HIV/AIDS Skepticism

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

Posts Tagged ‘nevirapine’

NEVIRAPINE — P.S.

Posted by Henry Bauer on 2008/08/06

No sooner had we posted about the toxicity of nevirapine than it was featured in another story:
Stanford Study Finds HIV Drug Can Persist in Mothers’ Milk, Increasing Risk to Them and Their Babies” (SOURCE: Stanford University Medical Center)

“STANFORD, Calif., Aug 05, 2008 (BUSINESS WIRE) — A drug commonly used in the developing world to prevent transmission of HIV from mother to child persists in the breast milk and blood of the mothers, putting them and their babies at risk for developing drug-resistant strains of the virus, according to researchers at the Stanford University School of Medicine” [emphasis added].

Over and over again, HIV/AIDS researchers show that the only thing they care about is THE VIRUS.

God forbid that THE VIRUS should escape our drugs! If we have to ruin the livers of mothers and babies in order to kill the virus—well, that’s unavoidable collateral damage. What’s intolerable is that the drugs should be so ineffective as to allow mutant strains of THE VIRUS to evolve.

“The researchers found that the drug, nevirapine, stays in the blood and breast milk of the infected mothers for at least two weeks. During that time, the virus has ample opportunity to transform itself into drug-resistant strains of HIV, the human immunodeficiency virus that causes AIDS, which can be very difficult to treat.”

What about the hepatotoxicity? What happens to the livers of those newborns during those two weeks?

“In the short term, nevirapine is better than nothing,” said David Katzenstein, MD, professor of infectious diseases and principal investigator of the study. [Some might argue, on rather solid grounds, that “nothing”—doing nothing— would actually be much better than nevirapine.]  “But in the long term, I’m concerned about conferring resistance. If you’re talking about resistance on a broad scale, it could jeopardize future treatment for mothers and infants” [assuming, of course, that in the meantime they haven’t succumbed to liver failure or other “side”-effects of antiretroviral drugs].

“Seble Kassaye, MD, instructor in infectious diseases and first author of the study, will present the results Aug. 5 at the International AIDS Conference in Mexico City”
where many other studies will also be presented in which THE VIRUS is the focus, not the quality of life of people who happen to test “HIV-positive”.

As is characteristic of the HIV/AIDS scene, facts are ignored in favor of shibboleths and myths:
“Sixty-five percent [of the mothers] had drug-resistant strains in their breast milk as well, with the potential to pass this on to their babies through breastfeeding, a common mode of viral transmission”.
But study after study has shown that the more there is breast-feeding, the LESS likely that the baby becomes “HIV-positive” [MORE HIV, LESS INFECTION: THE BREASTFEEDING CONUNDRUM, 21 November; HIV and BREASTFEEDING AGAIN, 13 February 2008].

“Last year, 420,000 babies were born HIV-positive, the large majority of them to HIV-infected mothers in sub-Saharan Africa, according to figures from the United Nations Joint Programme on HIV/AIDS. The centerpiece of public health programs in the developing world to stop mother-to-child transmission of HIV are both zidovudine (AZT) and nevirapine, which have been used as preventive tools in nearly 900,000 women and infants worldwide”.
Several of my posts have addressed the question, how can the HIV/AIDS bandwagon be stopped? [HOW CAN THE HIV/AIDS BANDWAGON BE STOPPED?, 27 January 2008; STOPPING THE HIV/AIDS BANDWAGON—-Part II, 1 February 2008; A SMALL HITCH IN THE BANDWAGON?, 29 May 2008; The CASES AGAINST HIV: Strategies for Halting the Bandwagon, 29 July 2008].

Here’s one unpleasant possibility. AZT and nevirapine continue to be administered to increasing numbers of African women and babies. Over time, the liver damage to mothers and babies and life-long mitochondrial damage to the babies become so obvious that they can no longer be ignored.

To coin a phrase, there will then be hell to pay.

Posted in antiretroviral drugs, clinical trials, experts, HIV in children, HIV transmission | Tagged: | 1 Comment »

NEVIRAPINE, TB, and HIV/AIDS

Posted by Henry Bauer on 2008/08/06

TB hampers HIV treatment — study
Patients being treated for tuberculosis (TB) may not get the full benefits from HIV therapy, researchers say. Nevirapine — a cheap antiretroviral drug used to treat HIV in developing countries — did not work as well in patients also on TB treatment. . . . Around 40% of HIV patients in the South African study were also treated for TB. . . . Nevirapine is a common choice because of its cost and can be used in women of child-bearing age.”

That TB patients test HIV-positive at a very high rate has been known for a long time, from data gathered in the United States:

Are TB patients particularly promiscuous sexually, or incessantly sharing infected needles for drug abuse? [IS TUBERCULOSIS AN APHRODISIAC?, 4 January 2008] Or is it that HIV tests, which react “positive” on a wide range of conditions, are particularly prone to test positive in the presence of TB? Surely the latter interpretation is much the more plausible.

As to the benefits of nevirapine and its utility in pregnant women, read Celia Farber’s “Out of Control” [Harper’s magazine, March 2006]: a pregnant woman taking nevirapine in a clinical trial died thereby; and the main initial trial of the drug in Africa had been so flawed that the claims based on it should have been disregarded.

Nevirapine is a known cause of liver disease, sometimes fatal, as well as of other potentially fatal “side”-effects. The following quotes are taken from the January 2008 revision of the official HIV/AIDS treatment guidelines:

“Nevirapine may be used as an alternative to efavirenz for the initial NNRTI-based regimen in women with pretreatment CD4 counts <250 cells/mm3 or in men with pretreatment CD4 counts <400 cells/mm3 (BII). Symptomatic and sometimes serious or life-threatening hepatic events have been observed with much greater frequency in women with pretreatment CD4 counts >250/mm3 and in men with pretreatment CD4 counts >400/mm3. Nevirapine thus should be initiated in these patients only if the benefit clearly outweighs the risk. Close monitoring for elevated liver enzymes and skin rash should be undertaken for all patients during the first 18 weeks of nevirapine therapy. . . . nevirapine was associated with greater toxicity (see below) and did not meet criteria for non-inferiority compared with efavirenz. . . . Two deaths were attributed to nevirapine use. One resulted from fulminant hepatitis and one from staphylococcal sepsis as a complication of Stevens-Johnson syndrome (pp. 18-19).”
“Serious hepatic events have been observed when nevirapine was initiated in treatment-naïve patients. These events generally occur within the first few weeks of treatment. In addition to experiencing elevated serum transaminases, approximately half of the patients also develop skin rash, with or without fever or flu-like symptoms. . . . A 12-fold higher incidence of symptomatic hepatic events was seen in women (including pregnant women) with CD4 counts >250 cells/mm3 at the time of nevirapine initiation . . . . Most of these patients had no identifiable underlying hepatic abnormalities. In some cases, hepatic injuries continued to progress despite discontinuation of nevirapine [129, 131]. . . . More detailed recommendations on the management of nevirapine-associated hepatic events can be found in Table 18a [whose heading is, ‘Potentially Life-Threatening and Serious Adverse Events’] (p. 19).”
“female patients seem to have a higher propensity of developing Stevens-Johnson syndrome and symptomatic hepatic events from nevirapine (p.29).”
“Because nevirapine is an inducer of the drug-metabolizing hepatic enzymes, administration of full therapeutic doses of nevirapine without a 2-week, low-dose escalation phase will result in excess plasma drug levels and potentially increase the risk for toxicity (p. 41).”
“. . . . Hepatic failure and death have been reported among a small number of pregnant patients (p. 48).”
“DISADVANTAGES (Table 9):
• Higher incidence of rash than with other NNRTIs, including rare but serious hypersensitivity reactions (Stevens-Johnson syndrome or toxic epidermal necrolysis)
• Higher incidence of hepatotoxicity than with other NNRTIs, including serious and even fatal cases of hepatic necrosis”

There is also a “Black Box Warning” for nevirapine (Table 20, p. 86):
“• Severe, life-threatening, and in some cases fatal hepatotoxicity, including fulminant and cholestatic hepatitis, hepatic necrosis, and hepatic failure, has been reported. Patients may present with nonspecific prodromes of hepatitis and progress to hepatic failure.
• Women with CD4 counts >250 cells/mm3, including pregnant women receiving chronic treatment for HIV infection, are at considerably higher risk of hepatotoxicities.
• Severe, life-threatening, and even fatal skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and hypersensitivity reactions characterized by rash, constitutional findings, and organ dysfunction have occurred with nevirapine treatment.
• Patients should be monitored intensively during the first 18 weeks of nevirapine therapy to detect potentially life-threatening hepatotoxicity or skin reactions.
• A 14-day lead-in period with nevirapine 200 mg daily must be followed strictly.
• Nevirapine should not be restarted after severe hepatic, skin, or hypersensitivity reactions”

“Nevirapine has also been shown in animal studies to cause cancer: “hepatocellular adenomas and carcinomas in mice and rats” (Table 26).”

THAT’s the drug that HIV/AIDS experts describe as “can be used in women of child-bearing age”.
THAT’s the drug widely used in Africa to supposedly protect newborn babies from their “HIV-positive” mothers.

Posted in antiretroviral drugs, clinical trials, experts, HIV tests | Tagged: , , , | 1 Comment »

WHAT HIV DRUGS DO

Posted by Henry Bauer on 2007/12/15

The previous post (OFFICIAL GUIDELINES FOR HIV TREATMENT, 14 December 2007) offered some extracts from the text of the official Guidelines for treating “HIV-1 infected” people, even when they don’t feel ill and are not visibly ill. The Guidelines also have detailed Tables listing the frequent and serious “side” effects of antiretroviral drugs.

The scare quotes are around “side” to emphasize how evasive a euphemism this is. Molecules, chemicals, drugs can’t choose to do only what we want them to do. Any foreign substance disturbs our physiology, which is an intricate system of balances and feedbacks where any one change is likely to induce others as well. The more powerful a molecule, the more likely it is to disrupt our metabolism in multiple ways. Antiretroviral drugs are extremely powerful molecules that can kill cells and block receptors and incapacitate enzymes. As in cancer chemotherapy, antiretroviral treatment kills or disables innocent as well as guilty cells.

All examples in the following are taken from the 1 December 2007 version of the Treatment Guidelines.

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The overriding aim of antiretroviral treatment is to lower viral load or increase CD4-T-cell counts. At several points this seems to take explicit priority over the patient’s condition. For example, as “acceptable [emphasis added] but inferior to preferred or alternative” is included the combination “Stavudine + lamivudine” despite “Significant toxicities including lipoatrophy, peripheral neuropathy, hyperlactatemia including symptomatic and life-threatening lactic acidosis, hepatic steatosis, and pancreatitis” (Table 6b, p. 60).

Drugs “not recommended” for initial therapy include “Indinavir (ritonavir-boosted)” because of “High incidence of nephrolithiasis”, or ritonavir by itself because of “Gastrointestinal intolerance” (Table 7, p. 61). Nevertheless, both indinavir and ritonavir are countenanced for therapy other than “initial”. For example, “Abacavir (ABC) + zidovudine (ZDV) + lamivudine (3TC) only” has “Inferior virologic responses when compared with . . . indinavir-based regimens” (p. 64). Indinavir (trade name CRIXIVAN) is available in “200, 333, 400 mg capsules”, suggesting rather common use, even though the listed “Adverse events” include “nephrolithiasis, GI intolerance, nausea, indirect hyperbilirubinemia, hyperlipidemia, headache, asthenia, blurred vision, dizziness, rash, metallic taste, thrombocytopenia, alopecia, and hemolytic anemia, hyperglycemia, fat maldistribution, possible increased bleeding episodes in pts [patients] with hemophilia” (p. 76). When liver damage (“hepatic impairment”) ensues, it is merely recommended that the dose of 800 mg be reduced to 600 mg (Table 15, p. 82). There is a minimum effective concentration desired when indinavir is used (p. 104), and there is a rationale for using it in pregnant women: “Alternate PI to consider if unable to use nelfinavir or saquinavir-HGC/ritonavir, but would need to give indinavir as ritonavir-boosted regimen. Optimal dosing for the combination of indinavir/ritonavir in pregnancy is unknown” (p. 109).

Ritonavir seems to be widely used to “boost” other drugs even though “Potentially more adverse effect on lipids than unboosted atazanavir”. By itself, ritonavir (NORVIR) is known to produce these “adverse events”: “GI intolerance, nausea, vomiting, diarrhea, paresthesias – circumoral and extremities, hyperlipidemia, esp. hypertriglyceridemia, hepatitis, asthenia, taste perversion, hyperglycemia, fat maldistribution, possible increased bleeding episodes in patients with hemophilia” (p. 77). Once liver damage has ensued, “No dosage adjustment in mild hepatic impairment; no data for moderate to severe impairment, use with caution” (p. 81). What, one might wonder, could possibly constitute “cautious” use?

As noted in the previous post, antiretroviral drugs should not be taken with a multitude of quite commonly used medications; thus “Coadministration of ritonavir with certain non-sedating antihistamines, sedative hypnotics, antiarrhythmics, or ergot alkaloids may result in potentially serious or life-threatening adverse events because of possible effects of ritonavir on hepatic metabolism of certain drugs” (p. 92).
HIV patients must be exceptionally well briefed by their physicians, and exceptionally alert readers of fine print, to understand that these antiretroviral drugs should not be taken with commonly used, sometimes over-the-counter antihistamines, sleeping pills (sedative hypnotics), or anti-migraine compounds (ergot alkaloids). But that list seems not to be exhaustive, because later (Table 21a) caution is advised when using ritonavir together with antifungals (…conazoles), anti-mycobacterials (clarithromycin, rifabutin, rifampin), hormonal contraceptives, a couple of extra statins beyond those earlier mentioned, anti-convulsants, erectile dysfunction agents, and some miscellaneous substances.

Given all these immediate and short-term dangers, it may well be irrelevant that longer-term use of ritonavir has been shown to induce “liver adenomas and carcinomas in male mice” (Table 25).
Similarly worrisome details about many other of these drugs confront the reader. It is discomforting that different members of a given group of drugs are likely to have similar “side” effects, in kind if not in intensity, and that the large number of individual names represents only 3 classes of drugs, two of which are present in the standard “combination” “cocktail” treatment. The third class is represented by only two substances, efavirenz (SUSTIVA) and nevirapine (VIRAMUNE). The former has the disadvantage of neuropsychiatric “side” effects and that it produces birth defects in non-human primates. The latter has been the subject of much controversy because of flawed trials in Africa and the death of a pregnant woman in the USA (Celia Farber, “Out of control”, Harper’s, March 2006). The Guidelines describe its “disadvantages” as “Higher incidence of rash than with other NNRTIs, including rare but serious hypersensitivity reactions (Stevens-Johnson Syndrome or toxic epidermal necrolysis); Higher incidence of hepatotoxicity than with other NNRTIs, including serious and even fatal cases of hepatic necrosis; Treatment-naïve, female patients and treatment-naïve patients with high pre-NVP CD4 counts (>250 cells/mm3 females, >400 cells/mm3 males) are at higher risk of symptomatic hepatic events. NVP not recommended in these patients unless benefit clearly outweighs risk.”
One wonders what conceivable benefits could outweigh those risks. The only ones mentioned are “Less fat maldistribution and dyslipidemia than PI-based regimens”.

Nevertheless, those PIs (protease inhibitors) just judged relatively disadvantageous form part of the standard drug combinations, their advantage being “Save NNRTI for future use”. In other words, it is expected that the standard treatment will be effective only for a limited time. In addition to the fat maldistribution, various of these PIs produce such “side” effects as diarrhea, gastric troubles, hyperlipidemia, and skin rash (pp. 63-4).

Still used is AZT (also called Zidovudine, ZDV), the chemical too toxic to be used in cancer chemotherapy. It is an NRTI (Nucleoside Reverse Transcriptase Inhibitor). The general disadvantage of this class of compounds is “Rare but serious cases of lactic acidosis with hepatic steatosis reported (d4T>ddI=ZDV>TDF=ABC=3TC=FTC)”.
That equation states that d4T is even more dangerous than ddi, which is just as dangerous as AZT/ZDV. Nevertheless, these apparently more dangerous members of this class are in common use. They feature such additional “side” effects as peripheral neuropathy and pancreatitis (ddI + 3TC); peripheral neuropathy, lipoatrophy, hyperlactatemia and lactic acidosis, reports of progressive ascending motor weakness, potential for hyperlipidemia with stavudine use (d4T + 3TC); higher incidence of mitochondrial toxicity with d4T than with other NRTIs ; bone marrow suppression owing to ZDV (Table 9, p. 63).

Table 10 reports some clinical trials of 48-week duration, with 2-7% dropping out because of side effects. Four-drug combinations brought dropout rates as high as 23%. Similarly high dropout rates were experienced with two-drug combinations using ZDV or 3TC. Quite a large number of such trials are listed here, though these are described as no more than “selected” examples.

Table 11 lists details of individual NRTIs, including “adverse events”. Among the inscrutable annotations are “Minimal toxicity” [!!] followed immediately by “lactic acidosis with hepatic steatosis (rare but potentially life-threatening toxicity with use of NRTIs)”, with EMTRIVA (FTC) and 3TC as well as commercial combinations of 3TC with another NRTI as COMBIVIR, EPZICOM, TRIZIVIR.

Table 12 similarly lists NNRTIs (Non-Nucleoside Reverse Transcriptase Inhibitors), and Table 13 lists PIs. Table 14a describes the new class of “entry inhibitors”. Enfuvirtide (FUZEON) produces “local site injection reactions” in almost 100% of patients, increased rate of bacterial pneumonia, and allergic reactions. One wonders how severe the rate of bacterial pneumonia must be to have been noted already at this early stage. Maraviroc (SELZENTRY) offers “Abdominal pain, cough, dizziness, musculoskeletal symptoms, pyrexia, rash, upper respiratory tract infections, hepatotoxicity, orthostatic hypotension”. Table 14b introduces the latest class of drug, “integrase inhibitor”, raltegravir (ISENTRESS), dosage 400 mg twice daily, producing “nausea, headache, diarrhea, pyrexia, and CPK elevation”.

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The treatments are so unpleasant that there is a Table 16, “Strategies to improve adherence to antiretroviral therapy”. Table 17, stretching over 6 pages (84-9), then lists potentially life-threatening and serious adverse events and recommendations for managing them. Table 18 lists “overlapping toxicities” of “HIV-related” drugs. Table 19 cites “black box warnings” for these drugs. Tables 20 and 21 list numerous commonly used medications that should not be taken with antiretroviral drugs.

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There’s lots more. Read as much as you can stomach. Bear in mind that these drugs and regimens are intended to kill a retrovirus that has never been isolated in the form of active, infectious particles from HIV-positive people; and that “HIV-infection” is expected to show no symptoms of illness for an average of 10 years after infection, in absence of antiretroviral drugs.

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