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

DRAFT
Capron, 1991; Terai et al., 1991; Laurent-Crawford et al., 1991). Recent reports indicate that
apoptosis occurs to a greater extent in HIV-infected individuals than in non-infected persons,
both in the peripheral blood and lymph nodes (Muro-Cacho et al., submitted for publication;
Ruxrungtham et al., 1994). It has also been observed that HIV infects precursors of CD4+ T
cells in the bone marrow and thymus, and damages the microenvironment of these organs
necessary for the optimal sustenance and maturation of progenitor cells (Schnittman et al.,
1990b; Stanley et al., 1992). These findings may help explain the lack of regeneration of the
CD4+ T cell pool in patients with AIDS (Fauci, 1993a).
Recent studies have demonstrated a substantial viral burden and active viral
replication in both the peripheral blood and lymphoid tissues even early in infection (Fox et al.,
1989; Coombs et al., 1989; Ho et al., 1989; Michael et al., 1992; Bagnarelli et al., 1992;
Pantaleo et al., 1993b; Embretson et al., 1993; Piatak et al., 1993). Taken together, these
studies strongly suggest that HIV has a central role in the pathogenesis of AIDS, either
directly or indirectly by triggering a series of pathogenic events that contribute to progressive
immunosuppression.
Defining the Role of HIV in AIDS
Koch's Postulates
Recent developments in HIV research provide some of the strongest evidence for the
causative role of HIV in AIDS and fulfill the classical postulates for disease causation
developed by Henle and Koch in the nineteenth century (Koch's postulates reviewed in Evans,
1976, 1989a; Harden, 1992). The development of DNA PCR has enabled researchers to
document the presence of cell-associated proviral HIV in virtually all patients with AIDS, as
well as in individuals in eariier stages of HIV disease (Kwok et al., 1987; Wages et al., 1991;
Bagasra et al., 1992; Bruisten et al., 1992; Petru et al., 1992; Hammer et al., 1993). RNA
PCR has been used to detect cell-free and/or cell-associated viral RNA in patients at all
stages of HIV disease (Ottmann et al., 1991; Schnittman et al., 1991; Aoki-Sei, 1992; Michael

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