A sunny day here has been followed by a bright and clear starry night, and our thoughts are in tune with those who seek romance in the excitement of the Dating Night in the Big City, whose innocent efforts to form lasting relationships with those they find inspiring the staff of SG/NAR is always trying to protect from those who want to drag them into the gutter of revolting misinformation which even macaques (we include macaques in those we are trying to save) should be rescued from.

The nature of this horrid topic is such that it is usually protected from outside examination in this way ie as off putting to most readers and we fervently congratulate all those here who face the task with such cool objectivity, for all future romantics will be indebted to them.

“A Pubmed search on tenofovir and gel suggests no animal testing of this particular formulation”.

Quite true, but once tenofovir was approved for use by the FDA, I don’t think there was any restrictions as to which orifices it could or should be taken in.

I certainly think that if one is to choose to take it, it is by far safest to be taken analy, where at least it could be more quickly and easily expelled!

All I can say is,

Party Pooper!

Or to quote your very self:

(insert deity) Bless.

I trust you already know JP’s email address. I’m sure he would appreciate your input.

In the meantime, please give this guy hell. I don’t even know what the f… he is talking about:

“MEC,

Since you seem to be so interested in the HPV vaccine, and so impressed with Cathy’s comments on it, I read the remainder of the op-ed she allegedly wrote.

In your words, MEC,
he fact is it was Merck’s statistics that were wishful, and it was you who couldn’t come up with anything to defend them.

It would help if you could point out which of Merck’s statistics were wishful. Cathy tried and in my view failed. The only fault I find with Merck’s reports is their assertion (in marketing material) that HPV is associated with all cervical cancers. They could be right, but there could also be a few HPV-negative cases. Merck’s fine print (on the marketing brochure I read, anyway) is better: they cite a study (Walboomers, JM, et al, J Pathol, Sept 1999) of over 900 archived patient samples in which 99.7% test positive for HPV, up from 93% in a previous study using earlier methods.

It’s too bad Merck didn’t insert a little “almost”, but 99.7%, let’s be realistic, isn’t that far away from 100%, particularly for the marketing side of business. It’s also closer to the data than Cathy’s “HPV DNA has been found in ~ 80% of cervical squamous carcinoma”.

Another example? Let’s examine Cathy’s claim, her second “point” in the “Evidence-Based Medicine?” section, that Merck’s Study 015 data actually prove Gardasil’s target HPV strains do not associate with a majority of external genital lesions (EGL).

Cathy writes that, “According to Merck’s own results, strains 6 and 11 contribute less than 40% to all genital warts.” (According to her, Merck has stated that 6 and 11 cause 90%.) An obvious contradiction, right?

Not so fast. Cathy presents a table illustrating that one Gardasil recipient developed target-strain-related EGL while 96 had any-strain EGL. A second table shows that 70 placebo recipients got target-strain EGL, but 177 developed any-strain lesions. Cathy thinks this means that only 70 of 177 (39.5%) EGL cases are due to HPVs 6, 11, 16, or 18.

And it very well might….if the two tables were at all comparable.

Cathy didn’t notice or concealed from “Scoop” readers that the two tables she modified (Tables 5 and 6 found at http://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4222B3.pdf) present data, respectively, from the “per-protocol” population of women who tested negative at study entry for all four target strains and from the “MITT-3″ population including enrollees who tested positive at entry. These two tables can’t be compared directly. The second table includes the cases of HPV 6, 11, 16, and 18 excluded from the first. It’s likely that most or all of the additional cases of any-strain lesions in Cathy’s second table are in 6-, 11-, 16-, or 18-positive women.

That’s right, MEC: the trusty invalid comparison technique straight out of the School of Wishful Statistics. As if once were not enough, Cathy repeats the technique for her next point, Point 3.

MEC, if you insist, we can review Cathy’s letter to the editor claim by claim. I say it’s not worth our time. The article is worthless, except perhaps to show that anger and bitterness can impair one’s judgment…or as a tool in the science classroom (note to self).

As I’ve already stated, I’m willing to look past spelling errors and (at least two, if you must know) poorly-crafted sentences. The editor may have been on vacation, the electronic version I read could be slightly different from the “official” on-line or print version, or Merck cyber-spies may have deliberately sabotaged Cathy’s work. Personally, I’m leaning towards that last one. But I’m not willing to excuse Cathy’s proudly diplayed ignorance of biology and stats.”

Posted by: ElkMountainMan | April 5, 2008 9:11 AM

http://scienceblogs.com/aetiology/2008/03/objection_to_vaccination_they.php#comment-821194

What I found most interesting about the Eurekasleep sycophantic Newspeak was what it didn’t say. From the numbers cited, 59% didn’t like the microbicide gel for one reason or another, 81% didn’t have any faith in its potential to protect against HIV despite being enrolled in a trial designed to test the safety of a gel purported to prevent the transmission of HIV (cynical lot), 61% found it difficult to use, 86% thought it smelled and looked bad, and 88% found it made sex less pleasurable.

Effects on vaginal tissue, vaginal flora, and inflammatory cytokines “not yet available”! Potential effects on a developing embryo/foetus unknown, so let’s test in pregnant women anyway. A Pubmed search on tenofovir and gel suggests no animal testing of this particular formulation. But then the effects of leaving a concentrated toxic substance in the vaginal vault for hours/days are exactly the same as oral administration aren’t they? If I swallow a condom everyone knows I won’t get pregnant.

J Womens Health (Larchmt). 2008 Apr;17(3):383-92.
Acceptability of tenofovir gel as a vaginal microbicide among women in a phase I trial: a mixed-methods study.
Rosen RK, Morrow KM, Carballo-Diéguez A, Mantell JE, Hoffman S, Gai F, Maslankowski L, El-Sadr WM, Mayer KH.
The Miriam Hospital, Providence, Rhode Island.
ABSTRACT Objectives: In this phase I safety trial of tenofovir gel, a candidate vaginal microbicide for human immunodeficiency virus (HIV) prevention, a mixed-methods design was used to gather acceptability data among women participants. The impact of acceptability factors on use of the gel and the relationship between qualitative and quantitative acceptability data are explored. Methods: Participants included low-risk, HIV-uninfected, and clinically stable HIV-infected women. Participants were enrolled into cohorts stratified by HIV serostatus, sexual activity, gel concentration, and frequency of use. Quantitative data were collected via interviewer-administered structured questionnaires. Qualitative data were collected via semistructured small group discussions. Results: Although 94% of participants stated they would “probably” or “definitely” use tenofovir gel, a range of responses emerged on multiple domains relevant to microbicide acceptability during the qualitative discussions. Lubrication, leakage, sexual pleasure, and the possibility of covert use were central to women’s qualitative assessments of tenofovir gel. Conclusions: Quantitative results indicate that tenofovir vaginal gel was acceptable to almost all users, while qualitative findings indicate that acceptability is complex, varies among users, and is likely shaped by a variety of contextual factors that manufacturers will need to consider to optimize use-effectiveness. Because of the differences in the qualitative and quantitative responses, the authors argue that future trials of candidate microbicides should include strategic collection of mixed-methods microbicide acceptability data.

Reading between the knowledge-management speak lines here I’d say on the whole the women weren’t overly impressed.

AIDS. 2006 Feb 28;20(4):543-51.
Safety and tolerability of tenofovir vaginal gel in abstinent and sexually active HIV-infected and uninfected women.
Mayer KH, Maslankowski LA, Gai F, El-Sadr WM, Justman J, Kwiecien A, Mâsse B, Eshleman SH, Hendrix C, Morrow K, Rooney JF, Soto-Torres L; HPTN 050 Protocol Team.
Miriam Hospital/Brown University, Providence, Rhode Island 02906, USA. Kenneth_Mayer@brown.edu
OBJECTIVES: To establish the highest practical dose and frequency (HPDF) of 0.3% or 1% tenofovir vaginal gel applied once or twice daily by sexually abstinent HIV-uninfected women, and to evaluate the safety, tolerability and systemic pharmacokinetics of the HPDF in abstinent and sexually active HIV-negative and HIV-infected women. METHODS: Eighty-four women, enrolled in sequential cohorts, used the study product for 14 consecutive intermenstrual days. Safety laboratory assessments and pelvic examinations were carried out during five study visits, with colposcopy at enrollment and on day 14. Samples for pharmacokinetics were collected before and after the initial tenofovir gel use and at day 13. RESULTS: The 1% tenofovir gel used twice daily was as well tolerated as other regimens used by the 48 HIV-negative sexually abstinent women, establishing the HPDF. Although 92% of the women reported at least one adverse event, the majority were mild (87%) and involved the genitourinary tract (70%). One possibly product-related severe adverse event involving lower abdominal cramping was reported by a sexually abstinent woman who used 0.3% gel twice daily. Serum tenofovir levels were low but detectable in 14 of the 25 women. No new HIV RNA resistance mutations were detected after 2 weeks of tenofovir gel in the 24 HIV-infected participants. No significant systemic toxicity was detected. CONCLUSION: A 2-week course of 1% tenofovir vaginal gel used twice daily was well tolerated in sexually abstinent and sexually active HIV-negative and HIV-positive women. Systemic tenofovir absorption occurred. Expanded safety and effectiveness testing is warranted.

92% adverse events, detectable serum levels in a population that is “uninfected” and healthy? How did this get ethics approval?

It seems to be with such a low HIV “transmission” rate there would need to be a rather large prospective, long-running, placebo-controlled trial of microbicide gel. We should support Dr Mooreau in his noble attempts to get funding for such a trial because we all know what the results are going to be.