In Part 1 we attempted to contextualize the recently concluded 14th International AIDS Conference held in Barcelona, Spain coming at year 21 of the epidemic, glossed over its opening ceremonies, and reviewed the presentations of four speakers at the conference's first plenary session on Monday morning.

We also tried to convey the continuing dilemma of the impact of AIDS playing itself out in two worlds -- one rich and one poor. Now we turn to a some of the issues raised from the treatment & prevention racks of the conference and the activist role at the conference. This Barcelona series concludes with a brief look at a handful of public policy presentations and a comment on the closing ceremonies.

Treatment

Little really new treatment information came out of Barcelona. Indeed, these international AIDS conferences have become "too large for efficient scientific exchange and therefore, many investigators choose not to present novel data," commented University of California, San Francisco's doctor Steven Deeks. Deeks noted that as a consequence, "these conferences are largely political in nature. Their primary purpose is to bring clinicians, investigators, activists and political leaders together to discuss AIDS in resource-poor settings."

"Having said that," he continued, "these conferences do offer some relevance to patients in San Francisco." For example, "the FRAM data presented by Carl Grunfield from the San Francisco V.A. was very interesting. Provocative data were presented suggesting that fat accumulation, the so-called buffalo hump and protease paunch, is not HIV-related and, according to Grunfield, more common in HIV negative rather than HIV positive adults. This can have a huge impact on how we think about HIV lipodystrophy." But Matt Sharp, an AIDS treatment activist, warns that the Grunfield data is still very preliminary noting that "many believe it's simply flawed since there are lots of us walking around with protease paunch." Even Grunfield admits its cross sectional, meaning it is only looking at one point in time.

Regarding new drugs in development, while noting that much of the information was "old news," Deeks was nevertheless encouraged by the continued good prospect of T-20. There are some 21 new drugs & 25 vaccine candidates in the pipeline hoping to compete with the 16 most common HAART drugs in widespread use. Another 50 or so are in very early animal or laboratory testing stages, years away from even a whiff of promise to PWA's. One oral presentation in Barcelona attempted to review over 40 of these in less than 30 minutes including everything from recycling an old insecticide to more promising adjunctive therapy drugs like the immunomodulating stimulating agent Interleukin-2 (IL-2), a cytokine once referred to as T-cell growth factor.

T-20 is the first of an entirely new class of fusion inhibitor drugs preventing HIV replication in an entirely new manner. T-20 also seems to work in the face of multidrug-resistant virus. One caution mentioned with IL-2 based on the large ESPRIT study was that CD4 nadir probably does impact its efficacy, although this was not new news.

Commenting on the separate International Drug Resistance conference he attended in Seville immediately before the Barcelona conference began, Deeks expressed his interest with data presented there on the Bristol-Myers-Squibb's experimental drug atazanavir (Zrivada), the first once-daily PI. Data were presented "suggesting that resistance to atazanavir might result in hypersensitivity (boost efficacy) with other protease inhibitors." The history of AIDS treatment is replete with promising initial findings turning sour, so much more study needs to be done to confirm this early data.

Finally, Deeks mentioned the work of Diane Havlir who presented the most definitive data to date indicating that "most patients with undetectable viral load on HAART (still) have persistent viral replication at levels below that which we can detect with current assays." Indeed, throughout the conference speakers like Michael Saag noted that the use of viral load levels to trigger treatment initiation is becoming more and more suspect.

Marty Markowitz from the Aaron Diamond Institute reviewed HIV specific immunity response therapies, including vaccine research. His presentation of "exogenous immunogen" therapies introduced into one's system included various vaccines using genetically engineered protein-based HIV antigens like ALVAC [recombinant canarypox] or AIDSVAX and Remune.

AIDSVAX, also referred to as gp120, is developed by VaxGen and is the largest AIDS vaccine study of some 5,400 patients in the U.S., Canada & the Netherlands aimed at actually preventing HIV infection. Phase III results are expected by early 2003 but it is still years away from possible use. In contrast, Remune is constructed from inactivated virus instead of genetically engineered vaccines like ALVAC or AIDSVAX.

Other introduced exogenous therapies reviewed in Markowitz's talk were passive antibody infusion, and immune-based therapies like cytokines (IL-2 for example) and adjuvant therapy like HAART combined with vaccine therapy. Markowitz also reviewed more inate "endogenous immunogens" like reexposure to one's own autologous virus with STI to boost anti-HIV specific immunity.

Even with much of AIDS research driven by the pharmaceutical industry's desire for us to use their products, Barcelona did offer many presentations on the use of structured treatment interruption (STI) in both chronic (long-term) and primary (initial: anywhere up to 6 months postexposure) HIV infection settings. Both the oral sessions and posters offered a variety of time on/time off drug plans and, overall, the use of STI when closely monitored is clearly one part of the wave of the future. STI allows for "drug holidays," reduces toxicity burden, may help reverse mutations of genotypic resistance to antiretroviral drugs, and can alleviate some drug side effect problems.

STI may also offer patients a kind of therapeutic vaccination, harnessing a person's own immune system to control HIV through repeated autologous reexposure to their own virus. This is particularly promising for primary HIV infected (PHI) patients who opt for STI after discontinuing successful drug therapy. The rationale is that by putting newly-infected patients on AIDS drugs regardless of CD4 levels or current CDC guidelines, this may produce less aggressive virus and assist thymic function, the engine of CD4 production which is impaired early in HIV infection. STI may also offer chronically infected patients benefit in a salvage therapy setting.

Dr. Bruce Walker from Massachusetts General presented on the results of his colleague, Eric Rosenberg, who found virologic benefit in PHI patients on drugs for 18 months following by two STI cycles. Nearly two-thirds of these patients were still able to remain off drug after 74 weeks. Preliminary data on PHI patients show a higher CD4 setpoint for patients who begin treatment immediately after exposure than those that either defer treatment or choose to not treat. Early data suggests this difference can be as great as 200 CD4's.

However, Walker went on to report about one Mass General PHI patient who, although he successfully acquired immune response via therapeutic vaccination, was nevertheless infected again from a separate unprotected exposure with a different HIV strain. The second strain varied less than 12% from the originally infecting one. Walker noted that another similar superinfection case will shortly be published in the Journal of the American Medical Association (JAMA), raising some concern about the implications of viral diversity upon global vaccine development. A handful of other reinfection cases were reported on throughout the conference, typically in a PHI context. Walker concluded his remarks by commenting that "HIV vaccine development has been characterized by too much emphasis on single aspects of immune activation."

Some of the preliminary STI findings were that pretreatment CD4 levels were more predictive of the initial rate of CD4 loss that occurs following drug discontinuation than were presumably higher post treatment CD4 levels at the time of interruption. Also, that viral load is not a useful marker in this context. Walker noted that once STI begins, a quick viral rebound may be better than a slow, gradual accent. PHI patients were less likely to suffer a sudden CD4 loss once STI begins than were chronically infected patients.

Presenters like Tony Fauci were wary of STI and its effect on latent HIV reservoirs and possible viral resistance issues. Others noted their concerns regarding precipitant CD4 decline and viral rebound. However, almost none of the STI presentations ever warned of the problematic use of STI for patients using abacavir, for HCV-HIV co-infected patients, or for patients with HIV and Hepatitis B (HBV) on some HAART drugs.

Compared to other drugs, abacavir patients run an increased risk of drug reaction when either missing doses or when starting and stopping abacavir in an STI context. In HIV-HCV co-infected patients, STI can lead to HIV viral rebound, exacerbating HCV-related liver damage. Finally, for HIV-HBV coinfected patients, HIV medications like 3TC and tenofovir can also provide benefit to combat Hep B. Let's hope these messages begin to get out before patients unilaterally begin experimenting with STI without the benefit of regular monitoring, testing, and the adequate counsel of their healthcare provider.

Several presenters reviewed data of more aggressive therapy by adding either or both IL-2 &/or hydroxyurea (HU) to a patient's drug regiment, sometimes referred to as an "optimized background." Given the toxicity problems associated with HU, that drug may well be limited to short course adjuvant therapy, especially in the context of PHI patients. When different HU doses were compared, a 600 mg bid dosing seemed most effective in one abstract presentation.

Finally, many PWA's crowded around the Newfill poster presentation. Newfill is an injectable polylactic product many AIDS patients are attempting to access to combat the side effect of facial wasting (lipoatrophy). The product is approved and available in Europe and Mexico. Doctors in major U.S. cities like San Francisco, Chicago, and New York have been trained to perform the procedure which generally takes 3 to 4 cycles of two vials each time.

Median reported increases in the dermis layer were between 7 and 10 mm. However, with only limited observational studies of ten patients at six months out, the unanswered question is how long the improvement will last. Anecdotally, most patients are pleased with the results they achieve with this product. One patient I spoke with in Barcelona who underwent the procedure shows little diminution in benefit after one year. Locally, the cosmetic physician with the most expertise in performing this procedure is Dr. Michael Echavez on Post Street. The FDA recently prevented personal importation of Newfill from abroad by reclassifying it from a drug to the nonexempt "medical devise" category, but other less direct sources of access are still available.

Prevention

University of California Dr. Fred Hetch presented data obtained from the San Francisco "options" project that followed HIV+ patients and their lovers. Some resistant HIV strains were found to transmit and infect partners. This information became a sensational international news story about a new mutant resistant virus looming. The actual data showed that resistant virus infection was very treatable and patients who presented with resistant virus had higher T cells-- indicating that such virus might actually cause less initial damage to the newly infected immune system. Local AIDS activists in San Francisco suggested the presentation was intentionally hyped, overblown, and calculated to create a needless media firestorm. Some even suggested that gay men in San Francisco may want to reconsider participation in the program if this is the manner in which the data is manipulated.

The Germans once again provided some of the most compelling prevention visuals we have ever seen. Their booth in the exhibition hall was swamped with people hoarding postcards, posters, and bar coasters with explicit and effective men having sex with men (MSM) graphics. It made this activist want to gather up all those federal monitors who resently descended on the Stop AIDS Project in San Francisco along with the so-called activists who invited the feds into our bedrooms, remove the wide stick stuck up their collective ass, and replace it with a broom for them to fly to Germany to see how relatively anemic American HIV prevention efforts really are.

Finally, L. Yvonne Stevenson reported a 13% condom failure rate when used for anal sex. She noted that 15% still use saliva as a lubricant with condoms, about 8% put lube inside the condom, and 15% fuck greater than 30 minutes with the same condom. According to the CDC, condom use by teenagers in the U.S. stands at 58%, up 12% since 1991.

Activism

Would it really be an international AIDS conference without AIDS activists? Activists, especially those from Philadelphia, Oakland, New York, Paris, and South Africa, arrived in Barcelona with an agenda and repeatedly brought it through the doors of the exhibition hall and even onto the lecture hall stage during a political lecture by U.S. Health and Human Services (HHS) Secretary Tommy Thompson.

The first major demo came as activists entered the exhibition hall crammed with high-tech PHARMA booths plying their wares, surrounded the Roche booth, taped it off with neon yellow tape stamped in black with the word "caution," and demanded to speak with the highest ranking Roche official attending the conference.

I left the end of a PHI lecture when I heard the noise to find myself in the new and uncomfortable position of an observant on the wrong side of the fence. With the decline of San Francisco treatment activism over the past few years, I committed to attending this conference to gather as much information as possible, leaving my battered whistle back in San Francisco. Yet, I confess to being more than a bit uneasy in my new role, feeling guilty for not being able to wear two hats simultaneously.

As activists literally began negotiating with a Roche vice-president hastily summoned to the center of the activist-ringed booth, I suddenly remembered my B.A.R. press pass, grabbed my reporter's notebook, and jumped the tape to record the discussion. Better, much better.

Confronted by members of ACT UP Paris, John Iverson from ACT UP East Bay, South Africans Mark Heywood and Nomfundo Dubula from the Treatment Action Campaign, they sought reductions in the price of Roche's drug nelfinavir on par with reductions made by other drug companies for AIDS meds in South Africa. According to the group Doctors Without Borders, while other drug companies lowered the cost of their AIDS drugs some 70% in southern Africa, Roche's best was only 50%.

This confrontation followed a nonresponsive meeting held with Roche representatives in South Africa one week before the conference began. Nelfinavir is priced so high that, according to Roche's own internal reports, virtually no one accesses it, even those South Africans with drug insurance. Sales of the drug there amounted to only a few thousand rand per year.

The group also demanded that Roche perform its PCR (viral load) testing for children in Africa without profit. Given the reductions by other drug companies in Africa, the costs of diagnostic testing such as the PCR testing Roche controls can exceed the cost of frontline AIDS medications, now estimated at only $100. (US) per month. Other cheaper alternatives to HIV serostatus, CD4, viral load, and resistance monitoring tests may soon offer some relief in this area.

Finally, activists were upset by the access delays for Roche's drug, T-20. Roche's vice president David Reedy said he was not fully unaware of all these issues but agreed to look into them quickly. Admittedly, T-20 is a very difficult drug to produce compared to other AIDS meds and the company has been faced with production problems for this drug. They've even had to build a new plant to produce the complicated 26-step drug.

Activists did get Reedy to agree "not to contest any generic copies of Roche wholly-owned drugs that come to market at a lower cost in seven of the poorest and hard hit nations of southern Africa." He also agreed that Roche would "issue non-exclusive voluntary licenses to generic companies" to allow this process to move forward.

On another day, activists had a giant 40 foot replica of a Coke bottle poised at the entrance of the exhibition hall with the word greed plastered down its side. The issue here is that it takes hundreds of thousand of workers in South Africa to bring Coke to market, including bottlers, truckers, and white-collar workers. But, by outsourcing most of the blue-collar functions whose uninsured workforce is primarily black and estimated 20% HIV+, Coke effectively washes its hands of its corporate responsibility to provide its "workers" with health insurance. Coca Cola, therefore, only provides insurance to a limited white-collar, predominately HIV negative, white workforce.

There were a few other smaller protests. However, the last major demo and the one which received the most media attention was directed at U.S. HHS Secretary Tommy Thompson. Activists from the Health Gap Coalition, ACT UP members from Philadelphia & New York stormed the stage and effectively drowned out the cabinet secretary speech by chanting "where's the ten billion?"-- a reference to the U.N. estimate of the U.S. fair share to the global AIDS fund. At present, the U.S. is only committed to about $500 million.

Louis Sullivan, a former HHS director in the Reagan administration and himself the target of similar actions over 15 years ago, was seated in the front row. The subsequent media coverage produce a storm of hate mail into the ACT UP/New York website, including these indelicate comments: "As far as I'm concerned, the more of you freaks that die from aids (sic), the better off this world will be." Another wrote that "in the good old days they would have shot ass hole groups like you on the White House lawn." Go Texas. But my favorite comment was: "If you FAGS quit puttin' it up your INFECTED asses, AIDS would be under control. More money??? HELL NO!!! You want to reduce AIDS in the U.S.? Drop a fuckin' h-bomb on SF."

Public Policy

Veteran AIDS advocate Brenda Lein from Project Inform, a national AIDS treatment organization based in San Francisco, gave a great presentation on the problematic state of U.S. AIDS research not well-suited to confronting an epidemic. We need only look to the often tangential presentations in Barcelona to notice how we have abandoned the focus on a "search for a cure."

One presenter from Argentina also reviewed the savings associated with reduced medical care, lab work, testing and meds when using STI as part of a treatment strategy. If privately insured, the cost can average over $10,000 (US) compared to $4,100 if publicly insured and between $800 -$1,600 for the STI patient.

Closing Ceremonies

Nelson Mandela and Bill Clinton both spoke at the closing ceremonies on Friday. Like the opening ceremonies, I skipped them. Clinton apologized to the crowd for not doing more to fight AIDS (like screwing us on needle exchange I suppose), saying he would hold himself accountable to the AIDS community in the future. One conference insider privately confided that the former president collected $150,000 for this speech.

Perhaps Clinton can get an early jump on his promise and turn all that money over to the Global Fund to Fight AIDS.
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