Blood Testosterone Levels And HIV-POSITIVE Hypogonadal Men

From the book: Built to Survive, available at medibolics.com and amazon.comBlood Testosterone Levels And HIV-POSITIVE Hypogonadal Men
The Normal Scale Doesn’t Seem To Apply

As was stated in the sectionon lipodystrophy, the standard “normal” range for total testosterone blood levels, may be too low for HIV-POSITIVE people. In an article in the Body Positive newsletter (May 1994, p. 22) regarding hypogonadal HIV-POSITIVE men, progressive researcher Judith Rabkin, Ph.D. of New York City, stated that in her study “those who experience significant improvements in sexual functioning tend to have higher serum testosterone levels, usually between 1000 and 1900 ng/dl….” (Remember the normal scale for men is generally about 300 to 1000 ng/dl.) In private correspondence Dr. Rabkin stated that a few of the men in her study did respond at blood levels that were as low as 700 to 800 ng/dl. The important point is that “normal” is a relative term when all things are considered.

We suggest that if the patient is not responding appropriately to testosterone doses that delivers blood test levels in the low and even mid-range of the normal scale, the physician should consider working with doses that deliver testosterone blood test measurements that register in the high end and sometimes above the upper limit of the “normal” scale. Optimum dosing can be very individual and it is best to work with the patient and find the dose that gets the desired effects of improvement in lean body mass, functional strength, energy, mood, increased appetite, and sexual function. Physicians might also consider that the “normal” scale may be an inadequate measurement for HIV-POSITIVE people in general, whether they are hypogonadal or not. Thus we suggest that the physician listen to the patient themselves rather than relying solely on the standard testing mechanisms and scales when making a determination of whether to prescribe testosterone replacement therapy and what supplemental hormone dosage will be found to be optimal. For women, the physician should exert great care in finding the optimal dose without overdosing, as excessive testosterone levels can virilize women, as women are significantly more sensitive to testosterone (and other anabolic steroids) than men.

Measurements – Free And Total Testosterone – Men And Women

While “total testosterone” is frequently the only measurement taken when hypogonadism is suspected, free testosterone, may be a more relevant barometer for assessment of HIV-positive individuals. For instance, free testosterone has been shown to be more correlative with lean body mass than total testosterone in wasting HIV-positive men 42 and women. 41 According to the Merck Manual, normal free testosterone measurements for men generally range between 3.06 and 24 ng/dl. For women the range is generally between .09 to 1.28 ng/dl. We suggest that it may be best to take both free and total testosterone measurements, but that free testosterone may provide more relevant information when addressing the patient’s muscle mass and quality of life.

Hypogonadism and HIV Progression – Men and Women

With progression of HIV, hormonal changes have significant correlations with immune function. Studies show that decreasing testosterone function (hypogonadism) in HIV-positive people significantly correlates not only with loss of lean body mass, 41, 47 but also decreasing t-cell count, 47 and increasing morbidity. 49 And one recent study give indication that testosterone replacement therapy might decrease apoptosis in HIV-positive hypogonadal males. 43

In another men’s study, DHEA, and free testosterone levels decreased as CD4+ T-cells decreased in all patients. The authors stated that hypogonadism occurred as the CD4+ T-cells decreased. 48 In this study, low levels of free testosterone were common in all HIV and AIDS patients, and total testosterone and androstenedione were lower in those patients whose CD4+ T-cells were below 200. DHEA (an adrenal androgen steroid) blood levels were decreased in patients with CD4+ counts below 500.

Therefore, we strongly suggest that the physician address hypogonadism, or decreased free testosterone by supplementing with weekly administration of testosterone enanthate or cypionate as continuous replacement therapy. We also suggest measuring DHEA-S (sulfate), and instituting DHEA supplementation if DHEA-S measures low. More information on DHEA appears later in the section on dietary supplements.

The Anti-Depressive Effect of Testosterone

We frequently hear HIV-positive people tell of how testosterone replacement therapy ended a long-time feeling of depression. One comparative study stated that testosterone replacement therapy produces equivalent effects to common anti-depressive drugs (imipramine, fluoxetine, and sertraline) in the treatment of clinical depression in HIV-positive people. 44 While testosterone is not specifically defined as an “anti-depressive agent”, restoring testosterone levels in hypogonadal patients can produce a powerful anti-depressive effect via its effects on neurological systems, 94 and dramatically improve feelings of “quality of life”. Testosterone also has a very important effect on enhancing healthy libido for men and women. 80, 81 Dr. Judith Rabkin is now conducting a study to compare testosterone to Prozac.

For Hypogonadal People – Testosterone First

Those men and women who are on testosterone replacement therapy because they don’t produce adequate amounts of testosterone, or have low free testosterone levels, may need to employ cycles of anabolic steroids that are added to the person’s replacement testosterone if they lose weight for some reason. For these people, the higher dose anabolic cycles are periodically added to their regular replacement dose of testosterone, so that the total of the testosterone plus the additional steroid creates an “anabolic level” of the combined drugs that will produce best muscle growth during the cycle. After the cycle, the replacement testosterone dose should be resumed at a level that is sufficient to basically maintain their lean muscle mass, and quality of life. They may need to institute another cycle at some time due to a bout with a catabolic illness where they again lose weight. But some people only have to use one high powered “PoWeR” cycle to gain 30-40 pounds. From then on they stay on a replacement dose. Others need several cycles, but usually after they attain sufficient lean muscle mass, the proper testosterone replacement dose may be all that is necessary, unless there is a catabolic event.

Testosterone Patches – Men
Use of a testosterone patch like the Alza Testoderm or Smith/Kline Beecham Androderm, or the Alza Testoderm TTS products may be considered for those who need replacement testosterone therapy. For many men, a patch will usually effectively bring them into the midrange (650 ng/dl) of testosterone blood tests, and they will feel a significant improvement in libido, mood, and energy.

We don’t recommend patches for those who are wasting, as a study detailed at the NIH Wasting Syndrome Conference, May 20, 1997, at Bethesda, Maryland, showed that patches are not effective for treatment of HIV-wasting. While the patch is not an effective wasting therapy, it can improve basic quality of life for people who need basic testosterone replacement therapy.

We question whether there might be problems for some men with long-term use of Alza’s scotal patch, as one review article stated that it causes dihydrotestosterone (DHT) levels to rise inordinately relative to the increase in testosterone because of the enhanced 5-alpha reductase activity in scrotal skin. 50 Elevated DHT increases the potential for prostatic hypertrophy, and hair loss. We also do not know if increased DHT would have a negative or positive effect on HIV-positive men’s immune metabolism.

ALZA is now making the “TTS” version of Testoderm that delivers 6 mg. Of testosterone that can be placed on other parts of the body. While the Androderm patch can also be placed on other parts of the body, the Testoderm TTS patch is preferrable because it has a new high-tech non-sticky adhesive, so it doesn’t irritate skin the way the Androderm patch can. (A lot of people complain of pink irritated skin with Androderm.)

Testosterone Creams and Gels – Women and Men
We are in the beginning stages of reviewing testosterone creams and gels that are being used for testosterone replacement therapy for both women and men. These are being compounded by pharmacies according to a doctor’s prescription. The logical caveats are that the cream application should probably be applied two (or even three) times per day, starting first thing in the morning to mimic the rise in testosterone that occurs naturally. While placing a testosterone cream or gel on an area of skin that contains fat will slow the release of the testosterone somewhat, the duration of testosterone activity once it gets into the bloodstream is rather short. After a few weeks of twice daily application, a relatively steady state blood testosterone level is generally attained. Once a day application may result in only short term improved blood testosterone levels, so the person would feel a decline in energy several hours later in the day. Also, the usually recommendation is that it is best to rotate the sites of application around the body, so that optimal absorption is maintained. The best application areas include the inner elbows, under the chin and on the neck, the stomach, the inner thighs, and breasts or pectorals. Unimed Pharmaceuticals will be bringing a testosterone gel for men to the US market soon. The creams and gels are currently available from compounding pharmacies like Womens’ International Pharmacy (1-800-279-5708) and College Pharmacy (800-575-7776).

Testosterone Injections – Women
While we have had some positive feedback about the creams and gels, we have also had women say that they felt little improvement until they were given weekly testosterone enanthate or cypionate injections. The dosage range for effectiveness and safety we have seen for injections has been from as little as 2.5 mg. per week to 20 mg. per week. A first tell-tale sign that the dose is too high is acne and oily skin. If the dose isn’t reduced immediately when these symptoms appear, then virilizing effects like dark peach fuzz, or itching and growth of the clitoris may result. It is best to start at a low dose, like 2.5 mg., and check the patients’ subjective evaluation of themselves, also testing free testosterone two days after the fourth weekly injection. Increase incrementally and retest as necessary if more is needed.

Cycling For People With Healthy Testosterone Function

Generally speaking, a minority of people who suffer from wasting have healthy testosterone function. Cycling may be appropriate for these people because cycling reduces long-term inhibition of the feedback loop that controls testosterone production in the body. Cycling at the doses and durations in this protocol allows the body time to resume its normal testosterone production after the cycle is ended. Additionally, there is reason to believe that the body loses some sensitivity to the anabolic effects of the steroids when it is “flooded” with high doses of steroids over a long period of time. These are two of the reasons that we advocate anabolic steroid cycles of about twelve weeks, with breaks between cycles of a minimum of sixteen weeks for those people whose bodies can produce healthy levels of their own natural testosterone. We suggest that breaks be as long as possible. Note that Dr. Shalender Bhasin of UCLA, confirms that it took no more than four months for HIV-negative healthy men to return to normal testosterone production after his 600 mg./week, 10 week testosterone enanthate study. 72 He also says that the return to normal took no more than six months for the healthy men in his male contraceptive study that employed 200 mg. per week of testosterone enanthate for one year. While long-term very high dose steroid or testosterone abuse could elicit a more negative result and take even longer to return to normal, Dr. Bhasin’s data suggests that the body will
resume its natural testosterone production after the use of the medically sound and reasonable steroid doses in this protocol. Whether this is true for HIV-positive men is not known, however.

US patent office rejects Gilead Viread patents

US patent office rejects Gilead Viread patents

Wed Jan 23, 2008 3:46pm EST
By Deena Beasley

LOS ANGELES, Jan 23 (Reuters) – U.S. patent officials have rejected four patents on Gilead Sciences Inc’s (GILD.O: Quote, Profile, Research) AIDS drug Viread, but the ruling is not final and the company said on Wednesday it is confident that the patents will be upheld.

The nonprofit Public Patent Foundation had challenged the Viread patents last year. The group said it submitted evidence that the scientific knowledge on which the patents were based had existed before the U.S. Patent and Trademark Office granted the patents to Gilead.

Viread, or tenofovir disoproxil fumarate, is also sold as part of Gilead’s two-drug combination AIDS pill Truvada and as a component of the newer Atripla, which combines Truvada with Bristol-Myers Squibb Co’s (BMY.N: Quote, Profile, Research) Sustiva into a single pill.

Daniel Ravicher, executive director of the patent-challenging foundation, said there was no single source of the “prior art” the group says preceded Gilead’s claims. “It was generally known, ubiquitous knowledge,” he said.

The nonprofit group said Gilead now has the right to respond to the Patent Office’s decision, adding that third-party requests for reexamination, like the ones it has filed against the four Gilead patents, are successful in causing the reviewed patents to either be revoked or changed more than two-thirds of the time.

“This is a typical step in the reexamination process,” said Gilead spokeswoman Amy Flood. “The process may take some time, but we don’t believe the exclusivity of our product is in jeopardy.”

Morgan Stanley analyst Sapna Srivastava said invalidation of the patents “creates an overhang” for Gilead’s HIV franchise.

“While, with our limited knowledge, we strongly believe that Gilead will be able to defend its patents, the PTO rejection does create some uncertainty about Gilead’s core franchise. We expect it will take roughly three to four years to get a final binding decision on these patents,” the analyst said in a research note.

Ravicher said his group has challenged patents from company’s including Microsoft Corp (MSFT.O: Quote, Profile, Research), Pfizer Inc. (PFE.N: Quote, Profile, Research) and Monsanto (MON.N: Quote, Profile, Research) for technologies ranging from stem cells to Internet technologies.

Gilead’s shares fell about 20 cents to $44.00 in late-afternoon trading on Nasdaq. (Reporting by Deena Beasley; editing by Braden Reddall, Richard Chang, Gary Hill)

Four Gilead patents tentatively rejected
SUCH ACTIONS ARE COMMON, BUT FOES CHEER

By Steve Johnson
Mercury News
Article Launched: 01/24/2008 03:35:22 AM PST

A federal agency has tentatively rejected four patents for one of Gilead Sciences’ key drugs for treating people afflicted with the AIDS virus.

The decision by the U.S. Patent and Trademark Office to initially nullify the patents as it re-examines them is considered common, several experts said. But if the agency later makes a final determination that the patents should be revoked, it could have serious consequences for Gilead.

The patents are for Viread, which is used in three HIV treatments that account for most of the Foster City biotechnology company’s sales. If they are revoked, other companies could seek permission from the U.S. Food and Drug Administration to sell competing versions of the drug.

The agency’s action was made public Wednesday by the Public Patent Foundation, a New York-based consumer advocacy group that filed a petition in March seeking to revoke the patents for the drug, also known generically as tenofovir.

The group contends Viread never should have been patented in the first place, because, unknown to the patent office at the time, it claims the technology used to make the drug had been publicly disclosed previously.

Gilead spokeswoman Amy Flood said it is common for the federal agency to tentatively rule patents invalid after it has been asked by a third party to re-examine them. But she stressed that the company expects the patents’ legitimacy to be reaffirmed.

“We will vigorously defend each and every claim that supports our patent protection, and we remain confident in the outcome,” she said.

Daniel Ravicher, the Public Patent Foundation’s executive director, acknowledged that only about 10 percent of the patents the agency re-examines based on third-party challenges are revoked. And even then, he noted, the patent holder can appeal the agency’s decision, a process that can stretch out for several years.

Nonetheless, the tentative ruling “is a pretty huge deal,” Ravicher said. “These are patents which are being used to create market exclusivity for critical technology. . . . The game isn’t over, but we’ve put several touchdowns on the board.”

Ravicher’s organization claims that Gilead has used the Viread patents to charge exorbitant prices for the drug, limiting public access to the treatment. Although retail prices vary widely, a 30-day supply of Viread can easily cost more than $1,000.

Although a previous challenge by Ravicher’s group got Columbia University to stop claiming a right to one of its biotechnology patents in 2004, he couldn’t recall any biotechnology company having a patent revoked.

Neither could Charles Van Horn, a partner in the law firm of Finnegan Henderson, who previously oversaw biotechnology intellectual-property challenges at the Patent and Trademark Office. But if a company lost a key patent, Van Horn added, “that could certainly result in a loss of significant value.”

Gilead sells Viread under that name and in combination with other drugs as Truvada and Atripla. Taken together, the three HIV treatments generated $3.1 billion in sales last year, according to the company, which reported its earnings Wednesday. That accounted for 83 percent of Gilead’s 2007 product sales.

Overall, the company earned $1.6 billion in profit on $4.3 billion in revenue last year. Its stock price rose 61 cents Wednesday to $44.81.

Gilead patent case to help Indian firms

25 Jan 2008, 0027 hrs IST,Rupali Mukherjee,TNN
http://timesofindia.indiatimes.com

NEW DELHI: The US Patent & Trademark Office’s rejection of four patents held by Gilead Sciences on a key HIV drug Tenofovir, paves the way for a more affordable treatment for millions of patients suffering from AIDS.

The US patent office decision strengthens the pre-grant opposition filed in 2006 by Indian Network for People Living with HIV/AIDS (INP+) to several patent applications filed by Gilead on tenofovir disoproxil fumarate (TDF) in India, on the ground that they did not meet the country’s patentability standards.

For the domestic generic industry, the development encourages production of the drug in the country, and gives them opportunities to export to developing countries.

US public interest organization, Public Patent Foundation (PUBPAT) challenged the patents in the US patent office, saying that Gilead’s patent on TDF did not fulfil the criteria of novelty.

With this rejection, Gilead Sciences faces an uphill task to get a patent in India, and other developing countries. Legal experts say, Gilead will now have to share this information with the Indian patent office, which is in the process of examining patent applications on TDF by Gilead.

TDF is important for people suffering with AIDS as a first line treatment, and also for those who have developed resistance to first-line antiretroviral therapy. WHO treatment guidelines include TDF in first and second-line antiretroviral regimens.

INP+, which filed a pre-grant opposition in India is concerned that if patents on TDF are granted access to affordable generic versions of the drug will be affected. Patents granted on TDF by other countries denied people living with HIV/AIDS access to this important anti-retroviral. In fact, Brazil who has granted the patents on TDF has not been able to produce the generic version and has been forced to pay high prices to Gilead to provide the drug to its patients.

The lowest price that Gilead offers TDF (300 mg) in Brazil is $2766 per patient per year, which was nearly halved at $1400 after it threatened invoking a compulsory licence.

The cost of treatment would be one-seventh of that price, if an Indian generic such as Hetero Drugs, Cipla and Matrix offers the drug – at $195 per patient per year.

HPV does not descriminate among gay men, straight men and women

As we live longer, more long term related problems are appearing in HIV positive men and women.

As you can read in the report below, HPV is not a problem that only “bottoms” or gay men have in their butts. HPV can cause anal warts and cancer in all.

I want to remind everyone (men and women) to get their butts checked at least once a year. For a list of doctors who are trained in high resolution anoscopy, visit this link that we provided in the past:

READ THIS EMAIL:
_______________________________________________
http://www.analcancerinfo.ucsf.edu/

Welcome to the Anal Cancer Information website! This website is designed to provide patients and their doctors with some of the latest information on anal cancer, its likely precursor, anal intraepithelial neoplasia (AIN), and the virus that we believe to be responsible for AIN and anal cancer, human papillomavirus (HPV). HPV is also the cause of warts.

—–UCSF has compiled a list of providers trained in HRA (high resolution anoscopy) It’s the procedure that follows any positive anal pap smear, to determine if there are any precancerous lesions which need to be treated. It involves inserting an anoscope in the rectum after the area is first soaked with a vinegar swab so any dysplasia shows up as white patches, and a color camera takes pictures. While up there, they can also take small biopsies of suspicious areas to confirm whether there is dysplasia or cancer.—–Too many people die or end up with colostomies because they aren’t screened for this easily preventable cancer (much as women used to die of cervical cancer before paps become standard of care)—-

Anal cancer is a growing problem in the United States and many other developed countries. Like cancer of the cervix, it is caused by HPV. As you will learn by going to different links, HPV infection of the anal canal is surprisingly common. Anal HPV infection is most commonly acquired through anal intercourse, but it can also be acquired from other genital areas that are infected, particularly from the vulva in women, or from the penis in men. Fingers, toys, etc, can probably lead to anal HPV infection as well. Our research tells us that sexually active individuals, both men and women, may be at risk. The good news is that only a fraction of people with anal HPV infection will develop a lasting case of AIN, and even fewer will develop anal cancer. Men and women who are immunocompromised by human immunodeficiency virus (HIV) infection, organ transplant or other reasons are at especially high risk. So who should be interested in this website?
• Men and women with a history of anal intercourse
• Men and women with a history of perianal (outside the anus) or vulvar warts
• Men and women who are immunocompromised, such as those who are HIV positive, or have received organ transplants

This website was made possible by the generous support of the American Cancer Society. It is designed to tell patients and their doctors about:
• Who is at risk for anal HPV infection, AIN and anal cancer
• Who should be screened for AIN and anal cancer
• How screening should be performed
• How AIN and anal cancer can be treated
• Names and contact information of clinicians around the United States and Canada with experience treating AIN

Who are we?
This website is the creation of a team of highly dedicated clinicians and scientists at the UCSF Comprehensive Cancer Center. The group, led by Dr. Joel Palefsky, Professor of Medicine at UCSF, is devoted to performing research to promote awareness of and screening for AIN and anal cancer, identify the causes of AIN and anal cancer, and develop new and better therapies for these diseases. Through their activities at the Anal Neoplasia Clinic of the UCSF Comprehensive Cancer Center, they provide state of the art care for men and women with AIN and anal cancer. Through this website and other tools the group works to educate patients and their doctors about AIN and anal cancer. As you navigate through this website, we welcome your comments and feedback.

********************************************************************

NATAP http://natap.org/
_______________________________________________

High Prevalence of Anal Human Papillomavirus (HPV) Infection and Anal Cancer Precursors among HIV-Infected Persons in the Absence of Anal Intercourse

Annals of Internal Medicine
18 March 2003 | Volume 138 Issue 6 | Pages 453-459

Christophe Piketty, MD; Teresa M. Darragh, MD; Maria Da Costa, MSc; Patrick Bruneval, MD; Isabelle Heard, MD; Michel D. Kazatchkine, MD, PhD; and Joel M. Palefsky, MD

“….our data indicate that possibly all HIV-positive men with a CD4+ cell count less than 500 x 106 cells/L, especially those with severe immunodeficiency, should be considered for anal cytologic screening, regardless of history of receptive anal intercourse….

…We studied men with CD4+ cell counts less than 500 x 106 cells/L who acquired HIV through injection drug use and who reported no history of receptive anal intercourse. Our results demonstrate a high prevalence of abnormal anal histologic or cytologic findings and anal HPV infection in this group. Among HIV-infected injection drug users, 36% had histologic or cytologic abnormalities. Half of these abnormalities were HSIL, and the overall prevalence of HSIL was similar among HIV-positive injection drug users and men who had sex with men. Risk factors for abnormal anal histologic or cytologic findings in the injection drug users included immunosuppression, high plasma HIV RNA level, and anal HPV infection. Although our study did not include HIV-negative injection drug users, these data indicate that immunosuppression plays an important role in detecting anal HPV infection and anal histologic or cytologic abnormalities in HIV-positive men in the absence of anal intercourse….

…In this cross-sectional study of HIV-positive men, 46% of 50 heterosexual men who reported no history of receptive anal intercourse had anal HPV infection…Human papillomavirus was detected more often in men who had sex with men than in injection drugs users (85% vs. 46%; P < 0.001)….. The mechanisms by which anal HPV infection is acquired in the absence of anal intercourse are not known but could include insertion of transiently infected fingers or toys as well as shedding from other infected genital sites. Immunosuppression may permit replication of what may otherwise have been low-level, possibly undetectable HPV infection, with subsequent development of anal SIL. Anal HPV infection may therefore behave as both a sexually transmitted infection and an opportunistic infection during HIV disease…. the most important risk factors for anal lesions in HIV-infected men who had sex with men were anal HPV infection and the number of lifetime episodes of receptive anal intercourse…. …. Some of the injection drug users enrolled in the study may have had receptive anal intercourse, although they did not report this in the self-administered questionnaire. However, we consider this unlikely because most of the injection drug users were followed at the clinic for years and were not known by their treating physicians to have had anal intercourse, even by means of commercial sex work. Injection drug users were not interrogated for history of incarceration and homosexual rape in prison. However, the prevalence of homosexual rape during imprisonment is estimated to be as low as 1% in French prisons (27). If the patients under-reported anal intercourse, our results may have overestimated the importance of acquisition of anal HPV infection through other means….” Background: Anal cancer and its precursor lesion, anal squamous intraepithelial lesions (SILs), are associated with human papillomavirus (HPV) infection. Anal HPV infection and anal SIL are common in HIV-positive men who have sex with men; receptive anal intercourse is presumed to be the mode of acquisition of HPV. Objective: To assess the prevalence and risk factors for anal HPV infection and anal SIL in HIV-positive men with no history of anal intercourse. Design: Cross-sectional study. Setting: Hôpital Européen Georges Pompidou outpatient clinic, Paris, France. Patients: 118 HIV-infected men. Measurements: 50 HIV-positive heterosexual male injection drug users with no history of anal intercourse and 67 HIV-infected men who had sex with men were evaluated by using anal cytologic, anal histologic, and anal HPV DNA testing. Results:

23 of the 50 heterosexual injection drug users (46%) had anal HPV infection. Low-grade SIL (LSIL) was found in 8 patients (16%) and high-grade SIL (HSIL) in 9 patients (18%).

Among the 67 men who had sex with men, anal HPV infection was found in 57 patients (85%), LSIL in 33 patients (49%), and HSIL in 12 patients (18%).

In univariate analysis, risk factors for abnormal anal cytologic or histologic findings in injection drug users included CD4+ cell counts less than 250 x 106 cells/L (odds ratio, 5.7 [95% CI, 1.6 to 20.4]), plasma HIV RNA viral load greater than 1.7 log copies/mL (odds ratio, 8.9 [CI, 1.1 to 76.0]), previous AIDS-defining event (odds ratio, 4.3 [CI, 1.2 to 15.6]), and anal HPV detection (odds ratio, 5.7 [CI, 1.6 to 20.4]).

Risk factors among men who had sex with men included having more than 10 lifetime receptive anal intercourse episodes (odds ratio, 5.6 [CI, 1.6 to 19.8]) and anal HPV detection (odds ratio, 8.7 [CI, 1.9 to 39.0]).

Conclusions: Anal HPV infection and anal SIL may be acquired in the absence of anal intercourse in HIV-positive men. The prevalence of HSIL is high among HIV-positive injection drug users. All HIV-positive men with CD4+ cell counts less than 500 x 106 cells/L, regardless of history of anal intercourse, should be considered for anal cytologic screening; however, additional studies are needed to determine the efficacy of this procedure to prevent anal cancer in these populations.

The incidence of anal cancer among men with a history of receptive anal intercourse before the HIV epidemic was several times higher than the current rate of cervical cancer in women in the United States; the incidence of anal cancer is estimated to be as high as 35 per 100 000 in this population (1, 2). Anal cancer is associated with human papillomavirus (HPV) infection (3, 4). Earlier studies of the risk for anal cancer in HIV-negative populations showed that a history of receptive anal intercourse was an important risk factor (2, 5), presumably because it increased the risk for acquiring anal HPV infection.

Both anal squamous intraepithelial lesions (SILs) and anal HPV infection are more common in HIV-positive than in HIV-negative men who have sex with men (6-13). Recent studies estimated that the incidence of anal cancer was twofold higher in HIV-infected than in HIV-negative men who had sex with men (14, 15); in addition, the relative risk for developing anal cancer among HIV-positive men was 37-fold higher than in the general population (16). Human immunodeficiency virus-positive men who had sex with men were at 60-fold higher risk. Human immunodeficiency virus-positive injection drug users were also at increased risk (6-fold), although less so than the HIV-positive men who had sex with men. In HIV-positive men who have sex with men, it is difficult to ascertain the role of anal intercourse as a risk factor for anal HPV infection or anal SIL, given the high prevalence of this behavior in this population. Immunosuppression probably plays a role, as indicated in studies showing an association between anal SIL and low CD4+ cell counts (6, 10, 13). In addition, evidence shows that the risk for anal SIL is increased in renal allograft recipients in the absence of receptive anal intercourse (17-19).

Cervical cytologic screening to detect cervical high-grade SIL (HSIL) followed by treatment of the lesions substantially reduces the incidence of cervical cancer. Studies of anal cytologic screening to determine whether the incidence of anal cancer can similarly be reduced have not yet been done. However, according to cost-benefit modeling over a wide range of assumptions, anal cytologic screening in HIV-positive men who have sex with men has been projected to be cost-effective for preventing anal cancer (20, 21).

In this cross-sectional study, we compared the prevalence of and risk factors for abnormal anal histologic or cytologic findings in HIV-positive men who have sex with men with male HIV-positive injection drug users who reported no history of anal intercourse. This was done to assess the role of HIV-related immunodeficiency in detecting anal HPV infection and anal disease in the absence of anal intercourse. In addition, we sought to determine whether the prevalence of anal HPV infection and anal SIL was high enough in HIV-positive injection drug users to warrant additional studies of potential benefit from anal cytologic screening in this population.

Methods

Study Design
Between June 1999 and October 2000, 120 HIV-seropositive men attending the outpatient clinic of Hôpital Européen Georges Pompidou, Paris, France, were recruited in a cross-sectional study of anal HPV infection and anal SIL in HIV-seropositive men. Men were eligible for the study if they had acquired HIV through homosexual or bisexual contact or through injection drug use, were older than 18 years of age, and had absolute CD4+ cell counts less than 500 x 106 cells/L. Injection drug users who had sex with men were excluded from the study. The patients were recruited from a cohort of 1198 HIV-infected patients who were followed at the Clinical Immunology unit of Hôpital Européen Georges Pompidou. All patients were consecutively enrolled into the study. No eligible patient declined participation. The Ethics Review Board of Hôpital Pitié-Salpetrière, Paris, and the Committee on Human Research of the University of California, San Francisco, approved the protocol and written informed consent documents. Patients provided signed written consent before inclusion in the study.

All men were interviewed by using a standardized, comprehensive, self-administered questionnaire that included questions on age, education status, professional activity, tobacco use, route of HIV infection, medical history, history of sexually transmitted diseases, history of HPV-related disease, history of treatment for anal disease, drug use, age at first intercourse, total number of sexual partners, total number of receptive and insertive anal intercourse, and history of commercial sex work with men. The questionnaire was a French translation of a questionnaire used in other published studies conducted at the University of California, San Francisco (10). The questionnaires were self-administered, and the investigators were blinded to the results to better ensure patient privacy and accuracy of the data.

Cytologic and Histologic AnalysesPatients had a thorough anal examination that included insertion of a Dacron swab (Eurotubo, Rubi, Spain) for anal cytologic and HPV testing. The swab was immediately rinsed in a vial of PreservCyt fixative fluid (Cytyc Corp., Boxborough, Massachusetts). Each vial was used for HPV testing and ThinPrep cytologic screening (Cytyc Corp.). An aliquot was taken from the vial for HPV testing; slides were then prepared from the vial by using the ThinPrep 2000 processor (Cytyc Corp.). When cytologic abnormalities were found, consenting patients underwent anoscopic examination and biopsy with the use of a colposcope (22). Biopsy specimens were fixed in 10% formalin for routine histopathologic examination. Anal cytologic and histologic results were evaluated independently of each other, without knowledge of clinical status and HIV risk group of the patient or HPV results. Anal cytologic results were classified as normal, atypical squamous cell of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL), or HSIL by using the Bethesda system criteria for evaluation of cervical cytologic results. If both cytologic and histologic results were available for analysis, a patient’s diagnosis was categorized as the more severe result.

Detection of Anal HPV DNAPolymerase chain reaction (PCR) for anal HPV DNA detection was performed in a blinded fashion. To determine specimen adequacy, genomic DNA was isolated from the ThinPrep vial and amplified by using MY09/MY11 consensus HPV L1 primers as well as primers to amplify the human ß-globin gene (9). After 40 amplification cycles, specimens were probed with a biotin-labeled HPV L1 consensus probe mixture. A separate membrane was probed with biotin-labeled probes for the human ß-globin gene.

We performed type-specific probing for the following HPV types individually: 6; 11; 16; 18; 26; 31; 32; 33; 35; 39; 40; 45; 51; 52; 53; 54; 55; 56; 58; 59; 61; 66; 68; 69; 70; 73; Pap 155; Pap 291; AE2; and a mix containing 2, 13, 34, 42, 57, 62, 64, 67, 72, and W13B. We designated samples that were positive with the consensus probes but negative with the individual type-specific probes as having one or more “other” types.

Polymerase chain reaction can be used to discriminate between low-level HPV infection and high-level HPV infection on the basis of intensity of the PCR signal on Southern blot analysis (23), which was recorded on a scale from 0 (negative) to 5. For the purpose of the analysis, a sample that was positive for more than one HPV high-risk types was categorized as the higher PCR signal from the sample.

CD4+ Cell Count and Plasma HIV RNA Viral Load
We used the CD4+ cell counts and plasma HIV RNA viral loads closest to the period within 2 months of the anal examination. The nadir CD4+ cell count was defined as the lowest count recorded before the study. Absolute numbers of CD4+ T cells were determined by standard flow cytometry. Plasma HIV RNA levels were determined by the branched-chain DNA signal amplification assay (Quantiplex HIV-RNA, Chiron Diagnostics Corp., Emeryville, California).

Statistical AnalysisWe analyzed data by using StatView 5 software (SAS Institute, Inc., Cary, North Carolina). Because most variables had skewed distribution, data are presented as median and ranges. Differences across HIV risk groups were tested with the Fisher exact test (categorical variables) and the nonparametric Mann-Whitney U test (continuous variables). Patients with HPV infection and histologic or cytologic abnormalities were compared with patients with no evidence of HPV infection or anal disease. To identify risk factors for histologic or cytologic abnormalities, the following dichotomous variables were entered into a logistic regression model: age (35 years), age at first intercourse ( 0.2]). However, the mean nadir CD4+ cell count was significantly lower in injection drugs users who exhibited HSIL than in those who did not (16 vs. 140 x 106 cells/L; P = 0.03).

Anal HPV DNA was detected in 80 of the 117 patients (68%). One or more high-risk HPV types was present in 47 of the 80 positive samples (59%). Table 3 presents data on HPV in the two groups. Human papillomavirus was detected more often in men who had sex with men than in injection drugs users (85% vs. 46%; P < 0.001). Of the HPV-infected men who had sex with men, 61% had infection with more than one HPV type compared with 26% of the HPV-infected injection drug users (P = 0.006). Table 3. Proportion of Patients with Anal HPV Infection, Stratified by HIV Risk Group
The proportion of men exhibiting at least one high-risk HPV type and a high-risk PCR signal (>/=2) did not differ between the HPV-infected men who had sex with men and the HPV-infected injection drug users (65% vs. 44% [P = 0.08] and 89% vs. 90% [P > 0.2], respectively). Overall, 27 different genotypes were detected. Human papillomavirus 16 was the most common high-risk genotype found in the two groups [30% in the men who had sex with men and 22% in the injection drug users; P > 0.2]. Human papilloma virus 18 was found in 16% of the men who had sex with men and 4% of the injection drug users; P > 0.2). Human papillomavirus 6 was the most common low-risk genotype found in the two groups (32% in the men who had sex with men and 17% in the injection drug users; P > 0.2). Among the patients with histologic or cytologic abnormalities, HPV was detected in 13 of 18 injection drug users (72%) and 45 of 48 men who had sex with men (94%) (P = 0.03).

Risk Factors for Abnormal Anal Cytologic and Histologic Findings and Anal HPV InfectionTable 4 presents univariate analyses of risk factors for abnormal anal histologic or cytologic findings among injection drug users. All factors significant in the univariate analysis remained significant in the multivariate models that incorporated these factors. These included CD4+ cell counts less than 250 x 106 cells/L, nadir CD4+ cell count less than 100 x 106 cells/L, a previous AIDS-defining event, plasma HIV RNA level greater than 1.7 log copies/mL, and positive results on HPV PCR (Table 4). Overall, no significant risk factors were observed for HPV when defined by positivity with the consensus primers. In univariate analysis, CD4+ cell counts less than 250 x 106 cells/L and a previous AIDS-defining event were risk factors for HPV 16 or 18 infection.

Table 4. Risk Factors for Abnormal Anal Histologic or Cytologic Findings in HIV-Positive Men Who Have Sex with Men and HIV-Positive Injection Drug Users

Among the men who had sex with men, abnormal anal histologic or cytologic findings were associated in univariate analysis with HPV infection and with more than 10 lifetime episodes of receptive anal intercourse (Table 4). In univariate analysis, no significant risk factors for HPV 16 or 18 infection or HPV overall were identified.

Discussion

We studied men with CD4+ cell counts less than 500 x 106 cells/L who acquired HIV through injection drug use and who reported no history of receptive anal intercourse. Our results demonstrate a high prevalence of abnormal anal histologic or cytologic findings and anal HPV infection in this group. Among HIV-infected injection drug users, 36% had histologic or cytologic abnormalities. Half of these abnormalities were HSIL, and the overall prevalence of HSIL was similar among HIV-positive injection drug users and men who had sex with men. Risk factors for abnormal anal histologic or cytologic findings in the injection drug users included immunosuppression, high plasma HIV RNA level, and anal HPV infection. Although our study did not include HIV-negative injection drug users, these data indicate that immunosuppression plays an important role in detecting anal HPV infection and anal histologic or cytologic abnormalities in HIV-positive men in the absence of anal intercourse.

Our findings are consistent with data previously reported in renal allograft recipients in the absence of receptive anal intercourse (17-19). The mechanisms by which anal HPV infection is acquired in the absence of anal intercourse are not known but could include insertion of transiently infected fingers or toys as well as shedding from other infected genital sites. Immunosuppression may permit replication of what may otherwise have been low-level, possibly undetectable HPV infection, with subsequent development of anal SIL. Anal HPV infection may therefore behave as both a sexually transmitted infection and an opportunistic infection during HIV disease.

A wide range of HPV types were detected in the anal canal of HIV-positive injection drug users. As in the group of HIV-positive men who had sex with men, the single most frequently detected type was HPV 16. However, infection with several HPV types was seen less frequently in injection drug users than in the men who had sex with men.

In contrast to injection drug users, the most important risk factors for anal lesions in HIV-infected men who had sex with men were anal HPV infection and the number of lifetime episodes of receptive anal intercourse. The prevalence of anal SIL and anal HPV infection observed in our cohort of 67 HIV-infected men who had sex with men was within the range observed in previous studies (7, 9, 10, 24, 25).

Our study has several limitations. An anal biopsy was performed only in patients with cytologic abnormalities. Because some of the men with normal cytologic findings may have had a false-negative cytology result (26), the true prevalence of anal SIL may be even higher than what we observed. Comparisons between the injection drug users and men who had sex with men may have been biased toward overestimating their similarities because the CD4+ cell counts were significantly lower and the prevalence of current smokers was significantly higher in the injection drug users than in the men who had sex with men. However, these limitations do not alter the interpretation of our findings, which show a high prevalence of anal HPV infection and anal SIL in the absence of anal intercourse.

Some of the injection drug users enrolled in the study may have had receptive anal intercourse, although they did not report this in the self-administered questionnaire. However, we consider this unlikely because most of the injection drug users were followed at the clinic for years and were not known by their treating physicians to have had anal intercourse, even by means of commercial sex work. Injection drug users were not interrogated for history of incarceration and homosexual rape in prison. However, the prevalence of homosexual rape during imprisonment is estimated to be as low as 1% in French prisons (27). If the patients under-reported anal intercourse, our results may have overestimated the importance of acquisition of anal HPV infection through other means.

Finally, our data indicate that possibly all HIV-positive men with a CD4+ cell count less than 500 x 106 cells/L, especially those with severe immunodeficiency, should be considered for anal cytologic screening, regardless of history of receptive anal intercourse. However, our sample size was small, and additional studies are needed to determine the efficacy of anal cytologic screening to prevent anal cancer in injection drug users and men who have sex with men. Notably, the prevalence of HSIL was similar to that of HIV-positive men who had sex with men, for whom screening is projected to be cost-effective (20). Many factors that have not yet been defined may affect the efficacy of screening among injection drug users; one of these is the rate of progression from HSIL to cancer in this group.

Additional studies are needed to better understand the natural history of anal SIL in HIV-positive injection drug users. In addition, studies of anal SIL and anal HPV infection in other groups, such as women and HIV-negative heterosexual persons, will provide necessary data.

New HIV Drug Concern: How can long term survivors with archived NNRTI resistance know if Intelence is really an “intelligent” choice ?

Intelence (TMC 125- etravirine) is a new NNRTI just approved today for the treatment of HIV.

Many of us developed resistance to Nevirapine and Efavirenz years ago and are now showing “sensitivity” to NNRTIs after years of not taking them since NNRTI resistance gets archived after years. Many of the key resistance mutations that render TMC 125 useless were not listed in old genotypes that doctors can pull from our old records,so we do not really know if this new NNRTI will be an active agent for us. I am R5 tropic and need at least one (preferably two) more active agents.

Question: How can long term survivors with archived NNRTI resistance from years ago know if Intelence is really an “intelligent” choice for them as part of a 2 or 3 active drug regimen?

These are the key mutations they list:

— The presence of K103N, which was the most prevalent NNRTI substitution in DUET-1 and -2 studies at baseline, did not affect the response in the INTELENCE arm.
— The presence at baseline of the substitutions V179D, V179F, V179T,
Y181V, or G190S was associated with a decreased virologic response to INTELENCE.
— In the DUET-1 and -2 studies, the presence at baseline of three or more 2007 IAS-USA-defined NNRTI substitutions (V90I, A98G, L100I, K101E/P, K103N, V106A/I/M, V108I, V179D/F, Y181C/I/V, Y188C/H/L, G190A/S, P225H) resulted in a decreased virologic response to INTELENCE.
— For patients in the DUET-1 and -2 studies experiencing virologic
failure on an INTELENCE-containing regimen, the substitutions that
occurred most commonly were V179F, V179I, Y181C, and Y181I which usually emerged in a background of multiple other NNRTI resistance-associated substitutions. Other NNRTI resistance-associated substitutions which emerged in patients on INTELENCE treatment in
< 10 percent of the virologic failure isolates included K101E, K103N,
V106I/M, V108I, Y188L, V189I, G190S/C and R356K.
— Cross-resistance to delavirdine, efavirenz, and/or nevirapine is
expected after virologic failure with an INTELENCE-containing regimen.

New HIV drug to be approved soon: Intelence

This is from Rob Camp’s blog, a well known treatment activist that sends letters to the FDA before an HIV drug gets approved with his comments and observations about that drug. If you are considering taking this new NNRTI, read this:
http://mundocamp.vox.com/

I still wonder how people like me with NNRTI resistance from years ago can predict if this drug would work for us. Our resistance is archived and even if our doctors digged out old genotype or phenotype tests, most of the TMC 125 associated key mutations were not measured back then. I guess that if in doubt, NEVER start Intelence with only one more active agent. Many people like me will get on this drug as part of a 3 active drug combo and really have no idea about the real contribution of this drug. The DUET study saw no added benefit of those starting Prezista + TMC 125 (intelence) + Fuzeon + nukes versus Prezista+ Fuzeon + nukes.

I am glad there will be a new HIV drug in the market, though. I hope that the incidence of rash is not high in those starting this drug.

Bristol-Myers Slammed By AIDS Group Over Pricing

Bristol-Myers Slammed By AIDS Group Over Pricing

January 16th, 2008 7:20 am By Ed Silverman

The Fair Pricing Coalition, an independent community group that works to contain the prices of drugs used to treat HIV, is condemning price increases announced this week by Bristol-Myers Squibb, which failed to meet with the umbrella group, as most other drugmakers do, to discuss pricing.

The increases, which ranged from 6.9 percent to 9 percent for all of Bristol’s HIV products “are well beyond any increases in the Consumer Price Index and above the increases taken by any other company”, says Martin Delaney of the FPC, in a statement. “These drugs have been on the market for several years and their development costs have long been recovered. There is no justification for this kind of increase.”

Another FPC spokesperson, Lynda Dee of the AIDS Treatment Activist Coalition and AIDS Action Baltimore, further stated “This is exactly the kind of behavior that gives the pharmaceutical industry such a bad name with the public. Bristol is doing very little if any further research in HIV and overall has poor relations with the patient community. This action makes it clear they don’t care what their customers think or need.”

Bristol currently markets four HIV drugs, including: Zerit, a 15-year-old drug with plummeting sales due to side effects; Sustiva, a very popular drug the company acquired after it was already successful development costs recovered; Atripla, a top-selling drug that combines Sustiva in a single pill with a two drug combo made by Gilead; and Reyataz, a popular drug sold to patients at all stages of HIV and the only good-selling drug for HIV developed by Bristol alone.

“Considering how little this company has spent developing its portfolio of HIV drugs, especially in recent years, and how well their products are selling, it’s unconscionable for BMS to do this, they’ve got a lot of nerve pushing the limits with these annual price increases,” Dee adds.

The FPC goes on to say its “very concerned” that Bristol’s actions will prompt other drugmakers to follow suit. “The last thing we need right now is a round of excessive price increases for these drugs, which are already extremely expensive and burdening the health care system,” says Paul Dalton of the FPC and Project Inform, another activist group.

“Even though the increase to government payers is limited to the increases in the Consumer Price Index, these increases affect the co-pays that patients must pay out of pocket. The price hikes also put pressure on other companies to levy similar increases, triggering round after round of price escalation.”

The FPC adds that nearly every other drugmakers takes part in pricing discussions with the group, which acts on behalf of the interests of hundreds of community groups. “We meet with other companies before any new drug is priced and we talk with them prior to any significant price increases,” says Delaney.

“We haven’t heard a word out of Bristol in years, though we’ve been doing this work for more than a decade. The company continues to show the kind of arrogance and disregard for the public that lead to the extraordinary fines it has had to pay. We’ve already seen the price increases spread as Gilead, BMS’s partner in the combination drug Atripla which they both sell, has already raised its price to match Bristol’s.”

The FPC is urging Bristol to roll back its 2008 price increases completely, or at the very least to no more than what is warranted by the Consumer Price Index. Additionally, the group “strongly recommends” the drugmaker renew communications with the FPC, the AIDS Treatment Activist Coalition, individual community organizations and all relevant patient groups nationally and internationally.

Supreme Court Declines to Hear Experimental Drug Case

Supreme Court Declines to Hear Experimental Drug Case
Petitioners Argue Terminally Ill Should Have Right to Drugs Not Yet Approved by FDA

By Robert Barnes
Washington Post Staff Writer
Monday, January 14, 2008; 4:36 PM

The Supreme Court today declined to consider whether dying patients have a right to be treated with experimental drugs not yet approved by the Food and Drug Administration.

The court, without comment or recorded dissent, let stand a ruling by the U.S. Court of Appeals for the D.C. Circuit, which said the terminally ill have no constitutional right to drugs the agency had considered safe enough for additional testing.

The challenge was brought by the Washington Legal Foundation and the Abigail Alliance for Better Access to Developmental Drugs. The latter organization is headed by Frank Burroughs of Fredericksburg, and named in honor of his daughter, Abigail Burroughs, who was diagnosed at 19 and died at 21 of a form of cancer rare in someone her age.

The young woman died in 2001, and the drug she was seeking was later approved.

“Petitioners contend that a terminally ill patient with no approved treatment options has a right to decide for himself, in consultation with his own doctor, whether to take a drug that the FDA concedes is safe and promising enough to be tested in substantial numbers of human subjects,” the two groups told the court.

“This case is about the patients who cannot get into the trials — because they are too young, too sick, cannot qualify for the trial protocol, cannot travel, or because the trial is simply too small.”

The groups lost in the lower courts last summer when, after a pair of conflicting rulings, the full D.C. Circuit ruled 8-2 that “there is no fundamental right deeply rooted in this nation’s history and tradition of access to experimental drugs for the terminally ill.”

The Bush administration, representing the FDA, asked the Supreme Court not to hear the case.

“On the one hand, when existing treatments have been tried and have proven ineffective, patients who are suffering from serious diseases have an understandable interest in trying potentially effective investigational drugs, particularly when the patient’s illness is life-threatening,” U.S. Solicitor General Paul D. Clement said in a brief filed with the court.

“On the other hand, allowing patients to obtain and use unproven drugs carries a host of risks and potential detriments for the public health.”

Clement said FDA studies have shown that “preliminary expectations of safety and efficacy often prove to be unfounded, and drugs that initially appear promising are frequently found ineffective or even affirmatively dangerous to life and health.

“Worse still, the drug may be affirmatively unsafe, and taking it may sicken the patient or even kill him.”

Clement also argued on the agency’s behalf that “unfettered access to investigational drugs for treatment uses may harm society at large by undermining the clinical trial process itself.”

SIGN ON PETITION: ads for prescription and over the counter drugs should include a toll-free number and a website to report side effects

IMPORTANT: If you’re interested in signing onto the attached petition, please contact Consumers Union directly (Bill Vaughan at wvaughan@consumer.org or Susan Herold at herosu@consumer.org)

December 31, 2007

Divison of Dockets Management

Food and Drug Administration

Department of Health and Human Services

5630 Fishers Lane, Room 1061

Rockville, Maryland 20852

Citizen Petition

Consumers Union, the independent, non-profit publisher of Consumer Reports[1]

submits this petition pursuant to 4(d) pf the Administrative Procedure Act, 5 USC 553(e), 21 CFR 10.25 & 10.30, and PL 110-85, section 906.

Section 906 of the FDA Amendments Act of 2007 provides that the

Secretary of Health and Human Services shall conduct a study to determine if the [following] statement [“You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088”] required with respect to published direct-to-consumer advertisements is appropriate for inclusion in…television advertisements.

Action Requested

Consumers Union (CU) requests the Food and Drug Administration require that all television advertisements for prescription drugs and over the counter drugs include a toll-free number and a website address for the public to report side effects to the agency. All television advertisements for prescription drugs should include the following, “You are encouraged to report adverse effects of prescription drug medication. Log onto www.fda.gov/Medwatch or call 1-800-FDA-1088.”

The FDAAA (P.L. 110-85) requires all print advertisements to include this statement, but this should be expanded to include TV advertisements.

Statement of Grounds

All too often, drug advertisements fail to present the benefits and risks of using prescription drugs in an accurate and balanced way. It is often the newest drugs that are the most heavily advertised, and it is these drugs whose side effects we know the least about. Two-thirds of all drug withdrawals occur within the first three years of release and it estimated that only half of all label changes occur in the first seven years that a drug is on the market.[2] The recent action by the FDA on the use of over-the-counter cold remedies on young children is a clear example of why the public should be encouraged to report adverse events from not just prescription drugs but from over the counter products, even those long considered safe. Therefore, it is important to have information on TV advertisements where consumers can report side effects.

Currently, it is estimated that adverse drug event reporting system catches only a small fraction of all adverse incidents of drugs.[3] Adverse drug reactions are responsible for as many as 700,000 emergency room visits annually.[4] Including a toll-free number and a website to report side effects will increase the information the FDA has on drug risks and would also increase awareness to consumers.

And television drug ads run far more frequently than print ads. Consumers are repeatedly faced with TV ads, with their pictorial power, compared to what is generally a one time scan in the print media. Including this number and website in TV ads would reach far more Americans than through print ads.

The FDA has stated about MedWatch:

“The MedWatch program has four goals:

To clarify what should and should not be reported to FDA.
To increase awareness of serious reactions caused by drugs or medical devices.
To make the reporting process easy.
To give the health community regular feedback about product safety issues.
While participation in MedWatch is voluntary, FDA encourages anyone aware of a serious adverse reaction, including consumers, to make a MedWatch report.”[5]

Including a toll-free number and a website to report side effects would certainly help the FDA achieve the above goals and it would help encourage many more consumers to report adverse reactions with medications.

Increased reporting and use of MedWatch would help in the earlier detection and better analysis of problems. All television ads should contain information on how patients should report unusual side effects to the FDA.

Environmental Impact

We believe that pursuant to section 21 CFR 25.30(a), this petition is excluded from the requirement for an environmental impact statement.

Certification

The undersigned certifies, that, to the best knowledge and belief of the undersigned, this petition includes all information and views on which the petition relies, and that it includes representative data and information known to the petitioner which are unfavorable to the petition.

Sincerely,

Kim Witczak

2414 West 54th St

Minneapolis, Minnesota 55410

Elizabeth Foley

Consumers Union

Grassroots Coordinator

101 Truman Ave

Yonkers, NY 10703

914-378-2421

——————————————————————————–

[1] Consumers Union is a nonprofit membership organization chartered in 1936 under the

laws of the State of New York to provide consumers with information, education and

counsel about goods, services, health, and personal finance. Consumers Union’s income

is solely derived from the sale of Consumer Reports and ConsumerReports.org, its other publications and from noncommercial contributions, grants and fees. In addition to reports on Consumers Union’s own product testing, Consumer Reports and ConsumerReports.org, with approximately 6.5 million combined paid circulation, regularly carry articles on health, product safety, marketplace economics and legislative, judicial and regulatory actions that affect consumer welfare. Consumers Union’s publications carry no advertising and receive no commercial support. EXPERT • INDEPENDENT • NONPROFIT®

[2] Matthew F. Hollon, MD., “Direct-to-Consumer Advertising: A Haphazard Approach to Health Promotion,” JAMA, April 27, 2005. Vol. 293, No. 16, p. 2032.

[3] Institute of Medicine, “The Future of Drug Safety, 2006, p.53

[4] Daniel S. Budnitz, MD., “National Surveillance of Emergency Department Visits for Outpatient Adverse Drug Events,” JAMA, October 18,2006. Vol. 296, No. 15 p.1863

[5] John Henkel., “Medwatch: FDA’s Heads Up on Medical Product Safety,” FDA Consumer Magazine, November-December 1998.

Insulin, Leptin, Diabetes, and Aging: Not So Strange Bedfellows

As we know from several studies, insulin levels seem to be higher in HIV positives than negatives. We also have more problems with increased triglycerides, low HDL, lower bone density, increased visceral fat, and glucose intolerance/insulin resistance.

You will read some radical statements in the link below, among which this is one:

“Incidentally, two of the most popular diabetic medications today, Actos and Avandia, wrongly claimed by their manufactures as being insulin sensitizers, actually work by multiplying fat cells, thereby creating more wastebaskets in which to store sugar as fat. They actually make you fatter and more leptin resistant, and they accelerate your rate of aging”

“Elevated insulin plays an important role in osteoporosis. Insulin promotes the excretion of calcium in the urine…This is a major source of osteoporosis and far exceeds in importance a lack of calcium in the vast majority of people. There is a high correlation between osteoporosis and calcification of arteries. In other words, most people with osteoporosis have the calcium – it’s just in the wrong places.”

http://www.diabeteshealth.com/read/2008/01/13/5617.html

What is the best delivery method for testosterone in men?

Dear Nelson:

I was wondering what your opinion, Nelson, is self
injecting testosterone a better way to administer
testosterone, or do you recommend the gels? I also see
where you have mentioned appliedpharmacyrx. Would they
also be able to supply Deca (Nandrolone)? I feel like
I can bulk up better when I am a taking this as well.
What are your thoughts about this? Thanks for all the
good work that you do for the HIV community.

*****************************
The choice of testosterone delivery methods depends on: 1- How disciplined one may be for daily application, 2- How well and how sustained the method takes you above 500 nanograms per deciliter of total testosterone in your blood, 3- How much testosterone gets aromatized to estrogen in your body (estrogen can cause water retention and increased breast size), 4- How much testosterone is metabolized into DHT (dehydrotestosterone, the culprit for acne, hair loss).

Some guys like injections of 100 mg a week or 200 mg every two weeks. I have used this method for years with good results, but the ups and down are a lot more noticeable than using more sustained daily methods. Some love the “peak” caused by the injections.

I have tried Androgel and Testim (both 1% testosterone gels) in the past and they have been OK for me. Testim has a smell that many dislike, but the company claims 30% better absorption than Androgel. Androgel came up with a cool pump that you can use to increase the daily dose if needed. The folks from Androgel are coming up with a 2.5% testosterone version soon. Some guys never reach levels above 500 nanograms with either gel and get better results with a more concentrated gel from compounding pharmacies (you can order 5 or 10% gels at a cheap cost from them). I think Androgel and Testim are a rip off when it comes to price, though, and their patient assistance programs do not seem to be working that well.

2007 was an interesting year for me when it comes to testosterone. I tried Nebido, a 1000 mg shot of testosterone undecanoate (not yet approved in the US) that keeps your testosterone above 500 nanograms for 3 months. It worked beautifully for me. I did not need naps, my sex drive was pretty good and constant for weeks, my appetite was great, and my mood was excellent. After that I tried Testopel pellets and got 12 pellets inserted under the skin of my left gluteous maximus. After a month, my testosterone has gone up from 300 to 800 nanograms and I feel great. I am watching to see if 12 pellets will take me to 120 days of good testosterone levels, as claimed by the maker. So far, they are not noticeable to the naked eye and I am very happy with them. The key will be if it gets insurance and Medicare reimbursement.

Before you start testosterone, make sure your doctor tests your blood for prostatic specific antigen (PSA), gives you a digital rectal exam, he/she measures your hemoglobin/hematocrit, and your total and free testosterone along with thyroid and estradiol levels. Some check sex hormone binding globulin, a protein that seems high in many HIVers that binds testosterone and does not allow it to do its job. This is one of the reasons some people do not feel much after testosterone supplementation.

Have your doctor check your testosterone and estradiol again 3 weeks after you start to see where you are. You may have to increase your dose if your free testosterone is not above 35 picograms per mL . I like to at least be mid range since the free testosterone range is 35- 155 pg/mL. But at the end, what really matters is how you feel. Have her/him also check your hemoglobin/hematocrit after a month to see if you are not one of those unlucky people whose red blood cells increase so dramatically which makes your blood gets too thick to be pumped by your heart. This is called polycethymia and it can be a huge problem. People with this problem have to get phlebotomized ( give blood) or stop testosterone all together.

On the subject of nandrolone, I have very strong biases for that drug, as you guys know. I think nandrolone decanoate is one of the best drugs to be used for improved quality of life, body composition, bone strength, energy, and improved body image. It has helped many HIVers “balance out” thin extremities that were afected by years of lipoatrophy. It has a lot of good data in HIV for men and women, and you can ready more in medibolics.com or our book “Built to Survive”. My doctor once joked that “Nelson Vergel wants nandrolone in the drinking water” LOL

Watson pharmaceuticals, the makers of nandrolone stopped maufacturing it without telling the comunity Nandrolone is available through several compounders. We posted a list here

http://archive.constantcontact.com/fs020/1101823881298/archive/1101825972178.html

I am writing a book about all my experiments with my health in the past 22 years to disclose practical tips that do not require too much reading and medical knowledge. I hope this information helped you!