PrEP Kidney Function Monitoring to Be Fine-Tuned, Updated WHO Guidance Planned

By Marilynn Larkin

March 18, 2022

NEW YORK (Reuters Health) - The risk of kidney-related adverse events among patients receiving tenofovir disoproxil fumarate (TDF)-based oral HIV pre-exposure prophylaxis (PrEP) is small, a systematic review and meta-analysis revealed.

Therefore, less frequent monitoring may be appropriate for some younger people, Dr Robin Schaefer of the World Health Organization (WHO) in Geneva and colleagues reported in The Lancet HIV.

The findings prompted WHO to revisit its guidance for kidney function screening and monitoring for PrEP, with new guidance expected to be published in the second quarter of 2022, according to a statement from the agency.

"Due to the small potential for kidney toxicity, previous WHO guidance suggested frequent kidney function monitoring among PrEP users," the organization said in the statement emailed to Reuters Health. "Kidney function measurements before initiation of PrEP and regularly thereafter have been reported as a barrier to uptake and use by clients, and create costs for health systems and users."

The study's authors searched the literature through June 2021 for randomized controlled trials (RCTs) or cohort studies that reported on graded kidney-related adverse events among oral PrEP users (TDF-based PrEP alone or in combination with emtricitabine or lamivudine).

They also analyzed largely unpublished participant data from 17 PrEP implementation projects and two RCTs for an individual participant data meta-analysis, estimating the risk of a decline in creatinine clearance to less than 60 mL/min.

Eleven RCTs with 13,523 participants were included in the literature meta-analysis. PrEP use was associated with an increased risk of grade 1 and higher kidney adverse events (pooled odds ratio, 1.49) and a nonsignificant increased risk of grade 2 and higher events (OR, 1.75), which were rare (13 out of 6,764 in the intervention group vs. six of 6,782 in the control group).

The patient-level meta-analysis included 18,676 individuals from 15 countries (7.8% from RCTs). At baseline, 79 (0.42%) had an estimated creatinine clearance of less than 60 mL/min, and proportions increased with increasing age.

Longitudinal analyses included 14,368 PrEP users; 349 (2.43%) individuals experienced a decline to less than 60 mL/min creatinine clearance, with higher risks associated with increasing age and a baseline creatinine clearance of 60.00 - 89.99 mL/min (adjusted hazard ratio, 8.49) or less than 60 mL/min (aHR 20.83).

WHO said the findings provide "real-world" evidence that very few individuals screened for PrEP (<0.5%) have impaired kidney function - a contraindication for oral PrEP - and the risks of kidney-related adverse events are very small. Slightly higher risks of nephrotoxicity were identified among older individuals (particularly those aged 50 or older) and those with minor impairments of kidney function at baseline.

"These results suggest that kidney function screening can be considered optional among younger individuals with no kidney-related comorbidities," according to the agency's email. "Less frequent monitoring, such as once within 1-3 months after PrEP initiation, may be appropriate for older individuals without comorbidities, although risks remain low even in the 30-49 year age group, particularly those aged 30-39 years."

"For individuals older than 50 years, those with baseline indications of impaired kidney function, and those with comorbidities, more regular monitoring might be required," according to WHO. "Moreover, PrEP use is commonly used during periods of risks, with individuals starting, stopping, and re-starting PrEP, which further diminishes risks."

Dr. Christina Wyatt of Duke University Medical Center in Durham, coauthor of a related editorial, commented in an email to Reuters Health, "As guidelines evolve based on these results, clinicians should continue to use their clinical judgement and exercise more caution in PrEP users with high adherence - who had the greatest benefit but might also be at increased risk for kidney injury and other adverse effects of PrEP, particularly with long-term use - and those with risk factors for kidney injury, including the factors identified in the study and others, such as low body weight or use of nephrotoxic medications."

WHO partly funded the study and employs three of the 24 authors.

SOURCE: https://bit.ly/3u3mHYh and https://bit.ly/365bRJ6 The Lancet HIV, online March 7, 2022.

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