The Relationship between the Human Immunodeficiency Virus and the Acquired Immunodeficiency Syndrome (Draft)

DRAFT
Cross-sectional studies in adults and children have shown that levels of infectious HIV
or proviral DNA in the blood are substantially higher in patients with AIDS than in
asymptomatic patients (Ho et al., 1989; Coombs et al., 1989; Saag et al., 1991; Srugo et al.,
1991; Michael et al., 1992; Aoki-Sei et al., 1992). In both blood and lymph tissues from HIVinfected individuals, researchers at the National Institutes of Healths found viral burden and
replication to be substantially higher in patients with AIDS than in early-stage patients
(Pantaleo et al., 1993b). This group also found deterioration of the architecture and
microenvironment of the lymphoid tissue to a greater extent in late-stage patients than in
asymptomatic individuals. The dissolution of the follicular dendritic cell network of the lymph
node germinal center and the progressive loss of antigen-presenting capacity are likely critical
factors that contribute to the immune deficiency seen in individuals with AIDS (Pantaleo et al.,
1993b).
More recently, the same group studied eight long-term non-progressors, defined as
individuals infected for more than seven years (usually more than 10 years) who received no
antiretroviral therapy and showed no decline in CD4+ T cells. They found that viral burden
and viral replication in the peripheral blood and in lymph nodes, measured by DNA and RNA
PCR, respectively, were at least one log lower than in 20 HIV-infected individuals whose
disease progression was more typical. In addition, the lymph node architecture in long-term
non-progressors remained intact (Pantaleo et al., 1994). Levels of virus in the plasma of nonprogressors are much lower than those seen in patients with disease progression (Pantaleo et
al., 1994; Ho, 1994).
Longitudinal studies also have quantified viral burden and replication in the blood and
their relationship to disease progression (Schnittman et al., I1990a; Connor et al., 1993;
Connor and Ho, 1 994a; Saksela et al., 1994). In asymptomatic HIV-infected patients who
ultimately develop rapidly progressive disease, the number of CD4+ T cells in which HIV DNA
can be found increases over time, whereas this does not occur in patients with stable disease

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