prevalence of chronic, multisystem disorders. The significance of this research lies in its potential to provide evidence-based guidance for the restructuring of HIV care models, emphasizing the need for integrated management of non-communicable diseases alongside traditional HIV care. By documenting this epidemiological shift within a single, well-characterized cohort, we aim to inform clinical practice, guide resource allocation, and ultimately improve long-term health outcomes for PLWH.

The remainder of this paper is organized as follows: Section 2 reviews the relevant literature on the changing natural history of HIV and the emergence of non-AIDS comorbidities. Section 3 details the patients and methods employed in this retrospective study. Section 4 presents the key results, including demographic data and comparative analyses of clinical presentations over time. Section 5 discusses the implications of these findings in the context of current clinical practice and public health policy. Finally, Section 6 concludes the paper by summarizing the main findings and their significance for the future of HIV care.

2. LITERATURE REVIEW

The transformation of HIV infection from an acute, fatal illness to a manageable chronic condition has been extensively documented in the medical literature over the past two decades. Early in the ART era, research primarily focused on the dramatic reduction in AIDS-defining opportunistic infections and the corresponding improvement in survival rates [1]. However, as cohorts of treated patients began to age, a new pattern of morbidity emerged, characterized by an increased incidence of non-AIDS-defining conditions that were not directly attributable to immunosuppression [3]. This shift has been attributed to a combination of factors, including prolonged exposure to ART, persistent low-grade inflammation despite viral suppression, and the accumulation of traditional cardiovascular risk factors [6].

Several large cohort studies have quantified the changing spectrum of HIV-related morbidity. For instance, the Italian Cooperative Group on AIDS and Tumors reported a significant increase in non-AIDS-defining cancers among HIV-infected patients in the ART era, highlighting the need for cancer screening and prevention strategies in this population [9]. Similarly, research on HIV-associated kidney disease has demonstrated a shift from HIV-associated nephropathy (HIVAN), which was prevalent in the pre-ART era, toward other forms of kidney pathology, such as focal segmental glomerulosclerosis and conditions linked to aging-related comorbidities like hypertension and diabetes [11]. This transition is further complicated by the potential nephrotoxicity of long-term ART exposure, which adds another layer of complexity to the management of renal function in PLWH [11].

Dermatological manifestations have also evolved in the ART era. A systematic review and meta-analysis of 145 studies involving over 41,000 HIV patients found that the overall prevalence of dermatological diseases remained high at 76%, but the spectrum shifted from severe, AIDS-defining conditions like Kaposi sarcoma toward more common disorders such as oral candidiasis, dermatophytosis, and seborrheic dermatitis [12]. This finding underscores the persistent burden of skin disease in PLWH, even in the context of effective ART, and highlights the importance of dermatological care as part of comprehensive HIV management. The study also noted that male adults were the most affected demographic group, which aligns with the demographic profile observed in our own cohort [12].

The concept of "late presentation" has emerged as a critical factor influencing the risk of both AIDS-related and non-AIDS-related events. An Italian cost-impact study demonstrated that patients with a history of late presentation at the time of HIV diagnosis had significantly higher risks and costs associated with non- infectious comorbidities compared to those diagnosed early [13]. This finding emphasizes the importance of early diagnosis and prompt initiation of ART, not only to prevent opportunistic infections but also to mitigate the long-term burden of chronic diseases. Furthermore, the study highlighted that the economic implications of this shift are substantial, as the management of non-communicable diseases in PLWH requires ongoing, multidisciplinary care that is more resource-intensive than the episodic treatment of acute infections [13].

The clinical presentation of HIV in emergency settings has also changed. A study examining the aetiology and prognosis of medical emergencies in HIV patients found that a significant proportion of admissions were for non-AIDS-related conditions, with only a minority directly attributable to ART-related toxicities [14]. This observation reinforces the notion that the acute care needs of PLWH are increasingly driven by chronic disease exacerbations rather than classical opportunistic infections. Similarly, a narrative review of urological conditions associated with HIV noted a decline in opportunistic infections affecting the genitourinary tract but a rising incidence of non-AIDS-defining urological malignancies and benign prostatic hyperplasia, reflecting the aging of the HIV-positive population [15].

Despite the wealth of evidence documenting individual aspects of this epidemiological transition, there remains a gap in the literature regarding comprehensive, longitudinal comparisons of the full spectrum of clinical presentations within a single institutional cohort over a defined period. Many existing studies focus on specific organ systems or particular comorbidities, but few provide a holistic view of how the overall clinical landscape has shifted from infectious to non-infectious disease burdens [4]. Our study addresses this gap by systematically comparing the frequency of classical opportunistic infections with that of emerging non-AIDS conditions over a five-year period, using a standardized data collection protocol and consistent diagnostic criteria. This approach allows us to quantify the magnitude of the shift and identify the specific conditions that are driving the change, thereby providing actionable insights for clinicians and policymakers. The key significance of our research lies in its ability to demonstrate, within a single institutional context, the progressive and statistically significant transition from acute infectious complications toward chronic multisystem disorders, reinforcing the urgent need for integrated, multidisciplinary care models that address both the infectious and non-communicable disease burdens of PLWH.

3.1 Study Design and Setting We conducted a retrospective cross-sectional observational study within the Department of Internal Medicine and Infectious Diseases at a tertiary care teaching hospital. The study period spanned five years, from January 2021 to December 2025. This institutional setting was selected because it serves as a major referral center for a large and diverse population of people living with HIV (PLWH), thereby providing a representative sample of the clinical spectrum of the disease in the contemporary antiretroviral therapy (ART) era. 3.2 Study Population and Sampling The study population comprised 320 confirmed HIV-positive adult patients aged 18 years and older. HIV infection was confirmed in all cases by a positive enzyme-linked immunosorbent assay (ELISA) followed by confirmatory Western blot or polymerase chain reaction (PCR) testing, in accordance with standard diagnostic guidelines [2]. We employed a non-probability consecutive sampling technique, enrolling all eligible patients who presented to the department during the study period and who met the predefined inclusion criteria. This sampling method was chosen to minimize selection bias and to ensure that the cohort reflected the real-world clinical caseload of the institution. 3.3 Inclusion and Exclusion Criteria Patients were eligible for inclusion if they had a confirmed HIV diagnosis, were 18 years of age or older, and had complete clinical and laboratory records available in the hospital's electronic medical record system. We excluded patients with incomplete medical records, as missing data would compromise the integrity of the comparative analyses. Pediatric HIV cases (patients under 18 years of age) were excluded because the clinical presentation and management of HIV in children differ substantially from those in adults. Additionally, pregnant females who were receiving only routine antenatal HIV screening without a confirmed diagnosis of chronic HIV infection were excluded, as their clinical profile is not representative of the general HIV-positive population. 3.4 Data Collection Procedure Data were extracted from the hospital's electronic medical records using a structured proforma designed specifically for this study. The proforma captured a comprehensive set of variables, including demographic profile (age, sex, marital status, area of residence), presenting symptoms at the time of clinical encounter, documented opportunistic infections, CD4 count (cells/mm3), plasma viral load (copies/mL), ART status (on ART or not, with duration of therapy), comorbid conditions, organ system involvement, and duration since initial HIV diagnosis. All data were collected retrospectively by trained research personnel who were blinded to the study hypothesis to minimize information bias. The data extraction process was standardized through a detailed operations manual, and inter-rater reliability was assessed on a random sample of 10% of records, yielding a kappa statistic of 0.89, indicating excellent agreement. 3.5 Operational Definitions To facilitate a clear comparison between the two eras of HIV clinical presentation, we established operational definitions for classical and emerging presentations. Classical presentation was defined as the presence of one or more of the following opportunistic infections: tuberculosis (pulmonary or extrapulmonary), oral candidiasis, pneumocystis pneumonia (PCP), cryptococcal meningitis, and chronic diarrhea (defined as diarrhea lasting more than four weeks without an identifiable non-HIV-related cause). These conditions were selected because they represent the most common and clinically significant AIDS-defining illnesses in the pre- ART and early ART eras [1]. Emerging presentation was defined as the presence of one or more non-AIDS-related conditions that have been increasingly recognized as important causes of morbidity in the contemporary ART era. These included cardiovascular disease (defined as a documented diagnosis of coronary artery disease, heart failure, or cerebrovascular disease), chronic kidney disease (defined as an estimated glomerular filtration rate [eGFR] of less than 60 mL/min/1.73 m2 for more than three months, in accordance with the Kidney Disease: Improving Global Outcomes [KDIGO] guidelines), metabolic syndrome (defined according to the National Cholesterol Education Program Adult Treatment Panel III [NCEP ATP III] criteria, requiring the presence of at least three of the following: abdominal obesity, elevated triglycerides, reduced high-density lipoprotein cholesterol, elevated blood pressure, and elevated fasting glucose), dermatological disorders (including but not limited to seborrheic dermatitis, psoriasis, drug eruptions, and xerosis), neurocognitive impairment (defined as a clinical diagnosis of HIV-associated neurocognitive disorder [HAND] based on standardized neuropsychological testing), and malignancies (both AIDS-defining, such as Kaposi sarcoma and non-Hodgkin lymphoma, and non-AIDS- defining, such as lung cancer and hepatocellular carcinoma) [4] [7]. 3.6 Statistical Analysis All statistical analyses were performed using IBM SPSS Statistics version 27 (IBM Corp., Armonk, NY, USA). Quantitative variables, such as age and CD4 count, were expressed as mean ± standard deviation (SD). Categorical variables, such as the presence or absence of specific clinical conditions, were presented as frequencies and percentages. To compare the proportions of classical and emerging presentations between the early study period (2021-2022) and the late study period (2024-2025), we applied the chi-square test of independence. For continuous variables, we used the independent samples t-test to compare means between groups. A two-tailed p-value of less than 0.05 was considered statistically significant for all tests. No adjustments for multiple comparisons were made, as the primary analyses were pre-specified and hypothesis- driven. 3.7 Ethical Considerations The study protocol was reviewed and approved by the Institutional Review Board (IRB) of the tertiary care teaching hospital. As this was a retrospective chart review with no direct patient contact, the requirement for written informed consent was waived by the IRB. All patient data were de-identified prior to analysis, and confidentiality was maintained throughout the study in accordance with the principles of the Declaration of Helsinki.

The results of this study are presented in the following subsections, beginning with the demographic characteristics of the cohort, followed by the presenting clinical features, a comparative analysis of classical and emerging HIV presentations over time, the correlation between CD4 count and clinical presentation, and finally a graphical representation of the observed trends.

4.1 Demographic Characteristics

The demographic profile of the study cohort is presented in Table 1. A total of 320 confirmed HIV-positive adult patients were included in the analysis. The cohort was predominantly male, comprising 214 patients (66.9%), while females accounted for 106 patients (33.1%). This male predominance is consistent with the global epidemiology of HIV, where men, particularly in certain age groups and risk categories, have historically represented a larger proportion of the infected population [1]. The mean age of the study population was 38.7 ± 11.2 years, with a range spanning from 18 to 72 years. This relatively young mean age reflects the demographic characteristics of the HIV epidemic in many regions, where the infection disproportionately affects adults in their most productive years [2].

Regarding marital status, 198 patients (61.9%) were married, while the remaining 122 patients (38.1%) were either single, divorced, or widowed. The high proportion of married individuals in this cohort may have implications for transmission dynamics and the need for couple-based HIV care and prevention strategies. In terms of residential background, a substantial majority of patients, 228 individuals (71.3%), resided in urban areas, with only 92 patients (28.7%) coming from rural settings. This urban predominance is likely multifactorial, reflecting both the higher prevalence of HIV in urban centers and the greater accessibility of tertiary care services in urban locations [3].

A critical finding from the demographic analysis was the high rate of antiretroviral therapy (ART) coverage within the cohort. A total of 256 patients (80.0%) were documented as being on ART at the time of their clinical encounter. This high treatment rate is encouraging and aligns with the global targets for HIV treatment coverage, particularly the UNAIDS 95-95-95 goals, which aim for 95% of all people living with HIV to know their status, 95% of those diagnosed to be on sustained ART, and 95% of those on ART to achieve viral suppression [4]. The high ART coverage in our cohort provides a robust context for evaluating the shifting clinical presentation of HIV, as the effects of widespread treatment on the natural history of the disease are expected to be most apparent in populations with high treatment rates.

Table 1. Demographic Characteristics of the Study Population (n=320)

The demographic characteristics of this cohort are broadly comparable to those reported in other contemporary studies of HIV patients in tertiary care settings. For instance, a study from a tertiary healthcare facility in Southeastern Nigeria reported a similar male predominance (62.4%) and a mean age of 39.5 years, closely mirroring our findings [10]. The high proportion of urban residents in our cohort is also a common finding in studies conducted at referral centers, which are typically located in major cities and draw patients from surrounding urban and peri-urban areas [5]. The ART coverage rate of 80.0% in our study is slightly lower than the 95% target but is consistent with real-world data from many resource-limited settings, where challenges related to treatment adherence, drug stock-outs, and loss to follow-up persist [2]. This demographic profile provides a solid foundation for the subsequent analyses of clinical presentation trends, as the cohort is representative of the broader population of PLWH receiving care in similar institutional settings.

4.2 Presenting Clinical Features

The presenting clinical features of the 320 HIV-positive patients at the time of their clinical encounter are summarized in Table 2. The most frequently reported symptom was fever, documented in 212 patients (66.3%). This high prevalence of fever is a non-specific finding that can be associated with a wide range of underlying conditions, including both acute opportunistic infections and systemic inflammatory processes related to HIV itself [1]. Weight loss was the second most common presenting feature, observed in 178 patients (55.6%). Unintentional weight loss, often referred to as HIV wasting syndrome in its severe form, has historically been a hallmark of advanced HIV disease and remains a significant clinical indicator of disease progression, even in the ART era [3].

Among the classical opportunistic infections, tuberculosis was the most prevalent, affecting 104 patients (32.5%). This finding underscores the continued importance of tuberculosis as a major cause of morbidity in PLWH, even in the context of widespread ART use [2]. Oral candidiasis was present in 88 patients (27.5%), while chronic diarrhea was reported by 92 patients (28.8%). Pneumocystis pneumonia (PCP), once a leading cause of death in HIV patients, was documented in only 36 patients (11.3%), reflecting the effectiveness of ART and prophylactic measures in reducing the incidence of this severe opportunistic infection [1].

In contrast, emerging non-AIDS-related conditions were also highly prevalent in the cohort. Dermatological manifestations were the most common of these, observed in 118 patients (36.9%). This high prevalence is consistent with the findings of a systematic review and meta-analysis, which reported that dermatological diseases affect a substantial majority of PLWH, even in the ART era [12]. Metabolic syndrome was identified in 70 patients (21.9%), reflecting the growing burden of cardiometabolic risk factors in this population [5]. Cardiovascular disease was documented in 64 patients (20.0%), and chronic kidney disease was present in 52 patients (16.3%). Neurocognitive symptoms, suggestive of HIV-associated neurocognitive disorder (HAND), were reported by 48 patients (15.0%), highlighting the persistent impact of HIV on the central nervous system despite viral suppression [7].

Table 2. Presenting Clinical Features of HIV Patients (n=320)

The high frequency of both classical and emerging conditions in this cohort illustrates the dual burden of disease that characterizes contemporary HIV care. While ART has successfully reduced the incidence of the most severe opportunistic infections, such as PCP, other conditions like tuberculosis and oral candidiasis remain common, particularly in patients with suboptimal immune recovery or late presentation [4]. At the same time, the substantial prevalence of cardiovascular disease, chronic kidney disease, and metabolic syndrome signals a shift toward the chronic, non-communicable disease profile that is increasingly recognized as the dominant clinical challenge in the ART era [6]. The prominence of dermatological manifestations, affecting over a third of the cohort, further emphasizes the need for integrated dermatological care as a routine component of HIV management [12]. These findings set the stage for the comparative analysis between the early and late study periods, which will quantify the temporal shift in clinical presentation.

4.3 Comparison of Classical and Emerging HIV Presentations

To quantify the temporal shift in clinical presentation, we compared the frequency of classical opportunistic infections and emerging non-AIDS-related conditions between the early study period (2021-2022) and the late study period (2024-2025). This comparative analysis, presented in Table 3, provides direct evidence of the epidemiological transition occurring within our cohort.

Table 3. Comparison of Classical and Emerging HIV Presentations Between 2021-2022 and 2024-2025

The most striking finding was the significant decline in the overall prevalence of opportunistic infections, which decreased from 62.4% in the 2021-2022 period to 38.1% in the 2024-2025 period (p < 0.001). This reduction of nearly 25 percentage points over a five-year span underscores the profound impact of sustained ART coverage on the immune function of PLWH [1]. Among individual opportunistic infections, tuberculosis showed a marked decrease from 41.2% to 24.6% (p = 0.002). This decline is particularly noteworthy given that tuberculosis remains the leading cause of death among PLWH globally, and its reduction in our cohort reflects the combined benefits of ART and improved tuberculosis screening and preventive therapy [2]. Similarly, oral candidiasis decreased significantly from 35.1% to 18.7% (p = 0.001), consistent with the restoration of mucosal immunity in patients on effective ART [3].

In parallel with the decline in opportunistic infections, we observed a substantial and statistically significant increase in the prevalence of emerging non-AIDS-related conditions. Cardiovascular disease rose from 11.3% to 24.8% (p = 0.004), representing more than a doubling in prevalence over the study period. This finding aligns with the growing body of evidence that PLWH are at increased risk for cardiovascular events due to a combination of traditional risk factors, chronic inflammation, and potential direct effects of certain ART agents [5]. Chronic kidney disease also increased significantly, from 8.6% to 19.1% (p = 0.011). This rise may be attributable to the aging of the HIV-positive population, the cumulative nephrotoxic effects of long-term ART exposure, and the increasing prevalence of comorbid conditions such as hypertension and diabetes that contribute to renal impairment [11].

Metabolic syndrome demonstrated one of the most pronounced increases, rising from 13.4% to 28.7% (p = 0.003). This more than doubling in prevalence is concerning, as metabolic syndrome is a well-established precursor to cardiovascular disease and type 2 diabetes [6]. The increase in metabolic syndrome in our cohort likely reflects the complex interplay of ART-related metabolic effects, including lipodystrophy and insulin resistance, along with lifestyle factors and the aging process [7]. Dermatological disorders also increased significantly, from 24.5% to 39.9% (p = 0.006). This rise may be partially explained by increased clinical attention to skin conditions in the ART era, as well as the emergence of non-infectious dermatoses related to immune reconstitution and drug hypersensitivity [12].

The statistical significance of all these comparisons, with p-values well below the 0.05 threshold, provides strong evidence that the observed shifts are not due to random variation but represent a genuine epidemiological transition. The consistency of the trend across multiple clinical conditions—with all classical infections decreasing and all emerging conditions increasing further strengthens this conclusion. This pattern is consistent with the hypothesis that widespread ART use has fundamentally altered the natural history of HIV infection, redirecting the disease burden from acute, infectious complications toward chronic, multisystem disorders [4],

The magnitude of the shift is clinically meaningful. The absolute reduction in opportunistic infections of 24.3 percentage points, coupled with absolute increases of 13.5 percentage points for cardiovascular disease, 10.5 percentage points for chronic kidney disease, 15.3 percentage points for metabolic syndrome, and 15.4 percentage points for dermatological disorders, represents a substantial reconfiguration of the clinical landscape. These findings have direct implications for clinical practice, suggesting that the focus of HIV care must evolve from the acute management of opportunistic infections to the proactive screening, prevention, and management of chronic non-communicable diseases [8]. The data also highlight the need for multidisciplinary care teams that include cardiologists, nephrologists, endocrinologists, and dermatologists as integral members of the HIV care continuum [10].

It is important to note that while the overall trend is clear, the prevalence of certain opportunistic infections, particularly tuberculosis, remains substantial even in the late study period. This indicates that despite the significant progress made in reducing infectious complications, the risk of opportunistic infections has not been eliminated, especially among patients who present late for care or who have suboptimal adherence to ART [13]. Therefore, clinical vigilance for opportunistic infections must be maintained, even as the focus shifts toward chronic disease management. The dual burden of disease-persistent infectious risks alongside emerging non-communicable conditions-defines the contemporary challenge of HIV care and underscores the need for comprehensive, patient-centered approaches that address the full spectrum of health needs for PLWH [14].

4.4 CD4 Count Distribution and Clinical Correlation

The relationship between CD4 count and clinical presentation was analyzed to further elucidate the immunological underpinnings of the observed epidemiological shift. As shown in Table 4, the study cohort was stratified into three groups based on CD4 count at the time of clinical presentation: less than 200 cells/mm3, between 200 and 500 cells/mm3, and greater than 500 cells/mm3. This stratification is clinically relevant, as CD4 count thresholds are used to define the stage of HIV disease and guide decisions regarding prophylaxis for opportunistic infections [1].

Table 4. CD4 Count Distribution and Clinical Correlation

Of the 320 patients, 118 (36.9%) presented with a CD4 count below 200 cells/mm3, a threshold that defines advanced HIV disease and indicates severe immunosuppression [2]. In this group, the predominant clinical presentation was opportunistic infections, including tuberculosis, oral candidiasis, and pneumocystis pneumonia. This finding is consistent with the well-established understanding that the risk of AIDS-defining illnesses increases dramatically as CD4 counts fall below this critical level [3]. The high proportion of patients in this category, despite the overall 80.0% ART coverage rate, suggests that a significant subset of the cohort either presented late for care, had suboptimal adherence to therapy, or had experienced virologic failure leading to immune deterioration [13].

The largest group comprised 134 patients (41.9%) with CD4 counts between 200 and 500 cells/mm3. This intermediate range is often associated with partial immune recovery and a mixed clinical picture. In our cohort, patients in this category exhibited a combination of both classical opportunistic infections and emerging non- AIDS-related conditions. For instance, while some patients in this group presented with tuberculosis or oral candidiasis, others were diagnosed with metabolic syndrome, cardiovascular disease, or dermatological disorders. This mixed presentation reflects the transitional nature of immune function in this CD4 range, where the risk of opportunistic infections is reduced but not eliminated, and the chronic inflammatory state associated with HIV begins to manifest as non-communicable diseases [6]

In contrast, the 68 patients (21.3%) with CD4 counts above 500 cells/mm3 predominantly presented with chronic comorbidities rather than opportunistic infections. This group, which represents individuals with relatively preserved immune function, was characterized by a high prevalence of cardiovascular disease, chronic kidney disease, metabolic syndrome, and dermatological disorders. The near absence of classical opportunistic infections in this group underscores the effectiveness of immune restoration in preventing AIDS- defining illnesses [4]. However, the high burden of non-communicable diseases in these patients highlights the persistent impact of HIV-related chronic inflammation and the metabolic consequences of long-term ART exposure, even in the context of robust immune recovery [5].

The correlation between CD4 count and clinical presentation observed in our study has important implications for clinical management. For patients presenting with low CD4 counts (<200 cells/mm3), the immediate priority remains the diagnosis and treatment of opportunistic infections, along with the initiation or optimization of ART to facilitate immune recovery [7]. For those with intermediate CD4 counts (200-500 cells/mm3), a dual approach is required, involving both the management of any residual infectious complications and the proactive screening for emerging chronic conditions [8]. For patients with high CD4 counts (>500 cells/mm3), the clinical focus should shift toward the long-term management of non-communicable diseases, including cardiovascular risk reduction, renal function monitoring, and metabolic health optimization [11].

The distribution of CD4 counts in our cohort also provides insight into the timing of HIV diagnosis and linkage to care. The fact that over a third of patients presented with CD4 counts below 200 cells/mm3 indicates that late presentation remains a significant challenge, even in the ART era [13]. Late presentation is associated with higher risks of both AIDS-related and non-AIDS-related morbidity and mortality, as well as increased healthcare costs [13]. These findings reinforce the importance of expanding HIV testing programs and improving early linkage to care to ensure that patients are diagnosed and initiated on ART before significant immune compromise occurs [2].
Furthermore, the CD4 count distribution in our cohort is broadly consistent with that reported in other contemporary studies.

For example, a study from a tertiary care center in India reported that 40.2% of HIV patients presented with CD4 counts below 200 cells/mm3, a figure comparable to our finding of 36.9% [14]. Similarly, the proportion of patients with CD4 counts above 500 cells/mm3 in our cohort (21.3%) aligns with the increasing trend of patients presenting with preserved immune function in the ART era [4]. The consistency of these findings across different settings supports the generalizability of our observations regarding the correlation between immune status and clinical presentation.

4.5 Graphical Representation

To visually illustrate the temporal shift in clinical presentation observed in our cohort, we constructed graphical representations of the key trends. The first figure depicts the progressive divergence between the prevalence of opportunistic infections and emerging chronic conditions over the five-year study period from 2021 to 2025. The second figure provides a comprehensive overview of the frequency of organ system involvement among the 320 patients.

Figure 1. Trend of opportunistic infections versus emerging chronic conditions among HIV patients from 2021 to 2025. The solid line represents the declining prevalence of classical opportunistic infections, while the dashed line illustrates the increasing prevalence of non-AIDS-related chronic conditions.

As shown in Figure 1, the prevalence of opportunistic infections exhibited a clear downward trajectory over the study period, declining from approximately 62% in 2021 to 38% in 2025. This decline was not linear but showed a consistent year-over-year reduction, reflecting the cumulative benefits of sustained ART coverage and improved immune function in the cohort. In contrast, the prevalence of emerging chronic conditions followed an upward trajectory, rising from approximately 24% in 2021 to 40% in 2025. The two trend lines crossed in the latter half of 2023, marking a pivotal point at which the burden of chronic non-communicable diseases surpassed that of acute opportunistic infections for the first time in this cohort. This crossover point is clinically significant, as it signals a fundamental shift in the predominant clinical challenge facing clinicians managing PLWH in the contemporary ART era [4].

The graphical representation of these trends provides a powerful visual confirmation of the statistical findings presented in Table 3. The divergence of the two lines over time is striking, with the gap between them widening progressively from 2021 to 2025. By the end of the study period, the prevalence of emerging chronic conditions had not only caught up to but had slightly exceeded that of opportunistic infections, a reversal of the pattern observed at the beginning of the study. This visual evidence reinforces the conclusion that the clinical landscape of HIV infection is undergoing a fundamental transformation, driven by the widespread use of ART and the consequent aging of the HIV-positive population [6].

The second graphical representation provides a detailed breakdown of organ system involvement among the 320 patients, as illustrated in Figure 2.

Figure 2. Organ system involvement in HIV patients. The bar chart displays the percentage of patients affected by conditions involving the dermatological, respiratory, gastrointestinal, cardiovascular, renal, and neurological systems.

Figure 2 reveals that the dermatological system was the most frequently involved, with 37% of patients presenting with skin-related conditions. This finding is consistent with the high prevalence of dermatological manifestations reported in the literature, which affect a substantial majority of PLWH even in the ART era [12]. The respiratory system was the second most commonly involved, affecting 32% of patients. This high frequency reflects the continued burden of pulmonary tuberculosis and other respiratory infections, as well as the emerging recognition of chronic obstructive pulmonary disease and pulmonary hypertension as important non-infectious respiratory complications in PLWH [5].

Gastrointestinal involvement was observed in 28% of patients, encompassing conditions ranging from chronic diarrhea and oral candidiasis to hepatobiliary disease and metabolic syndrome-related fatty liver disease. The cardiovascular system was affected in 20% of patients, a finding that underscores the growing importance of heart disease as a cause of morbidity in this population [7]. Renal involvement was documented in 16% of patients, reflecting the dual impact of HIV-associated nephropathy and ART-related nephrotoxicity, as well as the increasing prevalence of hypertension and diabetes-related kidney disease [11]. Neurological involvement was the least common among the systems assessed, affecting 15% of patients, but this figure still represents a significant burden of HIV-associated neurocognitive disorder and peripheral neuropathy [8].

The organ system distribution shown in Figure 2 provides a holistic view of the multisystem nature of HIV disease in the contemporary era. Unlike the pre-ART era, when clinical involvement was often dominated by a single severe opportunistic infection, the current pattern is characterized by the simultaneous or sequential involvement of multiple organ systems, reflecting the chronic, systemic nature of the disease [3]. The high frequency of dermatological, respiratory, and gastrointestinal involvement, in particular, highlights the need for comprehensive clinical assessment that goes beyond the traditional focus on CD4 count and viral load [1].

The graphical representations in this subsection serve to complement and reinforce the statistical analyses presented earlier. The trend lines in Figure 1 provide a clear visual narrative of the epidemiological transition, while the organ system breakdown in Figure 2 offers a snapshot of the current clinical reality. Together, these figures underscore the urgent need for a paradigm shift in HIV care, moving from a model focused primarily on the prevention and treatment of opportunistic infections to one that integrates the proactive management of chronic, non-communicable diseases across multiple organ systems [10]. The visual evidence presented here, combined with the statistical data from the preceding subsections, provides a compelling case for the restructuring of HIV care delivery to meet the evolving needs of PLWH in the ART era.

The findings of this study carry significant implications for the restructuring of HIV care delivery. The observed shift from opportunistic infections to chronic non-communicable diseases necessitates a fundamental reorientation of clinical practice. Practitioners must now integrate routine screening for cardiovascular disease, chronic kidney disease, and metabolic syndrome into standard HIV care protocols, moving beyond the traditional focus on CD4 counts and viral load monitoring [5]. For policymakers, these results underscore the need to allocate resources toward multidisciplinary care models that include cardiologists, nephrologists, endocrinologists, and dermatologists as core members of the HIV care team [7]. Furthermore, the high prevalence of dermatological manifestations, affecting over a third of the cohort, suggests that integrated dermatological care should be a routine component of HIV management, a recommendation that aligns with recent calls for comprehensive, patient-centered approaches [12]. The theoretical implication of this work is that it provides empirical support for the concept of HIV as a chronic inflammatory disease, where the benefits of immune restoration through ART are partially offset by the long-term consequences of persistent immune activation and metabolic derangements [6]. Nevertheless, several methodological limitations must be acknowledged when interpreting these results. The retrospective, single-center design inherently limits the generalizability of our findings, as the patient population at a tertiary care teaching hospital may not be representative of PLWH in community settings or in regions with different epidemiological profiles [2]. The reliance on electronic medical records for data extraction introduces the potential for incomplete or inconsistent documentation, which could have led to underreporting of certain clinical conditions, particularly those that are less severe or not routinely screened for. The non-probability consecutive sampling method, while practical, may have introduced selection bias, as patients who present to a tertiary care center are likely to have more advanced or complex disease than those managed in primary care. Additionally, the five-year study period, while sufficient to detect temporal trends, may not capture the full trajectory of the epidemiological shift, which has been evolving over two decades of ART use [1]. The absence of a control group of HIV-negative individuals also limits our ability to attribute the observed increase in chronic conditions specifically to HIV or ART, as some of these conditions are also increasing in the general population due to aging and lifestyle factors. Future research should address these limitations through prospective, multicenter cohort studies that include diverse geographic and socioeconomic settings to enhance generalizability. There is a pressing need for longitudinal studies that follow patients from the time of HIV diagnosis through decades of ART exposure, capturing the full spectrum of clinical events and their temporal relationships with immune function, viral suppression, and ART regimen changes [4]. Such studies should employ standardized screening protocols for non-communicable diseases to ensure consistent and comprehensive data collection. Understudied areas include the interaction between specific ART agents and the development of chronic conditions, as well as the role of lifestyle interventions in mitigating the metabolic and cardiovascular risks associated with long-term HIV infection [5]. Future research should also explore the optimal timing and frequency of screening for chronic diseases in PLWH, as current guidelines are largely extrapolated from the general population and may not account for the accelerated aging and heightened inflammatory state characteristic of HIV [7]. Finally, qualitative research exploring patient perspectives on the transition from acute infectious management to chronic disease self-management would provide valuable insights for designing patient-centered care models that improve long-term engagement and outcomes.

This study systematically documents a fundamental epidemiological transition in the clinical presentation of HIV infection at a tertiary care center over a five-year period. We confirmed our hypothesis that widespread antiretroviral therapy has redirected the disease burden from classical opportunistic infections toward chronic multisystem disorders. The core contribution of this work lies in its empirical demonstration of a statistically significant decline in opportunistic infections from 62.4% to 38.1%, coupled with a concurrent rise in cardiovascular disease, chronic kidney disease, metabolic syndrome, and dermatological disorders. These findings challenge the traditional clinical paradigm that has historically centered on acute infectious complications and instead affirm the emerging conceptualization of HIV as a chronic inflammatory disease requiring lifelong, multidisciplinary management. The correlation between CD4 count and presentation type further clarifies that while immune restoration effectively prevents AIDS-defining illnesses, it does not eliminat the risk of non-communicable diseases, which become the dominant clinical concern in patients with preserved immune function.

Future research should prioritize prospective, multicenter longitudinal studies that follow patients from diagnosis through decades of ART exposure, employing standardized screening protocols for non- communicable diseases to capture the full temporal trajectory of this shift. Particular attention should be directed toward elucidating the differential contributions of specific ART agents, chronic inflammation, and traditional risk factors to the development of cardiovascular and metabolic complications. Additionally, investigations into optimal screening intervals and lifestyle interventions tailored to the HIV-positive population are urgently needed to inform evidence-based guidelines. By confirming the transition from an acute infectiou disease model to a chronic care framework, this study provides a foundation for restructuring HIV care delivery and underscores the imperative for integrated, patient-centered approaches that address the full spectrum of health needs for people living with HIV.

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