Epivir (also referred to as 3TC) and AZT are members of the nucleoside analogue class of drug compounds, which both interfere with the replication of HIV, the virus that causes AIDS.
The 3TC/AZT approval was based on data from four clinical trials enrolling approximately 1,000 HIV-infected adults who received either the combined 3TC/AZT therapy, 3TC as a single therapy, AZT as a single therapy, or AZT and ddC (Roche Company's anti-AIDS nucleoside analogue, which received accelerated approval in 1992).
The trials showed subjects treated with the 3TC/AZT combination sustained higher increases of CD4 cells than subjects on the other three regimens. On average, CD4 cell counts in subjects on the 3TC/AZT combination increased by 30 to 50 cells above the levels at the start of the 24-week trials.
Adverse effects were similar to those associated with other nucleoside analogue drugs: nausea, diarrhea, anemia, low white blood cells, pancreatitis (especially in children who had received prior nucleoside analogue therapy), and neuropathy. Some of the more severe adverse reactions required withdrawal from therapy.
3TC has been studied in humans since April 1991. Since October 1993, the drug has been available to subjects outside of controlled clinical trials under an open-label protocol. More than 35,000 subjects have received the drug under this expanded program, which allows access to promising drugs for serious diseases prior to marketing approval.
3TC was granted an accelerated approval, a regulatory mechanism which allows FDA to grant early marketing status for a product based on laboratory markers such as CD4 cell counts (a reflection of immune system strength) rather than on clinical endpoints such as delay in death or reduction in opportunistic infections. Clinical benefit must eventually be demonstrated for products receiving accelerated approval. Trials designed to demonstrate the clinical benefit of the 3TC/AZT treatment regimen are currently ongoing.