Original Article
A Controlled Trial of Nonoxynol 9 Film to Reduce Male-to-Female Transmission of Sexually Transmitted Diseases
N Engl J Med 1998; 339:504-510August 20, 1998
- Abstract
Background
Nonoxynol 9 is a proved spermicide, but whether it is also a microbicide is uncertain. A truly effective vaginal microbicide would reduce the susceptibility of women to sexually transmitted diseases, including infection with the human immunodeficiency virus (HIV).
Methods
We enrolled 1292 HIV-negative female sex workers in Cameroon in a double-blind, placebo-controlled study in which the participants were randomly assigned to use either a film containing 70 mg of nonoxynol 9 or a placebo film, inserted into the vagina before intercourse. All of the women were provided with latex condoms and were instructed to have their male sexual partners use them. At monthly follow-up visits, we examined the women with a colposcope for genital lesions, tested endocervical specimens for gonorrhea and chlamydia infection with DNA probes, tested for HIV infection, and treated the women for curable sexually transmitted diseases.
Results
The rates of HIV infection (cases per 100 woman-years) were 6.7 in the nonoxynol 9 group and 6.6 in the placebo group (rate ratio, 1.0; 95 percent confidence interval, 0.7 to 1.5). The rates of genital lesions were 42.2 cases per 100 woman-years in the nonoxynol 9 group and 33.5 in the placebo group (rate ratio, 1.3; 95 percent confidence interval, 1.0 to 1.6). The rates of gonorrhea were 33.3 and 31.1 cases per 100 woman-years in the nonoxynol 9 and placebo groups, respectively (rate ratio, 1.1; 95 percent confidence interval, 0.8 to 1.4). The corresponding rates of chlamydia infection in the nonoxynol 9 group and the placebo group were 20.6 and 22.2 cases per 100 woman-years (rate ratio, 0.9; 95 percent confidence interval, 0.7 to 1.3). The women reported that condoms were used during 90 percent of sexual acts.
Conclusions
The use of a nonoxynol 9 vaginal film did not reduce the rate of new HIV, gonorrhea, or chlamydia infection in this group of sex workers who used condoms and received treatment for sexually transmitted diseases.
Media in This Article
Figure 1
Progress of Women through the Study and Reasons for Discontinuation.Table 1
Selected Base-Line Characteristics Used to Assess Randomization in the Primary-Analysis Population.Article Activity
- Article
Nonoxynol 9 is a nonionic detergent that has been used as a spermicide since the 1950s. By disrupting the membranes of epithelial cells, bacteria, and viruses, nonoxynol 9 inactivates many sexually transmitted pathogens in vitro, including Neisseria gonorrhoeae, 1,2 Chlamydia trachomatis, 3-5 Haemophilus ducreyi, 6 Treponema pallidum, 1 Trichomonas vaginalis, 2 and the herpes simplex virus.5,7,8 Nonoxynol 9 appears to be moderately effective in vivo as prophylaxis against cervical infection by N. gonorrhoeae and C. trachomatis 9-12 and vaginal infection by T. vaginalis and the bacteria associated with bacterial vaginosis,13 providing a 25 percent reduction in the rate of infection.
Evidence from in vitro studies14-17 and animal models18,19 shows that nonoxynol 9 can inactivate the human immunodeficiency virus (HIV), but three clinical studies12,20,21 have had conflicting results. A randomized, controlled trial of the 1000-mg nonoxynol 9 vaginal sponge, conducted among 138 female sex workers in Kenya, was stopped early because of an increase in HIV infection among the users of the sponge (rate ratio, 1.6; 95 percent confidence interval, 0.8 to 2.8).12 This same study reported an increase in genital lesions and a decrease in cervical gonorrhea. A cohort study conducted among 273 female sex workers in Cameroon reported a lower rate of HIV infection among women who consistently used suppositories containing 100 mg of nonoxynol 9 than among those who used the suppositories less consistently (rate ratio, 0.1; 95 percent confidence interval, 0.1 to 0.6).20 A cohort study conducted among 110 couples in Zambia in which only the man was HIV-positive reported a crude rate ratio for HIV transmission of 0.5 (95 percent confidence interval, 0.1 to 3.8) among women who reported 100 percent use of nonoxynol 9 as compared with those who reported less than perfect use.21
We conducted a randomized, controlled trial to determine the effect of a film containing 70 mg of nonoxynol 9, inserted vaginally before intercourse, on the rate of sexually transmitted diseases, including HIV type 1, among women. This study was performed in the context of the current recommendations for prophylaxis against HIV infection: promotion of condom use by men and treatment of curable sexually transmitted diseases.
Methods
Study Participants
All participants were HIV-seronegative female sex workers residing in Yaoundé or Douala, Cameroon, who averaged at least four sexual partners per month; were between the ages of 18 and 45 years; were not known to be allergic to latex or nonoxynol 9; were not pregnant or desiring to become pregnant in the next year; and were willing to learn their HIV-test results. We asked each woman to return monthly for follow-up visits for at least one year.
Study Size
We anticipated an incidence of HIV of 10 cases per 100 woman-years in the placebo group after the promotion of condom use, on the basis of the previous cohort study in Cameroon.20 We estimated that 1000 women would need to be enrolled, given our assumptions of a rate ratio of 0.5 for HIV, 90 percent power to detect a 50 percent reduction in the rate of HIV infection, an alpha level of 0.05, a 20 percent loss to follow-up per year, a period of one year to recruit the cohort, and a period of at least one year of follow-up. For the study to have 90 percent power, 88 seroconversions would have to occur.
Study Procedures
Study recruiters invited potential participants to attend a session at the study clinic, during which the staff described the study requirements, conducted the HIV-testing consent process, gave pretest counseling, tested for HIV infection, and asked interested women to return in one month for study enrollment. At the return visit, each woman was given the results of her HIV test and post-test counseling. The HIV-negative women who consented to participate in the study proceeded to the base-line phase. The protocol and consent process were approved by the national ethics committee, the University of Yaoundé School of Medicine board in Cameroon, and an institutional review board at Family Health International; we obtained written informed consent from all the women for the initial determination of HIV serostatus and again one month later at enrollment.
Randomization
Family Health International produced randomization schedules, stratified according to clinic, using a computerized random-number generator to select permuted blocks of eight. The treatment-group assignments were concealed in sequentially numbered, sealed opaque envelopes. The envelopes were opened only after enrollment. The clerk at each clinic gave the assignment envelopes to the interviewer, who made the assignments. This method of randomization prevents bias in randomized, controlled trials.22
Blinding and Study Products
The study was double-blinded — that is, neither the women nor the study staff, including the biostatisticians from Family Health International, knew which group was using the nonoxynol 9 film. The nonoxynol 9 film contained 28 percent nonoxynol 9 (70 mg), glycerin, and polyvinyl alcohol. The placebo film contained glycerin, polyvinyl alcohol, and less than 2 percent polysorbate 60. The two films were identical in appearance, packaging, and labeling.
We chose film as the vehicle for nonoxynol 9 because it has characteristics that are likely to make it acceptable for widespread use — i.e., it is small (5 cm by 5 cm and paper thin), requires no applicator, is easy to use, dissolves in two to five minutes, and is not messy or affected by heat. The nonoxynol 9 film has been used as a spermicidal product for more than 15 years. We tested both films for in vitro inactivation of HIV. The nonoxynol 9 film inactivated HIV at a dilution of 0.035 percent but did not inactivate all the virus at 0.0035 percent. We do not know the concentration of nonoxynol 9 achieved in vaginal fluids when film is used during coitus; however, one study has found a concentration of 7 to 11 percent in vaginal fluid after application.23 The placebo film had no cell toxicity and did not inactivate HIV.
The condoms provided were made of latex, were not lubricated with spermicide, and were 52 mm wide and 180 mm long. We urged all the women to use a film and have their male partners use a condom with each coital act. If a condom could not be used, the women were instructed to use the film alone.
Data Collection
We collected information on demographic characteristics and base-line sexual behavior during the screening visit to the clinic. Information needed to assess the randomization process and potential confounders was collected one month later when the women were enrolled. This information included data on the women's history of sexually transmitted diseases, the frequency of intercourse according to type (oral, anal, or vaginal), condom and film use during vaginal intercourse, antibiotic use, method of contraception, blood transfusions, receipt of injections, and use of other vaginal agents (e.g., douches).
Questions about the women's sexual networks were designed to obtain information about types of sexual partners, such as new clients, regular clients, and nonclients, and about the use of condoms and nonoxynol 9 with these various types of partners. To enhance recall, the women were interviewed monthly. Pictorial coital logs recorded information on each episode of vaginal intercourse, including the type of sexual partner (client or nonclient), whether a condom or a film was used (or both), and whether the condom broke. An interviewer tallied the coital log monthly. The logs served as a counseling tool for condom and film use and indicated whether the use of condoms and film was similar in the two study groups. The logs were not reliable enough to be used to assess compliance with recommendations for the use of film and condoms.
We conducted an examination for genital ulcers, signs of genital irritation, and infections at the time of enrollment and at each monthly follow-up visit. We used colposcopes to examine the vulva, vagina, and cervix at each visit as a means of locating microulcerations. We focused on the areas of the vagina that were exposed to the highest concentrations of nonoxynol 9. We palpated the inguinal lymph nodes, inspected the vulva and perineum for lesions, and inspected the introitus, vagina, and cervix. We placed a swab from the vaginal pool in a test tube with a few drops of normal saline for preparation of a wet mount (saline and potassium hydroxide). We took a specimen from the endocervix for the gonorrhea and chlamydia DNA-probe tests and performed a bimanual pelvic examination.
The PACE 2 assay (Gen-Probe, San Diego, Calif.) was used to test for N. gonorrhoeae and C. trachomatis (sensitivity, 92 percent; specificity, 98 percent, as compared with culture for both organisms) and provided the information required for a diagnosis of cervical infection. A supplemental test to detect nonspecific signal was used to confirm positive results. The manufacturer of the PACE assay states that spermicide does not interfere with the assay.
We determined HIV serologic status by the sequential method (in which positive status requires two positive enzyme immunoassays followed by positive Western blot analysis).
Outcome Measures
The primary objectives of this clinical trial were to determine the effect of the nonoxynol 9 vaginal film on the rate of HIV infection, to measure its effect on the rate of genital ulcers, and to measure its effect on the rate of cervical gonorrhea and chlamydia infection. The measures used for determining the occurrence of infection were the crude incidence-density rates and the Kaplan–Meier estimates of the cumulative probability of the detection of HIV and other sexually transmitted diseases. All measures of effectiveness considered the time to the first evidence of infection.
Safety
The main issues of safety associated with the use of nonoxynol 9 are whether it increases the risk of HIV infection and, secondarily, whether it increases the incidence of breaks in the genital epithelium. The measures for determining the incidence of breaks in the genital epithelium were the crude incidence-density rates and the cumulative probability of lesions on the vulva, vagina, cervix, or any of the three sites.
Statistical Analysis
We used prevalence ratios to compare the base-line characteristics of the two groups. We used the log-rank statistic to test differences between the groups in Kaplan–Meier estimates of survival for the variables of time to a first event and study discontinuation. We calculated rate ratios using Cox proportional-hazards regression models, with the clinic site as a covariate. We performed all analyses on an intention-to-treat basis.
The population included in the primary analysis with respect to HIV consisted of all the HIV-negative women enrolled in the study who were randomly assigned to a treatment group and who had at least one additional HIV test. To be included in the gonorrhea, chlamydia, or genital-lesion analysis, a woman had to have been in the population included in the HIV primary analysis, not to have had the disease being analyzed at the time of her initial physical examination, and to have had a follow-up examination.
Interim Analysis
One interim analysis was conducted, and the results were presented to an independent data and safety monitoring board organized by the National Institute of Allergy and Infectious Diseases after one third of the total expected events had occurred. A two-sided log-rank test gave a critical value of 1.76 with a P value of 0.54. The Lan–DeMets24 spending function was used to determine that 0.004 of the type I error of 0.05 was spent on the interim analysis. The board recommended that the study continue.
Results
Randomization began in March 1994, and the last follow-up visits were conducted in December 1996. Of the 2290 women initially tested for HIV infection and interviewed, 1317 enrolled in the trial and received nonoxynol 9 or placebo film. Of the women not enrolled, 40 percent were HIV-positive, 51 percent did not return after screening, and 9 percent were excluded for other reasons. Among the randomized women, 25 were not clearly HIV-negative at enrollment, including 8 who were seropositive at screening, 15 who had seroconversion in the month between screening and enrollment, 1 who was not screened but was seropositive at enrollment, and 1 who was never tested. Of the 1292 women eligible for the study, 69 in the placebo group and 53 in the nonoxynol 9 group never returned for a follow-up HIV test. The remaining 1170 women (575 in the placebo group and 595 in the nonoxynol 9 group), who were HIV-negative at screening and enrollment and had at least one HIV test after enrollment, constituted the population for the primary analysis with respect to HIV.
Characteristics of the Study Participants at Base Line
Base-line characteristics were similar in the two groups (Table 1Table 1
Selected Base-Line Characteristics Used to Assess Randomization in the Primary-Analysis Population.). Other variables that were similar in the two groups included marital status (95 percent were unmarried in the nonoxynol 9 group, and 97 percent in the placebo group), whether the woman was living with a man (2 percent and 1 percent), use of medicine in the previous 30 days (12 percent and 11 percent), whether the woman ever practiced oral sex (24 and 27 percent) or anal sex (16 percent and 17 percent), whether the woman's male partners used a condom, and the numbers and types of sexual partners the woman had.The prevalence of sexually transmitted diseases at base line was similar in the nonoxynol 9 and placebo groups, and the percentage of women with genital ulcers at the time of physical examination in the two groups was similar. Eight percent of the women in the placebo group and 10 percent of those in the nonoxynol 9 group reported that they had contracted a sexually transmitted disease in the previous three months. No evidence suggests that the women excluded from the primary-analysis population or the women who withdrew from the study early were significantly different from those included in the HIV primary-analysis population.
Disposition of Study Participants
There were no differences according to treatment group in the number of women who completed follow-up or withdrew from the study. Withdrawal curves for the two treatment groups were similar (P=0.39), with about 73 percent of each group continuing in the study at 1 year and with a mean follow-up period of approximately 14 months. The number of women who withdrew from the study and the reasons for withdrawal from the study were similar in the two treatment groups (Figure 1Figure 1
Progress of Women through the Study and Reasons for Discontinuation.). There were three deaths, which were not related to study participation — one in the placebo group and two in the nonoxynol 9 group.Prospectively Measured Potential Confounding Factors
The women in the two groups were involved in about the same total number of coital acts during the course of the study (Table 2Table 2
Reported Use of Condoms and Films for Vaginal Sexual Acts during the Study, According to Type of Sexual Partner.). Condom use was reported for 90 percent of vaginal sexual acts and was slightly less common in the nonoxynol 9 group than in the placebo group. Condom and film use varied according to type of sexual partner. Film use without a condom was more likely to occur with nonclients (16 percent) than with clients (3 percent). The use of neither condoms nor film was more likely to occur with nonclients (6 percent) than with clients (1 percent).Nonvaginal Sexual Acts
The prevalence of oral and anal sex was similar in the two treatment groups. Eleven percent of the women in the placebo group reported ever having had oral sex, as compared with 10 percent of the women in the nonoxynol 9 group (one seroconversion was detected in each group among the women who had had oral sex). Six percent of the women in the placebo group and 5 percent of those in the nonoxynol 9 group reported ever having had anal sex (two seroconversions were detected in each group among these women). The number of seroconversions among the women reporting nonvaginal sex was small, as compared with the total number of seroconversions (6 of 94).
Effect on HIV, Gonorrhea, and Chlamydia
There were a total of 94 HIV seroconversions — 48 in the nonoxynol 9 group and 46 in the placebo group. The event rates in the two groups were almost identical (Table 3Table 3
Rates of HIV, Gonorrhea, and Chlamydia Infection in the Placebo and Nonoxynol 9 Groups.). The curves for HIV seroconversion for the two groups showed no divergence (P=0.85). Similar results were noted for gonorrhea and chlamydia, with virtually identical event rates in the two groups.Effect on Genital Lesions
The women in the nonoxynol 9 group were more likely to have genital lesions than those in the placebo group, although this difference was not significant (Table 4Table 4
Rates of Genital Lesions in the Placebo and Nonoxynol 9 Groups.). Most lesions were on the vulva and included excoriations, fissures, and ulcers. Genital lesions did not predict HIV seroconversion in this study. The HIV-infection rate per 100 woman-years in the placebo group was 5.9 among those with lesions and 5.0 among those without lesions. The HIV-infection rate for women in the nonoxynol 9 group was 5.0 among those with lesions and 5.3 among those without lesions.Blinding
We asked 126 staff members their opinions of which film was the placebo. Eighteen percent thought film A (the placebo) was the placebo, 13 percent thought film B (nonoxynol 9) was the placebo, and 69 percent had no opinion about which film was the placebo. Of the 68 peer educators (the staff members most likely to reflect the opinion of the participants), 16 percent thought film A was the placebo, 13 percent thought film B was the placebo, and 71 percent had no opinion.
Discussion
Nonoxynol 9 film did not give the women in this study any additional protection against infection with HIV, gonorrhea, or chlamydia beyond that provided by condoms and treatment for sexually transmitted diseases. Our instructions to the women were that the vaginal film should be used in addition to condoms for greater protection against sexually transmitted diseases; if a condom could not be used, the film should be used alone.25
Our results with respect to HIV infection are consistent with the findings of the only other randomized, controlled trial.12 However, we did not find that nonoxynol 9 provided protection against gonorrhea, as found in the earlier study. The previous study used the ratio of the number of events to the number of visits for each treatment group as the measure of effect. The number of events and person-years were not reported, so we cannot make a direct comparison with our results. This difference in outcome measures could account for some of the difference in the two findings regarding gonorrhea. The nonoxynol 9 sponge used in the earlier study may also act as a physical barrier that prevents N. gonorrhoeae from infecting the endocervix.
As expected, there was an increase in genital ulcers in the nonoxynol 9 group. As was the case in the sponge study,12 the majority of lesions were external rather than internal; the highest concentration of nonoxynol 9 is internal. However, in our study, the women who had genital ulcers did not have a higher rate of HIV infection, and there was no difference in the rate of infection between the women who had genital ulcers and used nonoxynol 9 and those who had genital ulcers and used placebo.
There are many possible reasons for the fact that the nonoxynol 9 film did not prevent sexually transmitted diseases. The film may not be the optimal formulation; nonoxynol 9 may not be an adequate microbicide; the women may not have used the product correctly or as frequently as necessary (every time as opposed to most of the time); or condoms may have been used too frequently to allow the nonoxynol 9 film to have a large effect. We believe that the women used the nonoxynol 9 film and that they used it correctly. We provided monthly counseling about how to use the product and held regular community meetings that dealt with problems of film use and demonstrated correct use. When asked, the women were able to explain how to use the film properly.
Although the women reported condom use more frequently than we had anticipated, HIV seroconversion still occurred in 94 women, which means that the study had a power of at least 90 percent to detect a 50 percent reduction in HIV infection with nonoxynol 9. Although a high rate of condom use may have attenuated the effect of nonoxynol 9, it is not likely to have reduced the effect to zero, as we found in this study. It is likely that condom use and film use were overreported in this study, as in many studies.26 We also found many more gonorrhea and chlamydia infections than HIV infections, and the study had a power of more than 90 percent to detect any effect on the incidence of these infections.
Three pieces of circumstantial evidence indicate that the women used the barrier methods. First, between the time we screened potential participants and the time we enrolled them, 15 women had seroconversion, a rate of 14 per 100 woman-years. The rate of seroconversion during the study was about 7 per 100 woman-years, indicating that the study intervention may have reduced the rate of HIV infection. Second, when we compared the women with a high rate of condom use (>75 percent) with those who had a low rate of condom use (≤50 percent), we found a rate ratio of 0.4, indicating some protection provided by the condom. Third, the increase in genital lesions in the nonoxynol 9 group may be evidence that the nonoxynol 9 was used.
The particular product we tested did not show evidence of protection against sexually transmitted diseases, but the results cannot be overly generalized. Other formulations of nonoxynol 9, as well as additional microbicidal compounds with different mechanisms of action, need to be tested as prophylaxis against these diseases. Barrier methods controlled by women are urgently needed, and the efforts of the research community to provide women with multiple means of protection against sexually transmitted diseases should increase.
Supported by grants from the Agency for International Development, the Mellon Foundation, and the National Institutes of Health (AI34714). The views expressed here do not necessarily reflect those of the funding agencies.
We are indebted to the members of the Cameroonian study staff who made the completion of this complex study possible for their willingness to work hard and try innovative approaches whenever problems arose; to the study participants for their great contribution and courage and for their willingness to submit to monthly examinations and interviews and use the film products despite knowing that some were using a placebo and that there was no guarantee that the nonoxynol 9 film would be protective; and to Dr. E. René Owona, Director of Community Health at the Ministry of Public Health, and Dr. Lazare Kaptué at the University of Yaoundé School of Medicine for their assistance and guidance.
Source Information
From the Epidemiology Unit (R.E.R., K.A.R., S.S.W.) and the Biostatistics Division (E.L.W.), Family Health International, Durham, N.C.; and the Ministry of Public Health, Yaoundé, Cameroon (L.Z., U.T.).
Address reprint requests to Mr. Roddy at Family Health International, P.O. Box 13950, Durham, NC 27709.
- References
References
1
Singh B ,Cutler JC ,Utidjian HMD . Studies on the development of a vaginal preparation providing both prophylaxis against venereal disease and other genital infections and contraception. II. Effect in vitro of vaginal contraceptive and non-contraceptive preparations on Treponema pallidum and Neisseria gonorrhoeae. Br J Vener Dis 1972;48:57-64
Medline2
Bolch OH Jr ,Warren JC . In vitro effects of Emko on Neisseria gonorrhoeae and Trichomonas vaginalis. Am J Obstet Gynecol 1973;115:1145-1148
Web of Science | Medline3
Benes S ,McCormack WM . Inhibition of growth of Chlamydia trachomatis by nonoxynol-9 in vitro. Antimicrob Agents Chemother 1985;27:724-726
Web of Science | Medline4
Kelly JP ,Reynolds RB ,Stagno S ,Louv WC ,Alexander WJ . In vitro activity of the spermicide nonoxynol-9 against Chlamydia trachomatis. Antimicrob Agents Chemother 1985;27:760-762
Web of Science | Medline5
Judson FN ,Ehret JM ,Bodin GF ,Levin MJ ,Rietmeijer CAM . In vitro evaluations of condoms with and without nonoxynol 9 as physical and chemical barriers against Chlamydia trachomatis, herpes simplex virus type 2, and human immunodeficiency virus. Sex Transm Dis 1989;16:51-56
CrossRef | Web of Science | Medline6
Jones BM ,Geary I ,Lee ME ,Duerden BI . Susceptibility of Haemophilus ducreyi to spermicidal compounds, in vitro. Genitourin Med 1991;67:268-269
Medline7
Singh B ,Posti B ,Cutler JC . Virucidal effect of certain chemical contraceptives on type 2 herpesvirus. Am J Obstet Gynecol 1976;126:422-425
Web of Science | Medline8
Asculai SS ,Weis MT ,Rancourt MW ,Kupferberg AB . Inactivation of herpes simplex viruses by nonionic surfactants. Antimicrob Agents Chemother 1978;13:686-690
Web of Science | Medline9
Roddy RE ,Schulz KF ,Cates W Jr . Microbicides, meta-analysis, and the N-9 question: where's the research? Sex Transm Dis 1998;25:151-153
CrossRef | Web of Science | Medline10
Louv WC ,Austin H ,Alexander WJ ,Stagno S ,Cheeks J . A clinical trial of nonoxynol-9 for preventing gonococcal and chlamydial infections. J Infect Dis 1988;158:518-523
CrossRef | Web of Science | Medline11
Niruthisard S ,Roddy RE ,Chutivongse S . Use of nonoxynol-9 and reduction in rate of gonococcal and chlamydial cervical infections. Lancet 1992;339:1371-1375
CrossRef | Web of Science | Medline12
Kreiss J ,Ngugi E ,Holmes KK , et al. Efficacy of nonoxynol 9 contraceptive sponge use in preventing heterosexual acquisition of HIV in Nairobi prostitutes. JAMA 1992;268:477-482
CrossRef | Web of Science | Medline13
Barbone F ,Austin H ,Louv WC ,Alexander WJ . A follow-up study of methods of contraception, sexual activity, and rates of trichomoniasis, candidiasis, and bacterial vaginosis. Am J Obstet Gynecol 1990;163:510-514
Web of Science | Medline14
Hicks DR ,Martin LS ,Getchell JP , et al. Inactivation of HTLV-III/LAV-infected cultures of normal human lymphocytes by nonoxynol-9 in vitro. Lancet 1985;2:1422-1423
CrossRef | Web of Science | Medline15
Polsky B ,Baron PA ,Gold JWM ,Smith JL ,Jensen RH ,Armstrong D . In vitro inactivation of HIV-1 by contraceptive sponge containing nonoxynol-9. Lancet 1988;1:1456-1456
CrossRef | Web of Science | Medline16
Malkovsky M ,Newell A ,Dalgleish AG . Inactivation of HIV by nonoxynol-9. Lancet 1988;1:645-645
CrossRef | Web of Science | Medline17
Rietmeijer CAM ,Krebs JW ,Feorino PM ,Judson FN . Condoms as physical and chemical barriers against human immunodeficiency virus. JAMA 1988;259:1851-1853
CrossRef | Web of Science | Medline18
Miller CJ ,Alexander NJ ,Gettie A ,Hendrickx AG ,Marx PA . The effect of contraceptives containing nonoxynol-9 on the genital transmission of simian immunodeficiency virus in rhesus macaques. Fertil Steril 1992;57:1126-1128
Web of Science | Medline19
Moench TR ,Whaley KJ ,Mandrell TD ,Bishop BD ,Witt CJ ,Cone RA . The cat/feline immunodeficiency virus model for transmucosal transmission of AIDS: nonoxynol-9 contraceptive jelly blocks transmission by an infected cell inoculum. AIDS 1993;7:797-802
CrossRef | Web of Science | Medline20
Zekeng L ,Feldblum PJ ,Oliver RM ,Kaptue L . Barrier contraceptive use and HIV infection among high-risk women in Cameroon. AIDS 1993;7:725-731
CrossRef | Web of Science | Medline21
Hira SK ,Feldblum PJ ,Kamanga J ,Mukelabai G ,Weir SS ,Thomas JC . Condom and nonoxynol-9 use and the incidence of HIV infection in serodiscordant couples in Zambia. Int J STD AIDS 1997;8:243-250
CrossRef | Web of Science | Medline22
Schulz KF ,Chalmers I ,Hayes RJ ,Altman DG . Empirical evidence of bias: dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA 1995;273:408-412
CrossRef | Web of Science | Medline23
Mauck CK ,Allen S ,Baker JM ,Barr SP ,Abercrombie T ,Archer DF . An evaluation of the amount of nonoxynol-9 remaining in the vagina up to 4 h after insertion of a vaginal contraceptive film (VCF) containing 70 mg nonoxynol-9. Contraception 1997;56:103-110
CrossRef | Web of Science | Medline24
Lan KKG ,DeMets DL . Discrete sequential boundaries for clinical trials. Biometrika 1983;70:659-663
CrossRef | Web of Science25
For women only: what women can do to protect themselves from AIDS. Albany: New York State Department of Health, 1994 (brochure).
26
Turner CF ,Miller HG . Zenilman's anomaly reconsidered: fallible reports, ceteris paribus, and other hypotheses. Sex Transm Dis 1997;24:522-527
CrossRef | Web of Science | Medline
- Citing Articles (132)
Citing Articles
1
Lindsay M Ferguson, Lisa Cencia Rohan. (2011) The importance of the vaginal delivery route for antiretrovirals in HIV prevention. Therapeutic Delivery 2:12, 1535-1550
CrossRef2
L A Lagenaur, B E Sanders-Beer, B Brichacek, R Pal, X Liu, Y Liu, R Yu, D Venzon, P P Lee, D H Hamer. (2011) Prevention of vaginal SHIV transmission in macaques by a live recombinant Lactobacillus. Mucosal Immunology 4:6, 648-657
CrossRef3
Do Won Hahn, John L. McGuire, Joachim Kuhnke. 2011. Contraception. .
CrossRef4
Rabeea F. Omar, Michel G. Bergeron. (2011) The future of microbicides. International Journal of Infectious Diseases 15:10, e656-e660
CrossRef5
C. G. Kelly, R. J. Shattock. (2011) Specific microbicides in the prevention of HIV infection. Journal of Internal Medicineno-no
CrossRef6
Leolin Katsidzira, James G. Hakim. (2011) HIV prevention in southern Africa: why we must reassess our strategies?. Tropical Medicine & International Health 16:9, 1120-1130
CrossRef7
Terence Hull, Adriane Martin Hilber, Matthew F. Chersich, Brigitte Bagnol, Aree Prohmmo, Jennifer A. Smit, Ninuk Widyantoro, Iwu Dwisetyani Utomo, Isabelle François, Nazarius Mbona Tumwesigye, Marleen Temmerman, on behalf of the WHO GSV. (2011) Prevalence, Motivations, and Adverse Effects of Vaginal Practices in Africa and Asia: Findings from a Multicountry Household Survey. Journal of Women's Health 20:7, 1097-1109
CrossRef8
Ayman Akil, Michael A. Parniak, Charlene S. Dezzutti, Bernard J. Moncla, Marilyn R. Cost, Mingguang Li, Lisa Cencia Rohan. (2011) Development and characterization of a vaginal film containing dapivirine, a non-nucleoside reverse transcriptase inhibitor (NNRTI), for prevention of HIV-1 sexual transmission. Drug Delivery and Translational Research 1:3, 209-222
CrossRef9
Salim S Abdool Karim, Barbra A Richardson, Gita Ramjee, Irving F Hoffman, Zvavahera M Chirenje, Taha Taha, Muzala Kapina, Lisa Maslankowski, Anne Coletti, Albert Profy, Thomas R Moench, Estelle Piwowar-Manning, Benoît Mâsse, Sharon L Hillier, Lydia Soto-Torres. (2011) Safety and effectiveness of BufferGel and 0.5% PRO2000 gel for the prevention of HIV infection in women. AIDS 25:7, 957-966
CrossRef10
Kevin K. Ariën, Vicky Jespers, Guido Vanham. (2011) HIV sexual transmission and microbicides. Reviews in Medical Virology 21:2, 110-133
CrossRef11
David R. Friend. (2010) Pharmaceutical development of microbicide drug products. Pharmaceutical Development and Technology 15:6, 562-581
CrossRef12
Kevin K Ariën, Guido Vanham. (2010) First real success for anti-HIV gel: a new start for HIV microbicides?. Future Microbiology 5:11, 1621-1623
CrossRef13
IM Poynten, F Jin, GP Prestage, JM Kaldor, S Kippax, AE Grulich. (2010) Defining high HIV incidence subgroups of Australian homosexual men: implications for conducting HIV prevention trials in low HIV prevalence settings. HIV Medicine 11:10, 635-641
CrossRef14
Z Mike Chirenje, Jeanne Marrazzo, Urvi M Parikh. (2010) Antiretroviral-based HIV prevention strategies for women. Expert Review of Anti-infective Therapy 8:10, 1177-1186
CrossRef15
Mélanie Caron, Guillaume Besson, Sonia Lekana-Douki Etenna, Armel Mintsa-Ndong, Spyridon Mourtas, Antonia Radaelli, Carlo De Giuli Morghen, Roberta Loddo, Paolo La Colla, Sophia G. Antimisiaris, Mirdad Kazanji. (2010) Protective properties of non-nucleoside reverse transcriptase inhibitor (MC1220) incorporated into liposome against intravaginal challenge of Rhesus Macaques with RT-SHIV. Virology 405:1, 225-233
CrossRef16
Gita Ramjee. (2010) Microbicide research: current and future directions. Current Opinion in HIV and AIDS 5:4, 316-321
CrossRef17
Paul J. Feldblum, Che-Chin Lie, Mark A. Weaver, Lut Van Damme, Vera Halpern, Adesina Adeiga, Rashidi Bakare, Jill Schwartz, Marissa Becker, Suniti Solomon. (2010) Baseline Factors Associated With Incident HIV and STI in Four Microbicide Trials. Sexually Transmitted Diseases1
CrossRef18
Salim S Abdool Karim. (2010) Results of effectiveness trials of PRO 2000 gel: lessons for future microbicide trials. Future Microbiology 5:4, 527-529
CrossRef19
C. M. Wetmore, L. E. Manhart, J. N. Wasserheit. (2010) Randomized Controlled Trials of Interventions to Prevent Sexually Transmitted Infections: Learning From the Past to Plan for the Future. Epidemiologic Reviews 32:1, 121-136
CrossRef20
José das Neves, Maria Helena Amaral, Maria Fernanda Bahia. 2010. Vaginal Drug Delivery. .
CrossRef21
Ian McGowan, Douglas J. Taylor. (2010) Heterosexual Anal Intercourse Has the Potential to Cause a Significant Loss of Power in Vaginal Microbicide Effectiveness Studies. Sexually Transmitted Diseases1
CrossRef22
Nancy S Padian, Sandra I McCoy, Jennifer E Balkus, Judith N Wasserheit. (2010) Weighing the gold in the gold standard: challenges in HIV prevention research. AIDS 24:5, 621-635
CrossRef23
Robert W. Buckheit, Karen M. Watson, Kathleen M. Morrow, Anthony S. Ham. (2010) Development of topical microbicides to prevent the sexual transmission of HIV. Antiviral Research 85:1, 142-158
CrossRef24
Poornima Chandran, Syed N Kabir. (2010) Dual action microbicides: reappraisal of their roles in contraceptive research. Reproductive BioMedicine Online 20:1, 103-113
CrossRef25
Devon J. Shedlock, Guido Silvestri, David B. Weiner. (2009) Monkeying around with HIV vaccines: using rhesus macaques to define 'gatekeepers' for clinical trials. Nature Reviews Immunology 9:10, 717-728
CrossRef26
De-Yu Chen, Li-Min Liu, Qing-Dong Xie, Lan Xu, Tian-Hua Huang. (2009) In vitro and in vivo studies evaluating antisemen antibodies as a potential spermicidal agent in hamsters. Fertility and Sterility 92:3, 1116-1123
CrossRef27
Priyankar Paira, Abhijit Hazra, Shrabanti Kumar, Rupankar Paira, Krishnendu B. Sahu, Subhendu Naskar, Pritam saha, Shyamal Mondal, Arindam Maity, Sukdeb Banerjee, Nirup B. Mondal. (2009) Efficient synthesis of 3,3-diheteroaromatic oxindole analogues and their in vitro evaluation for spermicidal potential. Bioorganic & Medicinal Chemistry Letters 19:16, 4786-4789
CrossRef28
Arthur J Ammann. (2009) Advances in HIV care and treatment in resource-poor countries. HIV Therapy 3:4, 329-338
CrossRef29
P Pala, V R Gomez-Roman, J Gilmour, P Kaleebu. (2009) An African perspective on mucosal immunity and HIV-1. Mucosal Immunology 2:4, 300-314
CrossRef30
Salim S Abdool Karim, Cheryl Baxter. (2009) PRO 2000: next steps for microbicide development. Future Virology 4:4, 317-320
CrossRef31
I Mary Poynten, Iona Y Millwood, Michael O Falster, Matthew G Law, David N Andresen, Lut Van Damme, John M Kaldor. (2009) The safety of candidate vaginal microbicides since nonoxynol-9: a systematic review of published studies. AIDS 23:10, 1245-1254
CrossRef32
Michele N. Austin, Lorna K. Rabe, Sharon L. Hillier. (2009) Limitations of the Dye-Based Method for Determining Vaginal Applicator Use in Microbicide Trials. Sexually Transmitted Diseases 36:6, 368-371
CrossRef33
Lisa Cencia Rohan, Alexandra B. Sassi. (2009) Vaginal Drug Delivery Systems for HIV Prevention. The AAPS Journal 11:1, 78-87
CrossRef34
Susan M. Graham, Prakesh S. Shah, Zoë Costa-von Aesch, Joseph Beyene, Ahmed M. Bayoumi. (2009) A Systematic Review of the Quality of Trials Evaluating Biomedical HIV Prevention Interventions Shows That Many Lack Power. HIV Clinical Trials 10:6, 413-431
CrossRef35
O. Heikinheimo, P. Lahteenmaki. (2008) Contraception and HIV infection in women. Human Reproduction Update 15:2, 165-176
CrossRef36
Blayne Cutler, Jessica Justman. (2008) Vaginal microbicides and the prevention of HIV transmission. The Lancet Infectious Diseases 8:11, 685-697
CrossRef37
Jared M. Baeten. (2008) New biomedical strategies for HIV-1 prevention in women. Current Infectious Disease Reports 10:6, 490-498
CrossRef38
David P Wilson, Paul M Coplan. (2008) Mathematical models and health economic aspects of microbicides. Current Opinion in HIV and AIDS 3:5, 587-592
CrossRef39
Joseph Romano, R Karl Malcolm, Sanjay Garg, Lisa C Rohan, Paulina E Kaptur. (2008) Microbicide delivery: formulation technologies and strategies. Current Opinion in HIV and AIDS 3:5, 558-566
CrossRef40
Nancy S Padian, Anne Buvé, Jennifer Balkus, David Serwadda, Ward Cates. (2008) Biomedical interventions to prevent HIV infection: evidence, challenges, and way forward. The Lancet 372:9638, 585-599
CrossRef41
Maryam Shahmanesh, Vikram Patel, David Mabey, Frances Cowan. (2008) Effectiveness of interventions for the prevention of HIV and other sexually transmitted infections in female sex workers in resource poor setting: a systematic review. Tropical Medicine & International Health 13:5, 659-679
CrossRef42
Myron S. Cohen, Nick Hellmann, Jay A. Levy, Kevin DeCock, Joep Lange. (2008) The spread, treatment, and prevention of HIV-1: evolution of a global pandemic. Journal of Clinical Investigation 118:4, 1244-1254
CrossRef43
Osmond J. D'Cruz, Fatih M. Uckun. (2008) Evaluation of local tolerance of the antiretroviral spermicide (WHI-07)-loaded gel-microemulsion in the porcine female reproductive tract. Journal of Applied Toxicology 28:3, 303-314
CrossRef44
Jocelyne Piret, Geneviève Laforest, Martin Bussières, Michel G. Bergeron. (2008) Subchronic (26- and 52-week) toxicity and irritation studies of a novel microbicidal gel formulation containing sodium lauryl sulfate in animal models. Journal of Applied Toxicology 28:2, 164-174
CrossRef45
Vera Halpern, Wes Rountree, Elizabeth G. Raymond, May Law. (2008) The effects of spermicides containing nonoxynol-9 on cervical cytology. Contraception 77:3, 191-194
CrossRef46
Michael J. Haas. (2008) New roadblock to HIV infection. Science-Business eXchange 1:3, 1-4
CrossRef47
Zeda F. Rosenberg, Mark Mitchnick, Paul Coplan. 2008. Vaginal Microbicides Against HIV. , 595-601.
CrossRef48
Michele Montandon, Nuriye Nalan Sahin-Hodoglugil, Elizabeth Bukusi, Kawango Agot, Brigid Boland, Craig R. Cohen. (2008) Sexuality, HIV risk and potential acceptability of involving adolescent girls in microbicide research in Kisumu, Kenya. Sexual Health 5:4, 339
CrossRef49
Janneke HHM van de Wijgert, Robin J Shattock. (2007) Vaginal microbicides: moving ahead after an unexpected setback. AIDS 21:18, 2369-2376
CrossRef50
Regine Sitruk-Ware, Vivian Brache, Robin Maguire, Horacio Croxatto, Narender Kumar, Sushma Kumar, Juan Carlos Montero, Ana Maria Salvatierra, David Phillips, Anibal Faundes. (2007) Pharmacokinetic study to compare the absorption and tolerability of two doses of levonorgestrel following single vaginal administration of levonorgestrel in Carraguard® gel: a new formulation for “dual protection” contraception. Contraception 75:6, 454-460
CrossRef51
Alexandra M. Minnis, Angella Muchini, Stephen Shiboski, Magda Mwale, Charles Morrison, Tsungai Chipato, Nancy S. Padian. (2007) Audio computer-assisted self-interviewing in reproductive health research: reliability assessment among women in Harare, Zimbabwe. Contraception 75:1, 59-65
CrossRef52
Zeda F Rosenberg, Annalene Nel, William Heyward, Mark Mitchnick. (2006) Microbicides for the prevention of HIV infection in women: an overview of recent trials. Current Opinion in HIV and AIDS 1:6, 514-519
CrossRef53
Janneke van de Wijgert, Heidi Jones. (2006) Challenges in Microbicide Trial Design and Implementation. Studies in Family Planning 37:2, 123-129
CrossRef54
Kenneth H Mayer, Lisa A Maslankowski, Fang Gai, Wafaa M El-Sadr, Jessica Justman, Antonia Kwiecien, Benoît Mâsse, Susan H Eshleman, Craig Hendrix, Kathleen Morrow, James F Rooney, Lydia Soto-Torres. (2006) Safety and tolerability of tenofovir vaginal gel in abstinent and sexually active HIV-infected and uninfected women. AIDS 20:4, 543-551
CrossRef55
David A Grimes, Laureen M Lopez, Elizabeth G. Raymond, Vera Halpern, Kavita Nanda, Kenneth F Schulz, Laureen M Lopez. 2005. Spermicide used alone for contraception. .
CrossRef56
Smita N. Joshi, Usha Katti, Sheela Godbole, Kapila Bharucha, Kishore Kumar B, Sangeeta Kulkarni, Arun Risbud, Sanjay Mehendale. (2005) Phase I safety study of Praneem polyherbal vaginal tablet use among HIV-uninfected women in Pune, India. Transactions of the Royal Society of Tropical Medicine and Hygiene 99:10, 769-774
CrossRef57
Fred C. Krebs, Shendra R. Miller, Mary Lee Ferguson, Mohamed Labib, Robert F. Rando, Brian Wigdahl. (2005) Polybiguanides, particularly polyethylene hexamethylene biguanide, have activity against human immunodeficiency virus type 1. Biomedicine & Pharmacotherapy 59:8, 438-445
CrossRef58
Bernard J. Moncla, Sharon L. Hillier. (2005) Why Nonoxynol-9 May Have Failed to Prevent Acquisition of Neisseria gonorrhoeae in Clinical Trials. Sexually Transmitted Diseases 32:8, 491-494
CrossRef59
Osmond J. D'Cruz, Fatih M. Uckun. (2005) Vaginal contraceptive activity of a chelated vanadocene. Contraception 72:2, 146-156
CrossRef60
Matthew R. Golden, Lisa E. Manhart. (2005) Innovative Approaches to the Prevention and Control of Bacterial Sexually Transmitted Infections. Infectious Disease Clinics of North America 19:2, 513-540
CrossRef61
Sharon L Hillier, Thomas Moench, Robin Shattock, Roberta Black, Patricia Reichelderfer, Fulvia Veronese. (2005) In Vitro and In Vivo. JAIDS Journal of Acquired Immune Deficiency Syndromes 39:1, 1-8
CrossRef62
Emelita L. Wong, Ronald E. Roddy, Heidi Tucker, Ubald Tamouf??, Kelley Ryan, Falimatou Ngampoua. (2005) Use of Male Condoms During and After Randomized, Controlled Trial Participation in Cameroon. Sexually Transmitted Diseases 32:5, 300-307
CrossRef63
Robert J Smith, Erin N Bodine, David P Wilson, Sally M Blower. (2005) Evaluating the potential impact of vaginal microbicides to reduce the risk of acquiring HIV in female sex workers. AIDS 19:4, 413-421
CrossRef64
Lisa E. Manhart, King K. Holmes. (2005) Randomized Controlled Trials of Individual‐Level, Population‐Level, and Multilevel Interventions for Preventing Sexually Transmitted Infections: What Has Worked?. The Journal of Infectious Diseases 191:s1, S7-S24
CrossRef65
Jonathan Weber, Kamal Desai, Janet Darbyshire, . (2005) The Development of Vaginal Microbicides for the Prevention of HIV Transmission. PLoS Medicine 2:5, e142
CrossRef66
Lut Van Damme. (2004) Clinical microbicide research: an overview. Tropical Medicine and International Health 9:12, 1290-1296
CrossRef67
Irving F Hoffman, Taha E Taha, Nancy S Padian, Clifton W Kelly, Julia D Welch, Francis E Martinson, Newton I Kumwenda, Zeda F Rosenberg, David A Chilongozi, Joelle M Brown, Michael Chirenje, Barbra A Richardson. (2004) Nonoxynol-9 100 mg gel. AIDS 18:16, 2191-2195
CrossRef68
Gustavo F. Doncel, Neelima Chandra, Raina N. Fichorova. (2004) Preclinical assessment of the proinflammatory potential of microbicide candidates. JAIDS Journal of Acquired Immune Deficiency Syndromes 37:Supplement 3, S174???S180
CrossRef69
Latifa Bousarghin, Antoine Touz
, Bernard Yvonnet, Pierre Coursaget. (2004) Positively charged synthetic peptides from structural proteins of papillomaviruses abrogate human papillomavirus infectivity. Journal of Medical Virology 73:3, 474-480
CrossRef70
Gustavo Doncel, Christine Mauck. (2004) Vaginal microbicides: A novel approach to preventing sexual transmission of HIV. Current HIV/AIDS Reports 1:1, 25-32
CrossRef71
Pai-Lien Chen, Hsiao-Chuan Tien. (2004) Semi-Markov Models for Multistate Data Analysis with Periodic Observations. Communications in Statistics - Theory and Methods 33:3, 475-486
CrossRef72
Meirav Apel-Paz, T Kyle Vanderlick, Neelima Chandra, Gustavo F Doncel. (2003) A hierarchy of lipid constructs for the sperm plasma membrane. Biochemical and Biophysical Research Communications 309:4, 724-732
CrossRef73
Karl Malcolm, David Woolfson, Julie Russell, Chris Andrews. (2003) In vitro release of nonoxynol-9 from silicone matrix intravaginal rings. Journal of Controlled Release 91:3, 355-364
CrossRef74
Tara Rithaporn, Manoj Monga, Mahadevan Rajasekaran. (2003) Curcumin: a potential vaginal contraceptive. Contraception 68:3, 219-223
CrossRef75
Stephen R. Tabet, Marianne M. Callahan, Christine K. Mauck, Fang Gai, Anne S. Coletti, Albert T. Profy, Thomas R. Moench, Lydia E. Soto-Torres, Alfred N. Poindexter, Ron G. Frezieres, Terri L. Walsh, Clifton W. Kelly, Barbra A. Richardson, Lut van Damme, Constance L. Celum. (2003) Safety and Acceptability of Penile Application of 2 Candidate Topical Microbicides: BufferGel and PRO 2000 Gel. JAIDS Journal of Acquired Immune Deficiency Syndromes 33:4, 476-483
CrossRef76
Anna M Foss, Peter T Vickerman, Lori Heise, Charlotte H Watts. (2003) Shifts in condom use following microbicide introduction. AIDS 17:8, 1227-1237
CrossRef77
Gordon Mansergh, Gary Marks, Melissa Rader, Grant N Colfax, Susan Buchbinder. (2003) Rectal use of nonoxynol-9 among men who have sex with men. AIDS 17:6, 905-909
CrossRef78
Kenneth H Mayer, Salim Abdool Karim, Clifton Kelly, Lisa Maslankowski, Helen Rees, Albert T Profy, Jennifer Day, Julie Welch, Zeda Rosenberg. (2003) Safety and tolerability of vaginal PRO 2000 gel in sexually active HIV-uninfected and abstinent HIV-infected women. AIDS 17:3, 321-329
CrossRef79
M.A. Kuyoh, C. Toroitich-Ruto, D.A. Grimes, K.F. Schulz, M.F. Gallo. (2003) Sponge versus diaphragm for contraception: a Cochrane review. Contraception 67:1, 15-18
CrossRef80
Naomi Low-Beer, Rhian Gabe, Sheena McCormack, Valerie S. Kitchen, Charles J. Lacey, Andrew J. Nunn. (2002) Dextrin Sulfate as a Vaginal Microbicide: Randomized, Double-Blind, Placebo-Controlled Trial Including Healthy Female Volunteers and Their Male Partners. JAIDS Journal of Acquired Immune Deficiency Syndromes 31:4, 391-398
CrossRef81
SHARON L. ACHILLES, PRIYA B. SHETE, KEVIN J. WHALEY, THOMAS R. MOENCH, RICHARD A. CONE. (2002) Microbicide Efficacy and Toxicity Tests in a Mouse Model for Vaginal Transmission of Chlamydia trachomatis. Sexually Transmitted Diseases 29:11, 655-664
CrossRef82
Lourens J.D Zaneveld, Robert A Anderson, Xiao-Hui Diao, Donald P Waller, Calvin Chany, Kenneth Feathergill, Gustavo Doncel, Morris D Cooper, Betsy Herold. (2002) Use of mandelic acid condensation polymer (SAMMA), a new antimicrobial contraceptive agent, for vaginal prophylaxis. Fertility and Sterility 78:5, 1107-1115
CrossRef83
David Wilkinson, Maya Tholandi, Gita Ramjee, George W Rutherford. (2002) Nonoxynol-9 spermicide for prevention of vaginally acquired HIV and other sexually transmitted infections: systematic review and meta-analysis of randomised controlled trials including more than 5000 women. The Lancet Infectious Diseases 2:10, 613-617
CrossRef84
A.J Quayle. (2002) The innate and early immune response to pathogen challenge in the female genital tract and the pivotal role of epithelial cells. Journal of Reproductive Immunology 57:1-2, 61-79
CrossRef85
Lut Van Damme, Gita Ramjee, Michel Alary, Bea Vuylsteke, Verapol Chandeying, Helen Rees, Pachara Sirivongrangson, Léonard Mukenge Tshibaka, Virginie Ettiègne-Traoré, Charn Uaheowitchai, Salim S Abdool Karim, Benoît Mâsse, Jos Perriëns, Marie Laga. (2002) Effectiveness of COL-1492, a nonoxynol-9 vaginal gel, on HIV-1 transmission in female sex workers: a randomised controlled trial. The Lancet 360:9338, 971-977
CrossRef86
Maureen A Kuyoh, Cathy Toroitich-Ruto, David A Grimes, Kenneth F Schulz, Maria F Gallo, Laureen M Lopez, Laureen M Lopez. 2002. Sponge versus diaphragm for contraception. .
CrossRef87
David Wilkinson, Gita Ramjee, Maya Tholandi, George W Rutherford, David Wilkinson. 2002. Nonoxynol-9 for preventing vaginal acquisition of HIV infection by women from men. .
CrossRef88
JENNIFER G. CLARKE, JEFFREY F. PEIPERT, SHARON L. HILLIER, WALTER HEBER, LORI BOARDMAN, THOMAS R. MOENCH, KENNETH MAYER. (2002) Microflora Changes With the Use of a Vaginal Microbicide. Sexually Transmitted Diseases 29:5, 288-293
CrossRef89
Kenneth F Schulz, David A Grimes. (2002) Blinding in randomised trials: hiding who got what. The Lancet 359:9307, 696-700
CrossRef90
David Wilkinson, Gita Ramjee, Maya Tholandi, George W Rutherford, David Wilkinson. 2002. Nonoxynol-9 for preventing vaginal acquisition of sexually transmitted infections by women from men. .
CrossRef91
Osmond J D'Cruz, Barbara Waurzyniak, Fatih M Uckun. (2002) Subchronic (13-week) toxicity studies of intravaginal administration of spermicidal vanadocene acetylacetonato monotriflate in mice. Toxicology 170:1-2, 31-43
CrossRef92
Christine Mauck, Gustavo Doncel. (2001) An update on vaginal microbicides. Current Infectious Disease Reports 3:6, 561-568
CrossRef93
Erica L. Gollub, Pamela French, Mary Latka, Carol Rogers, Zena Stein. (2001) Achieving Safer Sex with Choice: Studying a Women's Sexual Risk Reduction Hierarchy in an STD Clinic. Journal of Women's Health & Gender-Based Medicine 10:8, 771-783
CrossRef94
Osmond J. D’Cruz, Barbara Waurzyniak, Fatih M. Uckun. (2001) Subchronic (13-week) toxicity studies of intravaginal administration of spermicidal vanadocene dithiocarbamate in mice. Contraception 64:3, 177-185
CrossRef95
Thomas R. Moench, Tsungai Chipato, Nancy S. Padian. (2001) Preventing disease by protecting the cervix: the unexplored promise of internal vaginal barrier devices. AIDS 15:13, 1595-1602
CrossRef96
JOCELYNE PIRET, NATHALIE GAGN??, SYLVIE PERRON, ANDR?? D??SORMEAUX, MICHEL J. TREMBLAY, PIERRETTE GOURDE, RABEEA F. OMAR, AND MICHEL G. BERGERON. (2001) Thermoreversible Gel as a Candidate Barrier to Prevent the Transmission of HIV-1 and Herpes Simplex Virus Type 2. Sexually Transmitted Diseases 28:8, 484-491
CrossRef97
L. Morison, H. A. Weiss, A. Buvé, M. Caraël, S.-C. Abega, F. Kaona, L. Kanhonou, J. Chege, R. J. Hayes. (2001) Commercial sex and the spread of HIV in four cities in sub-Saharan Africa. AIDS 15, S61-S69
CrossRef98
Jonathan Weber, Andrew Nunn, Tim O'Connor, Don Jeffries, Valerie Kitchen, Sheena McCormack, Jim Stott, Neil Almond, Alan Stone, Janet Darbyshire. (2001) `Chemical condoms’ for the prevention of HIV infection: evaluation of novel agents against SHIV89.6PDin vitro and in vivo. AIDS 15:12, 1563-1568
CrossRef99
Samuel Baron, Joyce Poast, Derrick Nguyen, Miles W. Cloyd. (2001) Practical Prevention of Vaginal and Rectal Transmission of HIV by Adapting the Oral Defense: Use of Commercial Lubricants. AIDS Research and Human Retroviruses 17:11, 997-1002
CrossRef100
Kurt Barnhart, E.Scott Pretorius, Alan Stolpen, Daniel Malamud. (2001) Distribution of topical medication in the human vagina as imaged by magnetic resonance imaging. Fertility and Sterility 76:1, 189-195
CrossRef101
Sanjay Garg, Robert A Anderson, Calvin J Chany, Donald P Waller, Xiao Hui Diao, Kavita Vermani, Lourens J.D Zaneveld. (2001) Properties of a new acid-buffering bioadhesive vaginal formulation (ACIDFORM). Contraception 64:1, 67-75
CrossRef102
BARBRA A. RICHARDSON, LUDO LAVREYS, HAROLD L. MARTIN, CLAIRE E. STEVENS, ELIZABETH NGUGI, KISHORCHANDRA MANDALIYA, JOB BWAYO, JECKONIAH NDINYA-ACHOLA, JOAN K. KREISS. (2001) Evaluation of a Low-Dose Nonoxynol-9 Gel for the Prevention of Sexually Transmitted Diseases. Sexually Transmitted Diseases 28:7, 394-400
CrossRef103
Salim S. Abdool Karim. (2001) Clinical testing of microbicides: a global research priority. AIDS 15:7, 929-930
CrossRef104
Christopher Elias, Christiana Coggins. (2001) Acceptability Research on Female-Controlled Barrier Methods to Prevent Heterosexual Transmission of HIV: Where Have We Been? Where Are We Going?. Journal of Women's Health & Gender-Based Medicine 10:2, 163-173
CrossRef105
K. H. Mayer, J. Peipert, T. Fleming, A. Fullem, T. Moench, S. Cu-Uvin, M. Bentley, M. Chesney, Z. Rosenberg. (2001) Safety and Tolerability of BufferGel, a Novel Vaginal Microbicide, in Women in the United States. Clinical Infectious Diseases 32:3, 476-482
CrossRef106
Ronald E. Roddy. (2001) Up-date on microbicide clinical trials for the Microbicide 2000 Conference. AIDS 15, S12-S13
CrossRef107
Richard Marlink, Helen Kao, Evelyn Hsieh. (2001) Clinical Care Issues for Women Living with HIV and AIDS in the United States. AIDS Research and Human Retroviruses 17:1, 1-33
CrossRef108
Osmond J D’Cruz, Seang H Yiv, Barbara Waurzyniak, Fatih M Uckun. (2001) Contraceptive efficacy and safety studies of a novel microemulsion-based lipophilic vaginal spermicide. Fertility and Sterility 75:1, 115-124
CrossRef109
Michael E. Blocker, Myron S. Cohen. (2000) BIOLOGIC APPROACHES TO THE PREVENTION OF SEXUAL TRANSMISSION OF HUMAN IMMUNODEFICIENCY VIRUS. Infectious Disease Clinics of North America 14:4, 983-999
CrossRef110
Theodore M. Hammett, Giulia D. Norton, Theresa H. Mason, Stacia Langenbahn, Kenneth H. Mayer, Rafaela R. Robles, Rudy Feudo, George R. Seage. (2000) Drug-Involved Women as Potential Users of Vaginal Microbicides for HIV and STD Prevention: A Three-City Survey. Journal of Women's Health & Gender-Based Medicine 9:10, 1071-1080
CrossRef111
T. Kawamura, S. S. Cohen, D. L. Borris, E. A. Aquilino, S. Glushakova, L. B. Margolis, J. M. Orenstein, R. E. Offord, A. R. Neurath, A. Blauvelt. (2000) Candidate Microbicides Block HIV-1 Infection of Human Immature Langerhans Cells within Epithelial Tissue Explants. Journal of Experimental Medicine 192:10, 1491-1500
CrossRef112
Gita Ramjee, Neetha S. Morar, Michel Alary, Leonard Mukenge-Tshibaka, Bea Vuylsteke, Virginie Etti??gne-Traor??, Verapol Chandeying, Salim Abdool Karim, Lut Van Damme. (2000) Challenges in the conduct of vaginal microbicide effectiveness trials in the developing world. AIDS 14:16, 2553-2557
CrossRef113
O.A. Ladipo, Marcos P. De Castro, Lois C.C.T. Filho, Elsimer Coutinho, Donald P. Waller, Fred Cone, Lourens J.D. Zaneveld. (2000) A new vaginal antimicrobial contraceptive formulation: phase I clinical pilot studies. Contraception 62:2, 91-97
CrossRef114
Lawrence J. Severy, Jeffrey Spieler. (2000) New methods of family planning: Implications for intimate behavior. Journal of Sex Research 37:3, 258-265
CrossRef115
J. van de Wijgert, C. Elias, C. Ellertson, E. McGrory, K. Blanchard, B. Friedland, B. Winikoff, G. Brown. (2000) Condom promotion in microbicide trials. American Journal of Public Health 90:7, 1153-1154
CrossRef116
K. M. Wittkowski. (2000) Further thoughts about vaginal microbicide testing. American Journal of Public Health 90:7, 1155a-1156a
CrossRef117
Carol Tévi-Bénissan, Maria Makuva, Audrey Morelli, Marie-Claude Georges-Courbot, Mathieu Matta, Alain Georges, Laurent Bélec. (2000) Protection of Cynomolgus Macaque Against Cervicovaginal Transmission of SIVmac251 by the Spermicide Benzalkonium Chloride. Journal of Acquired Immune Deficiency Syndromes 24:2, 147-153
CrossRef118
Carol Tévi-Bénissan, Maria Makuva, Audrey Morelli, Marie-Claude Georges-Courbot, Mathieu Matta, Alain Georges, Laurent Bélec. (2000) Protection of Cynomolgus Macaque Against Cervicovaginal Transmission of SIVmac251 by the Spermicide Benzalkonium Chloride. JAIDS Journal of Acquired Immune Deficiency Syndromes 24:2, 147-153
CrossRef119
Johan Neyts, T. Kristmundsd
CrossRef120
Theodore M. Hammett, Theresa H. Mason, Carol L. Joanis, Susan E. Foster, Patricia Harmon, Rafaela R. Robles, H. Ann Finlinson, Rudy Feudo, Sandra Vining-Bethea, Garry Jeter, Kenneth H. Mayer, Paula Doherty-Iddings, George R. Seage. (2000) Acceptability of Formulations and Application Methods for Vaginal Microbicides Among Drug-Involved Women. Sexually Transmitted Diseases 27:2, 119-126
CrossRef121
M. Potts. (2000) Thinking about vaginal microbicide testing. American Journal of Public Health 90:2, 188-190
CrossRef122
Lut Van Damme, Verapol Chandeying, Gita Ramjee, Helen Rees, Pachara Sirivongrangson, Marie Laga, Jos Perriëns. (2000) Safety of multiple daily applications of COL-1492, a nonoxynol-9 vaginal gel, among female sex workers. AIDS 14:1, 85-88
CrossRef123
Eliana Amaral, Anibal Faúndes, Lourens Zaneveld, Donald Waller, Sanjay Garg. (1999) Study of the vaginal tolerance to acidform, an acid-buffering, bioadhesive gel. Contraception 60:6, 361-366
CrossRef124
Michael Gross, Connie L. Celum, Stephen R. Tabet, Clifton W. Kelly, Anne S. Coletti, Margaret A. Chesney. (1999) Acceptability of a Bioadhesive Nonoxynol-9 Gel Delivered by an Applicator as a Rectal Microbicide. Sexually Transmitted Diseases 26:10, 572-578
CrossRef125
Stephen R. Tabet, Christina Surawicz, Scott Horton, Mary Paradise, Anne S. Coletti, Michael Gross, Thomas R. Fleming, Susan Buchbinder, Rodger C. Haggitt, Howard Levine, Clifton W. Kelly, Connie L. Celum. (1999) Safety and Toxicity of Nonoxynol-9 Gel As a Rectal Microbicide. Sexually Transmitted Diseases 26:10, 564-571
CrossRef126
Fred C Krebs, Shendra R Miller, Daniel Malamud, Mary K Howett, Brian Wigdahl. (1999) Inactivation of human immunodeficiency virus type 1 by nonoxynol-9, C31G, or an alkyl sulfate, sodium dodecyl sulfate. Antiviral Research 43:3, 157-173
CrossRef127
Frank M Biro. (1999) New developments in diagnosis and management of adolescents with sexually transmitted disease. Current Opinion in Obstetrics and Gynecology 11:5, 451-455
CrossRef128
Markus J. Steiner, Willard Cates, Lee Warner. (1999) The Real Problem with Male Condoms Is Nonuse. Sexually Transmitted Diseases 26:8, 459-462
CrossRef129
Prashant S. Savle, Gustavo F. Doncel, Stephen D. Bryant, M. Patricia Hubieki, R. Graham Robinette, Richard D. Gandour. (1999) Acylcarnitine analogues as topical, microbicidal spermicides.. Bioorganic & Medicinal Chemistry Letters 9:17, 2545-2548
CrossRef130
Krystyn Z. Bourne, Nigel Bourne, Shirley F. Reising, Lawrence R. Stanberry. (1999) Plant products as topical microbicide candidates: assessment of in vitro and in vivo activity against herpes simplex virus type 2. Antiviral Research 42:3, 219-226
CrossRef131
Osmond J D’Cruz, Zhaohai Zhu, Seang H Yiv, Chun-Lin Chen, Barbara Waurzyniak, Fatih M Uckun. (1999) WHI-05, a novel bromo-methoxy substituted phenyl phosphate derivative of zidovudine, is a dual-action spermicide with potent anti-HIV activity. Contraception 59:5, 319-331
CrossRef132
KATHLEEN IRWIN, MARGARET SCARLETT, ROBIN MOSELEY. (1998) Observations from the CDC: The Urgent Need for New HIV/STD Prevention Options for Women. Journal of Women's Health 7:9, 1081-1086
CrossRef
