Can Individualized Care for Kidney Disease in HIV Improve Outcomes?

Despite antiretroviral drugs with better renal profiles, the proportion of patients living with HIV who have advanced chronic kidney disease (CKD) increased fourfold to almost 2% over a decade, as revealed in a prospective cohort study published in HIV Medicine.

A multidisciplinary approach could be useful to anticipate drug-drug interactions and toxicities and to reduce death and hospitalization, the study authors conclude.

In a cohort study of the prevalence of advanced CKD in people living with HIV, researchers assessed CKD progression under individualized multidisciplinary clinical management for 48 weeks, said corresponding author Anna Bonjoch, MD, PhD, Department of HIV, Lluita Contra la Sida Foundation, Germans Trias i Pujol University Hospital, Barcelona, Spain. The clinical management included a critical review of treatment with continuous monitoring of the participants' progress and regular multidisciplinary meetings (with a nurse, nephrologist, HIV specialist, and nutritionist) to discuss cases and to design specific interventions.

Of 3090 individuals living with HIV who were attending the author's clinic in Barcelona, Spain, between June 2019 and June 2020, 55 people had advanced CKD, as determined on the basis of Kidney Disease Improving Global Outcomes (KDIGO) organization criteria (1.8% of the cohort; 95% CI, 1.31 – 2.25). All were White patients, and most were men (83.6%; median age, 58 years).

Among those with advanced CKD, the nadir CD4 T-cell count was 135.5 (interquartile range [IQR], 43.5 – 262.75) cells/μL, and the current CD4 T-cell count was 574 (IQR, 438.5 – 816) cells/μL. Viral suppression had been maintained in 96% of the participants. The most common comorbidity was arterial hypertension (85.5%), followed by dyslipidemia (49%). Most individuals had CKD of stage G3b+ (n = 29; 52.7%), followed by stage G3a+ (n = 18; 32.7%).

Through multidisciplinary monitoring, three individuals (5.5%) required dose adjustments or changes in antiretroviral therapy because of changes in their estimated glomerular filtration rate (eGFR), and 11 received warnings of possible near future need for dose reductions in the event of eGFR deterioration.

While no adverse events were reported among the participants, eight received interacting drugs, and five (9%) were warned about the use of cobicistat concomitantly with immunosuppressive drugs, clopidogrel, eplerenone, or apixaban. For one patient on the transplant list, a switch in antiretroviral therapy was recommended to prevent interactions.

During the 48-week follow-up, renal status improvements were observed in 9 of 55 patients (16.4%). One patient's CKD was reclassifed from stage G5 to G4, four were reclasisfied from G3b+ to G3a+, and four were reclassified from G3a+ to normal parameters.

CKD Has Emerged as a Problem for Aging HIV Patients

Kidney injury is three times more frequent among individuals living with HIV, and CKD-related proteinuria correlates strongly with increased cardiovascular events and mortality. In addition to traditional risk factors — arterial hypertension, dyslipidaemia, diabetes, potentially nephrotoxic drugs, and hepatitis coinfection — HIV-specific risk factors for CKD include time since infection, chronic systemic inflammation, immunologic status, and receiving certain antiretroviral drugs.

All of these, the authors state, necessitate specific and multidisciplinary clinical management for people living with HIV, especially those with end-stage renal disease.

Patients in the prospective cohort study were stratified according to KDIGO definitions: eGFR ≥45 and <60 mL/min/1.73 m² plus urine protein >300 mg/g (group G3a+); eGFR ≥ 30 and <45 mL/min/1.73 m² and proteinuria ≥30 mg/g (G3b+); eGFR ≥15 and <30 mL/min/1.73 m² (G4); and eGFR <15 mL/min/1.73 m² (G5).

Best individual management approaches were determined through in-person visits with a nephrologist (always the same) who was experienced with HIV infection and who optimized treatment of comorbid conditions and assessed the need for renal biopsy, transplant, and dialysis (renal replacement therapy). Patients also met twice a year with a nutritionist who evaluated nutrition and made recommendations.

Despite close management, renal parameters improved in fewer than one quarter of people, Bonjoch and her colleagues point out. A high percentage of the patients eventually needed renal replacement therapy, developed complications, were admitted to hospital, or died.

High rates (85.5%) of arterial hypertension (100% in G5), cardiovascular disease (32.7%), and dyslipidemia (49%) may be contributors to kidney disease in this aging population, the authors speculate.

Just over half (56%) had a sedentary lifestyle. "A sedentary lifestyle can worsen comorbidities (dyslipidemia, hypertension, for example)," Bonjoch told Medscape Medical News in an interview. "It is primarily an area of therapeutic focus, because the benefits of physical exercise include improving the aforementioned comorbidities and preventing frailty."

The major, multiple comorbid conditions in this population confirmed the need for close monitoring and a multidisciplinary approach, the authors write. "Comorbidities, along with advanced renal deterioration, make it difficult to experience improvement. The existence of many comorbidities worsens the situation and makes clinical events very frequent," Bonjoch added.

Need for Dose Adjustments and Potential Drug-Drug Interactions

Suboptimal medication management is the key finding of the study, commented F. Perry Wilson, MD, associate professor of medicine and director, Clinical and Translational Research Accelerator, Yale University School of Medicine, New Haven, Connecticut.

"This is not surprising," he told Medscape Medical News. "Dosing of HIV medications is complex and made more complex by the presence of kidney disease. The authors suggest that a multidisciplinary approach targeting these issues in this population might be beneficial. I agree it might, but this study can't show us that. This study highlights that there may be a problem, but we would need a larger study (with an appropriate control group) to demonstrate that there is a viable solution."

Wilson added, "Getting people on the right doses of medications is a good thing, but it does not necessarily mean they will have better outcomes. While dosing guidelines are often clearly delineated, physiologically, there is a lot of variability in how medications are metabolized. In other words, a future study may show that medication dosing can be made better in this population, but it will be harder to demonstrate that this leads to better clinical outcomes (like avoiding dialysis or continued HIV suppression)."

Speaking of the study's limitations, Bonjoch observed that the small size of the groups did not allow for creation of a control group to determine whether interventions were effective.

The study received no funding. The authors and Wilson have disclosed no relevant financial relationships.

HIV Med. Published online April 26, 2022. Abstract

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