Montagnier, who was born at Chabris in France, was educated at the universities of Poitiers and Paris. He joined the Viral Oncology Unit of the Pasteur Institute in 1972 and was appointed professor of virology in 1985.

Montagnier's team at the Institute were searching for, among other things, possible links between cancers and retroviruses. The retroviruses had been described in 1970 by Temin and Baltimore and were distinguished from other viruses by having RNA rather than DNA genes. In early 1983 they were presented with a blood sample from a patient showing early signs of AIDS. Reverse transcriptase, an enzyme characteristic of retroviruses, was found in the blood. Montagnier sought to identify the virus. It was not HTLV-1, a retrovirus recently discovered by Robert Gallo, as serum from the AIDS patient did not react with samples of HTLV-1 provided by Gallo. The virus was found in T-4 cells, specialized lymphocytes of the immune system, and was therefore named LAV as an acronym for ‘lymphadenopathy associated virus’. Electron micrographs taken of LAV differed from those of HTLV-1.

Montagnier went on to develop a blood test for the presence of LAV. Antibodies to LAV were found in a number of patients with AIDS. As the sensitivity of the test increased, Montagnier was able to identify more and more AIDS patients and by October 1983 he was convinced that LAV was the cause of AIDS. By this time, however, Gallo had isolated a new retrovirus, HTLV-3, which he was equally convinced was the cause of AIDS. It was eventually agreed, despite some considerable initial controversy, that HTLV-3 and LAV were to all intents and purposes the same virus. In 1986 it was officially renamed HIV and the patent for HIV blood tests carried the names of both Gallo and Montagnier.

A further advance was made by Montagnier in late 1985 while examining blood samples from Guinea-Bissau in West Africa. He was puzzled by the fact that some of the samples came from apparently HIV-negative AIDS patients, even though they had been tested with a sensitive new probe. Montagnier resolved the issue by isolating a virus from the samples which differed from electronmicrographs of HIV-1. Montagnier named the virus HIV-2 and demonstrated that antibodies to the new virus were commonly found in blood samples from West African AIDS patients.