Unlimited insanity: Truvada to prevent HIV

In my memoir of serving as an academic dean, I had written “I would find myself thinking, Now I’ve seen everything; nothing can surprise me anymore, only to experience a novel surprise the next day or the next week”. That’s how I’ve been feeling the last few days as the media have being hyping the approval by the Food and Drug Administration of prescribing Truvada to prevent HIV infection — administering Truvada to perfectly healthy people as supposed prevention.

Truvada is emtricitabine (FTC) plus tenofovir (TDF). In “HAART is toxic: Mainstream concedes it, in backhanded ways”, I cited earlier blogs about the toxicity of tenofovir  and a few salient bits:
— The federal warning that “Tenofovir  . . . alone or in combination . . . may cause serious damage to the liver and . . .  lactic acidosis”
— The manufacturer’s warning that “Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with . . . nucleoside analogs, including tenofovir”
— “increasing exposure to tenofovir was associated with a higher incidence of CKD [chronic kidney disease] . . . . and there are numerous studies . . . demonstrating that tenofovir is associated with impaired kidney function”.

For the combination of  FTC plus TDF, the NIH Treatment Guidelines (updated 14 October 2011) cite as advantages superiority in suppressing viral load and also these disadvantages:
“• Potential for renal impairment, including rare reports of Fanconi syndrome and acute renal insufficiency
• Potential for decrease in bone mineral density”
(as well as failure to suppress viral load when combined with nevirapine [!])

Given these serious and quite common toxicities, what is the supposed benefit of PrEP — pre-exposure prevention or prophylaxis — with Truvada?
A couple of years ago I discussed the failure of TDF in a PrEP trial: “Pre-exposure prophylaxis: A flawed clinical trial that no one should take seriously”. The media descriptions of the evidence on which the FDA and its Advisory Panel approved Truvada for PrEP suggest that this evidence is again anything but trustworthy:
“The committee voted 19-3 in favor of approval for the prevention indication — PrEP for HIV-uninfected men who have sex with men and 19-2 with one abstention for HIV-uninfected partners in couples where the other partner is infected. The committee recommended by 12-8 with two abstentions in favor of approving the drug for individuals who engage in risky sexual behavior that could result in their contracting the virus” (Panel recommends approving Truvada to prevent HIV infection, Sandra Young, CNN, 10 May). Those votes mean that the panel judged it a greater risk when HIV-negative men have sex with men, or when the uninfected partner in a couple where the other is infected, than when “individuals . . . engage in risky sexual behavior that could result in their contracting the virus”? What possible basis could there be for such a comparative judgment?
“Committee members also heard concerns about the drug’s side effects, which can include nausea, vomiting, dizziness, loss of appetite and diarrhea, liver and kidney toxicity and loss of bone density”. Those committee members will not be able in the future to deny that they were voting to cause iatrogenic harm to healthy individuals who had other options for protecting themselves.
As history lauds in retrospect the FDA officer who held off from approving thalidomide, so in future we may look back approvingly on the attempt to block Truvada PrEP by one member of the committee:
“Dr. Lauren Wood of the National Cancer Institute said she voted against all preventive applications because clinical studies did not measure the dangers of drug-related renal problems among black people, who are among the hardest impacted by HIV infection and the most susceptible to kidney problems linked to AIDS drugs”.

Two-faced arguments are ubiquitous in the HIV/AIDS Wonderland. Typical of the mainstream Janus-faced propaganda were such comments as, on the one hand,  “What we need currently is additional tools” even though, on the other hand, there already exists a “powerful tool box” which nevertheless hasn’t been any good: “We are not winning the battle” — all these comments are from the same individual.
“”Existing interventions have not reduced the number of new infections annually” (FDA panel backs Gilead’s Truvada to prevent HIV).
“Truvada first made headlines in 2010, when government researchers showed it could prevent people from contracting HIV. A three-year study found that daily doses cut the risk of infection in healthy gay and bisexual men by 42 percent, when accompanied by condoms and counseling” (Truvada for HIV prevention backed by advisory panel, FDA may decide by June). That’s the study I debunked in “Pre-exposure prophylaxis: A flawed clinical trial that no one should take seriously

Apparently this panel of experts was not aware of Nancy Padian’s success, more than a decade ago, in totally preventing infections merely by counseling and advising use of condoms: “We observed no seroconversions  after  entry  into the study” (Padian et al., American Journal of Epidemiology 146 [1997] 350-7) among 175 discordant couples with >280 couple-years of follow-up; and they attributed the lack of transmission to the success of counseling. Since counseling brings no serious physiological side-effects, and the preventive success is 100%, there would seem to be no need for Truvada with its serious side-effects.

The case against approving Truvada PrEP is entirely separate from AIDS Rethinking: Mainstream data speak against administering so toxic a drug to healthy people, no matter how high may be estimated their risk of contracting a virus that supposedly causes illness only after an average latent period of a decade or so, and that is controlled without medication among some proportion of the infected, the “elite controllers”. Truvada PrEP incurs the certainty of early iatrogenic illness in exchange for some probability, which is undoubtedly low, given that the transmissibility of HIV with sex is on the order of 1 per 1000 unprotected acts.

On the PBS NewsHour on May 11, Anthony Fauci was featured. Not a single word was spoken about the toxic “side” effects. Not mentioned was the very low transmissibility, nor Padian’s astounding success with counseling and condoms. The only concerns mentioned had to do with cost and the need to adhere strictly to a pill-a-day. Fauci’s statements were fine examples of bureaucratic mumbo-jumbo, for instance:
“[I]t would add to the armamentarium of proven prevention modalities.
Prevention for HIV is really a comprehensive, multifaceted group of prevention modalities that’s kind of a tool kit. This one can be potentially very effective. So if it’s approved and added to the recognized prevention modalities, it would be an important advance in making available for certain people a very effective way to prevent HIV infection.”

To me, Fauci looked very stiff, as though he was unenthusiastic but trying to make up for it with plenty of “clearly”, “absolutely”, and the like. Could the utter absurdity of this FDA approval perhaps have penetrated his armamentarium of cognitive-dissonance modalities?

As I said at the outset: I thought I was familiar with all the aspects of the HIV/AIDS blunder, only to hear about this scandalous extrapolation of earlier misdeeds: hyping faulty evidence to give official approval to the poisoning of innumerable healthy individuals in a hugely expensive way ($12,000-14,000 annually).

Prophylaxis via organ failure and bankruptcy

A year ago, I wrote:

“Clinical trials on human beings are under way to gauge how well tenofovir and emtricitabine protect against HIV infection, with the hope that a regular diet of them could be recommended as prophylaxis. It’s already known, mind you, that these drugs can produce bone demineralization with chronic use, kidney damage, lactic acidosis (including fatalities), liver damage (including fatalities), and liver cancer. The danger of side effects is greatest when first starting the drugs but also when one stops taking them.” Read the rest of this post [“To avoid HIV later, damage your kidneys and liver now” , 19 January 2008]

Why would anyone contemplate such a highly risky procedure to avoid a condition which, IF contracted, can be managed satisfactorily? After all:
“Today any HIV/AIDS patient who sticks with a medication regimen will be successful in keeping AIDS under control, . . . said clinical pharmacist Neha Sheth, PharmD, assistant professor at the University of Maryland School of Pharmacy. Sheth was among a panel of experts who presented a two-day minimester titled ‘Women: The Changing Face of HIV/AIDS’ this month for students from the University of Maryland schools of social work, dentistry, law, nursing, medicine, and pharmacy.”

But even if this is too rosy a painted picture: IF a person does happen to become “HIV-positive”, there follows on average a decade of asymptomatic life without drugs that have dangerous “side”-effects; and IF illness ensues at any time, it would be treated, at worst with the same medications having the same highly dangerous “side”-effects as from the “prophylaxis” under test, at best with newer medications with lesser “side” effects that are continually being introduced. Prophylaxis under these circumstances seems like a losing proposition — but clinical trials continue:

“HIV Prevention Pill Nearing End of Trial
In June, people on three continents will know if the pills they’ve been taking to prevent HIV infection were the real thing or placebos. As the test of tenofovir, said to be an HIV prevention pill, nears the end of the trial period, questions of its effectiveness remain. Researchers worry that the pill’s success may tempt people in high-risk lifestyles to be even more risky, thinking of the pill as a safety net against infection.
The tenofovir pill, PreP (pre-exposure prophylaxis for HIV prevention), is being studied as a result of the drug’s ability to boost temporarily the immune system enough to fend off HIV infection by about 80% when administered within just a few days after exposure. Study participants are taking the pill, or a placebo, on a daily basis, however, to determine how effective a prevention it can be.
At this time, the most effective means of preventing exposure to the AIDS-causing virus is to use condoms when engaging in sexual activity and to avoid other risky behaviors. Doctors fear potential patients taking the prevention pill may forego the use of condoms, expecting the pill to eliminate all risks of infection. The patients for whom the pill proves ineffective may unknowingly spread the virus to others before the pill’s performance on the individual is determined, a situation that may spread the AIDS epidemic even further rather than keeping it in check.
Dr. Albert Liu says he’s heard of people using PreP and other antiretroviral drugs in lieu of condoms outside the study’s parameters and before the drug went into the trial phase. Liu is director of HIV prevention intervention studies at San Francisco’s Department of Public Health. He and his colleagues fear this misuse of the drug will counterbalance any benefits.
Doctors warn PreP is not a pill to pop before a night on the town and other precautions must be maintained as well for maximum benefit. As tested, it is a daily medication that comes with side effects that have been linked to kidney and liver damage.
Another area of concern is cost. As currently marketed, a daily supply could cost between $500 and $900 per month, with cost depending upon an individual patient’s access to insurance coverage and variables from one insurance carrier to another. AIDS activists are hopeful the cost would drop if the drug becomes widely prescribed.”

——————————-

In sum: IF the process being tested were to prove effective in preventing people from becoming “HIV-positive”, it would be likely to encourage riskier behavior and a greater chance of spreading “HIV”, as well as exposing those taking the pills to highly dangerous “side”-effects a decade or more earlier than would be the case if they were not “taking advantage” of prophylaxis; all at an annual cost of ≥$6000.

This is a “lose – win” situation:
Lose for “pre-patients”, for their sexual partners, and for taxpayers, since payment for HIV/AIDS treatment is guaranteed by the federal government (unlike for any other illness, disease, or personal tragedy — in those cases, it would be unacceptable socialized medicine).
Win, however, once again, for the drug companies and their lobbyists — and, of course, for the researchers and doctors who get the grants and the consultant fees. Read what a former editor of the New England Journal of Medicine has to say about “Drug Companies & Doctors: A Story of Corruption”, even apart from the HIV/AIDS business.

TO AVOID HIV LATER, DAMAGE YOUR KIDNEYS AND LIVER NOW

Clinical trials on human beings are under way to gauge how well tenofovir and emtricitabine protect against HIV infection, with the hope that a regular diet of them could be recommended as prophylaxis.

It’s already known, mind you, that these drugs can produce bone demineralization with chronic use, kidney damage, lactic acidosis (including fatalities), liver damage (including fatalities), and liver cancer. The danger of side effects is greatest when first starting the drugs but also when one stops taking them.

The brilliant idea that this may be useful prophylaxis is based on studies in “humanized” mice—FIVE mice, that is—engineered to have a “human-type” immune system. The media (http://cbs11tv.com/local/HIV.Transmission.Prevention.2.631367.html) help everyone understand how significant this is by pointing out that “Humanized mice . . . have the same immune systems and infection fighting cells as humans”; which could make one wonder why there’s even a need for trials in actual human beings.

The concept of prophylaxis using drugs that treat the actual illness is in itself a remarkable advance. Perhaps instead of exposing babies to the dangers of vaccination, we should simply place them on life-long diets of antibiotics? Come to think of it, we do already practice this sort of prophylaxis by feeding antiretroviral drugs to every available pregnant woman who happens to be HIV-positive—see FIRST: DO NO HARM! (19 December 2007).

As to humanizing mice, I’m sorely tempted to speculate about the possibility of engineering mice to have human-type intelligence—sufficient, at the very least, for carrying on HIV/AIDS research and clinical trials.

* * * * * *

Here is what the Official Treatment Guidelines, December 2007 version, say about the side effects of tenofovir and emtricitabine, which are described in the media story below as “fewer . . . than other HIV treatments”:

“Renal impairment, manifested by increases in serum creatinine, glycosuria, hypophosphatemia, and acute tubular necrosis, has been reported with tenofovir use [152, 153]. The extent of this toxicity is still undefined. . . .
. . . .
Discontinuation of emtricitabine, lamivudine, or tenofovir in patients with hepatitis B coinfection. Patients with hepatitis B coinfection (hepatitis B surface antigen or HBeAg positive) and receiving one or a combination of these NRTIs may experience an exacerbation of hepatitis upon drug discontinuation [164, 165]. If any of the above agents is discontinued, the patients should be closely monitored for exacerbation of hepatitis or for hepatic flare (AII).
. . . .
Need to discontinue emtricitabine, lamivudine, or tenofovir: Monitor clinical course with frequent liver function tests, and consider the use of interferon, adefovir dipivoxil, or telbivudine to prevent flares, especially in patients with marginal hepatic reserve.
. . . .
Pertinent Black Box Warning Information:
Emtricitabine (EMTRIVA); or in combination product with tenofovir DF (TRUVADA) or with tenofovir DF and efavirenz (ATRIPLA):
—Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination with other antiretrovirals.
—Emtricitabine is not indicated for the treatment of hepatitis B infection (HBV), the safety and efficacy have not been established in patients with HIV/HBV coinfection.
—Severe acute exacerbations of hepatitis B have been reported in patients who discontinued emtricitabine – hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months after discontinuation of tenofovir in HIV/HBV coinfected patients.
—If appropriate, initiation of anti-HBV therapy may be warranted after discontinuation of tenofovir.
. . . .
Tenofovir (VIREAD); or in combination product with emtricitabine (TRUVADA) or with efavirenz and emtricitabine (ATRIPLA)
—Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs alone or in combination with other antiretrovirals.
—Tenofovir is not indicated for the treatment of chronic hepatitis B (HBV) infection, safety and efficacy in patients with HIV/HBV coinfection have not been established.
—Severe acute exacerbations of hepatitis B have been reported in patients who discontinued tenofovir – hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months after discontinuation of tenofovir in HIV/HBV coinfected patients.
—If appropriate, initiation of anti-HBV therapy may be warranted after discontinuation of tenofovir.
. . . .
Studies in monkeys show decreased fetal growth and reduction in fetal bone porosity within two months of starting maternal therapy [371]. Clinical studies in humans (particularly children) show bone demineralization with chronic use; clinical significance unknown [252, 372]. Significant placental passage in humans (cord:maternal blood ratio ~1.0).”

Tenofovir also produces liver cancer in mice.

* * * * * *

Here’s the media report of this study:

“After 25 years of researchers around the globe being confounded by HIV, scientists in Dallas have shown that the virus’s transmission can be stopped with medications. The scientific first, though performed only in lab mice, bodes well for a future when people at high risk for HIV infection would have a convenient way to protect themselves from the virus. . . . experts who have long advocated safe-sex practices are worried that people will seek these drugs without waiting for scientific proof from human studies. . . . One of the drugs, tenofovir, is reportedly being sold at gay dance clubs on both coasts as a protection against HIV. . . .
Someday, people at high risk of HIV infection could be encouraged by doctors to take a daily pill . . . .
The experiment involved injecting five mice for seven days with two drugs that are commonly used to treat AIDS patients, tenofovir and emtricitabine. On the third day, the mice were inoculated vaginally with HIV, to mimic how most women and girls become infected. ‘Women have no way of protecting themselves from … [sexually transmitted diseases] and HIV,’ said Dr. Garcia, a professor of internal medicine. A preventive medication ‘would empower them to at least have a fighting chance.’ . . .
An important step toward the current UT Southwestern study was Dr. Garcia’s 2006 development of a mouse that had been made susceptible to HIV via transplantation of a ‘humanized’ immune system’. . . .
The two [drugs] . . . have fewer side effects than other HIV treatments. The two drugs are part of several studies in people, funded by the U.S. government, that are testing safety and effectiveness in preventing HIV infection among intravenous drug abusers, young men and women who are sexually active and men who have sex with men. Test sites include San Francisco, Atlanta, Botswana, Thailand, Peru and Ecuador” [emphases added].
(“Dallas scientists stop HIV from spreading in mice—Experts caution that Dallas team’s findings were only in mice”, by Sue Goetinck Ambrose & Sherry Jacobson , Dallas Morning News, 15 January 2008).
The source article is “Antiretroviral pre-exposure prophylaxis prevents vaginal transmission of HIV-1 in humanized BLT mice” by Denton et al., PLoS Medicine 5 #1, e16 doi:10.1371/journal.pmed.0050016 in PLoS Medicine