June 7, 2000
Recent developments in HIV/AIDS research have shown that HIV fulfills these criteria as the cause of AIDS.
1) 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 earlier 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 et al., 1992; Piatak et al., 1993) (Table 3).
|Table 3. Assays to Detect/Measure HIV Antibody-Positive Patients|
|Assay||% of Antibody-Positive Patients||CD4+ Range (Cells/mm3)||Viral Parameter Measured|
|Free viral antigen in serum or plasma|
|Immune-complexed viral antigen in serum or plasma|
|Infectious cell-free virus|
|Infectious cell-associated and amplifiable virus|
|Cell-associated proviral DNA|
|Cell-free and/or cell-associated viral RNA|
|Modified from Hammer et al., 1993.|
2) Improvements in co-culture techniques have allowed the isolation of HIV in virtually all AIDS patients, as well as in almost all seropositive individuals with both early- and late-stage disease (Coombs et al., 1989; Schnittman et al., 1989; Ho et al., 1989; Jackson et al., 1990).
1-4) All four postulates have been fulfilled in three laboratory workers with no other risk factors who have developed AIDS or severe immunosuppression after accidental exposure to concentrated HIVIIIB in the laboratory (Blattner et al., 1993; Reitz et al., 1994; Cohen, 1994c). Two patients were infected in 1985 and one in 1991. All three have shown marked CD4+ T cell depletion, and two have CD4+ T cell counts that have dropped below 200/mm3 of blood. One of these latter individuals developed PCP, an AIDS indicator disease, 68 months after showing evidence of infection and did not receive antiretroviral drugs until 83 months after the infection. In all three cases, HIVIIIB was isolated from the infected individual, sequenced, and shown to be the original infecting strain of virus.
In addition, as of Dec. 31, 1994, CDC had received reports of 42 health care workers in the United States with documented, occupationally acquired HIV infection, of whom 17 have developed AIDS in the absence of other risk factors (CDC, 1995a). These individuals all had evidence of HIV seroconversion following a discrete percutaneous or mucocutaneous exposure to blood, body fluids or other clinical laboratory specimens containing HIV.
The development of AIDS following known HIV seroconversion also has been repeatedly observed in pediatric and adult blood transfusion cases (Ward et al., 1989; Ashton et al., 1994), in mother-to-child transmission (European Collaborative Study, 1991, 1992; Turner et al., 1993; Blanche et al., 1994), and in studies of hemophilia, injection drug use, and sexual transmission in which the time of seroconversion can be documented using serial blood samples (Goedert et al., 1989; Rezza et al., 1989; Biggar, 1990; Alcabes et al., 1993a,b; Giesecke et al., 1990; Buchbinder et al., 1994; Sabin et al., 1993).
In many such cases, infection is followed by an acute retroviral syndrome, which further strengthens the chronological association between HIV and AIDS (Pedersen et al., 1989, 1993; Schechter et al., 1990; Tindall and Cooper, 1991; Keet et al., 1993; Sinicco et al., 1993; Bachmeyer et al., 1993; Lindback et al., 1994).