HIV/STIs and Pregnancy Prevention, Using a Cervical Barrier and Microbicide

doi:10.4236/wja.2011.14018

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World Journal of AIDS, 2011, 1, 131-135

doi:10.4236/wja.2011.14018 Published Online December 2011 (http://www.SciRP.org/journal/wja)

131

HIV/STIs and Pregnancy Prevention, Using a

Cervical Barrier and Microbicide

Alfred A. Shihata1, Steven A. Brody2

1Scripps Institution of Medicine and Science, San Diego, USA; 2Department Endocrinology & Metabolism, School of Medicine,

University of California, La Jolla, USA.

E-mail: [email protected], [email protected]

Received August 5th, 2011; revised September 27th, 2011; accepted October 13th, 2011.

ABSTRACT

Objectives: 1) HIV prevention, using a mechanical cervical barrier in combination with microbicide. 2) Prevention of

pregnancy. 3) Shield the cervix to prevent sperm penetration and Gonorrhea, Chlamydia and HIV virus invasion. Me-

thods: We investigated a new FDA approved cervical barrier FemCap (Figure 1). The FemCap is a contraceptive de-

vice that is designed with a unique delivery system for microbicides on its cervical and vaginal sides (Figure 2) to en-

sure better coverage, and retention of gel on the cervix and va gina. We also compared the acceptability and adh erence

with the FemCap, and retention of a stained vaginal lubricant when delivered with the FemCap versus the vaginal lu-

bricant when delivered using a traditional vag inal applicator (Figure 3). We used th e same vaginal applicator utilized

in the CAPRISA 004 [1] study, to deliver Tenofovir microbicide. Thirty women compared the use of a vaginal applica-

tor to deliver a high viscosity stained vaginal lubricant before and after intercourse, versus the FemCap to deliver the

same lubricant once before intercourse. The acceptability and efficacy of this delivery system was evaluated. Results:

Forty percent (12) women missed the application of the lubricant with the vaginal applicator before intercourse and

10% missed it after intercourse. Amongst FemCap users (3) wom en (10%) missed application of the vaginal lubricant

before intercourse and all of them inserted it after intercourse. The stained gel was better retained over the cervix

(Figure 4) by single application with the FemCap versus two applications with the traditional applicator (Figure 3).

Conclusions: Women in this study preferred the FemCap due to elimination of leakage and the single application, me-

thod versus two applications with the traditional vaginal applicator. The use of the FemCap, can prevent pregnancy,

HIV mother-to-child tran smission, enhance compliance and retention of gel over the cervix and vagina that may poten-

tially prevent STIs and increase the efficacy of Tenofovir.

Keywords: HIV Prevention, Mi crobi ci de Tenofovir, FemCap Delivery System

1. Introduction

Despite numerous effective evidence-based preventive

interventions, such as the condom [2,3], circumcision,

Tenfovir gel [1], the HIV pandemic is still outpacing all

the above methods. Therefore the importance of innova-

tive practices employing the a bo ve mentioned methods as

well as novel interventions are need ed.

Women are the fastest growing population affected by

sexually transmitted infections and Acquired Immune

Deficiency Syndrome (STIs/AIDS) worldwide [4]. Women

are biologically vulnerable, and suffer disproportionately

more from the consequences of unplanned pregnancy and

STIs/HIV infections.

The cervix is the main portal of entry for the HIV virus.

This is due to the presence of high concentration of the

Chemokine receptors CCR5 and CRX4 on the cervix [5].

Gonorrhea and Chlamydia are intracellular organisms and

they invade and colonize the endocervical canal. These

non-ulcerative STIs, when present, enhance the invasion

of HIV [6]. Covering the cervix by a cervical barrier in

combination of spermicide/microbicide can 1) prevent

sperm penetration 2) potentially prevent Gonorrhea Ch-

lamydia, and 3) potentially prevent HIV virus invasion of

the cervix.

With no cure or vaccine anticipated in the near future,

HIV continues to spread despite the availability of the

condom and other preventive measures. Vaginal micro-

bicides are a female-initiated new class of drugs that are

intended to prevent the transmission of STIs/HIV fr om the

male to the female and from the female to the male. They

come in gels, creams, suppositories, films, and tablets.

HIV/STIs and Pregnancy Prevention, Using a Cervical Barrier and Microbicide

132

Almost all microbicides, even lemon juice and soap and

water, can kill the fragile HIV virus in-vitro. Some mi-

crobicides when inserted into the vagina, including,

Nonoxynol-9 [7], Cellulose Sulfate [8], Pro 2000 [9] and

Carragaurd [10] failed to prevent HIV/AIDS infections in

clinical trials.

Tenofovir gel, a nucleotide reverse transcriptase in-

hibitor, was shown to significantly reduce the risk for HIV

transmission in CAPRISA 004 [1]. Tenofovir vaginal gel

reduced the likelihood of HIV acquisition by an estimated

39% overall. Among women with good (>80%) (self-

reported), compliance, HIV seroconversion was 54%

lower in the Tenofovir arm compared with the placebo

arm (P = 0.025). Among those who had poor adherence

(self-reported) with Tenofovir application (<50%), the

reduction in HIV seroconversion in the Tenofovir arm

was only 28%. Tenofovir 1% gel would have far less

systemic absorption, side effects or developing resistance

and would have much higher concentration in the vagina

if compared with oral antiretroviral pre-exposure pro-

phylaxis. To improve on our previous study [11] and to

enhance detection of the vaginal lubricant we, mixed two

drops of Gentian Violet dye with every 10 ml of the lu-

bricant, and also increased the number of the participants.

This research in progress to validate and verify the re-

sult of our previous published article [11] .It should be

noted that the addition of the Gentian violet dye was a

major improvement over our previous research. The ad-

dition of the dye greatly enhanced the detection of re-

tained gel over the cervix and vagina (Figure 4). This

clearly distinguished the abse nce of the gel when applied

with the traditional vaginal applicator (Figure 5). We

considered the increase of participants from 20 to 30 is

also a major improvement, which markedly in creased the

power of the study. This is despite the difficulty of re-

cruitment of women to use a stained gel.

2. Methods

This is work in progress to validate our previous pilot

study [11] to compare the adherence, retention and effi-

cacy of two microbicide delivery systems. The FemCap

and the conventional vaginal applicator used in the CA-

PRISA 004 study to deliver the tenofovir gel.

The FemCap is a new contraceptive device, (Figure 1)

[12-19] that i s desi g ned with a unique del i ve ry sy st em for

the microbicide on its cervical and vaginal sides (Figure

2). The aim of this design is to allow for better adherence,

coverag e, dist r ibut i on a nd r et ent io n o f t he g el for u p to 24

hours.

We intended to build upon the partial success of the

Tenofovir gel 1% in prevention of HIV acquisition. We

investigated the feasibility and acceptability of the Fem-

Cap microbicide delivery system as an alternative to the

traditional vaginal applicator that was used in CAPRISA

004 [1] ((Figure 3). Participants selected for this study

were ages 18 to 40 years, were not pregnant, and did not

desire to be pregnant during the 4 week study duration.

All subjects were free from sexually transmitted diseases

and reported being sexually active. Thirty participants

(40% of wh om were sterilized an d 6 0% of whom were on

hormonal contraception), signed an informed consent and

underwent a complete physical and pelvic exam as well as

cervical colposcopic evaluation.

Fifteen women (Group A) were randomly assigned to

use the vaginal applicator, (Figure 3) and the other 15

women (Group B) were assigned to use the FemCap

(Figure 2) to deliver a high viscosity vaginal lubricant

stained with Gentian violet dye, as a substitute fo r Teno-

fovir gel for two weeks.

After one week of wash over group (A) then crossed

over an d us ed the Fem Cap an d gr oup (B) us ed t he va gina l

applicator for two additional weeks. Participants were

instructed to record and report the use of the vaginal ap-

plicator and the FemCap and any side effects on a calen-

Figure 1. New FDA approved cervical barrier FemCap.

Figure 2. FemCap cervical and vaginal sides.

HIV/STIs and Pregnancy Prevention, Using a Cervical Barrier and Microbicide133

dar. This facilitated a comparison between compliance

with the vaginal applicator to deliver a vaginal lubricant

before and after intercourse and with the FemCap to de-

liver the same lubricant only once before intercourse for

four weeks. Women in both groups had an average three

acts of intercourse per week.

We provided participants with hygienic pads to monitor

the expulsion of the stained gel.

We swabbed each participant’s vagina and introitus for

the presence or absence of the stained lubricant at 6, and

12, hours after insertion of the lubricant using both de-

vices. In addition cervical colposcopic exam was per-

formed and the cervix was swabb ed 24 hours after in ser-

tion of the lubricant using the applicator and the FemCap.

Finally the investigators conducted in-depth interviews

with each of these 30 women as to what they thought the

reasons might be why they inserted or failed to insert gel.

3. Results

None of the participants reported any significant side

effects using either device. Naked eye examination and

colposcopy did not show any significant lesions over the

cervix or the vagina. Women reported increased leakage

of the stained lubricant from the vagina following the use

of the vaginal applicator. This was verified by the pres-

ence of the stained gel on the hygienic pads.

Participants preferred the use of the FemCap, due to

elimination of leakage and the single a pplicati on protoc ol,

versus two applications with the vaginal applicator.

Women also stated that it was much easier to remember

one application with the FemCap for a span of 24 hours,

versus two applications, one before intercourse, (which

was unpredictable) and a second application after inter-

course.

Twelve women (40%) reported that they missed the

application of the stained lubrican t more than once before

intercourse by using the vaginal applicator and three dif-

ferent women (10%) missed it after intercourse. Nine

women 30% failed to apply the lubrican t with the vaginal

applicator after the cross over. With the FemCap, only

three women (10%) missed application of the stained

vaginal lubricant before intercourse and two different

women missed it after the cross-over Swabbing and col-

poscopy of the cervix and vagina after 6,12 and 24 hours,

in women who used the FemCap and the vaginal appli-

cator showed the following: The stained vaginal lubricant

was present over the cervix (Figure 4), and to a lesser

degree on t he upper vagina with m any bare a reas, and was

absent over the lower vagina and introitus 24 hours after

application with the FemCap. We failed however to detect

the presence of the st ained vaginal lu bricant after 12 hours

on the cervi x or the vagina (Figure 5) in wo men who use d

the vaginal applicator Table 1.

Therefore according to this study, a single application

of the stained vaginal lubricant using the FemCap deliv-

ery system has proven to have better acceptability, com-

pliance, gel distribution, and retention than two applica-

tions by the vaginal applicator.

Figure 3. Traditional vaginal applicator.

Figure 4. Retained gel over the cervix and vagina.

Figure 5. The vagina.

HIV/STIs and Pregnancy Prevention, Using a Cervical Barrier and Microbicide

134

Table 1. Comparison between distribution and retention of the vaginal lubricant.

24 hours

after gel application

The FemCap

Stained Vaginal Lubricant applied with t he F emCap once

before intercourse

The Vaginal Applicator

Stained Lubricant applied with the vaginal applicator t wi ce

before and after intercourse

Cervix Stained lubricant present (Figure 4) Absent (Figure 5)

Upper vagina Present with many bare spots (Figure 4) Absent (Figure 5)

Introitus Absent Absent (Figure 5)

4. Discussion

According to the CAPRISA 004 study [1] report, “In-

adequate adherence is the most serious challenge to ob-

taining an accurate estimate of product efficacy. “This

highlights the need to seek higher levels of adherence

and effectiveness with Tenofovir gel and to develop oth-

er effective prevention strategies for use in combination

with Tenofovir gel”.

Based on the CAPRISA 004 [1] result report above,

we investigated the feasibility and acceptability of an

alternative to the vaginal applicator (Figure 3) used in

CAPRISA 004. We agree with the authors of CAPRISA

004 study that poor adheren ce with Tenofovir application

was a major factor in its partial success. Prevention of the

spread of HIV transmission should be the front and cen-

tre of research studies. Adherence with Tenofovir gel

application significantly affected HIV seroconversion in

the CAPRISA 004 study.

This study validate and verify our previous pilot study

[11] to improve on the adherence and retention and thus

the effectiveness of Tenofovir gel microbicide applica-

tion. We utilized the FemCap delivery system to deliver

a stained vaginal lubricant as a substitute for Tenofovir

gel. We realize that the number of participants is small to

make a judgment about levels of compliance in relation

to type of product, however a larger study is planned that

will provide the tissue concentration level of Tenofovir

and a meaningful statistical analysis.

This methodology allowed us to compare compliance,

as well as the presence or absence of the stained vaginal

lubricant over the cervix and vagina after 24 hours. Fu-

ture studies will be conducted to show the exact inhibi-

tory level of Tenofovir in the epithelial surface of the

cervix and vagina at 6, 12, and 24 hours when applied

with the applicator and FemCap.

Participants were coun seled on the importance of hon-

est and truthful reporting for each and every time they

used the vaginal applicator and the FemCap. The major-

ity of women, 80%, liked the fact that they only needed

to use the FemCap once before intercourse and reapply it

after intercourse only if they neglected to use it before

intercourse. They also liked the lack of leakage of the

stained lubricant from the vagina and the FemCap is

proven to preven t pregnancy an d thus prev ent mother – to

child HIV transmission and could maintain contact be-

tween the microbicide and the cervix and vagina for up

to 24 hours.

Even a modest enhancement of adherence and reten-

tion of the gel, due to the higher acceptability of the

FemCap/ microbicide delivery system, has the potential

to increase Tenofovir effectiveness and save millions of

lives. The FemCap is well accepted among American

women [20] as well as African women [11]. If this sim-

ple strategy could reduce the risk of STI/HIV transmis-

sion, it would have an enormous impact worldwide. An-

other advantage of using the FemCap is the prevention of

unintended pregnancy and thus prevents the transmission

of the HIV virus from mother-to-child. Future studies are

needed to proof this concept and explore the safety of

Tenofovir gel app li cat i o n usi ng thi s n ovel d e vi ce.

5. Conclusions

This pilot study illustrated, that, participants had higher

acceptability of the FemCap due to elimination of leak-

age and the single application of the vaginal lubricant,

versus two applications with the vaginal applicator. The

use of the FemCap, can prevent pregnancy, HIV mother-

to-child transmission, and will enhance compliance, dis-

tribution and retention of gel over the cervix that may

potentially prevent STIs and increase the efficacy of Te-

nofovir gel.

6. Acknowledgements

This paper was prepared at the request of Jing Guo the

Editor of World Journal of AIDS (WJA). We are in-

debted to th e women who consented to p articipate in this

research study, and to Dr. Ramez Eskander who edited

this manuscript. No funding was requested or received

from any institution. The authors are responsible for the

content of this article

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