What is an HIV Microbicide?

[Guest guest]

Microbicides to Prevent Heterosexual Transmission of HIV: Ten

Years Down the Road " AIDScience (01.28.02) Vol. 2; No.1

(AIDScience.org/articles/aidscience015.asp)::Janneke van de

Wijgert; Christiana Coggins

The development of topical microbicides for HIV prevention

originated in response to the deepening spread of HIV despite the

availability of an effective HIV prevention tool (condoms).

Without an HIV vaccine, condoms or microbicides are the most

feasible method of HIV prevention. However, consistent condom use

remains difficult to achieve due to resistance to condom use in

some settings. Women often have limited ability to get their male

partners to use condoms due to social, cultural and economic

gender inequalities. The female condom has increased the options

of some women but their long-term acceptability is questioned,

and female condoms cannot be used without the cooperation of men.

A microbicide is a product applied topically inside the

vagina or rectum to prevent infection with HIV and potentially a

number of bacterial and viral STDs. These may take the form of a

gel, cream or suppository and may or may not be spermicidal (have

a contraceptive effect). There are some indications that some

microbicides may be used to prevent transmission of HIV from

women to their male partners and they may be versatile for use in

the rectum for anal sex.

The identification of novel microbicidal compounds is a

rapidly expanding area of HIV prevention research. An estimated

total of 56 products are currently in the pipeline: 34 are in

pre-clinical stages; 15 are in phase I safety trials, four are in

Phase II expanded safety and preliminary effectiveness trials

(Savvy cream, Emmelle gel, Lactobacillus crispatus suppository,

and Praneem Polyherbal suppository), and three are about to enter

Phase II/III trials (BufferGel and Pro-2000 gel), or Phase III

trials (Carraguard gel) effectiveness trials.

The candidates fall into four categories or combination of

categories:

1)

Products that kill or inactivate infectious pathogens - these

include detergents (like nonoxynol-9, Savvy), peroxides,

lipids, plant extracts (Praneem, gossypol), antimicrobial

peptides, monoclonal antibodies and acidic buffers. Early

hopes were pinned on over-the-counter spermicides containing

nonoxynol-9 as potential microbicides. Recent studies have

shown the nonoxynol-9 products are ineffective against HIV and

most STDs and increase the risk of genital ulceration.

2)

Products that block fusion, i.e. prevent attachment to the

mucosal surface of target cells - these include those that

specifically target HIV surface proteins or HIV receptors and

non-specific blockers that are active against multiple

organisms (Carraguard, Emmelle, Pro-2000 and Usercell).

3)

Products that inhibit post-fusion activity by interrupting HIV

life cycle after the virus has infected the cell - these

included nucleoside/tide RT inhibitors; non-nucleoside/tide RT

inhibitors; protease inhibitors; and post-binding fusion

inhibitors.

4)

Products that enhance naturally occurring vaginal defense

mechanisms. The natural vaginal flora of healthy women is

dominated by lactobacilli, which produce a number of compounds

that inhibit pathogenic microorganisms. These compounds also

maintain a low, acidic pH in the vagina. Other important

defenses are naturally occurring antimicrobial peptides and

antibodies in the vagina. A few newly developed microbicides

aim to enhance these natural defenses. They may be of

particular relevance to those countries in sub-Saharan Africa

where almost half the women of childbearing age have bacterial

vaginosis, characterized by a lack of vaginal lactobacilli.

(Products include Lactobacillus crispatus suppository,

BufferGel, Acidform gel, Protegrins, Plantibodies [monoclonal

antibodies]).

About 35 of the products currently in research are contraceptives

as well as microbicidal.

Much progress has been made on microbicides but many

challenges remain. Badly needed is a significant increase in

investment from both the public and private sectors. To date, no

major pharmaceutical company has made a significant investment in

this research and development. Innovative public-private

partnerships, similar to the International AIDS Vaccine

Initiative, are being explored.

Microbicides, once proven effective, need to be available

and accessible to all women who need them. Developers should aim

for over-the-counter availability and international agencies and

governments should begin early to explore distribution networks,

pricing, local manufacturing, education, regulatory processes and

increased awareness.

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