This cross-sectional comparative study systematically evaluated the performance of 4 AI models (DeepSeek-V3, DeepSeek-R1, ChatGPT-4o, and ChatGPT-o4-mini) and 12 clinicians in responding to CVD management questions among people living with HIV. A standardized question set was developed based on authoritative clinical guidelines to ensure consistency across all evaluations (Figure 1).

To ensure both the authority and timeliness of the question set, we selected 4 evidence-based guidelines as references. These included the Guidelines for Primary Prevention of Cardiovascular Diseases in China [22] and the Chinese Guideline for Diagnosis and Treatment of HIV/AIDS (2024 Edition) [23], which reflect local clinical practice, as well as 2 internationally recognized guidelines: the 2023 European AIDS Clinical Society Guidelines [24] and Antiretroviral Drugs for Treatment and Prevention of HIV in Adults: 2024 Recommendations of the International Antiviral Society-USA Panel [25]. All 4 were developed by leading academic institutions in the fields of CVD and HIV/AIDS, incorporating the most recent high-quality clinical evidence.

Based on the core content of these guidelines, we adopted a dual-framework strategy that integrates knowledge dimension stratification with clinical needs orientation to screen and classify the questions. Concurrently, we used a 2-round Delphi expert consultation method to systematically refine and optimize the question set. In the first round, 10 experts from multiple disciplines, including cardiology, infectious diseases, and public health, were invited to rate 35 candidate questions across 4 dimensions—importance, feasibility, answer clarity, and expression clarity—using a 1‐5 Likert scale, with open-ended suggestions also solicited. Based on the feedback from the first round, we merged, added, and deleted questions to form a standardized set of 25 questions. In the second round of Delphi consultation, the same panel of experts was asked to rerate each question in the revised set (using the same dimensions) and simultaneously evaluate the predefined reference answers in terms of reasonableness and guideline conformity (also using a 1‐5 Likert scale). Ultimately, questions with mean scores ≥4.0 and coefficients of variation (CVs) ≤0.25 across all dimensions were retained, and textual optimization suggestions from the experts were adopted, resulting in a final structured question set of 25 items.

The questionnaires used in the 2 rounds of Delphi surveys are detailed in Multimedia Appendix 1.

This standardized question set follows a progressive framework from basic theory to practical application and then to comprehensive clinical decision-making, covering all key elements of CVD management in people living with HIV. The specific categories are as follows (Table 1): the basic theory category focuses on theoretical understanding, assessing respondents’ mastery of fundamental concepts and standards of CVD management in HIV care; the medication management category addresses 2 common clinical challenges: interactions between ART and cardiovascular drugs, as well as adverse metabolic effects associated with ART; the clinical decision-making category concentrates on formulating diagnostic and treatment plans under specific clinical scenarios, requiring the integration of multidimensional knowledge; and the case analysis category evaluates respondents’ ability to conduct comprehensive clinical reasoning through complex real-world cases, including risk assessment, treatment planning, and management strategy optimization.

After the second round of Delphi expert consultation, we finalized reference answers to ensure objective and consistent evaluation. These answers were formulated by prioritizing authoritative guidelines, following a clear hierarchy: Chinese guidelines were prioritized over international guidelines, and guidelines specific to people living with HIV were prioritized over those for the general population, based on the study population’s characteristics. We then considered the levels of evidence and clarified points of controversy. This standardized reference then served as the benchmark for evaluation.

We selected 4 representative LLMs, namely, DeepSeek-V3, DeepSeek-R1, ChatGPT-4o, and ChatGPT-o4-mini. DeepSeek-V3 is a universal basic model suitable for handling daily tasks; DeepSeek-R1 specializes in complex reasoning and in-depth analytical tasks; ChatGPT-4o features multimodal capabilities and excels in handling routine workflows; and ChatGPT-4o-mini demonstrates notable strengths in science, technology, engineering, and mathematics-related tasks. All models were accessed independently via their respective official public interfaces or clients.

To ensure consistent and standardized assessment, a unified prompting framework was established for the AI model. The core stipulations embedded in the system prompt included assigning the model the identity of an HIV-specialized clinician, defining 4 categories of research questions (basic knowledge, medication management, clinical decision-making, and case analysis), requiring the model to learn 4 designated clinical guidelines, and setting a fixed evidence hierarchy to resolve inconsistent recommendations across guidelines. The full text of the standardized system prompt is provided in Multimedia Appendix 2 for reference.

Subsequently, the 25 structured questions were input verbatim into each model without any additional instructions attached to individual queries, ensuring that all models received identical information. Each question was submitted only once to avoid potential bias from prior interactions or model memory. Finally, the complete text responses for all 25 questions were collected from each model for subsequent evaluation.

We recruited 12 clinicians from 2 designated hospitals for HIV care in Guangdong Province, China: Shenzhen Third People’s Hospital and Dongguan Ninth People’s Hospital. The inclusion criteria were as follows: (1) holding a valid medical license and having at least 3 years of clinical experience, (2) being familiar with the diagnosis and treatment of either HIV infection or CVD, and (3) providing informed consent for voluntary participation. Based on their clinical specialties, the clinicians were categorized into 2 groups, with 8 in the infectious diseases group and 4 in the cardiology group. There were no statistically significant differences between the 2 groups in terms of professional title or years of clinical experience, ensuring comparability.

To balance the response conditions between the AI model and clinicians and control confounding bias, all interviews were conducted in quiet office settings as structured face-to-face verbal question-and-answer sessions with audio recording equipment, which also accommodated clinicians’ work schedules and facilitated natural responses from participants. Prior to each interview, researchers read a standardized introductory script to participating physicians uniformly (see Multimedia Appendix 3 for details). The script covered the study purpose, response restrictions (no access to any paper or electronic external resources throughout the interview), 4 reference guidelines with a predefined hierarchy of evidence, and classification criteria for the 4 major question categories. Formal questioning only commenced after physicians fully acknowledged comprehension of all rules and granted consent for audio recording. Each interview was scheduled to last 30-60 minutes, while the actual response duration ranged from 20 to 45 minutes (median 30 minutes).

All audio recordings were transcribed verbatim without subjective alterations to preserve original content. Transcripts were cross-checked by 2 independent researchers to guarantee accuracy and completeness. Any ambiguous or vague statements were verified against the original audio recordings to confirm the intended meaning. To mitigate information bias, transcription and coding were performed under a double-blind protocol; all researchers were blinded to participants’ identity information and group assignments throughout the entire process.

We constructed a multidimensional evaluation framework encompassing 4 core dimensions: accuracy, completeness, readability, and reliability. The determination of these dimensions was jointly established by multiple experts with clinical and research experience on the research team, through extensive literature searches and reviews followed by several rounds of collective discussion. Specifically, accuracy measures the degree of correctness of medical facts in the response; completeness assesses whether the response covers all key elements involved in the question; readability concerns whether the language expression is clear and the structure is reasonable; and reliability examines whether the response provides reliable guideline-based evidence or a sound clinical reasoning process. These 4 dimensions complement one another and aim to comprehensively characterize the quality of responses from different perspectives. Each dimension was rated on a 4-point scale, where 4 represented the highest performance and 1 the lowest. This system was designed to provide a thorough and detailed evaluation of the responses generated for each question (Table 2).

For the 2 complex case-based questions, which require the integration of multidimensional knowledge and comprehensive clinical reasoning, a single-dimensional score cannot adequately reflect their inherent hierarchical structure. Therefore, based on expert discussion, we developed independent weighted scoring schemes for these 2 case questions (Table 3). In these schemes, each subquestion was assigned a different weight according to its clinical relevance and contribution to the overall decision, ensuring that higher-priority elements contributed more substantially to the total score. The specific weight values were also collectively determined by the expert panel through reference to relevant literature and clinical practice consensus. To enhance the clarity and discriminability of the scoring process, we established a standardized rule for handling scores falling between 2 integers—when a score lay between adjacent integers, the midpoint of the interval was used as the cutoff value to guide the final scoring decision. This approach facilitated more robust between-group statistical comparisons in subsequent analyses.

Following the establishment of the evaluation criteria, we convened a panel of 6 experts, comprising 3 public health specialists and 3 clinical physicians. All panel members were independent of the question design and data collection phases. Prior to scoring, the evaluators underwent standardized training to ensure a consistent understanding and application of the scoring criteria. The assessment was conducted using a blinded, independent review protocol. All response texts were anonymized in advance by removing identifying information such as AI model names, clinician names, and institutional affiliations, and each entry was assigned a unique code. Experts then independently evaluated the responses without knowledge of their origin. Upon completion of individual assessments, all score sheets were retrieved and reviewed for interrater consistency.

All data analyses were performed using R software (version 4.4.2; R Foundation for Statistical Computing). The primary outcome was the expert-assigned rating scores, which were treated as ordinal categorical variables. To assess data distribution, the Shapiro-Wilk test was used to examine normality, and the Levene test was applied to assess the homogeneity of variances. Descriptive statistics including median and IQR, as well as mean and SD, were used to summarize overall and group-specific performance. Furthermore, to account for the hierarchical structure of the data while respecting the ordinal nature of the outcome variable, we constructed a cumulative link mixed model (CLMM) using the ordinal package in R. The model included group membership (AI models vs clinicians) as a fixed effect and random intercepts for both question and rater to capture the clustering of responses. The proportional odds assumption was verified via a likelihood-ratio test comparing models with and without nonproportional odds terms. Post-hoc pairwise comparisons among groups (eg, different AI models) were conducted using the Tukey method for CLMM contrasts, with adjustment for multiple testing.

To assess the reliability of the expert ratings, interrater agreement among the 6 evaluators was evaluated using the intraclass correlation coefficient (ICC), based on a 2-way random-effects model. Specifically, ICC(2,1) was used to assess the reliability of individual raters, while ICC(2,k) reflected the reliability of the average scores across the panel. An ICC value greater than 0.75 was interpreted as indicating good consistency.

All statistical tests were 2-sided, and a P value of less than .05 was considered statistically significant.

This study received ethics approval from the medical ethics committee of the Medical School of Shenzhen University (approval: PN-202500127). Given that this study solely used anonymous structured interviews with clinicians and a comparative evaluation of responses generated by AI models, no patient samples, clinical medical records, or sensitive personally identifiable information were collected throughout the study. The medical ethics committee approved the waiver of written informed consent. All research procedures were performed in strict accordance with the ethical principles outlined in the Declaration of Helsinki.

This study evaluated the performance of 4 AI models (ChatGPT-4o, ChatGPT-o4-mini, DeepSeek-V3, and DeepSeek-R1) against 12 clinicians (comprising cardiologists and infectious disease clinicians) in answering 25 structured questions related to CVD management in people living with HIV. Each response was independently assessed by 6 experts across 4 core dimensions: accuracy, completeness, readability, and reliability.

Descriptive analysis showed that the AI group had mean scores ranging from 3.44 to 3.68 across the 4 dimensions, with a median of 4.0 (IQR 3.0-4.0) and CV between 0.145 and 0.178, reflecting relatively high performance consistency. In contrast, the clinician group had mean scores between 1.78 and 2.05, a median of 2.0 (IQR 1.0-2.0), and CV values from 0.428 to 0.473. Across all 4 question types—basic knowledge, drug management, clinical decision-making, and case analysis—the AI group obtained higher scores than the clinician group. The highest scoring dimension for the AI group was completeness in case analysis questions (mean score 3.8, SD 0.39), while the lowest for clinicians was in drug management (mean score 1.6, SD 0.83). Detailed results are presented in Table 4 and Figure 2.

To formally evaluate differences while accounting for the hierarchical structure of the data (responses nested within questions and raters) and the ordinal nature of the Likert scale, a CLMM was fitted using restricted maximum likelihood. The model demonstrated good fit, with random intercepts for “Question” (variance=0.0795) and “Expert” (variance=0.0723), indicating moderate clustering effects. In the fixed effects analysis, the intercept was estimated at −4.422 (SE 0.117; P<.001). The coefficient for the clinician group was −5.066 (SE 0.121; P<.001), corresponding to a significantly lower likelihood of achieving higher scores. Specifically, the odds of the AI group receiving a higher score category compared to the clinician group were 83.6 times greater (odds ratio [OR] 0.012, 95% CI 0.010‐0.014; P<.001).

The performance of 4 AI models was further compared across 4 evaluation dimensions and 4 question categories. Descriptive statistics showed that DeepSeek-R1 achieved the highest scores across most evaluation dimensions, particularly in accuracy, with mean scores between 3.79 and 3.87. It performed particularly well in the basic knowledge questions (accuracy: 3.86; completeness: 3.89). Among the comparison group of the other 3 models, the overall performance was largely comparable. ChatGPT-o4-mini exhibited a nuanced advantage in handling complex questions, slightly outperforming others in accuracy (3.73) and readability (3.76) for basic knowledge questions, as well as in completeness (3.83) and readability (3.75) for case analysis questions. This aligns with its ability in managing complex scenarios (Figure 3).

To formally evaluate differences among the 4 AI models while accounting for the hierarchical data structure and the ordinal nature of the outcome, a CLMM was fitted, followed by post-hoc pairwise comparisons using the Tukey method. The CLMM revealed a significant overall effect of model type (likelihood-ratio test: c²=24.346; P<.001). Post-hoc comparisons showed a clear tiered differentiation in performance. DeepSeek-R1 demonstrated a substantial advantage over both ChatGPT-o4-mini and DeepSeek-V3. Specifically, DeepSeek-R1 had significantly higher odds of receiving a higher score compared to ChatGPT-o4-mini (OR 2.47, 95% CI 1.90‐3.21; P<.001) and 2.53 times higher than those of DeepSeek-V3 (estimate=0.929; OR 2.53, 95% CI 1.94‐3.31; P<.001). In contrast, pairwise comparisons among ChatGPT-4o, ChatGPT-o4-mini, and DeepSeek-V3 revealed no statistically significant differences across any of the evaluated dimensions (adjusted P values ranged from .55 to 0.99). For example, the comparison between ChatGPT-4o and ChatGPT-o4-mini yielded an estimate of −0.008 (OR 0.992, 95% CI 0.78-1.27; P=.99). These results indicate that DeepSeek-R1 occupies a distinct top tier, while the other 3 models perform at a comparable level.

We also compared the performance of cardiologists (n=4) and infectious disease clinicians (n=8) across overall scores, question categories, and evaluation dimensions. Descriptive analysis (consistent with Shapiro-Wilk test results indicating nonnormal distributions: cardiologists W=0.837; P<.001; infectious disease clinicians W=0.830; P<.001) showed comparable central tendencies: the median overall score was 2 (IQR 1.0-3.0) for cardiologists and 2 (IQR 1.0-2.0) for infectious disease clinicians (Figure 4A). To formally evaluate group differences while accounting for the ordinal nature of the outcome and hierarchical data structure, a CLMM was fitted, followed by Tukey post-hoc pairwise comparisons. The CLMM revealed a significant main effect of clinician group (likelihood-ratio test: c² (1)=19.34; P<.001).

Post-hoc comparisons highlighted domain-specific strengths (Figure 4B-D). In basic knowledge questions, cardiologists scored significantly higher than infectious disease clinicians (median difference 0.25; OR 2.41, 95% CI 1.83‐3.17; P<.001), driven by superior performance in CVD risk assessment (accuracy: median 2.26, IQR 1.0-3.0 vs median 1.83, IQR 1.0-3.0; Figure 5). Conversely, infectious disease clinicians excelled in drug management (median difference −0.46; OR 0.41, 95% CI 0.31‐0.54; P<.001), particularly in managing ART side effects (accuracy: median 2.23, IQR 1.0-3.0 vs median 1.65, IQR 1.0-2.0; Figure 5). In clinical decision-making, there was no statistically significant difference between the groups (median difference 0.22; OR 2.09, 95% CI 1.60‐2.74; adjusted P=.16). Similarly, in case analysis, the difference (median difference 0.16; OR 1.71, 95% CI 1.03‐2.85) also remained nonsignificant after multiple comparison correction (P_adj≥.99 for accuracy).

By evaluation dimension (Figure 4C and D), no significant group differences emerged (clinical decision-making: adjusted P=.16; case analysis: adjusted P≥.99). For accuracy, cardiologists had marginally higher scores (median 2.07, IQR 1.0-3.0 vs median 1.96, IQR 1.0-2.0), but this was not statistically significant (P_adj=.09). Similarly, completeness (median difference=0.02; P_adj=.67), readability (median difference=−0.09; P_adj=.52), and reliability (median difference=0; P_adj=.14) showed no meaningful divergence. A heat map (Figure 4D) further illustrated these specialty-specific patterns: cardiologists consistently scored higher on cardiovascular-related items (eg, CVD risk assessment and health indicator control), whereas infectious disease clinicians excelled in pharmacotherapy-focused tasks (eg, drug interactions and side effect management).

Interrater agreement was quantified using ICC (Table 5). For single-rater reliability (ICC(2,1)), both accuracy (ICC=0.755, 95% CI 0.712-0.794) and completeness (ICC=0.754, 95% CI 0.711-0.793) exceeded the commonly accepted threshold of 0.75 (P<.001), indicating acceptable consistency among individual expert ratings. In contrast, readability (ICC=0.681) and reliability (ICC=0.713) demonstrated only moderate agreement (P<.001), suggesting greater variability in individual assessments of these 2 dimensions.

To assess the robustness of aggregated expert scoring, average-measures ICC (ICC(2,k)) was further calculated. When ratings were averaged across all 6 experts, excellent consistency was observed across all dimensions: accuracy (ICC=0.949, 95% CI 0.937-0.960), completeness (ICC=0.949, 95% CI 0.937-0.960), readability (ICC=0.927, 95% CI 0.910-0.942), and reliability (ICC=0.937, 95% CI 0.923-0.949; all P<.001). All values were well above the 0.90 threshold, confirming high reliability of group-based scoring outcomes.

This study presents one of the first comprehensive, head-to-head comparisons between LLMs and human clinicians in the context of managing CVD in people living with HIV. By evaluating performance across multiple clinical domains and rating dimensions, our findings consistently demonstrate the superior capability of LLMs in generating accurate, complete, and clinically coherent responses, even within the complex interdisciplinary setting of HIV-CVD comorbidity. This performance advantage was observed across all question types, from basic knowledge to real-world case analysis, and was particularly evident in areas requiring integrative reasoning. Importantly, this advantage emerged despite the AI models receiving only a minimal system prompt specifying their role and the relevant guidelines, rather than being explicitly instructed to mimic a clinician. This suggests that the models’ pretraining on vast medical corpora inherently equips them with the knowledge and reasoning patterns necessary for complex comorbidity management, underscoring their readiness as decision-support tools.

This superiority stems from 2 fundamental advantages of LLMs: robust logical reasoning and broad knowledge coverage [26-28]. Built on advanced algorithmic architectures such as transformers, these models are capable of mining and extracting key features from massive repositories of medical literature, clinical guidelines, consensus statements, and case-based evidence [29,30]. This data-driven integration enables LLMs to conduct multisource, multidimensional information synthesis within milliseconds, allowing them to maintain consistency, accuracy, and completeness in complex clinical scenarios [31]—qualities that are often compromised in human decision-making due to cognitive biases, fatigue, and fragmented training. These results suggest that, when appropriately deployed, LLMs may serve as a powerful tool for bridging cognitive gaps between specialties and standardizing care quality in settings with limited access to multidisciplinary expertise.

It is important to address the clinical relevance of the observed statistical differences. On our 4-point ordinal scale, a score of 4 represents “fully accurate, with no medical errors, and strictly adheres to guideline recommendations,” while a score of 2 indicates “factually correct overall, but contains evident errors or misleading details.” The mean AI scores of 3.44‐3.68 therefore correspond to responses that are near-perfect in guideline adherence, whereas clinician mean scores of 1.78‐2.05 indicate responses that, on average, contain noticeable inaccuracies or omissions. This qualitative gap has direct implications for patient safety and care quality: even small numerical differences on this scale can translate into clinically meaningful distinctions, such as the difference between recommending a contraindicated drug combination versus a guideline-concordant alternative.

Furthermore, the extremely low CV in the AI group (CV 0.145‐0.178) compared with clinicians (CV 0.428‐0.473) underscores a critical advantage of AI: its ability to deliver uniformly high-quality advice regardless of question complexity or domain. In real-world settings, this consistency can reduce the “knowing-doing gap” and mitigate variability in clinical decision-making—a known driver of disparate patient outcomes. The clinical relevance is most pronounced in the context of complex comorbidities like HIV and CVD, where interdisciplinary knowledge silos are common. An AI model that integrates cardiology and infectious disease guidelines can directly support a clinician in making a safer, more holistic decision than they might achieve alone, particularly in resource-limited settings without easy access to multidisciplinary teams.

These findings also hint at an underlying complementarity between clinical specialties that merits closer examination, as discussed in the following section.

Notable performance differences among the 4 AI models highlight the impact of training strategies and model architecture on clinical reasoning outcomes. DeepSeek-R1 consistently outperformed other models, particularly in tasks requiring factual precision and logical integration, such as basic knowledge and drug safety. This may reflect its specialized training focus on reasoning-intensive tasks and optimized instruction-tuning processes, which likely enhanced its ability to synthesize structured clinical information [32]. It is important to note that all models were tested under identical conditions (same prompt and default temperature settings), so the observed differences can be attributed primarily to architectural and training differences rather than prompt engineering.

In contrast, general-purpose models like ChatGPT-4o and DeepSeek-V3 demonstrated relatively balanced but less domain-specific performance, while ChatGPT-o4-mini showed modest advantages in case analysis, possibly due to its science, technology, engineering, and mathematics–oriented pretraining [33]. These variations suggest that the clinical utility of LLMs is closely tied to the relevance and quality of their underlying training data. Domain-adaptive pretraining and instruction tuning—especially using medical guidelines, real-world case repositories, and multiturn clinical dialogue—may significantly improve model performance in complex decision-making scenarios.

From a translational perspective, these findings underscore the importance of aligning model selection with task characteristics in real-world deployment. For settings requiring high interpretability and decision fidelity, domain-optimized models like DeepSeek-R1 may be preferable. Future efforts should focus on dynamic fine-tuning, multilingual optimization, and integration with local clinical knowledge systems to enhance the safety, generalizability, and cultural adaptability of AI-assisted tools across health care environments.

Despite the overall performance gap between AI models and human clinicians, our analysis of subgroup differences revealed meaningful patterns within the clinician group itself [34]. Notably, while cardiologists and infectious disease clinicians achieved comparable total scores, their strengths diverged across task types. Cardiologists performed better in cardiovascular risk assessment and complex clinical decision-making, whereas infectious disease clinicians outperformed in drug management tasks, particularly in addressing side effects of drugs. These differences likely reflect each group’s clinical focus and training background—cardiologists are more experienced with risk stratification algorithms and long-term prognosis planning, while infectious disease clinicians are more attuned to the nuances of ART regimens, metabolic complications, and drug-drug interactions.

Such findings underscore the existence of “knowledge silos.” These silos are precisely the gaps that LLMs, with their ability to retrieve and synthesize cross-disciplinary knowledge, can help bridge. This divergence also reinforces the need for more integrated, team-based approaches to care. In real-world practice, the absence of consistent cross-specialty collaboration may lead to fragmented decision-making and missed opportunities for optimized management. From an educational and clinical workflow perspective, integrating LLMs into multidisciplinary team discussions could provide real-time, guideline-aligned suggestions that supplement each specialists’ blind spots, potentially reducing fragmentation and improving care coordination [35].

Moreover, the observed complementarity between specialties hints at a potential role for LLMs as integrative tools in bridging these knowledge gaps [36,37]. AI-driven decision support systems could offer real-time, cross-domain insights that align with both infectious disease and cardiovascular best practices, thereby supporting more cohesive clinical strategies [38]. Future research should explore how such tools can be embedded within multidisciplinary workflows to promote collaborative decision-making and improve outcomes in complex care scenarios.

Beyond the performance findings, this study offers methodological value for future evaluations of AI-assisted clinical decision support. Unlike previous studies that relied on simplified question-answer prompts or single-dimension metrics [39], we adopted a standardized, guideline-derived question set, incorporated structured case scenarios, and implemented a multidimensional evaluation framework to capture both the breadth and depth of clinical reasoning. The use of expert-developed reference answers ensured consistency in benchmarking, and the blinded scoring protocol minimized observer bias. Furthermore, we involved experts from both public health and clinical specialties. The interrater agreement, quantified through ICC analysis, demonstrated excellent agreement for average scores across all dimensions (ICC=0.93‐0.95). These measures ensured that the evaluation process was both reliable and generalizable. This design may serve as a practical assessment paradigm for future studies seeking to objectively measure the clinical utility of LLMs in complex, multidisciplinary contexts.

Despite its strengths, this study has several limitations. First, the sample size for clinician participants was relatively small, with only 12 clinicians from 2 HIV-designated hospitals in the same region (Guangdong Province, China). Although we ensured comparable experience levels between specialties and adopted a blinded evaluation approach, the findings may not be generalizable to broader clinical populations or health care systems, and the geographic concentration limits external validity. Second, each AI model was prompted only once per question under standardized conditions, which may not fully reflect their potential performance variability or capacity for interactive refinement—especially in real-world deployments where multiturn dialogues are common. Furthermore, the system prompt used (assigning the model the role of a clinician and specifying relevant guidelines) represents just one possible prompting strategy; alternative prompts could lead to different performance outcomes. Third, while our question set was carefully constructed based on authoritative guidelines, it cannot capture the full complexity and uncertainty of clinical practice, such as patient heterogeneity, comorbidities beyond HIV and CVD, or emerging clinical scenarios. Fourth, the weighting scheme for case analysis questions, although determined by expert consensus, introduces inherent subjectivity. Different weighting priorities (eg, emphasizing diagnostic accuracy over treatment planning) could alter the relative rankings of groups. Sensitivity analyses using alternative weighting methods would strengthen the robustness of our findings. Fifth, the evaluation framework, although multidimensional and rigorously implemented, remains inherently subjective, particularly in dimensions such as readability or reliability. Despite acceptable interrater reliability (single-rater ICC=0.68‐0.76; average-rater ICC=0.93‐0.95), some degree of rater bias is unavoidable. Finally, the assessment focused on textual response quality and did not evaluate downstream clinical outcomes, patient safety, or acceptability of AI integration in practice.

This study provides the first systematic comparison of LLMs and human clinicians in addressing CVD management for people living with HIV. The results show that AI models achieved significantly higher scores across all evaluation dimensions while also revealing complementary strengths between specialties. These findings highlight the potential of LLMs as decision-support tools that can augment, rather than replace, clinical expertise—particularly in complex comorbidity contexts where cross-specialty knowledge integration is essential. The strong domain-specific performance of DeepSeek-R1 further suggests that model selection should consider contextual alignment with real-world clinical needs, beyond size or architecture alone. Future work should prioritize prospective clinical validation and the integration of AI into multidisciplinary workflows, combining human judgment with machine precision to ensure safe and effective deployment.