AT AIDS 2016
DURBAN, SOUTH AFRICA (FRONTLINE MEDICAL NEWS) – The optimal frequency of kidney safety monitoring in patients using oral daily tenofovir/emtricitabine for pre-exposure prophylaxis against HIV infection is every 6 months, but less frequent monitoring may be reasonable in most low-risk patients, Renee Heffron, PhD, said at the 21st International AIDS Conference.
The occurrence and pattern of detection of a drop in creatinine clearance to less than 60 mL/min during the first 12 months of therapy didn’t differ significantly regardless of whether monitoring was done at 3- or 6-month intervals. The risk of a clinically relevant decline in creatinine clearance during the first 12 months of therapy appears to be largely confined to the subgroup of patients on tenofovir/emtricitabine (Truvada) for pre-exposure prophylaxis (PrEP) who weigh 55 kg or less, have a baseline creatinine clearance rate of 60-90 mL/min, or are at least 45 years old, according to Dr. Heffron of the University of Washington, Seattle.
The question of how frequently to monitor renal function is a key issue as PrEP with tenofovir/emtricitabine is ramped up to scale in sub-Saharan Africa and other parts of the developing world where the majority of new HIV infections occur – and where laboratory resources are often limited. The randomized clinical trials that led to marketing approval of tenofovir/emtricitabine for PrEP in the United States and elsewhere monitored creatinine clearance every 3 months. But the confirmatory demonstration projects used a range of kidney monitoring schedules, she explained.
She presented an analysis of clinically relevant kidney toxicity in 4,404 initially HIV-negative subjects on tenofovir/emtricitabine in the Partners PrEP Study, in which creatinine clearance was measured every 3 months, and in 955 participants in the Partners Demonstration Study, in which monitoring was performed every 6 months. All participants were at high risk for HIV acquisition because they were members of serodiscordant couples.
The occurrence and pattern of detection of a drop in creatinine clearance to less than 60 mL/min during the first 12 months of therapy didn’t differ significantly regardless of whether monitoring was done at 3- or 6-month intervals. The cumulative rate in the randomized trial was 0.4%, 0.5%, and 0.7% at 3, 6, and 12 months, and it was 0.2% at both 6 and 12 months in the demonstration project, Dr. Heffron reported.
These renal events were not only rare, they were reassuringly nonprogressive and resolved within a few weeks of PrEP discontinuation, she added.
Her analysis of the combined 5,359 subjects in the two Partners studies identified three independent predictors of a fall in creatinine clearance to below 60 mL/min during the first 12 months of therapy. A baseline age of 45 years or more was associated with an adjusted 2.5-fold increase, compared with younger patients. Subjects with a creatinine clearance of 60-90 mL/min at enrollment were 74 times more likely to experience a significant drop in creatinine clearance than those who started on PrEP with a creatinine clearance rate in excess of 90 mL/min. And patients weighing 55 kg or less had a 2.7-fold greater risk than those weighing more. But fewer than 5% of patients with any of these three predictors actually experienced a drop in creatinine clearance to below 60 mL/min.
The data from the two Partners studies support guidelines from the Centers for Disease Control and Prevention recommending creatinine monitoring every 6 months for people on oral daily PrEP. Still, patients with one of the defined risk factors might logically be candidates for targeted monitoring, Dr. Heffron observed.
The Partners studies were funded by the National Institutes of Health, the Bill and Melinda Gates Foundation, and the U.S. Agency for International Development. Dr. Heffron reported having no financial conflicts of interest.