Southern Sichuan HIV Cohort Study Protocol (SSHCSP)

Multi-source Data-integrated HIV Cohort in Four Cities of Southern Sichuan, China: a Mixed Retrospective-prospective Study Protocol

Multi-source data-integrated HIV cohort in four cities of southern Sichuan, China: a mixed retrospective-prospective study protocol.

Study Overview

• Status: Active, not recruiting
• Conditions: HIV - Human Immunodeficiency Virus

Detailed Description

This study is a mixed retrospective-prospective cohort study conducted across four prefecture-level cities in southern Sichuan Province, China: Luzhou, Zigong, Neijiang, and Yibin. These four cities together comprise 23 districts and counties, with HIV care delivered through a network of designated treatment institutions coordinated by local Centers for Disease Control and Prevention (CDC). The region exhibits substantial intra-regional variation in healthcare resources and HIV burden, with molecular epidemiological data showing predominant CRF01_AE (36.9%) and CRF07_BC (41.0%) subtypes and evidence of concentrated transmission clusters among older adults (aged ≥60 years).

Retrospective component Data are extracted from existing electronic medical records (EMRs), CDC surveillance registries, and pharmacy/insurance claims systems for the period from 1 January 2019 to 31 December 2025. This phase reconstructs individual-level historical trajectories of antiretroviral therapy (ART) engagement, laboratory monitoring (CD4, viral load), and clinical outcomes to establish the baseline cohort.

Prospective component From 1 January 2026 to 31 December 2026, newly diagnosed individuals and those transferring into care are enrolled consecutively with quota controls by city and age group (<50, 50-64, ≥65 years). At scheduled clinic visits, trained interviewers administer tablet-based structured questionnaires capturing patient-reported outcomes, including health-related quality of life (MOS-HIV, EQ-5D-5L), mental health (PHQ-9, GAD-7), HIV stigma (Berger Stigma Scale), self-management capacity, social determinants of health, and treatment preferences via a discrete choice experiment (5 attributes, 9 choice sets). Clinical data continue to be collected from routine sources.

Data integration A deterministic linkage procedure uses the unique ART treatment code as the primary key, with probabilistic linkage for records where the code is missing. A linkage failure threshold of 5% triggers manual verification. All data are harmonized (ICD-10 diagnoses, YPID medication codes, standardized laboratory units) and stored on encrypted servers with restricted access.

Sample size Target enrolment is 2,000 participants across the four cities, accounting for an anticipated 15% loss to follow-up. This ensures ≥1,700 participants with complete 12-month outcome data, providing ≥200 virological failure events (assuming a 12% failure rate) to satisfy the "10 events per variable" rule for multivariable analyses.

Primary analysis The primary outcome is 12-month virological suppression (HIV RNA <50 copies/mL). Logistic regression with stepwise variable selection (Akaike Information Criterion) is used, reporting adjusted odds ratios and 95% confidence intervals. Secondary analyses include time-to-event analysis for virological failure (≥1,000 copies/mL on two consecutive measures) using Cox proportional hazards models, with verification of the proportional hazards assumption.

Dynamic trajectory modeling Hidden Markov Models (HMM) are applied to repeated viral load and CD4 measurements to characterize unobserved latent states (e.g., stable suppression, immunological fluctuation, failure) and transition probabilities over time. Self-management capacity and socioeconomic status are included as time-invariant covariates.

Machine learning prediction Models are developed to predict 12-month virological failure (VL ≥50 copies/mL). Feature selection uses LASSO regression on a training set (70% of data). Four algorithms are compared: logistic regression (benchmark), Random Forest, XGBoost, and a stacked ensemble. Hyperparameter tuning uses grid search with five-fold cross-validation on a validation set (10%). Performance is evaluated on a held-out test set (20%) using AUC-ROC, Brier score, and calibration curves. Synthetic minority oversampling (SMOTE) is applied to the training set to address class imbalance. Model interpretability is enhanced with SHAP values.

Missing data Multiple imputation by chained equations (MICE) is performed for variables with >10% missingness under the missing at random assumption, generating five imputed datasets combined using Rubin's rules. Complete-case analysis serves as a sensitivity comparison.

Sensitivity analyses Alternative viral suppression thresholds (<200 copies/mL and <1,000 copies/mL), different loss-to-follow-up handling (inverse probability of censoring weighting), and restriction to participants with at least two viral load measurements are conducted to assess robustness of findings.

Ethics and dissemination The study has received approval from the Institutional Review Board of Southwest Medical University (approval number SWMUIRBKS-202509-0017) and is conducted in accordance with the Declaration of Helsinki. Written informed consent is obtained from all prospective participants (or legally authorized representatives for those with cognitive impairment). The study is registered with the Chinese Clinical Trial Registry (ChiCTR) prior to enrolment of the first prospective participant. Results will be published in peer-reviewed journals and presented at scientific conferences. De-identified analytical datasets will be made available upon reasonable request, subject to approval from the data governance committee and relevant ethics approvals.

• Study Type: Observational
• Enrollment (Estimated): 10

Contacts and Locations

Study Locations

• China
  • Sichuan
    • Luzhou, Sichuan, China, 646000
      • Southwest Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population consists of people living with HIV (PLWH) who receive care at designated HIV treatment institutions across four prefecture-level cities in southern Sichuan Province, China: Luzhou, Zigong, Neijiang, and Yibin. These four cities collectively comprise 23 districts and counties with considerable intra-regional variation in healthcare resources and HIV burden.

Participants are recruited from outpatient clinics and community follow-up encounters at the participating study sites. The study employs a consecutive enrolment strategy with quota controls applied by city and age group (<50, 50-64, ≥65 years) to ensure adequate representation across clinically relevant strata. The ≥65 years age stratum is deliberately oversampled to enable robust subgroup analyses of older adults, who face unique challenges including polypharmacy and age-related comorbidities.

The retrospective component includes individuals with historical records from 1 January 2019 to 31 December 2025. The

Description

Inclusion Criteria:

• People living with HIV (PLWH) or AIDS patients who are registered and diagnosed at the participating research centers in Luzhou, Zigong, Neijiang, or Yibin, China
• Key assessment information (clinical, laboratory, or follow-up data) obtainable during the study period
• Traceable medical treatment or follow-up records within the retrospective time window (1 January 2019 to 31 December 2025)
• Able to understand and complete the questionnaire and provide written informed consent (for the prospective component)
• Residing or visiting within the four southern Sichuan cities, or continuously managed at the local research centers

Exclusion Criteria:

• Missing key information that cannot be verified or supplemented from original records
• Unable to complete the questionnaire and no alternative data collection method available
• Obviously inconsistent or untrustworthy data that cannot be confirmed after verification
• Not suitable for inclusion under ethical and compliance requirements (e.g., unable to provide consent without a legally authorized representative when required)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Southern Sichuan HIV Cohort; People living with HIV (PLWH) enrolled from four prefecture-level cities in southern Sichuan, China (Luzhou, Zigong, Neijiang, and Yibin). Participants are recruited consecutively from outpatient clinics and community follow-up encounters, with quota controls applied by city and age group (<50, 50-64, ≥65 years). All participants receive standard antiretroviral therapy (ART) per Chinese national guidelines. There is no assigned intervention. Data collection includes retrospective extraction of routine clinical, laboratory, and pharmacy records (2019-2025) and prospective collection of patient-reported outcomes (mental health, quality of life, stigma, self-management, treatment preferences) via structured questionnaires at baseline and follow-up visits. The primary outcome is 12-month virological suppression (HIV RNA <50 copies/mL).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
12-month virological suppression	Proportion of participants achieving HIV RNA <50 copies/mL measured at the 12-month assessment window (±60 days). This binary outcome is derived from routinely collected viral load measurements extracted from CDC registries or hospital electronic medical records. If multiple measurements exist within the window, the value closest to the 12-month target date is used. This definition aligns with UNAIDS 95-95-95 targets and Chinese national treatment guidelines.	12 months (±60 days) after baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Virological failure	HIV RNA ≥1,000 copies/mL on two consecutive measurements after at least six months of antiretroviral therapy (ART), consistent with World Health Organization criteria. Analyzed as a time-to-event outcome, with event date corresponding to the first of the two confirmatory measurements.	Up to 24 months (prospective follow-up period)
Change in CD4 count	Absolute change in CD4 cell count (cells/µL) from baseline to 12 months, calculated as CD4 at 12 months minus baseline CD4.	Baseline and 12 months (±60 days)
Treatment persistence	Continuous antiretroviral therapy without interruption exceeding 30 days, derived from pharmacy dispensing records and CDC follow-up documentation. Interruptions identified based on gaps in medication refill records exceeding expected dispensing intervals.	12 months and 24 months
Health-related quality of life (MOS-HIV)	Physical health summary score and mental health summary score from the Medical Outcomes Study HIV Health Survey (MOS-HIV). Higher scores indicate better health-related quality of life.	Baseline and 12 months (±60 days)
Depressive symptom severity (PHQ-9)	Total score on the Patient Health Questionnaire-9 (PHQ-9), range 0-27, with higher scores indicating more severe depressive symptoms. Established cut-point for probable depression is ≥10.	Baseline and 12 months (±60 days)
Anxiety symptom severity (GAD-7)	Total score on the Generalized Anxiety Disorder-7 (GAD-7), range 0-21, with higher scores indicating more severe anxiety symptoms.	Baseline and 12 months (±60 days)
HIV-related stigma (Berger Stigma Scale)	Total score on the Berger HIV Stigma Scale (BHSS) at baseline, measuring perceived HIV-related stigma.	Baseline only

Collaborators and Investigators

• Sponsor: Southwest Medical University

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2026
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: April 2, 2026
• First Submitted That Met QC Criteria: April 2, 2026
• First Posted (Actual): April 9, 2026

Study Record Updates

• Last Update Posted (Actual): April 9, 2026
• Last Update Submitted That Met QC Criteria: April 2, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: China; Cohort study; HIV; Viral suppression; Antiretroviral therapy (ART); Real-world evidence
• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome
• Other Study ID Numbers: SWMUPH-2025001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Individual participant data (IPD) will not be made publicly available. De-identified data may be shared only upon reasonable request and subject to approval by the study's Data Governance Committee and relevant institutional ethics review, as stated in the protocol. IPD will not be directly shared because:

The study involves sensitive health information from people living with HIV, a vulnerable population.

Participant informed consent does not include unrestricted public data sharing. Data are derived from multiple sources (CDC registries, hospital EMRs, insurance claims) with strict data use agreements that prohibit open distribution.

Thus, IPD will not be shared as a public repository deposit. Access, if granted, would be controlled and require a signed data use agreement.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No