AZT (zidovudine, Retrovir) is a common component of combination anti-HIV regimens. AZT was taken as a single drug treatment when there were no other treatments available for HIV. However, single drug therapy is no longer used because it is a weak treatment for HIV and leads to rapid development of drug resistance.

AZT should be taken in combination with at least two other anti-HIV drugs to suppress HIV in the blood to very low levels. However, AZT monotherapy is sometimes taken during pregnancy, to avoid the possible side-effects of other anti-HIV drugs, as a way of reducing the risk of HIV being passed on from mother to child.

AZT successfully crosses the blood-brain barrier and is effective against HIV in the brain and the central nervous system. AZT is active against HIV-1 and HIV-2.

AZT was licensed in March 1987 after trials showed that a dose of 1200mg per day reduced opportunistic infections and increased CD4 counts and survival among people with AIDS, when compared to placebo over 24 weeks^[1]. However, longer-term follow-up of this study failed to show a benefit of AZT over placebo^[2]. Later studies confirmed that the lower dose of 600mg per day resulted in similar anti-HIV effects but with less toxicity^[3].

Further studies tested AZT monotherapy among HIV-positive people without symptoms of AIDS. A 1989 placebo-controlled trial called ACTG 019, which enrolled 1338 asymptomatic patients with CD4 cell counts below 500 cells/mm³, found that in the short-term 500 or 1500mg AZT every day delayed progression to severe symptomatic disease or AIDS^[4]. A separate arm of the study compared the effects of AZT or a placebo for people with CD4 cell counts above 500 cells/mm³, finding no clinical benefit of starting AZT early, although AZT recipients did sustain a higher CD4 count than those given placebo^[5]. However, a subsequent study concluded that the reduction in quality of life brought about by AZT’s side-effects in this study approximately equalled the increase in quality of life associated with the delay in disease progression^[6].

The largest single study of AZT monotherapy in asymptomatic HIV infection, known as Concorde, suggested that there was no advantage in starting AZT before symptoms develop in the longer term. Almost 1750 participants were randomly assigned either to start taking 1000mg AZT a day in four doses, or to receive a placebo until they developed symptoms or until they chose to switch from trial capsules to open AZT because of falling CD4 cell counts. The results showed that after three years there was no detectable difference between immediate versus deferred use of AZT in terms of disease progression, development of AIDS or survival, but that the patients treated immediately had more severe side-effects^[7].

Numerous other studies examined the effect of AZT monotherapy at various doses and in patients at various stages of HIV infection throughout the late 1980s and early 1990s^{[8][9][10][11][12][13]}. A meta-analysis of 15 of these trials by the HIV Trialists’ Collaborative Group published in 1999 confirmed these controversial findings of the Concorde Study - that AZT does not increase a person’s chances of AIDS-free survival in the long-term, although it does reduce rates of disease progression in the short-term. However, these studies revealed that adding another NRTI delayed both disease progression and death, paving the way for combination therapy in the treatment of HIV infection^[14].