Exploring the prevalence of renal impairment in virologically suppressed people living with HIV based on findings from the COCOMO study
In the four decades since HIV emerged as a global health threat, remarkable scientific advances have transformed it from a death sentence to a manageable chronic condition. Antiretroviral therapy (ART) has enabled millions of people living with HIV (PLWH) to achieve viral suppression, restoring their immune function and nearly matching the life expectancy of HIV-negative individuals. But as the HIV-positive population ages, a new concern has emerged: increased rates of organ damage and age-related diseases, even among those with well-controlled HIV. Among these concerning conditions, kidney disease stands out as a particularly silent yet significant threat.
Recent research has revealed that PLWH face a greater risk of renal impairment than the general population, but questions remain about whether this is driven by the virus itself, medication side effects, or other factors.
The Copenhagen Comorbidity in HIV Infection (COCOMO) study sought to answer these questions by examining renal function in virologically suppressed PLWH with otherwise low renal risk profiles. Their findings, which we explore in this article, provide crucial insights into this hidden health risk and underscore the importance of ongoing monitoring even for those doing well on antiretroviral therapy 1 .
Renal impairment refers to decreased kidney function, specifically a reduced glomerular filtration rate (GFR), which is the measure of how effectively the kidneys filter waste from the blood. Physicians typically estimate GFR (eGFR) using formulas that incorporate serum creatinine levels, a waste product generated by muscle metabolism. While an eGFR above 90 mL/min/1.73m² is considered normal, values below 60 indicate clinically significant impairment that warrants medical attention 1 .
Historically, researchers attributed kidney disease in PLWH to several factors:
However, recent studies have shown that even PLWH without these risk factors still experience higher rates of renal impairment than the general population, suggesting that chronic HIV infection itself – even when well-controlled – may contribute to kidney damage through persistent inflammation and immune activation 3 7 .
The COCOMO study, initiated in 2015, is an observational longitudinal cohort study designed to assess non-AIDS comorbidities in PLWH. The renal function component adopted a cross-sectional design comparing virologically suppressed PLWH against matched HIV-negative controls 2 .
| Inclusion Criteria | PLWH Group | Control Group |
|---|---|---|
| HIV Status | Virologically suppressed on ART | HIV-negative |
| Ethnicity | Caucasian | Caucasian |
| Age | Adults | Age- and sex-matched (1:4 ratio) |
| Additional Factors | No injecting drug use or hepatitis C | Participants from Copenhagen General Population Study |
Researchers employed standardized measurements to ensure consistency between groups:
The study defined renal impairment as a single measurement of eGFR ≤ 60 mL/min/1.73 m², consistent with established clinical guidelines 5 .
The study included 598 PLWH and 2598 matched controls. The results revealed:
| Group | Number of Participants | Prevalence of Renal Impairment | 95% Confidence Interval |
|---|---|---|---|
| PLWH | 598 | 3.7% | 2.3-5.5% |
| Controls | 2598 | 1.7% | 1.2-2.2% |
The difference was statistically significant (p = 0.0014), indicating that even among low-risk individuals, HIV status was associated with more than double the prevalence of renal impairment 1 5 .
Using adjusted logistic regression models, researchers identified several factors independently associated with renal impairment:
Notably, the association between HIV and renal impairment strengthened with increasing age (interaction p = 0.02), suggesting that HIV accelerates age-related decline in kidney function 3 .
Perhaps unexpectedly, the study found that HIV-specific factors – including current and nadir CD4 counts, duration of HIV infection, previous AIDS-defining diagnoses, and use of tenofovir disoproxil fumarate – were not associated with renal impairment in this virologically suppressed population 1 3 .
This suggests that the increased risk may be driven by persistent inflammatory processes or other mechanisms rather than traditional HIV-related factors 7 .
While the COCOMO study focused on a Caucasian population with low renal risk, a 2024 study from Uganda examined this issue in an older sub-Saharan African population, where the burden of HIV remains highest 4 6 .
This study enrolled 278 participants (50% PLWH, median age 66 years) and found strikingly different results:
| Group | Prevalence of Renal Impairment | Prevalence of Proteinuria |
|---|---|---|
| PLWH | 33.1% (95% CI: 25.7-41.4%) | 43.9% (95% CI: 35.8-52.3%) |
| Non-HIV | 12.9% (95% CI: 8.3-19.7%) | 19.4% (95% CI: 13.6-26.9%) |
These rates are substantially higher than those observed in the Danish cohort, likely due to differences in age, genetic factors, comorbidity burden, and healthcare access 6 .
Multivariable analysis confirmed that HIV infection strongly associated with renal impairment (OR = 3.89, 95% CI: 2.04-7.41) alongside traditional risk factors like hypertension and older age 4 .
Studying renal function in PLWH requires specific tools and methodologies. Here are key components of the research toolkit:
| Tool/Reagent | Function | Example Use in Research |
|---|---|---|
| Serum Creatinine | Waste product used to estimate GFR | Calculating eGFR via CKD-EPI equation |
| CKD-EPI Equation | Formula for estimating GFR from creatinine | Standardized assessment of renal function |
| Urine Dipstick | Semiquantitative protein detection | Screening for proteinuria |
| Transient Elastography | Non-invasive liver stiffness measurement | Assessing for liver disease confounding |
| Electronic Health Records | Source of demographic and clinical data | Collecting comorbidity and treatment data |
| Biobanked Samples | Storage of serum, plasma, urine for future studies | Enabling additional biomarker research |
These tools enable researchers to standardize measurements across studies, facilitating comparisons like those between the Danish and Ugandan cohorts 2 6 .
The COCOMO findings have several important implications for HIV care:
The study also highlights important research directions:
These findings reinforce the concept of the "fourth 90" in HIV care – ensuring that 90% of virally suppressed PLWH have good health-related quality of life, which includes preventing non-AIDS comorbidities like kidney disease 7 .
The COCOMO study provides compelling evidence that even among virologically suppressed PLWH with an otherwise low-risk profile, renal impairment remains a significant concern. While the absolute risk is relatively low in this Caucasian cohort (3.7%), it is still more than double that of matched controls, and comparable to the risk associated with diabetes 1 5 .
HIV status itself remains independently associated with impaired renal function, which suggests a pathway other than immunosuppression, ongoing viraemia and coinfections are driving the pathogenesis of renal impairment 3 .
These findings underscore that successful HIV care extends beyond viral suppression to include comprehensive health maintenance – regular monitoring of renal function, management of traditional risk factors, and continued research into the mechanisms underlying HIV-associated complications. As the population of PLWH continues to age, addressing these challenges will become increasingly important to ensure not just longer lives, but better ones 7 .
The remarkable success of antiretroviral therapy means that today, most PLWH can expect to live long enough to face age-related health challenges. By recognizing and addressing the heightened risk of kidney disease, healthcare providers can help their HIV-positive patients navigate these challenges successfully, enjoying not just longer lives, but healthier ones as well.