Antiretroviral therapy has transformed HIV into a chronic condition and shifted clinical attention toward non-communicable comorbidities. Among these, urate dysregulation—encompassing hyperuricemia and its clinical manifestation gout—is increasingly reported in people living with HIV (PLHIV). Mechanisms implicated include increased purine turnover from immune activation and viral replication, impaired renal urate excretion related to HIV-associated nephropathy and ART nephrotoxicity, and direct uricogenic effects of specific antiretroviral agents such as ritonavir-boosted protease inhibitors and older nucleoside analogues. More recently, integrase inhibitors, notably dolutegravir, have been associated with elevated serum uric acid in several cohorts, particularly in sub-Saharan Africa. Primary studies report wide prevalence ranges across regions and ART regimens, and gout has also been described as a rare immune reconstitution inflammatory syndrome (IRIS) manifestation after ART initiation.
This protocol defines a systematic review and meta-analysis to:
Included study designs are observational quantitative studies: cross-sectional, prospective and retrospective cohort, and case-control studies that report prevalence or incidence of hyperuricemia or gout in PLHIV. Case reports and case series with fewer than 10 participants, conference abstracts, reviews, editorials, qualitative and animal studies will be excluded. No restriction will be applied for publication year, language, or geographic setting.
Participants must be adults (≥18 years) with documented HIV infection regardless of ART status, CD4 count, clinical stage, or HIV-1 subtype. Studies mixing adult and pediatric data are eligible if adult-specific data are extractable or adults make up at least 80% of participants; authors will be contacted where necessary.
The review will search PubMed/MEDLINE, EMBASE, Web of Science, and CINAHL from database inception through May 2026. The protocol specifies comprehensive database searching with no language or year limits. Details of search terms and strategies are provided in the full protocol supporting materials.
Two independent reviewers will screen titles/abstracts and full texts, extract data, and resolve disagreements through discussion or third-party adjudication. Extracted data will include study design, setting, participant characteristics, ART regimen at time of urate measurement, definitions and thresholds for hyperuricemia and gout, CD4 count, viral load, metabolic comorbidities, and HIV duration.
Risk of bias for prevalence studies will be assessed using the Joanna Briggs Institute Prevalence Critical Appraisal Checklist. Cohort and case-control studies will be appraised using the Newcastle–Ottawa Scale (NOS). The protocol describes procedures to handle duplicate reports and missing data, including contacting corresponding authors.
Primary outcomes are the pooled prevalence of hyperuricemia and the pooled prevalence of gout among adults with HIV. Secondary outcomes include measures of association between urate dysregulation and potential risk factors: ART class (pre-ART, PI-based, NNRTI-based, INSTI-based/dolutegravir era), CD4 category, viral suppression status, comorbid metabolic conditions, and HIV disease duration. The protocol also captures reports of gout presenting as IRIS.
Prevalence estimates will be pooled using a random-effects meta-analysis applying the DerSimonian–Laird method. For prevalence data, the Freeman–Tukey double-arcsine transformation will be used to stabilize variances. Heterogeneity will be quantified with the I2 statistic and Cochran’s Q test. Analyses will be implemented in R software as described in the protocol.
Planned subgroup analyses aim to explore heterogeneity by ART class (pre-ART/ART-naive, protease inhibitor, NNRTI, INSTI/dolutegravir era), geographic region, CD4 categories, and study quality. Sensitivity analyses will examine the influence of study design and risk of bias on pooled estimates.
The review protocol follows PRISMA-P 2015 guidance and is registered on PROSPERO (CRD420261360734). The authors report that no primary datasets were generated or analysed during protocol preparation; relevant data will be made available upon study completion. The work received no specific funding and the authors declared no competing interests.
The protocol highlights a gap: no previous systematic review has synthesized global prevalence estimates or risk-factor data for urate dysregulation in PLHIV. By pooling prevalence and examining ART-class effects—notably the potential uricogenic signal of dolutegravir—the planned review aims to inform clinical monitoring strategies for urate dysregulation, especially in settings where INSTI-based regimens are dominant and rheumatology services are limited. The synthesis intends to support clinicians and policymakers in assessing the need for targeted uric acid monitoring and management in PLHIV.