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(Plummer et al., 1991; Nyange et al., 1994). Although the magnitude of the increased risk of transmission attributable to genital ulcers in these studies was expressed as risk ratios ranging from 3.3 to 4.7, Hayes and others (1995) have estimated that genital ulcer disease may increase the per exposure risk of transmission by a factor of 10 to 50 for male-to-female transmission and by a factor of 50 to 300 for female-to-male transmission. Boily and Anderson (1996) also have recently demonstrated that published cohort studies are very likely to underestimate the true magnitude of the increased risk of sexual transmission of HIV conferred by other STDs. Some of these studies have also found that gonorrhea of the cervix (Plummer et al., 1991; Laga et al., 1993; Nyange et al., 1994), chlamydial infection of the cervix (Laga et al., 1993) and vaginal trichomoniasis (Laga et al., 1993), all increase the risk of subsequent HIV infection. Although Laga and others initially reported no increase in HIV infection following genital ulcer disease among female sex workers (Laga et al., 1993), a later study involving the same study population did find such an association (Laga et al., 1994).
In the United States, the multi-center AIDS cohort study found no association between herpes simplex virus type 2 antibody and subsequent HIV infection among men who have sex with men (Kingsley et al., 1990). However, an earlier retrospective cohort study in gay men found that herpes simplex virus type 2 infection was a risk factor for HIV infection (Holmberg et al., 1988). In addition, a study of heterosexual men attending an STD clinic in New York showed that men presenting with chancroid were more likely to become infected with HIV than were men presenting with other STDs (Telzak et al., 1993).
Explaining the Association Between STDs and HIV Infection
The above prospective studies establish the temporal relationship of exposure to STD prior to HIV infection. The observed associations between STDs and HIV infection are compatible with three possible explanations, other than the confounding factors addressed by the study designs:
STDs increase infectivity of HIV. Persons who have both an STD and HIV infection may be more likely to transmit HIV to others due to the effects of the STD on HIV infectivity, such as increased shedding of HIV.
STDs increase susceptibility to HIV. Persons with an STD may be more susceptible to a subsequent exposure to HIV, since the STD may compromise the mucosal or cutaneous surfaces of the genital tract that normally act as a barrier against HIV.
The association between STDs and HIV remains confounded by sexual behavior and/or by immune suppression in persons with sexually acquired HIV. HIV-infected persons may be more likely than uninfected persons to have another STD due to high-risk sexual behavior or because HIV-related immune suppression predisposes to active STD (e.g., by reactivating genital ulcers or by