[6] Serious side effects include liver problems, muscle damage, and high blood lactate levels.

This approach is referred to as Highly Active Antiretroviral Therapy (HAART) and is used to prevent the likelihood of HIV resistance.

[15] Before tenofovir, a principal part of the clinical pathway for both pre-exposure prophylaxis and post-exposure treatment of mother-to-child transmission of HIV during pregnancy, labor, and delivery and has been proven to be integral to uninfected siblings' perinatal and neonatal development.

Consistent and proactive precautionary measures, such as the rigorous use of antiretroviral medications, cesarean section, face masks, heavy-duty rubber gloves, clinically segregated disposable diapers, and avoidance of mouth contact will further reduce child-attendant transmission of HIV to as little as 1–2%.

[23] As this treatment was lengthy and expensive, it was deemed unfeasible in the Global South, where mother-to-child transmission was a significant problem.

Promising results from in vitro and in vivo studies showed the efficacy of AZT also against multidrug-resistant gram-negative bacteria (including mcr-1 carrying and metallo-β-lactamase producing isolates), especially in combination with other active agents (e.g. fosfomycin, colistin, tigecycline).

[26][27] Most common side effects include nausea, vomiting, acid reflux (heartburn), headache, cosmetic reduction in abdominal body fat, trouble sleeping, and loss of appetite.

[30] Anemia due to AZT was successfully treated using erythropoetin to stimulate red blood cell production.

[31][32] Drugs that inhibit hepatic glucuronidation, such as indomethacin, nordazepam, acetylsalicylic acid (aspirin) and trimethoprim decreased the elimination rate and increased the therapeutic strength of the medication.

AZT works by selectively inhibiting HIV's reverse transcriptase, the enzyme that the virus uses to make a DNA copy of its RNA.

Reverse transcription is necessary for production of HIV's double-stranded DNA, which would be subsequently integrated into the genetic material of the infected cell (where it is called a provirus).

[39] At sufficiently high dosages, AZT begins to inhibit the cellular DNA polymerase used by mitochondria to replicate, accounting for its potentially toxic but reversible effects on cardiac and skeletal muscles, causing myositis.

[62][63] Shortly thereafter, Samuel Broder, Hiroaki Mitsuya, and Robert Yarchoan of the United States National Cancer Institute (NCI) initiated a program to develop therapies for HIV/AIDS.

In June 1984, Burroughs-Wellcome virologist Marty St. Clair set up a program to discover drugs with the potential to inhibit HIV replication.

Burroughs-Wellcome had expertise in nucleoside analogs and viral diseases, led by researchers including George Hitchings, Gertrude Elion, David Barry, Paul (Chip) McGuirt Jr., Philip Furman, Martha St. Clair, Janet Rideout, Sandra Lehrman and others.

Based in part on these results, AZT was selected by nucleoside chemist Janet Rideout as one of 11 compounds to send to the NCI for testing in that organization's HIV antiviral assay.

It also showed that levels of AZT that worked in vitro could be injected into patients in serum and suppository form, and that the drug penetrated deeply only into infected brains.

The Anti-Infective Advisory Committee to United States Food and Drug Administration (FDA) voted ten to one to recommend the approval of AZT.

[71] The paucity of alternatives for treating HIV/AIDS at that time unambiguously affirmed the health risk/benefit ratio, with inevitable slow, disfiguring, and painful death from HIV outweighing the drug's side effect of transient anemia and malaise.

Until 1991, 80% of the $420 million allocated to the National Institute of Health's AIDS Clinical Trials Group, went toward studies of AZT.

Subsequently, Barr Laboratories and Novopharm Ltd. also challenged the patent, in part based on the assertion that NCI scientists Samuel Broder, Hiroaki Mitsuya, and Robert Yarchoan should have been named as inventors, and those two companies applied to the FDA to sell AZT as a generic drug.