First Trial Proposed of a Candidate Microbicide for Women Living with HIV


On January 7, a welcome announcement came from the Microbicide Trials Network (MTN) that it would add the first clinical trial of a microbicide for women living with HIV to its research portfolio. At a meeting convened by the Forum for Collaborative HIV Research, Dr. Sharon Hillier, MTN’s Principle Investigator, included a trial called MTN 038 among the upcoming research studies in the research network’s five-year plan (pending federal funding).1

The study would enroll 45 women living with HIV in a Phase 1 safety and acceptability trial of a candidate microbicide containing Griffithsin. None of the candidate microbicides currently in human trials is suitable for testing among women living with HIV because they contain small amounts of the anti-retroviral (ARV) drugs developed to treat HIV infection. Griffithsin (GRFT), however, is not an ARV. It is a molecule created using transgenic plant technology (the transfer of genetic material into plants) that can be grown in the tobacco plant (nicotiana benthamiana).

This is done by tricking a virus that infects only tobacco plants (the Tobacco Mosaic virus) into carrying the GRFT gene into a young tobacco plant right after the seed sprouts. This gene forces the plant to make GRFT. The plant‐produced GRFT blocks both HIV and Herpes Simplex Virus (HSV) transmission, and has been shown in laboratory testing to be non‐irritating to animal and human vaginal cells. Developers of GRFT have calculated that an “environmentally controlled greenhouse producing 3,000 kg of leaf tissue per acre could yield… over 2 million doses per year”.2

A microbicide can be designed for either primary or secondary prevention, although this latter use is seldom discussed today. Most research is focused on testing ARV-based microbicides designed for primary prevention (to help HIV negative users stay negative). Their effectiveness is based on the ARV’s ability to keep HIV infection from establishing itself in the body if HIV exposure occurs during sex. But ARV-based microbicides are not appropriate for use by women living with HIV because of the potential for the active drug component of the microbicide to interact with the  ARVs used for treatment. Even if a woman is not yet on treatment, the HIV in her body could potentially develop resistance to the ARV in the microbicide and this might limit her future treatment options. 

Non-ARV based microbicides (although still in the very early stages of development) are an important tool to add to the combination HIV prevention toolbox. Women living with HIV need them to protect themselves from re-infection with other strains of HIV. Such products, if they prove to have bi-directional effectiveness (protecting the product user’s partner as well as the user), could also help women to reduce their risk of transmitting HIV to a negative partner.

They are also a much-needed option for women who do not know their HIV status because, if successful, non‐ARV‐based microbicides could potentially be available without a prescription. ARV‐based products are likely to be available only by prescription to people who are proven to be HIV negative. A non‐ARV‐based, over-the-counter microbicide (if proven safe and effective) could be made more readily available, especially to those with less access to health care and/or who have not been tested for HIV recently. Some women may also prefer not to use ARV‐based microbicides because of possible side effects and/or because of concern about the possible effects on pregnancy or breastfeeding.

Current data also suggest that Griffithsin may also be appropriate for rectal, as well as vaginal, use. Hillier announced that the MTN research portfolio contains a proposed Phase 1 trial (MTN 044) in which 45 women and men who have receptive anal sex would test its safety and acceptability for rectal use.3 No timeframe for either of these trials can be set until funding for them is confirmed.

As noted above, ARV‐based products are currently the primary focus of microbicide research and we are still several years away from knowing whether Griffithsin, or any of the non-ARV-based microbicide candidates, are effective. But it is very encouraging that MTN, one of the largest clinical trial networks working on microbicide development, is including non-ARV-based candidates in its research portfolio and preparing to move them into clinical trials.  Surely, advocates pushing for accessible ARV treatment to enable women and men living with HIV to extend their lifespans also need to advocate for development of a full range of secondary prevention options to help support the sexual and reproductive health of people living with HIV.


Footnotes

1. Hillier S. Overview of Products in Development-Topical. [Presenation] Forum for Coolborative HIV Research. meeting on Future of PrEP and Microbicides, Washington DC, 7 January 2013.

2. Zeitlin L, Pauley M, Whaley KJ. Second-generation HIV microbicides: Continued development of griffithsin. PNAS 2009 106 (15) 6029-6030.

3. Hillier S. Overview of Products in Development-Topical. [Presenation] Forum for Coolborative HIV Research. meeting on Future of PrEP and Microbicides, Washington DC, 7 January 2013.

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