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JAIDS Journal of Acquired Immune Deficiency Syndromes:
Epidemiology and Social Science

Safety, Acceptability, and Potential Efficacy of a Topical Penile Microbicide Wipe

Taha, Taha E MBBS, PhD*; Kumwenda, Newton PhD*; Mwakomba, Albert MBBS†; Mwenda, Robin MS‡; Kawonga, Harry CO§; Gaydos, Charlotte DrPH∥; Hoover, Donald PhD¶; Kafulafula, George MBBS, FCOG#

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From the *Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD; †Nchalo Sugar Estate, Malawi; ‡Queen Elizabeth Central Hospital, Blantyre, Malawi; §Johns Hopkins University College of Medicine Research Project, Blantyre, Malawi; ∥Johns Hopkins University School of Medicine, Baltimore, MD; ¶Department of Statistics, Rutgers University, New Brunswick, NJ; and #University of Malawi College of Medicine, Blantyre, Malawi.

Received for publication April 26, 2004; accepted October 7, 2004.

Partially funded by the Johns Hopkins University Fogarty International Center, National Institutes of Health, HIV/AIDS Training and Research Program (grant # D43-TW00010).

Reprints: Taha E. Taha, Rm. E7138, Department of Epidemiology, Infectious Diseases Program, Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205 (e-mail: ttaha@jhsph.edu).

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Summary: Innovative, low-cost, and acceptable measures are needed to reduce sexually transmitted infections (STIs) including HIV. Use of a topical microbicide wipe for penile cleaning before and after sex might be effective in preventing STIs. However, evaluation of this simple method has not been done. Two studies were conducted in Malawi to determine the safety, acceptability, and potential efficacy of a benzalkonium chloride topical penile microbicide wipe. The first study was a phase 1 dose-escalating clinical trial among low-risk circumcised or uncircumcised HIV-negative men. The second study was a pilot before-after efficacy study among uncircumcised HIV-negative or -positive men. In the first study 24 circumcised and 27 uncircumcised men were enrolled. During the entire study period, 18 adverse events (AEs) were reported, and 3 AEs were confirmed by physical examination. Acceptability concerns did not increase with dose escalation, and adherence to use of the wipe ranged from 89%-95%. In the second study, 27 men were enrolled. Gram stain and culture tests showed significant reductions in frequency of several organisms after use of the wipe, including STI-associated bacteria. This penile wipe is safe, acceptable, and can decrease the frequency of penile colonization with microorganisms. The clinical relevance remains to be determined in larger clinical trials.

The World Health Organization estimates that 28.5 million adults and children are currently living with HIV/AIDS in sub-Saharan Africa, accounting for >70% of the world's burden of infection.1 Malawi, a land-locked country of 12 million inhabitants in southeast Africa, has experienced an HIV epidemic, with approximately 15% of the adult population being infected.1 Studies among economically active men working at the Nchalo Sugar Estate (SUCOMA) in southern Malawi showed that HIV prevalence was 24.3% in 1994 and 21.0% in 1998. HIV incidence during 1998-1999 was 3.8% among men enrolled in a follow-up study. Sexually transmitted infections (STIs) were the most important risk factors associated with HIV infection.2,3

The results of these studies emphasized the urgent need for intervention measures to control HIV infection in this occupational setting. The choice of an appropriate intervention, however, requires careful considerations. Community-based STI interventions in Mwanza, Tanzania,4 and Rakai, Uganda5 have produced mixed results. Previous studies in Malawi also showed that the frequency of male condom use was low and inconsistent.6 Therefore, other innovative preventive measures to reduce risk of HIV infection are necessary. These measures should be simple, affordable, and sustainable.

We hypothesized that cleaning the genitals using a simple topical wipe saturated in a microbicide could be effective in reducing HIV and STI infections by physically (and chemically) removing infectious secretions. Such a measure could be more acceptable and adopted as a general hygienic practice. Use of soap and water as prophylaxis to control STIs was practiced in the past and has been suggested to limit genital ulcer disease and HIV infection in sub-Saharan Africa.7 We conducted preliminary studies of penile cleaning using a commercially available benzalkonium chloride (BZK 0.4%) topical microbicide wipe to determine safety, acceptability, and potential efficacy.

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Two pilot studies were conducted in Malawi to evaluate the feasibility and bactericidal/virucidal activity of a commercially available wipe.

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Study 1

A phase 1 clinical trial was conducted to determine dose frequency (escalating frequency) and tolerance of a topical penile wipe (BZK 0.4% with water: BZK antiseptic towelette, professional disposable international (PDI)) among low-risk men (defined as being HIV negative and in a self-reported stable monogamous sexual relationship) working at the Nchalo Sugar Estate in Malawi. The study was unblinded and any changes were compared with characteristics at baseline.

We planned to enroll at least 36 (18 circumcised and 18 uncircumcised) sexually active male volunteers aged 15-59. After providing written informed consent at the initial screening visit (visit 0), men were counseled, examined, and HIV tested. HIV testing was performed using a rapid test (Determine HIV 1/2, Abbott Laboratories, Tokyo, Japan) first and confirmed with a Wellcozyme enzyme-linked immunosorbent assay (ELISA) HIV test (Murex Biotech, Dartford, Kent, UK). All volunteers were pre- and posttest counseled. Inclusion criteria were ability and willingness to provide informed consent, being HIV negative, having had only 1 reported female sexual partner during the past 6 months, being free of STIs, willingness to allow female partner to be interviewed, and expecting to be sexually active during the period of the study. Exclusion criteria were inability or unwillingness to give informed consent, being HIV positive, having multiple sexual partners or STIs, and unwillingness to allow female partner to be interviewed.

Eligible men were interviewed and examined at enrollment after 1 week from screening (visit 1) (Table 1). This was followed by 2 weeks (weeks 1 and 2) of no wipe use to determine baseline prevalence of genital symptoms and signs. At the end of weeks 1 and 2 (at visit 3), an interview and a physical examination were conducted. During the subsequent 2 weeks (weeks 3 and 4) the wipe was used before and after each act of sexual intercourse. The average frequency of intercourse is 3-5 times per week in Malawi; therefore a 2-week period of observations with a lower frequency (use of the wipe only before and after sex) was considered adequate to detect potential adverse effects before proceeding to a higher dose. These first 2 weeks represented a lead-in control period. During weeks 5 and 6 the dose was increased to once-daily use of the wipe, and during weeks 7 and 8 the dose was again increased to twice daily (in the morning and afternoon); these once- and twice-daily doses were in addition to using the wipe before and after any sexual act.

Table 1
Table 1
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Biweekly evaluations (during weeks 3-4, 5-6, and 7-8) consisted of an interview regarding adherence and symptoms of local irritation (eg, pain, pruritis, dysuria, dyspareunia). At the end of each biweekly visit (visits 5, 7, and 9), the penis was examined including the shaft, glans, meatus, and foreskin (if present) by the naked eye and by using a hand-held magnifying glass. Evidence of inflammation (erythema, ulceration, discharge, etc.) was recorded. Urine was also collected for leukocyte esterase dipstick (LED) test to detect urethral inflammation at enrollment and subsequent biweekly visits (Table 1). Female partners were interviewed at visits 5, 7, and 9 to assess potential genital symptoms.

Acceptability interviews were completed at weeks 5, 7, and 9 among all men. At these time points their female partners were also interviewed to assess acceptability. Characteristics related to the product such as ease of use, confidentiality, sensory characteristics, ease of disposal of the product, timeliness of performing the wipe (before and after intercourse), and behavioral use factors were investigated. The questions were structured and coded on a scale to capture variable responses.

The primary outcomes of this phase 1 study were participant reports of urethral pain, burning, itching, rash, or ulceration; erythema (with or without induration), vesiculation, bullous reaction, and ulceration, of the penile shaft, foreskin, or glans, as determined by physical examination; erythema or ulceration of the urethral meatus, as determined by physical examination; other adverse events (AEs) judged to be related to product use; and acceptability outcomes, based on index and partner perceptions of ease of product use, actual use, and any positive and negative features associated with the wipe. To assess adherence, participants were issued a predetermined number of wipes at each visit and asked upon return whether exact instructions of wipe use were followed.

Routine clinical care was provided including referral, if necessary. Participants were instructed to wash off using water for any immediate reactions following cleaning with the wipe. All participating men and their female partners were adequately informed that unscheduled visits were allowed. No incentives were given to participate in the study. A nominal compensation (about US $3) was provided at each visit to reimburse for transportation or time spent in the clinic.

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Study 2

Study 2 was a before-after efficacy study that recruited male volunteers attending the STI clinic at the Queen Elizabeth Central Hospital in Blantyre. The aim of this pilot study was to assess the potential efficacy of the BZK wipe (the same wipe used in study 1 in reducing the frequency of microorganisms underneath the foreskin and at urethral meatus. Uncircumcised men, 12 HIV positive and 12 HIV negative, were enrolled after obtaining a signed informed consent. Enrollment was based on the results of a rapid HIV test (Determine HIV 1&2 Abbott Laboratories, Tokyo, Japan); men were counseled to return the following week to be recounseled about the results of a confirmatory HIV test (Wellcozyme ELISA HIV test; Murex Biotech, Dartford, Kent, UK). Participants were not provided incentives; however, transportation costs were reimbursed (about US $2-3). Enrollment criteria were age 15-59 years, ability to give an informed written consent, and willingness to be tested for HIV. Men who were not able to give consent and men with obvious genital ulcers were excluded. Multiple swabs (4 swabs before cleaning and 4 swabs after cleaning with the wipe) were obtained from each individual. The swabs were collected from the inner surface of the foreskin. To account for variability in distribution of microorganisms, 2 swabs were collected from the dorsal and 2 from the ventral surfaces of the penis. Wet microscopy, Gram stain, and culture were performed on 2 swabs collected from the dorsal and ventral surfaces of the penis. This was done on swabs collected before and after cleaning the foreskin, shaft, glans, and meatus with the wipe. These tests were performed at the local laboratory in Blantyre to detect microbial agents such as staphylococci, streptococci, Corynebacteria, Neisseria, Candida, and Trichomonas. In addition to detection of microorganisms before and after swabbing, these agents were quantified (graded) and given a score of 0, 1+, 2+, 3+, or 4+; 0 indicated no organisms being detected while 4+ indicated the highest score, suggesting predominance of bacteria or maximum growth. The laboratory tests performed in this study followed conventional standard microbiologic procedures. The other 2 swabs collected from the dorsal and ventral surfaces before and after wiping were stored for polymerase chain reaction (PCR; multiplex DNA PCR) testing in the United States (Dr. C. Gaydos and T. Quinn Laboratories, Johns Hopkins University School of Medicine, Baltimore, MD) for detection of herpes simplex virus type-2 (HSV-2), syphilis (Treponema pallidum), chancroid (Haemophilus ducreyi), HIV, and human papilloma virus (HPV). A sample of 12 HIV-positive and 12 HIV-negative individuals was not based on a previous estimate because we did not know, a priori, the rate of penile carriage of these agents before and after wiping. Our intent was to determine whether this simple wipe has an immediate effect on any of these agents.

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Data Analysis

Statistical analyses of both studies were mostly descriptive and qualitative. In study 1, all analyses were stratified by circumcision status. The frequency of primary outcomes after use of the wipe was compared with frequency at baseline (during the 2 weeks of no product use). In study 2, the results are presented as before and after penile cleaning with the wipe. In study 2 the findings were similar in HIV-infected and uninfected men, and therefore combined figures are presented. Likewise, in study 2 there were no differences between samples obtained from the dorsal and ventral surfaces of the penis, and therefore combined before and after results are shown. McNemar test was used for paired binary variables to test within-group baseline and follow-up differences in study 1 and between before and after cleaning differences in study 2. The Gram stain and culture results scores in study 2 were considered a continuous variable. For this variable, a nonparametric Wilcoxon signed rank test (which compensates for tied values) was used for testing any differences between before and after outcomes.

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Study Approvals

These studies were approved by institutional review boards in Malawi and the United States: the Malawi College of Medicine Research and Ethics Committee, and the Johns Hopkins University Bloomberg School of Public Health Committee on Human Research. Individuals with STIs (and their partners) were provided appropriate treatment (including partners) and were requested to return for follow-up.

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In study 1, 169 men volunteered to participate based on sensitization talks provided at different working places within the Nchalo Sugar Estate and therefore gave consent and were screened. Of these, 86 were not eligible based on the exclusion criteria (eg, they were HIV positive, reported multiple sexual partners, or had STIs; none was excluded for inability to provide written informed consent). Of the 83 men that were eligible, 51 were consecutively enrolled. The total enrolled (51 men) was adequate to satisfy sample size requirements and was considered logistically feasible to follow up over the study period. Of these, 24 were circumcised and 27 were uncircumcised. The demographic characteristics of the men who were enrolled are shown in Table 2. There were no statistically significant differences between circumcised and uncircumcised men; exceptions were significantly higher level of education among uncircumcised men and more Muslims compared with Christians being circumcised.

Table 2
Table 2
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Of the 24 circumcised men, 22 completed weeks 1 and 2 of no wipe use, 20 completed weeks 3 and 4 of wipe use before and after sex, 19 completed weeks 5 and 6 of wipe use with sex plus once-daily regimen, and 18 completed weeks 7 and 8 of wipe use with sex plus twice-daily regimen. Therefore, 18 circumcised men completed all visits. Of the 27 uncircumcised men, 26 completed weeks 1 and 2 of no wipe use, 23 completed weeks 3 and 4 of wipe use before and after sex, 21 completed weeks 5 and 6 of wipe use with sex plus once-daily regimen, and the same 21 men completed weeks 7 and 8 of wipe use with sex plus twice-daily regimen. Therefore, 21 uncircumcised men completed all visits. None was discontinued because of an AE.

Table 3 shows the frequency of reported and physical examination-based AEs in study 1. Throughout the study 18 AEs were reported: 7 among circumcised men and 11 among uncircumcised men. Of these reported AEs, 16 complained of cold/wet sensation after cleaning with the wipe, 1 complained of a burning sensation, and 1 complained of a rash. These complaints were described as “sometimes.” However, only 3 AEs were detected by physical examination during the study: 2 cases of rash on the shaft and 1 case of vesicles on the shaft. None of these events was statistically significant when compared with baseline events. During the entire study period 4 men had a positive LED test, 1 during weeks 3-4 and 3 during weeks 7-8, all among uncircumcised men.

Table 3
Table 3
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Acceptability of the wipe was determined at the biweekly visits in study 1. Among the circumcised men, during weeks 3-4, 5-6, and 7-8, 5% (1/19), 15% (3/19), and 11% (2/18), respectively, reported some acceptability concerns. Among the uncircumcised men, during the same period of weeks 3-4, 5-6, and 7-8, respectively, 32% (7/22), 14% (3/22), and 14% (3/21) reported similar acceptability problems. The concerns reported were difficulty of disposing the wipe, difficulty of carrying the wipe, partner felt sexual pleasure was interrupted, disliked the way wipe felt, more communication problems with use of the wipe, and not liking the smell of the wipe. Among the female partners (mean age 31 years), only 1 partner of a circumcised man reported having experienced genital itching during weeks 3-4 of the study. Two female partners, one of a circumcised man and the other of an uncircumcised man, reported that their male partners did not use the wipe before or after sexual intercourse; these nonadherence reports were during weeks 3-4 of the study. There were no reports of nonadherence during weeks 5-6 or 7-8 of the trial.

We also assessed adherence with use of the wipe before and after sexual intercourse in study 1. Among both the circumcised and uncircumcised men adherence was high. Among the circumcised men the rates of adherence during weeks 3-4, 5-6, and 7-8, respectively, were 95% (19/20), 90% (17/19), and 89% (16/18). Among the uncircumcised men the rates of adherence during weeks 3-4, 5-6, and 7-8, respectively, were 91% (21/23), 95% (20/21), and 95% (20/21).

In study 2 conducted in the STI clinic at Queen Elizabeth Central Hospital in Blantyre, 328 men attended the STI clinic during the days when study information was presented in a general health talk. Of these men, 113 were not willing to participate, 125 were not eligible, and 90 were eligible. Of those eligible, 27 men were enrolled, all were uncircumcised, 13 were HIV positive, and 14 were HIV negative, and their mean age was 29 years (range 18-51 years). On wet mount examination of 27 swabs collected from both the ventral and dorsal surfaces of the penis, the following results were obtained: no Trichomonas vaginalis organisms were detected either before or after cleaning with the wipe; yeastlike organisms were detected in 2 swabs (7.4%) collected before wiping and none after wiping; polymorphonuclear cells (PMNCs) were detected in 12 swabs (44%) before wiping and 4 (15%) after wiping (P = 0.01); and epithelial cells were detected in all 27 swabs (100%) before wiping and in 25 swabs (93%) after wiping.

In study 2, the Gram stain and culture results were graded from 0-4+ to show the quantity of microorganisms detected. Table 4 shows that for most of the Gram-positive and -negative cocci and the Gram-positive and negative bacilli listed, more grade 4+ and 3+ Gram stain scores were detected before cleaning with the wipe than after cleaning with the wipe. These differences before and after cleaning with the BZK wipe were statistically significant for almost all organisms detected. Likewise, based on culture as shown in Table 5, more organisms were detected before cleaning with the wipe (ie, more extensive growth) than after cleaning with the wipe (more no growth [score of 0] or minimal growth [score of 1]). Several of these differences were statistically significant.

Table 4
Table 4
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Table 5
Table 5
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The multiplex PCR testing showed that 2 (15%) of the 13 HIV-positive individuals in study 2 had HIV DNA detected in the swabs before using the wipe and none detected after cleaning with the wipe. HPV DNA was detected in 6 samples before cleaning with the wipe, and after cleaning with the wipe, 3 of the 6 samples were still positive. All samples, before and after cleaning with the wipe, were negative on multiplex PCR DNA testing for H. ducreyi, T. pallidum, and HSV-2 (with the exception of 1 sample that tested positive for H. ducreyi both before and after cleaning with the wipe).

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In 2 studies we assessed the safety, acceptability, and potential efficacy of a simple, commercially available, topical microbicide wipe (BZK 0.4%). BZK is a surfactant antiseptic with ability to inactivate HIV and other STIs in vitro.8,9 It is widely available and was reported to be safe in an earlier phase 2 trial among African women who used vaginal suppository of 1% BZK disinfectant.10 We chose a wipe that included only 0.4% BZK and water and that excluded alcohol and fragrance to avoid dryness and possible irritation of the penile skin. Our intention was to physically remove any infectious materials from the surface of the penis as well as from underneath the prepuce (if uncircumcised).

The phase 1 clinical trial we conducted showed that this wipe was safe and acceptable. In addition, neither toxicity nor acceptability concerns increased with increasing frequency of use of the wipe. For example, as shown in Table 3 there were very few physical examination-confirmed AEs during a period of use of about 8 weeks (1 AE among circumcised and 2 AEs among uncircumcised men). Most of the reported AEs were minimal in magnitude and transient. More acceptability concerns were reported with the lowest regimen of before-after use than with higher regimens of daily applications. The high rates of adherence (range 89%-95%) throughout the trial also suggest that the wipe is acceptable. Female partners also did not report major safety concerns (only 1 woman complained of itching), and their reports of having seen the wipe being used appear to corroborate male reports of high adherence with use of the wipe.

In addition to these reassuring safety and acceptability data from the phase 1 clinical trial, the laboratory results from the second study are encouraging. In the pilot study conducted among volunteers from the STI clinic, the aim was to provide limited data on the short-term efficacy of the BZK wipe we evaluated for safety and acceptability among men recruited from the communities at the sugar estate in Nchalo. Presence of microorganisms before application of the wipe and their disappearance (or reduction in frequency) immediately after wiping provide preliminary evidence of short-term bactericidal/virucidal efficacy. As shown by microscopy, culture, and DNA testing (Tables 4 and 5), there were significant reductions in the carriage rate of several organisms. Of most interest is that organisms that can cause STIs such as Neisseria gonorrhoeae were seen prior to cleaning with the wipe and were significantly reduced after cleaning with the BZK 0.4% wipe (Table 5). Some of these bacteria can cause wound infection if there is skin laceration or trauma due to sexual activity. In addition to facilitating entry of HIV through breaks in the skin, inflammation due to these microorganisms might attract HIV target cells, increasing the chances of being infected. In this study few individuals had a positive urine LED test, and in a substantial number of men PMNCs were detected before cleaning with the wipe; these might suggest genitourinary inflammation. The frequency of PMNCs was significantly reduced after cleaning with the BZK wipe (44% before cleaning and 12% after cleaning, P = 0.01). We also note that the frequencies of some viral infections (HIV and HPV) were lower after cleaning with the wipe. However, the numbers are too limited to draw any firm conclusions.

The goal of these studies was to provide preliminary data that will advance our knowledge of safety, acceptability, and efficacy to implement a randomized phase 3 clinical trial of a topical microbicide penile wipe to reduce male HIV acquisition. Among uncircumcised men in sub-Saharan Africa, lack of genital hygienic practices coupled with prevailing climatic conditions are likely factors that lead to development of balanitis, phimosis, paraphimosis, and breakage of the skin or lacerations. These lesions of the penis could facilitate entry of pathogenic agents. The foreskin traps HIV-contaminated vaginal secretions in a humid environment that favors longer survival of HIV and other STIs. These agents are retained for a longer period adjacent to the urethral meatus or abrasions on the penis. Consistent with these arguments, extensive data now exist from several studies in Africa showing that removal of the foreskin (ie, circumcision) reduces male HIV acquisition.11,12 These findings support our hypothesis that a penile pre- and postcoital cleaning procedure could reduce male HIV/STI acquisition by physically eliminating potentially infectious secretions from underneath the foreskin. In addition, cleaning with a wipe containing an antiseptic solution such as BZK could have a residual microbicidal effect. If successful, such a measure would be a simple, widely useable, and affordable hygienic practice with substantial public health significance. These wipes cost about US$ 0.02 each. This intervention might be more acceptable than conventional preventive measures (eg, use of condoms) due to lack of interference with the sex act and independence from cooperation of a partner. Nonetheless, consistent use of condoms should be encouraged because it is the best protective measure available. The findings from our studies in Malawi suggest that the BZK penile wipe is safe, acceptable, and potentially effective in reducing the frequency of several pathogens. Safety and acceptability are not dependent on frequency of application of the wipe.

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The authors thank the managements of the Nchalo Sugar Estate and the Queen Elizabeth Central Hospital and the research teams and clinic staff at Nchalo and Blantyre in Malawi for their excellent collaboration and for facilitating the conduct of this study. We are indebted to the men and their partners who participated in these studies. The following investigators contributed to various phases of this study: Peter Naysolo contributed to study conduct in Malawi, Dean Soko contributed to laboratory work in Malawi, Shu Chen contributed to data analysis, Thomas Quinn contributed to laboratory work in the United States, and David Celentano provided guidance throughout the study.

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1. United Nations Programme on HIV/AIDS (UNAIDS). Report on the Global HIV/AIDS Epidemic. Geneva, Switzerland: United Nations; 2002.

2. Kumwenda N, Taha TE, Hoover DH, et al. HIV-1 incidence among male workers at a sugar estate in rural Malawi. J Acquir Immune Defic Syndr. 2001;27:202-208.

3. Kumwenda N, Taha TE, Hoover DH, et al. HIV-1 prevalence and associated risk factors among male workers at a sugar estate in rural Malawi. Sex Transm Dis. 2002;20:366-371.

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5. Wawer MJ, Sewankambo NK, Serwada D, et al. Control of sexually transmitted diseases for AIDS prevention in Uganda: a randomized community trial. Lancet. 1999;353:525-535.

6. Taha TET, Canner JK, Chiphangwi JD, et al. Reported condom use is not associated with incidence of sexually transmitted diseases in Malawi. AIDS. 1996;10:207-212.

7. O'Farrell N. Soap and water prophylaxis for limiting genital ulcer disease and HIV-1 infection in men in sub-Saharan Africa. Genitourin Med. 1993;69:297-300.

8. Elias CL, Coggins C. Female-controlled methods to prevent sexual transmission of HIV. AIDS. 1996;10:543-551.

9. Pauwels R, de Clereq E. Development of vaginal microbicides for the prevention of heterosexual transmission of HIV. J Acquir Immune Defic Syndr. 1996;1:211-221.

10. Msellati P, Meda N, Leroy V, et al. Safety and acceptability of vaginal disinfection with benzalkonium chloride in HIV infected pregnant women in west Africa: ANRS 049b phase II randomized, double blinded placebo controlled trial. Sex Transm Infect. 1999;75:420-425.

11. Gray RH, Kiwanuka N, Quinn TC, et al. Male circumcision and HIV acquisition and transmission: cohort studies in Rakai, Uganda. AIDS. 2000;14:2371-2381.

12. Weiss HA, Quibley MA, Hayes RJ. Male circumcision and risk of HIV infection in sub-Saharan Africa: a systematic review and meta-analysis. AIDS. 2000;14:2361-2370.

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benzalkonium chloride; HIV; microbicide; penile wipe; sexually transmitted infections

© 2005 Lippincott Williams & Wilkins, Inc.


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