Heterosexual Transmission of HIV To the Editor. \p=m-\Thestudy by Padian et al1 of female-to-male transmission of human immunodeficiency virus (HIV) unfortunately did not consider specific sexual behavioral practices among the comparative cases of male-to-female transmission, even though examination of associated risk factors was said to be an objective. The only mention of anal intercourse was with regard to the one possible case of female-to-male transmission reported. The reader was left with the inference that all the comparative cases of male-to-female transmission occurred through vaginal intercourse because it was not stated otherwise. However, Dr Padian herself was the lead author in an earlier report2 in JAMA on male-to-female transmission of HIV in which anal intercourse specifically was considered and was found to discriminate significantly between seronegative and seropositive women to the extent that women who engaged in this practice were 2.3 times more likely to acquire infection than women who did not. Another study3 in JAMA on high-risk behavior among college students found that anal intercourse had been en¬ gaged in at least once by a greater percentage of coitally active women than men, 18.6% compared with 14.3%. Given these previous findings, it would have been helpful if Padian et al had again considered the prevalence of anal intercourse among the cases of male-to-female transmission in their current study instead of dismissing the female cases' infection routes with the brief sentence, "Detailed results from [their] group have been presented elsewhere." What would be most helpful in the future would be a comparative study of the relative efficiency of heterosexual transmission among men and women who practice only vaginal intercourse, if such a discriminate study is possible. Anal intercourse only confounds the issue for both genders.

Stephen E. Godfrey,

MD

St Peters, Mo

1. Padian NS, Shiboski SC, Jewell NP. Female-to-male transmission of human immunodeficiency virus. JAMA. 1991;266:1664-1667. 2. Padian N, Marquis L, Francis DP, et al. Male-to-female transmission of human immunodeficiency virus. JAMA. 1987;258:788-790. 3. MacDonald NE, Wells GA, Fisher WA, et al. High-risk STD/HIV behavior among college students. JAMA. 1990;263:3155-3159.

To the Editor.\p=m-\Diversecellular and immune factors in sexual fluids and the coital environment have been postulated to influence the sexual transmission of HIV type 1.1 The differences between male-to-female and female-to-male transmission that were documented recently by Padian et al2 suggest to us that an additional coital factor, vaginal pH, could also significantly influence the sexual transmission of HIV. Free virus and/or infected lymphocytes and macrophages (principal host cells for HIV) are thought to be the infectious Edited by Drummond Rennie, MD, Deputy Editor (West), and Bruce B. Dan, MD, Senior Editor.

unit(s) transmitted during coitus. Each can be found in semen

and in vaginal secretions of HIV-infected individuals. Free virus and lymphocytes are both inactivated at low pH, as illustrated in the Figure. For free virus, inactivation occurs within minutes.3 Vaginal secretions from healthy reproductive\x=req-\ aged women are characteristically acidic (pH values of 3.4 to 6.0) and thus present a hostile environment for HIV particles and infected lymphocytes. For this reason, it is probable that vaginal titers of infectious virus are much lower than serum titers in infected women. This could explain the low rate of HIV transmission from women to men. Vaginal pH is higher (less toxic to HIV and lymphocytes) in postpartum, postmenopausal, and menstru¬ ating women, as well as in women with vaginal bleeding or bacterial vaginosis.4 Women could be more infectious to sex¬ ual partners under these conditions. The situation is very different when one considers HIV transmission from an infected man. Normal semen is slightly alkaline (pH value of 7.0 to 8.0), which is the optimal pH condition for survival of HIV particles and infected cells. Furthermore, semen has a stronger buffering effect than vaginal secretions, and after ejaculation, the pH of the vagina increases rapidly to 7.0 or higher.5 Thus, women are exposed to seminal HIV and infected cells at optimal pH conditions for transmission to occur. Furthermore, the vagina is exposed to HIV deposited at coitus for a considerably longer period than the penis. These factors could explain the higher relative risk of HIV transmission from men to women. The buffering effect of semen in the vagina, which preserves HIV infectiousness, could also increase the risk of transmission from women to sub¬ sequent sexual partners, as postulated by Padian et al.2 In conclusion, the usually low vaginal pH could help explain the infrequency of transmission of HIV from women to men, and elevated vaginal pH may be associated with HIV trans¬ mission to men. Variation in vaginal pH might also contribute to the range in susceptibility to HIV reported among women. These observations underscore the need for further research in this area and the development of buffered, low pH sper-

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