[Letter to Tema Luft from Anthony Fauci]

October 15, 1991
Ms. Tema Luft
AVEUs will be central to selecting candidate vaccines suitable for large scale
efficacy trials in uninfected individuals.
The AVEUs also conduct small studies of candidate vaccines in infected
individuals. These trials currently enlist HIV infected individuals with CD4+
T cell counts greater than 600. The exact criteria are determined on a
protocol-by-protocol basis and depend on information available on each
particular product. We believe that the clearest results will be obtained if
trial participants are not taking another antiretroviral therapy during the
course of the trial. The 600 cut-off is used so that even if the count drops
during the trial, the results will not be confused or made impossible to
understand by the need to place the participant on additional antiretroviral
therapy and/or remove the individual from the trial. In addition, vaccines
are designed to stimulate the immune system, which may be more quickly and
readily demonstrated in individuals with higher T cell counts.
The ACTG also conducts small phase I trials in infected individuals for the
purpose of determining safety and immunogenicity prior to evaluation of the
candidate vaccine in larger therapeutic efficacy trials. The ACTG has the
more appropriate infrastructure, experience and support for evaluating new
candidate therapies in infected individuals, particularly those with less
intact immune systems. The ACTG is currently evaluating one rgpl60
preparation in asymptomatic HIV-infected individuals. Plans to evaluate other
vaccine products both alone and in combination with antiretroviral therapy are
being formulated. The combination studies, in which the candidate vaccine is
administered in combination with a proven antiretroviral will be more
appropriate for individuals with CD4+ T cell counts less than 500. We are
committed to moving candidate vaccines into clinical trial in individuals with
lower CD4+ T cell counts as soon as possible after safety in individuals with
more intact immune systems has been established.
I must correct one incorrect impression stated in your letter. The NIAID does
not carry out placebo controlled trials of anti-retrovirals, including
candidate vaccines, in HIV-infected individuals with T cell counts lower than
400 and for whom effective therapies are known. In the case of trials of
candidate vaccines in HIV-infected individuals with counts above 400, we know
that antibody and immune cell levels in HIV-infected individuals can vary
considerably over the course of the disease. This makes it difficult to
determine if the vaccine is responsible of any observed change in immune
status. Placebo-controlled trials of candidate vaccines by far the most
reliable means by which to discern the true effect; if the participants have
counts above 400, we believe that it is ethically reasonable, since they are
not being denied proven effective therapy.
There are other novel antiretroviral therapies, including several nonnucleoside inhibitors of reverse transcriptase, undergoing clinical evaluation
within the ACTG system. In addition, several ACTG sites, including Johns
Hopkins University, also conduct clinical trials under direct company