HIV/AIDS Skepticism

Pointing to evidence that HIV is not the necessary and sufficient cause of AIDS

Posts Tagged ‘Tenofovir’

Prophylaxis via organ failure and bankruptcy

Posted by Henry Bauer on 2009/01/28

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.

Posted in antiretroviral drugs, clinical trials, experts, Funds for HIV/AIDS, HIV absurdities, HIV transmission, sexual transmission, vaccines | Tagged: , , , , , , | 1 Comment »

The Research Trough — where lack of progress brings more grants

Posted by Henry Bauer on 2008/09/10

Erwin Chargaff wrote wonderfully acerbic essays about the gap between the traditional high ideals of science and the actual practices of scientists, for example, “in our time a successful cancer researcher is not one who ‘solves the riddle,’ but rather one who gets a lot of money to do so. It is all quite similar to the history of alchemy, another truly goal directed, though much less costly, enterprise” (Chargaff, Voices in the Labyrinth, 1977, p. 89).

What might Chargaff have said about the goal-directed missions of trying to invent vaccines and microbicides to prevent infection by HIV?

He would surely have expressed it much more memorably, but the gist would have been, “I told you so”:

NORFOLK, Va. – Eastern Virginia Medical School is receiving a $100 million grant to develop a product to prevent the transmission of the virus that causes AIDS. . . . Officials say the grant will further two decades of studying microbicides that would block HIV and other sexually transmitted diseases. Microbicides can come in forms such as topical gels, creams, tablets, films or oral pills. The grant will fund the school’s program known as CONRAD. . . . CONRAD researchers have been working on microbicides for 20 years and are focusing on several promising candidates that interfere with the process that allows HIV to replicate” [AP, 8 September 2008; emphases added].

That’s progress for you: after two decades, “some promising candidates”. Note how misleading is the stuff about “topical gels, creams, tablets, films or oral pills”, implying that it’s the vehicle that needs work when the very feasibility is at issue since an effective agent remains to be discovered.

Luddites like myself might suggest that this $100 million throws good money after bad. Naïve observers might ask whether there’s something basically wrong with our view of “HIV”, if twenty years has brought nothing better than some “promise”.

Here’s a short and random recent history of HIV-microbicide research:

Microbicide Trials On HIV Transmission Prevention Halted — The Chronicle Newspaper (Lilongwe) . . . 7 May 2007 . . . Malawi will continue with phase 3 Trials on the efficacy of a microbicide gel that is being tested for HIV prevention in women despite trials of a similar kind being halted in other participating countries. . . CONRAD, a reproductive health research organization had halted the phase 3 efficacy trials of its Cellulose Sulfate (CS) based microbicides . . . the public [is] asking why the trials . . . being carried out by John Hopkins Foundation in Malawi are still continuing. . . . on the Pro 2000 and Buffer Gel [trials] started in 2005 . . . . CS is a completely different product from Pro 2000 and Buffer Gel . . . preliminary results indicated that Cellulose Sulfate could lead to an increased risk of HIV infection . . . . ‘With these microbicide candidates in large scale efficacy trials and a new generation of microbicides well into safety studies, microbicides could be available in five to seven years’” .
That reminded me that an HIV vaccine, promised in 1984 within a couple of years, has not been delivered after more than a couple of decades.

FDA Mandates HIV Warning on Contraceptives — Contraceptive gels, foams, films, and inserts sold in the United States will now come with a warning that the products do not protect against HIV and other sexually transmitted diseases. The Food and Drug Administration will require the warning on all over-the-counter products containing nonoxynol-9 . . . . ‘FDA is issuing this final rule to correct the misconceptions that the chemical N-9 in these widely available stand-alone contraceptive products protects against sexually transmitted diseases, Janet Woodcock, FDA’s deputy commissioner for scientific and medical programs, said . . . . The warning was proposed in 2003 after a study in Africa and Thailand found women using the nonoxynol-9-based products were at higher risk of HIV than those on a placebo. The new warning states that because the products can irritate the vagina and rectum they may boost the risk of contracting HIV/AIDS” [emphases added].
Four years between proposing a warning and actually issuing it seems a bit long even for a federal bureaucracy; especially one that’s accustomed to approve new antiretroviral drugs virtually overnight.

Pfizer Seeks to Prevent HIV” — Wall Street Journal 30 January 2008 — “A new Pfizer Inc. HIV drug will soon be reformulated in an effort to prevent the transmission of the virus, offering a faint ray of hope in an arena littered with disappointments. . . . [Pfizer] will license its new medicine, Selzentry, to a nonprofit that investigates ways to turn HIV medicines for infected patients into vaginal substances to prevent transmission to women during sex. The partnership offers a low-risk way for Pfizer to find out if the medicine could become a frequently taken drug, while potentially offering an empowering concept to women in the developing world.  HIV preventives have proven elusive, with researchers and advocates still recovering from last year’s collapse of Merck & Co.’s once-promising vaccine trial. And Pfizer’s new venture with the International Partnership for Microbicides is a long shot that relies on an unproven theory. . . Pfizer’s drug was approved last year for patients who have undergone other HIV treatment. Pfizer is now giving the IPM a license to try to turn the medicine into a vaginal gel, ring or film that might prevent transmission. The Pfizer drug already has a safety portfolio approved by the Food and Drug Administration, potentially making it easier to get through testing in a new form.”

Re “approved safety profile”, note for Selzentry (equivalent generic is maraviroc, MVC) the following “Adverse Events” from the HIV/AIDS Treatment Guidelines, 29 January 2008: “Abdominal pain, cough, dizziness, musculoskeletal symptoms, pyrexia, rash, upper respiratory tract infections, hepatotoxicity, orthostatic hypotension” (Table 14, p. 74).
There’s also a “Pertinent Black Box Warning” (Table 20, p. 86):
Hepatotoxicity has been reported with maraviroc and may be preceded by evidence of a systemic allergic reaction (e.g., pruritic rash, eosinophilia, or elevated IgE). . . . Immediately evaluate patients with signs or symptoms of hepatitis or allergic reaction.”
The “GOOD” news about MVC (Table 26, p. 101), is that it doesn’t seem to cause cancer in animals.

“The first anti-AIDS vaginal gel to make it through late-stage testing failed to stop HIV infection in a study of 6,000 South African women” — AP, 18 February 2008 — “Scientists . . .plan more tests on a revamped gel containing an AIDS drug that they hope will work better. The gel used in the current study did prove safe, however, and researchers called that a watershed event.”
How Chargaff would have been delighted at this grist for his mill: it’s a watershed event when, finally, an intended medicine at least does no harm.
But the researchers were quite rightly delighted, because “A year ago, scientists stopped two late-stage tests of a different gel after early results suggested it might raise the risk of HIV infection instead of lowering it. . . . The study was paid for by the Bill & Melinda Gates Foundation and the U.S. Agency for International Development . . . . Jeff Spieler, an official at USAID, called the trial ‘groundbreaking work’ in a statement. ‘We have always known that the path to developing a successful microbicide would be a long one.’ The Population Council hopes to start tests this year of a revamped Carraguard containing an experimental AIDS drug, MIV-150. The group also has studies under way of a contraceptive version of the gel, Carraguard plus hormones.”
Sounds very good. Plenty of research needed, so grants will keep coming in for the “long” foreseeable future.

26th  February 2008: “CHICAGO (AFP) — The quest to develop a vaginal gel to prevent HIV infection took a step forward Monday when researchers announced that one such gel is safe [cheers!] for women to use on a daily basis. . . . The researchers found no disruption of liver, blood or kidney function . . . . ‘Based on what we have learned we can proceed with greater confidence on a path that will answer whether tenofovir gel and other gels with HIV-specific compounds will be able to prevent sexual transmission of HIV in women when other approaches have failed to do so,’ said lead investigator Sharon Hillier, director of reproductive infectious diseases at the University of Pittsburg School of Medicine.”
“The announcement comes a week after researchers announced that the first prototype to complete advanced clinical trials was ineffective in preventing infection. Microbicides are one of the most eagerly-sought avenues in the war on AIDS, where at present there is neither a cure nor a vaccine . . . . A number of different gels are currently being tested around the world but none have been proven to be effective and some have even increased the risk of contracting HIV.”
As to tenofovir (Viread; also in Atripla and Truvada), the Treatment Guidelines say:
Renal impairment, manifested by increases in serum creatinine, glycosuria, hypophosphatemia, and acute tubular necrosis, has been reported with tenofovir use . . . . The extent of this toxicity is not completely defined. . . . Renal function, urinalysis, and electrolytes should be monitored in patients while on tenofovir” (p. 23);
Adverse Events (Table 10, p. 69): “Asthenia, headache, diarrhea, nausea, vomiting, and flatulence; renal insufficiency; Lactic acidosis with hepatic steatosis (rare but potentially life-threatening toxicity with use of NRTIs).
Pertinent Black Box Warning (Table 20, p. 86): “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.”
Tenofovir has also caused liver cancers in mice.
Since microbicides are intended for use by women, yet another comment in the Treatment Guidelines is pertinent:
“Because of lack of data on use in human pregnancy and concern regarding potential fetal bone effects, tenofovir should be used as a component of a maternal combination regimen only after careful consideration of alternatives” (Table 27, p. 102).

Though the drugs had been approved as safe and effective by the FDA, the label for Selzentry and information about tenofovir make rather frightening reading.

Posted in clinical trials, experts, Funds for HIV/AIDS, HIV skepticism, HIV transmission, sexual transmission, uncritical media, vaccines | Tagged: , , , , , , , , , , , , , | 3 Comments »

TO AVOID HIV LATER, DAMAGE YOUR KIDNEYS AND LIVER NOW

Posted by Henry Bauer on 2008/01/19

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

Posted in antiretroviral drugs, clinical trials, HIV absurdities, vaccines | Tagged: , , , , , , , | 6 Comments »