The latest trials took place in a considerably different environment. They involved high microbicide use and longer periods of time. Trial enrollees also were much more likely to have untreated STDs. Under such conditions, vaginal irritation and lesions would be greatly elevated. Bleeding during sex then would be more frequent. The presence of cellulose sulfate could increase the risk of HIV if it prolonged such bleeding. But this scenario is completely speculative due to the lack of intermediate trials in similar populations. Such “phase II” trials are common in drug development. They confirm the agent’s safety within a larger population and provide initial measures of effectiveness.  
 

Van Damme commented, “We moved forward because the previous trials did not indicate safety issues. Only the larger trials can measure HIV transmission endpoint.” 
 

Researchers have generally felt that microbicide toxicity issues can be resolved with small, quick trials. In contrast, effectiveness is very difficult to measure. There is no preliminary indication of protection equivalent to the viral load declines seen with new anti-HIV drugs. Efficacy for microbicides is only observable by comparing how condoms plus microbicides decrease HIV rates compared to condoms plus placebo. Considering the effectiveness of condoms alone, that takes a very large trial indeed, even when a suitable high-risk population is selected. Still, cellulose sulfate results show the chances taken when so quickly ramping up. 
 

Some version of phase II trials may be in the offing. According to Heise, “To manage the uncertainty, the field is moving toward a phase II run-in and then rollover to phase III.” Such a strategy would imply looking at intermediate results in a moderate-size population before involving thousands of trial enrollees in a full-scale efficacy evaluation. 
 

A report on the CONRAD trial was presented Tuesday, February 27, 2007 at the 14^th Conference on Retroviruses and Opportunistic Infections (CROI):

Oral Abstract 106LB: Update on the CONRAD Cellulose Sulfate Trial, Gustavo Doncel and Lut van Damme, CONRAD, Arlington, VA, US. For a video of this presentation, go to the following web page and select the Tuesday session on Late Breaking Trials of New ARVs and Microbicides http://www.retroconference.org/2007/data/files/webpage_for_CROI.htm. 
 

See also the World Health Organization’s January 31, 2007 statement about the cellulose sulfate trial closure: http://www.who.int/mediacentre/news/statements/2007/s01/en/index.html. 
 

Other Microbicides Quietly Pine Away

More trials mean greater development costs for successful microbicides, and financing is already tenuous for the loose network of nonprofit organizations, small businesses and academic investigators who conduct microbicide research. Just how tenuous was illustrated last fall, when development of a new promising microbicide, cellulose acetate phthalate, or CAP, ground to a halt. CAP has a structure related to the sulfated anionic polymers but offers several potential advantages. It is particularly effective at deactivating HIV and does not retard blood-clotting. CAP is widely used to coat pills and considered innocuous.  
 

Scientists at the New York Blood Center spent nearly 10 years and $10 million doing lab studies. A consortium of research centers led by the Blood Center recently received $6 million from the NIH to conduct early human trials. But the chief researcher, Robert Neurath, has retired after a dispute with the Blood Center management over research funding. Neurath’s retirement left the new human trial consortium in limbo. He now says, “As far as I know, not much is happening now regarding a commercially and Medically viable CAP formulation since my efforts have been blocked.”

Suspension of Minority AIDS Initiative Funding A Major Blow to AIDS Care in Communities of Color

By Julie Davids

On March 1 – just days before the release of the long-awaited CDC prevention plan for African-Americans that (surprise, surprise) relies upon getting more folks tested who would then have to enter a severely overburdened care system – funding for care programs through the federal Minority AIDS Initiative (MAI) was suspended.

The funds are expected to flow again in the fall, once they have been incorporated into the Ryan White CARE Act process – but they will then be disbursed to regions through a competitive bidding process that may marginalize some current recipients.

So, the bottom line – programs serving communities of color just took a substantial funding hit, the infrastructure of AIDS care has been significantly undercut across the country, and there’s no guarantee that those programs that can hang in until the fall (and many can’t) will be refunded.

In some cases, people will be able to fight back. Project TEACH, for example, is a treatment education training program that I helped start in Philadelphia in 1996. It has graduated over 2,000 people, most of whom are low income African-Americans living with HIV. The program helps them learn and then share information about staying healthy with HIV. Two weeks ago, the service category that funds Project TEACH was eliminated wholesale in order to deal with the impact of funding cuts – including the MAI mess. The AIDS community has had to drop everything to mobilize to get the cuts reinstated, with TEACH graduates leading the effort.

In parts of the country with less resources to begin with and less of an organizing infrastructure, MAI-related cuts are, and will be, just as shocking, severe, and even harder to overturn, with few spare bucks available to keep essential programs afloat.

Over 70 groups across the country signed a letter urging the Tri-Caucus to deal with this situation. (The Tri-Caucus includes the Congressional Black Caucus, the Congressional Hispanic Caucus, and the Congressional Asian Pacific American Caucus. The Congressional Black Caucus started the MAI.) Unfortunately, there’s a lot of buck-passing going on. Some say that the Administration could interpret the law in such a way as to allow funding to continue as-is until the fall. Others say that Congress passed a law that ties HRSA’s hands and needs to deal with it. Can the authorizers of Ryan White light a fire that will get more people who are tasked to HRSA speed up the process so that the MAI gets up and running faster? Can the Administration reach out to Congress to address the quagmire of the new CARE Act and intervene on behalf of the MAI?

None of this is likely unless all parties hear a lot more from advocates. People at the grassroots are so busy gasping for air, fighting such a large epidemic with so few resources, that it’s hard to look upstream to go after the guys cutting off the oxygen. And how can you scream when you have no air? If you can, let your voice be heard now. Or hold your breath until September…

Prevention Takes to the Red Carpet at CROI - Community Lacks Tickets, But Everyone Can Watch at Home

By Julie Davids

The last week of February in Los Angeles was notable not just for the Academy Awards, but also for the annual Conference on Retroviruses and Opportunistic Infections (CROI). Those selected by the Academy (aka the Scientific Program Committee) for the best performances in HIV/AIDS bench and clinical research were called to the LA Convention Center for four days of frenetic activity, presentations, and discussions.

For nearly a decade, the dialogue at CROI has been enriched by the presence of AIDS treatment advocates, educators, and community press thanks to the vociferous insistence of activists such as the late Kiyoshi Kuromiya and ACT UP members, who demanded community inclusion and won a scholarship program for treatment community educators.

Now that key prevention data is being presented at CROI and the boundaries between treatment and prevention start to melt, CHAMP is calling for expansion of the scholarship program to include prevention-focused community members. In the course of the conference, 30 organizations and eight current and former members of the conference’s tiny Community Liaison Subcommittee endorsed a letter asking for the addition of five full and 15 partial scholarships for prevention community educators.

As in all places where people with ideas and resources gather, the chatter in the hallways between sessions provide some of the most productive parts of CROI – and make it imperative that more prevention people are included. Thankfully, everyone can now view the conference sessions via webcast at

http://www.retroconference.org/2007/data/files/webpage_for_CROI.htm