AIDS 1995, Vol 9 No 3: 310-1 (Correspondence)
It has been indicated that it will take several years until ethically sound studies demonstrate a new microbicide to be both save and effective in reducing the risk of HIV transmission [1], with all the desirable properties (e.g., non-contraceptive, postcoital effective, appropriate for anal sex) for all women [single, married, commercial sex workers (CSW)]. The required sample size (and consequently time) increases even further when the non-linear relationship between reduction in risk per contact and resulting risk per year is taken into account [2], especially if the number of drop-outs are high. In the meantime, given the urgent need for female-controlled methods [3], we have to consider all methods currently available, even if they might not be appropriate for all types and frequencies of sexual activity.
Nonoxinol9 (N9) was first demonstrated to be effective against HIV in vitro in 1985 [4]. In 1988, however, a poster on a study on Nairobi CSW appeared to show that N9 might increase the risk of HIV transmission [5]. When the study was published in 1992 [6], it became clear that this interpretation might be misleading, because a verum sponge had been compared with a placebo suppository. Thus, the observed result may have been an artifact due to (1) participants in the placebo group using condoms more frequently, (2) hygienic problems due to the requirement of watering (and the possibility of reusing) the sponge, or (3) long-term release of an extremely high dose (1000 mg) of N9, especially when used daily by CSW. A recent study [7] has reconfirmed the original conjecture [8] that, if condom use is considered as a confounding factor, N9 reduces the risk of HIV transmission. Thus, for the intravaginal interaction between cells and microbicides, in vitro results correlate with in vivo efficacy.
N9 has been in use as a contraceptive for several decades and was approved by the US Food and Drug Administration for 'over the counter' (intravaginal) human use in 1980 [9]. When used in low doses (70-250 mg) and applied in a formulation that allows it to be discharged with semen and vaginal fluids after intercourse, vaginal flora recovers within 8 h [10]. No relevant side effects have been reported with typical vaginal [11] and in one case even rectal use [12]. Irritations caused by N9 are often due to otherwise inapparent sexually transmitted diseases (STD), so that, with adequate counseling, use of N9 may also result in more STD being treated. N9 has been demonstrated to stabilize vaginal flora and not to disturb vaginal pH [13,14]. With the findings of Feldblum and Weir [7], there is sufficient evidence to conclude that possible minor abrasions of the multi-layered exudative vaginal skin are more than compensated by the protective effect of the chemical barrier.
If N9 were less effective than condoms, but more simple to use, some couples might switch to N9 and consequently increase their risk of HIV infection. In 1989 [2], a mathematical model was used to assess the efficacy of mechanical and chemical barriers against HIV transmission from pregnancy data [10,14]. It was concluded that N9, when applied in a formulation that is simple to use (e.g., as a suppository), is at least comparable in its effectiveness to condoms. Another mathematical model [15] showed that compliance playes a more important role than method effectiveness in user efficacy. Both conjectures have been demonstrated to hold in vivo by two recent studies [7,16].
It has been indicated that most of the above evidence was accumulated in the mid-1980s [8] and that many women have become infected since because of 'poor decision making, political cowardice, … and studies being neither scientifically valid nor ethically sound' [17]. To avoid even more women becoming infected due to lack of knowledge on all prevention methods available, spermicides containing N9 should be recommended as one of many strategies to reduce the risk of HIV transmission at least under the following conditions: (1) if contraception is acceptable or even desired; (2) if the women has intercourse at a frequency (on the average) of less than once per day; (3) if it can be applied in the given climate (room temperature) and sanitary conditions (water); (4) if the amount of N9 per application does not exceed 250 mg; (5) if the formulation allows it to be discharged naturally from the vagina after intercourse; and (6) if the woman is advised to see a doctor in case she should experience an irritation.
There is a substantial proportion of women worldwide for whom the above conditions are fulfilled. For these women, safety and efficacy of N9 is proven beyond any reasonable doubt. Moreover (depending on the formulation), N9 is affordable, undetectable, easy to use (even with other contraceptives), and chemically stable (transport and storage). These women should not be denied access to prevention, just because more research on finding new methods needs to be performed.
Knut M. Wittkowski , Department of Medical Biometry, Eberhard-Karls-University, Westbahnhofstr. 55, D-72070 Tübingen, Germany,kmw@uni-tuebingen.de
Date of receipt: 5 September 1994; accepted: 25 November 1994
1. ELIAS CJ, HEISE LL: Challenges for the development of female-controlled vaginal microbicides. AIDS 1994, 8
2 . WITTKOWSKI KM Die Abschätzung der Effektivität von Barriere-Methoden zur HIV-Prophylaxe. (Assessing the effectivity of barrier methods for HIV prevention.) AIDS-Forschung 1989, 4
3 . STEIN ZA: Women helping themselves. X International Conference on AIDS, Yokohama, August 1994 [abstract PS5].
4 . HICKS Y, MARTIN LS, GETSCHELL JP ET AL. : Inactivation of HTVL-III/LAV-infected cultures of normal human lymphocates by nonoxynol-9 in vitro. Lancet 1985, ii
5 . KREISS J: Efficacy of the spermicide nonoxinol9 (N-9) in preventing heterosexual transmission of HIV. IV International Conference on AIDS. Stockholm, June 1988 [abstract 6525].
6 . KREISS J, NGUGI E, HOLMES KK ET AL. : Efficacy of nonoxinol9 contraceptive sponge use in preventing heterosexual acquisition of HIV in Nairobi prostitutes. JAMA 1992, 268
7 . FELDBLUM PJ, WEIR MA: The protective effect of Nonoxynol-9 against HIV infection. Am J Public Health 1994, 84
8 . WITTKOWSKI KM Über die Bedeutung von Detergentien für die HIV-Prophylaxe unter Heterosexuellen. (On the impact of detergents on HIV prevention strategies for heterosexuals). AIDS-Forschung 1988 3
9 . FOOD AND DRUG ADMINISTRATION: Vaginal contraceptive drug products for over-the-counter human use. Federal Register 1980, 45
10 . BREHM H, HAASE W: Die Alternative zur hormonalen Kontrazeption. Med. Welt 1975, 26
11 . GOLLUB E, STEIN Z: Nonoxynol-9 and the reduction of HIV transmission in women. AIDS 6
12 . VOELLER B: Nonoxynol-9 and prevention of sexual transmission of HTLV-III/LAV. In: OSTROW DG (ed.) Behavioural control of AIDS. New York: Irvington, 1987, 170-175
13 . LAPPE E: Mehr als ein Kontrazeptivum. Sexualmedizin 1986, 8
14 . DIMPFL J, SALOMON W, SCHICKETANZ KH: Die spermizide Barriere. Sexualmedizin 1984, 13
15 . WITTKOWSKI KM Preventing the heterosexual spread of AIDS: What is the best advice if compliance is taken into account? AIDS 1989 3
16 . ROSENBERG MJ, DAVIDSON AJ, CHEN HJ ET AL. : Barrier contraceptives and sexually transmitted diseases in women: a comparison of female-dependent methods and condoms. Am J Public Health 82
17 . POTTS M: The urgent need for a vaginal microbicide in the prevention of HIV transmission. Am J Public Health 1994, 84 :890-891
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