AIDS Treatment News

Truvada PrEP, Gilead, AHF's Bizarre Attack: Our statement to the FDA

2012-04-27T20:18:00.001-04:00

Submitted to the FDA today, April 27, 2012, by John S. James, AIDS Treatment News:

I strongly support approval of Truvada for PrEP. In the large iPrEx study of men who have sex with men, "No one in iPrEx acquired HIV infection with a drug level that would have been expected with daily dosing" (Dr. Robert Grant, PI, CROI 2011, http://bit.ly/grjVUg). I reported the details exactly a year ago, at http://aidsnews.blogspot.com/2011/04/hiv-prep-explained-critical-prevention.html

The strongest argument against approval is that the mediocre intent-to-treat results reflect the real world, where people don't take their pills. But approval of a treatment that works close to 100% when used once a day opens all sorts of doors for improvement. For example, communication with patients and with future trial participants can be much clearer and more definitive than communication in the iPrEx trial.

Also remember that much of the epidemic results from relatively few superspreaders. The limit of treatment as prevention is that it's almost impossible to identify and treat them in time. PrEP is better, because these people know they are personally at risk; they are likely to protect themselves if given clear messages and an opportunity to do so, eliminating all transmission through them -- a powerful strategy to fight the HIV epidemic.

AHF Debacle: Does Gilead Really Want Truvada Approved for PrEP?

Events in India (not reported in the U.S. so far) raise this question. The full story is summarized in "Anti-AIDS blitz sees pharma firms locked in ugly battle," at http://economictimes.indiatimes.com/articleshow/2586967.cms

The AIDS Healthcare Foundation campaign against Gilead re Truvada PrEP is a roll-out of a similar AHF campaign run almost four years earlier in India, against Cipla -- and clearly run on Gilead's behalf. AHF spent considerable money on full-page ads in Indian newspapers, apparently to get Cipla in trouble with the Indian government for charging less for medicines in Africa than it did in India. While AHF supposedly paid for the anti-Cipla campaign, Gilead gave AHF a grant for far more, according to The Economic Times article cited above. AHF had no visible motive to go after Cipla, but Gilead sure did; alone among Indian pharmaceutical companies making a Truvada generic, Cipla did not accept Gilead's licensing terms, but planned to fight Gilead's claims in Indian courts.

Why might Gilead secretly campaign today against use of its own drug for PrEP? It is not very hard to see why.

Gilead is stuck because it cannot feasibly charge a different and vastly lower price for the same pill for prevention. It's hard enough to promote prevention; now try adding over $13,000 per year out-of-pocket retail price ($13,816 -- $3,406.79 per 90 tablets, on drugstore.com today). This cost will be out-of-pocket in many if not most cases. The Truvada price is what the market will bear to help save a life, and the market will bear much less to relieve a risk people typically think doesn't apply to them, and don't like to think about at all.

Even 10% of the existing price will be too much for prevention. So there will be no significant market for Truvada PrEP, and no significant profit -- while Truvada for treatment remains an enormous gravy train for Gilead.

And if Truvada for PrEP is approved, Gilead will be the "heavy," consistently blocking control of HIV in the U.S., year after year after year. This will be dangerous for the company, especially in the context of so much need and pressure to reduce medical costs. Similarly, Gilead would be the heavy if it refused to apply for PrEP approval.

The AHF campaign to turn the gay community against Truvada PrEP has failed. But Gilead can get about the same benefit by applying to the FDA and being rejected.

Of course we cannot be sure of Gilead's or AHF's intentions, without reading minds. Maybe Gilead and AHF had a falling out. But in considering this application for Truvada PrEP, you should consider that it may be unlike any other you have ever seen. Whatever Gilead's intentions, the company clearly has strong economic and political incentives for its own application to fail.

John S. James
AIDS Treatment News
www.aidsnews.org

Note to readers: This very controversial FDA Antiviral Advisory Meeting will be May 10, near Washington DC; recently the schedule was changed to allow an extra hour of public comment. You can submit written comments until May 17; however, written comments had to be submitted by 4 pm today to be distributed in advance to the committee members. (We got ours in with less than 10 minutes to spare, due to computer hassles when using a Linux netbook at the FDA site.) Comments will be published by the FDA, but not immediately.

For more information about speaking and/or submitting comments, Google the FDA's docket number, FDA-2012-N-0218

The AHF has been very active on this issue at the FDA. It has endless money, and it wants to win. We expect an echo chamber at the meeting.

Permalink: http://aidsnews.blogspot.com/2012/04/truvada-prep-gilead-ahf-our-statement.html

Notice re Comments below: Due to a computer problem, all comments submitted before 4:15 pm Eastern time today (April 30) disappeared -- except for #1. Your comment was not rejected. We never saw it. And we could not publish any comment ourselves.

A successful workaround was to change Blogger's 'Comment Location' setting from 'Embedded' to 'Full page'. Comments should work now. (We recommend this solution to anyone who publishes on Blogger, because 'Embedded' has long caused problems with some browsers. You could lose some but not all comments with no notice, and commenters will think they were rejected when they were not.)

Act Up-Paris on pharmaceutical data exclusivity, ACTA

2012-02-07T14:13:00.000-05:00

Please find below Act Up-Paris question to Karel De Gucht, European Commissioner for trade during a European Commission Civil society dialogue meeting* on trade, growth and development, that took place today in Brussels.

* there was more industry representative than NGOs in the room.

Best, Pauline
--

"Mr De Gucht.

I represent Act Up-Paris, an organisation of people living with HIV based in France. But today, I bring you a message from hundreds of groups worldwide that have signed a call of action to denounce the European Commission's deadly trade policy. For four years you have negotiated a bilateral agreement with India, for three years you negotiated ACTA in a total lack of transparency.
You have repeatedly stated that these agreements will will not affect affordable medicines.

Starting on Friday, you will represent E.C during a summit in India.

How can you claim that data exclusivity will not have an impact when the European Parliament itself has asked that this provision not be put in an FTA with developing countries?

How can you state that ACTA and the enforcement provisions in the EU-India FTA will not affect medicines when european customs authorities continue to seize generic medicines in transit, like it happened again last November?

How can you ask India to implement TRIPS-plus provisions and state these will not affect access to medicines when the United Nations, the WHO, UNITAID, the Global Fund, the UN Special Rapporteur on the Right to Health have all condemned these provisions for affected treatment?

The statements of the European Commission have always been vague and aiming at confusing the citizens of Europe and millions of people in need to treatment worldwide. But they are not fooling anyone.

The European Commission speaks only for the profits of a few companies and not for the lives of millions across the world. Your FTA only aims at strengthening pharmaceutical companies monopolies. While the consequences for firms will be more profits, in the real world many people will die because they will not have access to treatments because of their price.

Across Asia, Latin America and Africa protests against the European Union are taking place. Yesterday in London, last Friday in Nepal, AIDS activists asked you to stop this policy that will take peoples lives.

We ask you to stop this deadly trade policy."
-
Pauline Londeix

Russia: World AIDS Day ITPC events, patients need tenofovir

2011-12-09T14:05:00.001-05:00

December 1, 2011

ST. PETERSBURG

FlASHMOB AND STARS

December 1, 2011. The following activists and volunteers of non-governmental organizations in St. Petersburg and Leningrad region joined together for an unprecedented event associated with the World AIDS Day under the slogan “Know and Live”:

E.V.A. Non-Profit Partnership to increase the quality of life for women living with and affected by HIV-infection and other socially significant diseases,MadStyleGroup Creative Holding, MadMedia Communication Project, Dance4life Social Project, International Treatment Preparedness Coalition in Eastern Europe and Central Asia (ITPCru), Svecha Organization of People living with HIV, “Positive Dialogue” community of people living with HIV/AIDS, “Red Ribbon” Foundation and Salvation Army volunteers.

The event was held in two stages, the first part being a march from Anichkov Bridge to Gallery Trade Centre 6.30 p.m, joined by more than 200 people. The young activists walked along Nevskiy Prospect, telling the passers-by about the World AIDS Day. The participants stopped beside several subway stations, handing out booklets about HIV/AIDS and red ribbons to the passers-by with the following words: “HIV is not transmitted via information. Take care of your own health and the health of those you love”. In total, more than 2 000 copies were distributed. The second part took place in Gallery Trade Centre from 7.00 p.m. till 7.40 p.m. The people who were in the Gallery at that time got a chance to learn more about HIV epidemic, take part in a dance flashmob and enjoy a show involving stars of the Russian show business, T9 and In2nation pop groups and “Studio 17” dance group.

Another symbol of the event was a heart, to which everyone caring about the epidemic, being ready to take the responsibility for their own lives, and empathizing with those affected by the epidemic, could tie a red ribbon. By the event of the event, the heart was red with ribbons, and even after the end people with kept coming and tying their ribbons to the heart.

All the participants said that they managed to draw the attention of people in the Gallery and on the streets. In total, more than 400 people took part in the event.

DECEMBER 1 – MOSCOW

UNSANCTIONED PROTEST ACTION BESIDE THE MINISTRY OF HEALTH

Yet another protest action was held in front of the Ministry of Health of the Russian Federation by Patients Control Movement, with the funeral orchestra and two coffins representing failing treatment and prevention programmes in the country, leading to numerous deaths. The activists state that the absence of mandatory treatment guidelines puts the whole AIDS response in the country at risk. At the same time, several regions in Russia still face stock-outs of diagnostics and regimen changes due to non-clinical indications (as is underlined by the report issued within the framework of the Simona+ monitoring project). Russian patients still have no access to tenofovir, despite the facts that tenofovir-based regimens are included in the WHO guidelines.

The event received broad coverage in the mass media, some activists were detained by the police and then released.

PRESS CONFERENCE HELD BY THE MINISTRY OF HEALTH

One of the Patients Control Initiative representatives took part in the press conference of MoH. At the end of the press conference, Ilya Lapin asked questions about the unsolved problems, namely lack of test kits, nevirapine for children, which has not been purchased by MoH, and absence of HIV treatment guidelines.

PRESS CONFERENCE WITH V. POZNER AND DANCE4LIFE

Alexandra Volgina spoke about problems with access to diagnostics, stock-outs of ART, lack of communication with MoH, and other issues raising concerns among the activists regarding access to HIV treatment in Russia.

ARTICLE IN ROSSIYSKAYA GAZETA (THE RUSSIAN NEWSPAPER)

Gaps in the list – Russia lacks essential medications for combating AIDS

Official Newspaper of The Government of the Russian Federation.

Circulation: 185 445 copies (as of 2nd half of 2010). Coverage: 44 cities of Russia, with regional inserts and issue-related supplements. The newspaper issues a series of books with state documents and comments.

FAX ATTACK ON MoH

December 1

- 50 organizations from different countries sent a fax to MoH, drawing their attention to the issue of access to tenofovir and nevirapine.

Nevirapine for children has not been purchased by the MoH, despite the fact that only one month is left till the end of the year.

Tenofovir is not included in the list of essential drugs, and MoH does not purchase it for Russian patients.

On average, a fax from activists was sent every ten minutes.

Best regards,

Sergey Golovin

Public Relations Officer

http://itpcru.org

sergey.golovin@itpcru.org

+7953 345 9890

Skype: sergej.golovin

See right-hand column for current news =>

2011-08-12T00:30:00.003-04:00

HIV PrEP Explained: Critical Prevention Opportunity

2011-04-25T16:13:00.009-04:00

by John S. James, AIDS Treatment News, April 25, 2011

The Good News

In late 2010 the New England Journal of Medicine published an authoritative report of a trial of PrEP (pre-exposure prophylaxis) in over 2,000 HIV-negative but high-risk gay men, showing that one pill a day of the approved HIV medicine Truvada could prevent HIV infection.[1] Science magazine listed this study as one of the top 10 achievements of 2010 [2]; and President Obama issued a statement about this trial.[3] For background, see [4].

The headline result is that Truvada was 44% effective (compared to placebo) in preventing HIV transmission in this population. This sounds disappointingly low. Why then is the study considered so important?

Much of the answer is that 44% is not the whole story. In the group randomly assigned to take a placebo, 64 became infected during the study; in the group randomly assigned to take Truvada, 36 became infected. Because the sizes of the groups were almost exactly equal (1251 participants, vs. 1248), you can compute the 44% by simple arithmetic.

Fortunately the study did blood testing of the 36 people who became infected despite being assigned to take Truvada, to see if they were really taking the drug. About 90% of them (33 of the 36) had no drug in their body when tested, at the last blood draw before they were found to have HIV. (Truvada consists of two drugs, and no detectable level of either drug was found in any of the 33 people.) The drug-level testing methods had been carefully validated, and can detect the active form of at least one of the drugs two weeks after people stop using the pills. Clearly these study participants had not been taking the medicine when tested. When these trial volunteers who were assigned to take the drug (but had not in fact taken it) were not counted, the effectiveness was not 44%, but over 90%.

It gets better. The other 3 participants who became HIV infected during the trial had very low levels of the active forms of the drugs, just above the limit of detection. Clearly they had taken some Truvada, but were far from using it as directed.

So of the 100 participants who became HIV-infected during this trial, 97 had not used Truvada at the time of the last blood draw -- and the other 3 had used it very poorly. Of those who actually took one Truvada pill per day throughout the study, not one became HIV-infected during this trial (vs. 64 of those who had been given the placebo). So for those who actually used the drug as directed, throughout the entire study, it was 100% effective in this trial, which had over 1,000 high-risk gay men assigned to take Truvada.

But the blood draws occurred in this study at weeks 4, 8, 12, 16, 24, and then every 12 weeks. So we cannot rule out the possibility that one or more people who had not taken Truvada for about two weeks or more before one of those visits, then got religion after the visit, and starting taking the pills daily -- yet got infected despite having adequate drug levels. This seems unlikely in view of the overall findings. But if it did happen, then it would mean that the protection was less than 100% in those who were using the drug. It was not possible to have everyone wear a device that that could record drug levels continuously -- and also tell exactly when they got HIV. So there is no way to be sure that nobody had enough drug in their body when they were infected. For this reason, 100% effectiveness is not claimed or reported.[5]

Still, the fact remains that Truvada for HIV prevention worked very well in this trial. Truvada when used properly (once a day, throughout the trial) completely prevented HIV infection, in a study of over 1,000 people -- when a comparable, randomly chosen group of 1,000 other people given a placebo had 64 HIV infections during the same time. Almost no drug for anything works this well.

Using PrEP Now

Since doctors can legally prescribe Truvada for prevention now, the U.S. CDC (Centers for Disease Control and Prevention) in January 2011 published interim guidance for physicians who want to use it to prevent HIV infection in high-risk HIV-negative men who have sex with men.[6,7]. Guidance will change as more information becomes available from other studies currently ongoing.

The main obstacle now is the price. Gilead Sciences, which holds the patent on Truvada, charges about 100 times as much for Truvada in the U.S., as other companies charge profitably for the same generic medicine in countries where Gilead's patent does not apply. And unless the FDA approves a formal "indication" for prevention use, insurance is unlikely to pay. This means that you can get Truvada for prevention in the U.S. today -- if you have over $12,900 per year to spend out of pocket -- or possibly, very good health insurance. (Gilead raised the price early in April, 2011; on April 18 we checked retail prices on Drugstore.com, which offers 90 once-daily pills for $3,180,90.)

Clearly PrEP will not be used enough to impact the epidemic, if individuals must pay so much out of pocket. (Just taking a $35 pill before sex is not expected to work. The body must convert both drugs into their active forms, which takes time.)

Adherence Issues

Some of the media discussion on Truvada adherence (taking one pill a day consistently) vs. effectiveness for HIV prevention is confusing, because in this study adherence was measured in different ways. Drug-level testing was clearly the gold standard -- while other methods, like asking people how often they took the pills, or counting pills returned, were often confusing, and much less reliable.

If any drug is so hard to take correctly that people seldom do so, then that drug is much less valuable. This is part of the reason that studies are most conservatively reported as “intent to treat” (counting everybody assigned to take the drug or other treatment as being treated -- even if they never actually take any of that treatment at all), instead of “on treatment” (counting only those who actually did take the drug -- partially a self-selected group, which could make the trial results hard to interpret). The purpose of intent-to-treat reporting is to make the study results both more accurate and also more relevant to social policy -- since doctors can only recommend a treatment, not make sure it gets used. In this case, the difference in result was huge: 44% effective, vs. over 90% -- or even close to 100% effective in this trial (depending on how you count the three participants with extremely low drug levels who were using the medication very poorly).

Why did so many of the study participants not take the Truvada?

No one knows for sure at this time. But something unusual and unexpected happened in this study. This clinical trial took place at 11 sites in 6 countries -- with two of the 11 sites in the United States (Boston and San Francisco -- with 113 U.S. participants on Truvada, 114 on placebo). And adherence at the U.S. sites was much better than at the non-U.S. sites -- 97% among all the U.S. participants, considered extremely good, compared to far less overall. The "44% effective" headline just averages these very different situations.

We know of three theories about this difference: (1) The U.S. participants were about 10 years older on the average (though this would hardly explain the huge adherence differences observed); (2) Many of the non-U.S. participants were living at home and probably not “out” to their families, so they would have needed to conceal their participation in the study, making adherence difficult; or (3) Boston and San Francisco have excellent HIV treatment access, perhaps the best in the U.S., while in many countries most people with HIV are dying with no treatment at all. So trial participants may have given or sold their pills to someone with immediate need.

We think that the latter is most likely.

Whatever the reason, the excellent U.S. adherence shows that people can use the drug properly for prevention. And in the future, patients will know that they are getting the active drug (not a placebo), and that it has been proven to work -- both of which should boost adherence. Researchers need to find out what went wrong at some of the sites, and learn how fix it.

But the bottom line is that we do have proof of principle that Truvada prophylaxis can work in high-risk gay men, and prevent close to 100% of the HIV infections that would otherwise occur.

Who Should Take Truvada?

No one we know thinks that all gay men should take Truvada.

But using this new prevention option in a targeted way should help a lot to control the HIV/AIDS epidemic. Remember that in any epidemic, if each person infected infects fewer than one other person on the average, and this can be maintained, then the epidemic will end.

And it turns out that a disproportionate amount of transmission takes place very early in someone's HIV infection -- when viral load is extremely high, but people do not know and seldom even suspect that they are infected, so they are much less careful about risk to others, than if they did know their status.

Also, in HIV as in most epidemics, a few so-called “superspreaders” account for a very disproportionate amount of transmission.[8] In HIV, they are much like those in the Truvada prevention study -- high risk, meaning that they have many sexual partners, especially with unprotected anal intercourse. (In the iPrEx study, volunteers were interviewed by the researchers, and those considered not to be at high risk were rejected -- so that the trial would be more likely to answer the question of whether or not this PrEP treatment worked.)

So far, the big problem in targeting early infection and/or superspreaders has been getting them diagnosed in time. Many are not aware of being sick at all during their early “primary” HIV infection, when they are so dangerous to their sexual partners. Most do get sick, but with the flu-like symptoms of an ordinary viral infection. They or their doctors have no reason to suspect that they have HIV. And if they do take a standard HIV antibody test, they will test negative even though they have a very high HIV viral load, because the body has not formed antibodies against HIV yet.

Recently there has been much interest in trying to stop the HIV epidemic by a policy of “test and treat” -- find people and get them into treatment right away, because on treatment their HIV viral load will be hundreds of times less than before, and they will be much less likely to transmit the infection to anyone else. One recent study [9] concluded that test-and-treat alone will not be enough in the United States, where only 19% of people with HIV have an undetectable viral load -- a "shocking" figure due largely to poor access to care. And it is very hard to find newly infected people soon enough.

PrEP's Big Advantage with Test-and-Treat

With effective PrEP, the problem of early HIV diagnosis goes away. If the high-risk individual never gets infected in the first place, a whole branch of the epidemic tree can be cut off. And as we explained above, the effectiveness of Truvada PrEP in gay men has been close to 100% so far, when it has been used properly (one pill a day, taken consistently).

The way to identify high-risk individuals is to let them identify themselves. After a conversation with their doctor (or a specialist physician at an AIDS organization), and with testing to make sure they do not already have HIV (in which case they would need medical management, not PrEP), they should be able to get a one-pill-a-day supply of the drug without obstacles. Periodic testing could be required, to guard against side effects (such as possible kidney damage), and to make sure the patient is still using the drug, and does not have HIV.

Of course there will be some worried well who end up taking Truvada for prevention even though they do not need to. The doctor can explain the small but real risks of doing so. Truvada is one of the least problematic AIDS medicines.

Note that the “superspreaders” are usually the same high-risk individuals who have many sexual partners and do not take needed precautions. They know who they are. And their own interest in protecting themselves closely parallels the public interest in stopping the HIV epidemic.

Notice that PrEP gives people a new, big incentive to get tested -- the chance to avoid HIV entirely if they get the good news, perhaps even without changing their sexual practices -- not just the chance to start treatment earlier in case of bad news.

We need combination HIV prevention; no one size fits all. But we now know that Truvada PrEP can provide very good protection for high-risk men who have sex with men. And by doing so, it will also be a major tool to help control and eventually end the global HIV epidemics.

Note on FEM-PrEP Trial Closing

Shortly before we went to press, a similar Truvada PrEP trial in women failed, and was closed early. It was ended because exactly the same number of women were infected in the group assigned to take Truvada, as in the group assigned to take the placebo. The study's Independent Data Monitoring Committee secretly examined these interim results, and determined that this trial was very unlikely to show that Truvada PrEP worked in the women. Therefore, the trial was stopped, due to "futility."

Why did the same iPrEx study drug work in men but not in women? No one knows. Blood samples were saved, and drug-level testing and other data will need to be analyzed, to see what can be learned.

There are at least two plausible theories as to why this may have happened:

(1) The iPrEx trial focused on anal HIV transmission, FEM-PrEP on vaginal. It is possible that oral Truvada does not block vaginal transmission, probably because it does not reach high enough levels in the vagina.

(2) There is also another possibility. As explained above, the iPrEx trial worked much better at the U.S. sites (Boston and San Francisco) -- than at other sites, where participants would often have strong reason to give their medication to someone who was sick due to HIV, and not tell the researchers. All of the FEM-PrEP sites were in Africa, where access to life-saving HIV treatment is much worse than in Boston or San Francisco. Unlike iPrEx, FEM-PrEP had no U.S., European, or other sites where no one would need to divert the pills to save the life of a family member or friend.

Neither one of these two possibilities would contradict the iPrEx results -- or the CAPRISA 004 results. In either case, both these studies remain as solid as they ever were.

Note: Truvada alone is not considered proper HIV treatment today, since at least one other anti-HIV drug is needed to more fully suppress the virus and prevent it from developing drug resistance. But if no other treatment is available, Truvada alone might restore someone with AIDS to health and save their life for some time. It is probably better than any HIV treatment anywhere before 1996. Of course it would be much better to take Atripla (or a generic equivalent, or a comparable combination); Atripla is Truvada plus a third drug that works well with it, a modern HIV treatment in one pill per day.

We will report new information as it becomes available.

References and Footnotes

[1] Preexposure Chemoprophylaxis for HIV Prevention in Men Who Have Sex with Men. New England Journal of Medicine (full text free); December 30, 2010, published online November 3, 2010, http://www.nejm.org/doi/full/10.1056/NEJMoa1011205.

Later analysis of the trial, not ready for the above publication, was included at the 18th Conference on Retroviruses, especially in the March 1, 2011, 10:00 a.m. session, "Advances in PrEP," at http://www.retroconference.org/2011/data/files/webcast_2011.htm (you need to select 'Tuesday'). Besides the Scientific Overview, also note “Adherence Indicators and Interim Guidance: Preexposure Prophylaxis for the Prevention of HIV Infection in Men Who Have Sex with Men," and "PrEP Drug Levels in the iPrEx Study,” later in the same session.

[2] Science Magazine Names USAID-Funded HIV Research As Top 10 Breakthrough of the Year. [Both the CAPRISA trial (1% tenofovir vaginal gel for women) and the iPrEx trial (Truvada, a tenofovir + FTC pill for men) made the top-10 list.] Medical News Today, December 28, 2010, http://www.medicalnewstoday.com/articles/212499.php

[3] White House press release, November 23, 2010, http://www.whitehouse.gov/the-press-office/2010/11/23/president-obama-welcomes-new-hiv-prevention-research-results

[4] Background note: This international clinical trial is called iPrEx, which is an abbreviation for the Spanish name of the study; many participants were in Spanish-speaking countries. It used Truvada, a common HIV treatment marketed by Gilead Sciences; Truvada consists of two drugs, tenofovir and emtricitabine, combined in a single pill taken once a day. A related HIV prevention study in women, using a vaginal gel containing tenofovir, was also successful (CAPRISA 004, also recognized in the Science top-10 list. But a prevention trial using Truvada in women recently failed; see the discussion of FEM-PrEP in the text above.

[5] A major reason the "44%" effective (instead of "close to 100%") is widely headlined, instead of is that researchers are expected to highlight the study analysis that they planned in advance to do -- not other analyses that they may choose after looking at the study results. In this case, the planned analysis was the overall HIV-prevention result, with all the study sites considered together. The huge difference between the U.S. and some of the other sites was not expected.

The U.S. sites showed proof of principle that taking one Truvada pill a day can work very well to prevent HIV infection. The sites where people did not take the pills showed that these sites had other problems, which need to be investigated and addressed.

Those interested in statistical methods will note that headlining the pre-planned analysis turned out to be misleading in this case, because of the emergence of a "black swan" -- something totally unexpected which changes the entire picture. As seen also in the financial world (http://www.guardian.co.uk/business/2011/apr/05/world-economy-faces-black-swans-imf-strauss-kahn), modern analysis does not handle black swans well. In clinical research, a major purpose for favoring hypotheses stated in advance is to prevent researchers from falsely enhancing the value of their study by building hypotheses around the resulting data -- including its random variations.

We believe that an analysis revolution is possible here, since there must be better ways to handle these problems that what is done today. As a stopgap, we suggest letting medical researchers claim a black-swan exemption, when justified by an unexpected result that changes the whole picture -- giving them more freedom to highlight interpretations developed after they had seen the results, while also calling in more scrutiny from other professionals, to check that they were using the exemption in ways that were not misleading, and that made practical sense overall.

[6] Interim CDC Guidance on Pre-Exposure Prophylaxis for HIV Prevention in MSM (short overview with highlights for physicians, January 28, 2011), http://aids-clinical-care.jwatch.org/cgi/content/full/2011/214/1

[7] Interim Guidance: Preexposure Prophylaxis for the Prevention of HIV Infection in Men Who Have Sex with Men (the official document), http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6003a1.htm

[8] On the importance and the difficulty of reaching superspreaders in HIV, see: Autonomous targeting of infectious superspreaders using engineered transmissible therapies. PLoS Computational Biology; March 17, 2011, http://www.ploscompbiol.org/article/info%3Adoi%2F10.1371%2Fjournal.pcbi.1002015.

[9] Test-and-treat not enough to control HIV epidemic in the US, http://www.aidsmap.com/Test-and-treat-not-enough-to-control-HIV-epidemic-in-the-US/page/1724334/

Note: This post is Part I. We are researching Part II, on obstacles and opposition to using Truvada PrEP for individual protection, or to help end the HIV/AIDS epidemic. Part II will be controversial.

Changes to AIDS Treatment News blog

2011-03-10T18:10:00.000-05:00

I'm planning changes to this blog and would like to hear what you think (either publicly by a comment, or privately by email to aidsnews@aidsnews.org).

My current thinking is to move the news stories to the right-hand column (via Twitter, but you do not need to use Twitter to read them). Then the main column of the blog will be for discussion, usually around one or more of the news stories.

The previous format was not good for discussion - largely because readers seldom saw blog comments, since they quickly got buried by all the news items coming in. And Twitter encourages many equal voices - important for community discussion and idea development.

The new format should result in more news stories, fewer blog posts, more interaction, and more in-depth discussion.

Thoughts?

Get Twitter Announcements for Retroviruses Conference and Beyond - CURE4

2011-02-24T21:45:00.009-05:00

AIDS Treatment News set up Twitter account cure4 for communication at the 18th Conference on Retroviruses (formerly called CROI), February 27 - March 2 in Boston.

Main purpose: to let activists and writers at the conference know about important events before they happen. We also tweet conference and related news. We already have 58 tweets there, 3 days before CROI begins.

Anyone can read our tweets; you do NOT need a Twitter account. Just visit twitter.com/cure4. Or see the latest announcements on this page, in the right-hand column.

Alternatively, you can follow cure4 on almost any mobile phone (even without a Twitter account). Just send the text message:
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Statins Might Help HIV Patients, Study Suggests

2011-02-24T21:40:00.000-05:00

HON: "Preliminary research suggests that statins restrain the immune systems of HIV patients and may stave off progression of the AIDS-causing virus.

Although it's too soon to recommend the drug for this purpose, the findings of this small study raise the possibility that 'there might be drugs that can help adjust the immune response in HIV patients whether they're taking AIDS medications or not,' said Dr. Brian Agan, director of HIV research with the Infectious Disease Clinical Research Program at the Uniformed Services University in Bethesda, Md. He works with some of the study's authors."

U.S. & U.K political climate impacting HIV prevention

2011-02-24T12:37:00.000-05:00

Chelsea Now: "As each speaker came to our class, a clear theme of regression began to emerge. Where once these same speakers had talked about social and contextual influences of risky sex and substance use, they now spoke of campaigns based on overly simplistic notions of individual responsibility without context or social influence. We also heard about cuts to NHS funding and a shifting of responsibilities from medical providers who have spent years learning about and treating person with HIV to clinicians who are our equivalent of general practitioners/ family clinicians, untrained in the complexities of HIV medical care."

In Kato’s Africa, USAID Money Spurred Spread of HIV Criminalization Laws

2011-02-24T12:29:00.000-05:00

Housing Works: "A decade ago, not a single African country had a law that specifically criminalized HIV exposure. Now, at least 27 African nations punish exposure. These laws open the door for the jailing—or worse—of people with HIV who practice safer sex; mothers who transmit the virus to their children; and even those who have HIV but are undiagnosed.

"The spread of such laws is in part the result of a 2004 model law created by Action for West Africa Region-HIV/AIDS, a five-year project funded at just under $35 million by USAID.

“By funding the creation—and wide dissemination—of a ‘model’ HIV-specific law, USAID has sent mixed messages from the United States,” said Edwin Bernard, editor of HIV and the Criminal Law. “On the one hand, the model law supports human rights by criminalizing stigma and discrimination. But by using vague and imprecise language in its HIV criminalization statute it also creates fear, confusion and the further stigmatization of people living with HIV.”

Nano-sized vaccines

2011-02-22T23:07:00.000-05:00

MIT news release: "MIT engineers have designed a new type of nanoparticle that could safely and effectively deliver vaccines for diseases such as HIV and malaria."

CDC Estimates Half of New HIV Infections Occur Among Black Americans

2011-02-21T20:28:00.000-05:00

HIV/AIDS Clinical Care: "CDC researchers analyzed data on new HIV diagnoses from 2005 through 2008 in 37 states that had longstanding HIV surveillance systems. Although blacks made up only 14% of the population in these states, they accounted for half of the new HIV diagnoses made. Forty-five percent of the men with new diagnoses were black, as were 66% of the women."

Dr. Robert C Gallo Interview: HIV Research at a Crossroad?

2011-02-21T19:10:00.000-05:00

hiv-reservoir.net (Jan. 13, 2011): "Alain Lafeuillade: it looks like the terms ‘HIV sterilizing cure’ and ‘HIV functional cure’ are no longer ‘dirty’ words for scientists. What is the main gap in our knowledge about HIV persistence that should be resolved before we can envision new strategies to reach these goals?

"Robert C. Gallo: The answer is clearly demonstrating the precise cell types that are the source of persisting HIV. This means cells that go beyond the common memory T cells that currently are chiefly studied, and demonstrating that by so-called “purging” these cells by activation mechanisms will lead to death of these cells. At the moment this is the assumption."

Fast online review of antiretroviral advances at CROI, March 3

2011-02-20T22:51:00.001-05:00

ViralEd: "This 1.5-hour live Internet symposium will review and discuss the key studies on antiretroviral therapy presented at the 18th Conference on Retroviruses and Opportunistic Infections. The symposium will feature five well-known and recognized thought leaders in the HIV field, with four serving as presenting faculty/discussants and one as program moderator."

Comment (JSJ): There will be many reviews of the important Conference on Retroviruses and Opportunistic Infections (CROI) in Boston (Feb. 27 - March 2), most of them weeks or months later. This review has 5 top experts -- and happens on March 3, the day after the conference ends. It's free online for anyone, but you need to preregister.

I'm attending CROI, but will also watch this summary on the antiretroviral therapy advances presented there.

Positively Confined

2011-02-20T22:47:00.000-05:00

Positively Confined [POZ blog]: "An HIV positive man incarcerated somewhere in America shares his insight and advice from behind bars."

Safety, Efficacy, and Pharmacokinetics of TBR-652, a CCR5/CCR2 Antagonist, in HIV-1-Infected, Treatment-Experienced, CCR5 Antagonist-Naive Subjects

2011-02-20T22:36:00.000-05:00

JAIDS Journal of Acquired Immune Deficiency Syndromes: "Conclusions: TBR-652 caused significant reductions in HIV-1 RNA at all doses. Significant increases in MCP-1 levels suggested strong CCR2 blockade. TBR-652 was generally well tolerated with no dose-limiting AEs. PD indicate that TBR-652 warrants further investigation as an unboosted, once-daily, oral CCR5 antagonist with potentially important CCR2-mediated anti-inflammatory effects."

Most detailed 3D-model of HIV ever made

2011-02-18T20:10:00.000-05:00

Photoblog: "The winners of the 2010 International Science and Engineering Visualization Challenge, sponsored jointly by the journal Science and the National Science Foundation, share spectacular photographs, graphics, illustrations and videos that engage viewers by conveying the complex substance of science through different art forms. This detailed 3-D model of the human immunodeficiency virus won first place in the illustration category."

Statins as Anti-inflammatory Therapy in HIV disease? — J Infect Dis

2011-02-16T20:26:00.000-05:00

J Infect Dis: "The present study has additional limitations. Unfortunately, levels of inflammatory serum proteins, such as C-reactive protein, were not measured. Moreover, the duration of statin exposure was only 4 weeks, so it is not known whether the anti-inflammatory effects observed would be sustained with longer statin exposure.

"Unless other statins have modes of action that are different from those of high-dose atorvastatin, it seems unlikely that other statins will be found to suppress HIV replication. However, the present data suggest that statins merit evaluation over longer periods in HIV-infected adults who are receiving effective antiretroviral therapy but who have persistent T cell activation, given that ongoing inflammation in HIV-infected adults receiving therapy is associated with a greater risk of HIV disease progression and death. A very large study would probably be required to determine whether the potentially positive effects of statin therapy on inflammatory biomarkers will translate into less HIV disease progression and fewer cases of inflammatory non–AIDS-related illnesses, such as cardiovascular disease and end-stage liver disease."

Learn From Zim How To Fight HIV/AIDS

2011-02-16T20:21:00.000-05:00

RadioVop Zimbabwe: "'The modelling showed it couldn't just be the natural curve [of the epidemic]; the decline was too dramatic,' he told IRIN/PlusNews. 'The modelling suggested it was also due to behaviour change and behavioural data also suggested a change, but what was missing was the all important `why'.'

According to Halperin, Zimbabwe's success story points to the power of social change and the need for more detailed analyses of HIV success stories in Africa. He compared it to the role of partner reduction in the fight against HIV in Uganda, which promoted a reduction in concurrent partners as the key focus of its HIV prevention campaigns in the late 1980s and early 1990s."

Stop Using Laws as Weapons Against HIV Prevention

2011-02-16T20:15:00.000-05:00

Open Society Foundations Blog: "These stories stand beside countless others as testament that what is written in the statute books, and what is done by governments and others in the name of the law, can significantly increase the vulnerability of groups that are already at a high risk of HIV and other serious diseases. This week in Bangkok, Thailand, civil society groups that represent sex workers, drug users, men who have sex with men, people living with HIV, women and children, and those seeking access to essential medicines, will sit down with government officials and policymakers from across the Asia-Pacific region to share their experiences of how the law affects their daily lives."

Interim CDC Guidance on Pre-Exposure Prophylaxis for HIV Prevention in MSM - HIV/AIDS Clinical Care

2011-02-16T10:46:00.000-05:00

HIV/AIDS Clinical Care: "These guidelines provide basic recommendations for clinicians who are interested in implementing PrEP based on the data that are currently available."

New Cure-Related Research: Antabuse to Flush HIV Reservoir

2011-02-15T20:51:00.000-05:00

POZ, Feb. 8: "A new clinical trial has just gotten underway to test the ability of Antabuse (disulfiram)—a drug used for years to treat alcoholism—to flush out the hidden reservoir of HIV that evades both the immune system and antiretroviral (ARV) drugs. Though the trial will be small and isn’t seeking to cure the study participants, it could help propel HIV cure research forward."

Math Wizards Develop New HIV Drug Candidates

2011-02-15T20:47:00.001-05:00

POZ, Feb. 9: "Using a blend of high-level math and chemical engineering, a team of researchers at Princeton University has discovered several new drugs that their colleagues at Johns Hopkins University in Baltimore say are potent against HIV. Their process for finding new drugs against diseases, outlined in a paper published online November 17 in Biophysical Journal, could significantly speed up the laborious task of searching for and testing promising chemical compounds."

Sutherlandia plant begins HIV drug safety trials

2011-02-14T14:27:00.000-05:00

SciDev.Net: "A traditional medicine that may relieve symptoms in AIDS patients is to undergo safety and efficacy tests in South Africa.

"The department of science and technology (DST) has awarded 10 million rand (US$1.4 million) for the study of Sutherlandia frutescens, which is often called the 'cancer bush' and is credited with wide-ranging powers to alleviate symptoms.

"The phase IIb trial will be conducted at the University of the Western Cape's South African Herbal Science and Medicine Institute (SAHSMI), which has been conducting scientific and clinical studies on the plant for seven years."

HIV Protection Without Circulating Blood Antibodies

2011-02-14T14:12:00.002-05:00

Biomed Middle East: "New research shows that protective immunity against HIV can be achieved without the presence of virus neutralizing antibodies in the blood. The study, published by Cell Press in the February issue of the journal Immunity, demonstrates that a vaccine which stimulates production of specific anti-HIV antibodies in the vaginal tissue was sufficient to protect monkeys from exposure to live virus. The results may also help to explain why a few individuals who lack anti-HIV antibodies in the blood are able to resist infection, even when they are repeatedly exposed to HIV. ...

"We may have been able to recapitulate in a vaccine what a few individuals do naturally."