Thalidomide: A New Niche in HIV?

Mention thalidomide to a pharmacist who has been around for a few decades, and you may see a visible shudder. Prescribed in the 1960s to help people sleep, it was associated with some of the most severe — and notorious – teratogenicity in history. Never approved in the United States, almost all children with birth defects were born in other regions of the world.

In recent years, thalidomide and similar molecular entities have reentered the clinical milieu and have been approved for several indications. Its use in dermatologic conditions is noteworthy, especially in patients who have leprosy. When used in combination with dexamethasone, thalidomide is very effective for multiple myeloma.

Now, an editorial in the journal EBioMedicine discusses thalidomide’s potential as an HIV latency reversal agency. The authors discuss this small molecules’ immunomodulatory, anti-inflammatory, and antiangiogenic properties.

Traditionally contraindicated in individuals with HIV, thalidomide has utility in aphthous ulcers, gastrointestinal lesions, Kaposi sarcoma, and other HIV-associated developments.

HIV’s pathogenesis is often associated with immune activation and inflammation. Once these 2 conditions occur, CD4 T-cell loss accelerates. This known fact suggests that addressing HIV infection’s complications completely must include effective anti-inflammatory strategies. Thalidomide may be the one answer to that dilemma.

The editorial points to a study published in the same issue that hypothesizes that thalidomide may inhibit tumor necrosis factor-alpha, and that its mechanistic property may decrease HIV replication rates. This, subsequently, could reduce inflammation.

HIV proviral latency is a focus of global research efforts to cure HIV. Latency reversal agents are targeted strategies that increase immune clearance of latently-infected cells. Researchers call this a “shock and kill” care strategy.

Thalidomide has been considered contraindicated in HIV infection. This new information indicates that thalidomide may be safe and effective when used in individuals with HIV. However, current findings are limited by their open label design and small sample sizes. As with other indications for thalidomide, its use in HIV would be circumscribed by caution and precautions to prevent birth defects.

Reference

Vignesh R, Shankar EM. Thalidomide as a Potential HIV Latency Reversal Agent: Is It the Right Time to Forget the Ancestral Sins? EBioMedicine. 2017 Aug 30. pii: S2352-3964(17)30342-0. doi: 10.1016/j.ebiom.2017.08.025. [Epub ahead of print]