HIV/AIDS Skepticism

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

Posts Tagged ‘Emtricitabine’

More clinical trials in Africa

Posted by Henry Bauer on 2009/07/31

AIDS prevention trial in Zimbabwe targets women
Wed Jul 22, 2009 12:25pm EDT

About 5,000 sexually active women are expected to enrol at sites in Zimbabwe, South Africa, Uganda, Zambia and possibly Malawi as part of the study, conducted by the U.S-funded Microbicide Trials Network.
The study will determine whether some of the antiretroviral (ARV) medicines used to treat HIV can also be used to prevent the disease when given as a vaginal microbicide gel or as an oral tablet taken once daily.
In addition, the study, which will specifically test the ARV tablets tenofovir and Truvada, seeks to find out which of the two approaches women would prefer. Tenofovir was also the active ingredient in the vaginal gel.
‘We think its very unique because nobody has really tested the difference between an oral route of prevention compared to a vaginal route of prevention,’ Dr Mike Chirenje, protocol co-chair for the entire study, told Reuters on the sidelines of an AIDS conference. ‘Its not so much which was best, in so much as what would women prefer (to take),’ he said of a study expected to last three and a half years before first results in 2012.
Recent studies have shown that microbicides can protect women — who represent nearly 60 percent of adults living with HIV in the world’s worst affected sub-Saharan Africa region — from catching the virus.”

Those “recent studies” were not cited, however. For a summary of the failures of microbicide research, see “The Research Trough — where lack of progress brings more grants”, 10 September 2008.  Less than a year ago, it had been noted that “two decades of studying microbicides that would block HIV and other sexually transmitted diseases” had led to “several promising candidates that interfere with the process that allows HIV to replicate” — which is far from preventing “infection” in the first place, which is what microbicides or vaccines are intended to do.

What to say about a trial that will feed antiretroviral drugs for 3½ years to 5000 women who are not even “infected”?

For tenofovir (TDF) it is known, for example, that “Renal impairment, manifested by increases in serum creatinine, glycosuria, hypophosphatemia, and acute tubular necrosis, has been reported . . . . In patients who have some degree of pre-existing renal insufficiency . . . tenofovir dosage adjustment is required. However, because no safety and efficacy data that use the dosage adjustment guidelines for renal dysfunction are available, the use of alternative NRTIs (especially abacavir) may be preferred over dose-adjusted tenofovir in this setting” [p. 33, NIH Treatment Guidelines, 3 November 2008]. In addition to renal damage, “adverse events” of TDF include “asthenia [loss of energy], headache, diarrhea, vomiting, flatulence, Fanconi syndrome [a specific form of renal dysfunction], osteopenia [bone loss not yet as severe as osteoporosis]”. Truvada combines TDF with FTC (emtricitabine) which adds the risk of skin discoloration (p. 131).

The popular paraphrase of the Hippocratic Oath, “First, do no harm”, would seem difficult to reconcile with feeding dangerous drugs to healthy human beings when the only conceivable purpose is to find a means of protection that might be an alternative to the entirely non-dangerous use of condoms — leaving aside the fact that there’s not even a sexually transmitted “HIV” to be protected against.

Posted in antiretroviral drugs, clinical trials, HIV transmission, sexual transmission, vaccines | Tagged: , , , , , , , , | 8 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 »

 
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