Background. The reverse-transcriptase inhibitor
lamivudine has in vitro synergy with zidovudine
against the human immunodeficiency virus (HIV). We
studied the activity and safety of lamivudine plus zidovudine
as compared with either drug alone as treatment for
patients with HIV infection, most of whom had not previously
received zidovudine.
Methods. Three hundred sixty-six patients with 200
to 500 CD4+ cells per cubic millimeter who had received
zidovudine for four weeks or less were randomly assigned
to treatment with one of four regimens: 300 mg of
lamivudine every 12 hours; 200 mg of zidovudine every
8 hours; 150 mg of lamivudine every 12 hours plus zidovudine;
or 300 mg of lamivudine every 12 hours plus zidovudine.
The study was double-blind and lasted 24
weeks, with an extension phase for another 28 weeks.
Results. Over the 24-week period, the low-dose and
high-dose regimens combining lamivudine and zidovudine
were associated with greater increases in the
CD4+ cell count (P=0.002 and P=0.015, respectively)
and the percentage of CD4+ cells (P<0.001 for both)
and with greater decreases in plasma levels of HIV type
1 (HIV-1) RNA (P<0.001 for both) than was treatment
with zidovudine alone. Combination therapy was also
more effective than lamivudine alone in lowering plasma
HIV-1 RNA levels and increasing the percentage of
CD4+ cells (P<0.001 for all comparisons), and these advantages
persisted through 52 weeks. Adverse events
were no more frequent with combination therapy than
with zidovudine alone.
Conclusions. In HIV-infected patients with little or no
prior antiretroviral therapy, treatment with a combination
of lamivudine and zidovudine is well tolerated over a oneyear
period and produces more improvement in immunologic
and virologic measures than does treatment with either
agent alone. (N Engl J Med 1995;333:1662-9.