Oral HIV Drug Lamivudine Shows Vision Improvement in DME Patients, Early Trial Suggests

A widely available and inexpensive HIV drug, lamivudine, has shown promising results in improving vision for patients with diabetic macular edema (DME), according to findings from an initial randomized clinical trial. Unlike current DME treatments, which typically require monthly intraocular injections, lamivudine is taken orally, offering a potentially more accessible and cost-effective alternative.

Diabetic Macular Edema and the Need for New Treatments

Diabetic macular edema (DME) is a common and vision-threatening complication of diabetes, characterized by fluid accumulation in the retina. It affects approximately 1 in 14 individuals with diabetes. With over 37 million adults living with diabetes in the U.S. alone, the burden of DME on both patients and the healthcare system is substantial.

“An oral drug that improves vision in DME would be a game changer because it would be more convenient for patients than frequent, often monthly, injections into the eye,” said Dr. Jayakrishna Ambati, founding director of UVA Health’s Center for Advanced Vision Science. He added that lamivudine’s distinct mechanism of action opens the door for potential combination therapies.

Trial Design and Results

The clinical trial was led by Dr. Felipe Pereira and Dr. Eduardo Buchele Rodrigues at Universidade Federal de São Paulo in Brazil, in collaboration with Ambati. It involved two dozen adults with DME, who were randomized to receive either oral lamivudine or a placebo, followed by intraocular bevacizumab injections beginning at week four.

Key findings from the study, published in the journal Med, include:

       • After 4 weeks:

               • Lamivudine group improved by 9.8 letters on an eye chart (about two lines).

               • Placebo group declined by 1.8 letters.

       • After 8 weeks (4 weeks post-injection):

              • Lamivudine + bevacizumab group improved by 16.9 letters (more than three lines).

              • Placebo + bevacizumab group improved by only 5.3 letters.

These results suggest lamivudine may be effective alone or in combination with standard anti-VEGF therapies like bevacizumab.

Mechanism of Action and Future Directions

Lamivudine is believed to benefit DME patients by blocking inflammasomes—immune system components implicated in the development of retinal fluid accumulation. While inflammasomes play a protective role against infections, their activation has been linked to inflammation and disease progression in DME.

Ambati also introduced K9, a modified, safer version of lamivudine, which maintains inflammasome-inhibiting activity without the potential side effects of the original compound. “We are excited by the ongoing and planned clinical trials of K9 in DME as well,” he noted.

Broader Implications and Big Data Insights

Ambati’s research extends beyond DME. His prior work demonstrated that nucleoside reverse transcriptase inhibitors (NRTIs)—the class of drugs to which lamivudine belongs—may also reduce the risk of Alzheimer’s disease, diabetes, and macular degeneration, based on analysis of large health insurance databases. He refers to this data-driven approach as "Big Data Archaeology."

“A $20-a-month or even cheaper oral pill that improves vision as much as or more than therapy with injections into the eye that cost up to $2,000 per month could be transformative both for patients and the health care system,” Ambati said.

Reference:

Felipe Pereira et al, Oral lamivudine in diabetic macular edema: A randomized, double-blind, placebo-controlled clinical trial, Med (2025). DOI: 10.1016/j.medj.2025.100747