In the mid-1980s, the AIDS epidemic was a public health catastrophe characterized by high mortality and profound fear. Dr. Anthony Fauci became the Director of the National Institute of Allergy and Infectious Diseases (NIAID) in 1984, placing him at the center of the federal response to this unprecedented crisis. The disease, caused by the Human Immunodeficiency Virus (HIV), often led to death within months of diagnosis. Azidothymidine (AZT) was the first drug to show promise against HIV, and its development and approval under Fauci’s watch marked a dramatic turning point in the epidemic.
The Regulatory Context and Fauci’s Authority
The traditional process for drug approval through the Food and Drug Administration (FDA) often took many years. Given the immediate and life-threatening nature of AIDS, this slow pace was deemed unacceptable by affected communities and scientists. Fauci recognized that high mortality rates demanded an accelerated approach, placing NIAID in a coordinating role for federal research efforts.
This urgency led to new mechanisms designed to expedite treatment availability. One pathway was the Treatment Investigational New Drug (IND) status, which allowed unapproved drugs to be distributed outside of formal clinical trials to patients with life-threatening illnesses who had no other options. Fauci leveraged NIAID’s authority to champion these regulatory shifts, setting a precedent for prioritizing rapid action in public health emergencies.
Designing the Initial AZT Clinical Trials
NIAID and the pharmaceutical company Burroughs Wellcome structured the initial AZT trials, which began in 1986. The pivotal Phase II trial, known as BW 002, was a randomized, placebo-controlled study involving 282 people with AIDS or advanced HIV disease. Participants were randomly assigned to receive either AZT or a placebo over a planned 24-month period.
The trial was halted prematurely after just six months due to a clear difference in outcomes. Data showed that only one patient in the AZT group had died, compared to 19 patients in the placebo group, demonstrating a significant survival benefit. This efficacy led to the decision to stop the trial and grant all participants access to the drug. The FDA used these results to grant accelerated approval to AZT in March 1987, a remarkably fast timeline that prioritized speed over exhaustive long-term data collection.
Controversy and the Push for Immediate Access
Following its rapid approval, AZT became the subject of intense public debate and criticism. Patients soon discovered the drug’s high toxicity profile, including severe anemia and other debilitating side effects. Furthermore, Burroughs Wellcome held a monopoly on AZT, and its prohibitive cost made the drug inaccessible to many patients.
AIDS activist groups, most notably ACT UP (AIDS Coalition to Unleash Power), aggressively protested the drug’s price and restrictive trial designs. Activists argued that the scientific establishment, including Fauci and NIAID, was moving too slowly, resulting in unnecessary deaths. Fauci navigated this tension by opening communication with activist leaders, acknowledging their criticism of the slow bureaucratic process was valid.
This dialogue led Fauci to advocate for expanded access programs, such as the “parallel track” initiative. This concept provided investigational drugs to patients who could not enroll in conventional trials, without compromising the integrity of ongoing studies. Fauci’s willingness to collaborate with his critics helped redefine the relationship between government science, the pharmaceutical industry, and patient advocacy during the crisis.
Transitioning Beyond Monotherapy
The initial euphoria over AZT was short-lived as its limitations became apparent. The virus rapidly developed resistance to the drug when used alone, and its toxicity made long-term adherence difficult for patients. Fauci and NIAID quickly pivoted their research strategy to address the drug’s declining effectiveness.
NIAID’s AIDS Clinical Trials Group (ACTG) began extensive research into combination therapies, moving beyond the single-drug approach. Studies like ACTG 175 demonstrated that a two-drug regimen, combining AZT with another nucleoside reverse transcriptase inhibitor like didanosine (ddI) or zalcitabine (ddC), was significantly more effective than AZT monotherapy. This research laid the groundwork for the development of Highly Active Antiretroviral Therapy (HAART) in 1996, which combined AZT with two or more drugs, including a new class of protease inhibitors.