Why is the Washington Post not doing investigative reporting on the damage Truvada is doing and its potential long term effects?

https://www.washingtonpost.com/technology/2019/12/30/facebook-disables-some-misleading-ads-hiv-prevention-drugs-responding-growing-outcry/#comments-wrapper

Dear Journalists,

What most journalists do not understand: how deeply the HI virus has sunk into the LGBT culture and how strongly the life of gay men is affected by the HI virus.

However, being gay doesn’t make you an expert in biochemistry and/or HIV. But it makes you afraid.

Being young and being gay means to live a life in fear.

And here comes PreP. The I-solve-all-problems pill. It is from the same substance class, NRTIs, that is used in the antiretroviral therapy (ART) and it is itself also used in ART. And all NRTIs show the same broad range of severe side effects caused by their mitochondrial toxicity.

Every cell in a human being contains mitochondria. They come almost exclusively from the mother and deliver the energy to the cell. They have a DNA of their own which is damaged by NRTIs. That causes the many different symptoms in many different organs and tissues.

The mitochondrial toxicity of NRTIs is undisputed.

Now take away PreP and you take away all hope and all the fears come back.

So, ok, give them PreP, hand it out for free and everybody is fine. No, unfortunately not, as the severe side effects show. These are apart from possible classical infections healthy young men!

There is no such a thing like a wonder pill. The lawyers are right. The consequences should have been named before.

A much broader discussion is needed before young healthy men reduce their life spans by taking this pill, and we sacrifice the lives and the health of these young men because of the putative prophylactic effects of this pill in this highly asymmetric epidemic of a STI.

It is foolish to believe that the severe adverse effects of the TRUVADA substances tenofovir and emtricitabine would only show in HIV+ measured persons and not in HIV-negative persons as the open letter to Facebook by GLAAD alleges, see https://www.glaad.org/blog/open-letter-facebook.

One study cited in the open letter did find an increased risk of kidney injury. The other 2 are from the manufacturer (Gilead Science, DISCOVER trial) and compared tablets with 300 mg tenofovir disoproxil fumarate to tablets with 25 mg tenofovir alafenamide which amounts to a dosage reduction of tenofovir of 9 by molecular weight. Cf. on the trial https://clinicaltrials.gov/ct2/show/NCT02842086?term=f%2Ftaf

The dosage is reduced and the kidney values and the bone mineral density improve? You might call that a proof.

The claim is simply not true. Fear is a bad adviser.

Why is the scientific community so silent in this matter? They know that PreP and ART use the same substance class, NRTIs. We are not aware of one life expectancy study that separates the adverse and life threatening effects of ART in the HIV (not AID Syndrome!) epidemic and the changed drug regimes and reduced dosages in the last 2 decades.

Best regards,
Johannes Kreis

                                     

References:

• Bertrand et al., “Cerebral Vascular Toxicity of Antiretroviral Therapy.”, J Neuroimmune Pharmacol. 2019 Jun 17. doi: 10.1007/s11481-019-09858-x, https://www.ncbi.nlm.nih.gov/pubmed/31209776

“Indeed, increasing evidence demonstrates that the antiretroviral drugs used for HIV treatment have toxic effects resulting in various cellular and tissue pathologies.”

“A combination of Tenofovir and Emtricitabine can act as cellular stressors, leading to endothelial cell senescence, as demonstrated by a reduction in proliferation, and an increase in inflammatory markers (Cohen et al. 2018). This results in decreased BBB integrity and impaired endothelial cell functions. Exposure to Efavirenz has been shown to reduce endothelial viability at relatively low concentrations. This effect has been linked to multiple insults, such as a dysregulation of polymerase γ function, imbalance of intracellular calcium levels and depletion of ADP (Bertrand and Toborek 2015; Weiss et al. 2016; Faltz et al. 2017).”

• Liu et al., “Bone Mineral Density in HIV-Negative Men Participating in a Tenofovir Pre-Exposure Prophylaxis Randomized Clinical Trial in San Francisco”, PLoS One. 2011; 6(8): e23688, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3163584/

 “Ten percent of HIV-negative MSM had low BMD at baseline. TDF use resulted in a small but statistically significant decline in BMD at the total hip and femoral neck. Larger studies with longer follow-up are needed to determine the trajectory of BMD changes and any association with clinical fractures.”

• Owino et al., “Neurological syndrome in an HIV-prevention trial participant randomized to daily tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg) in Bondo, Kenya”, Int Med Case Rep J. 2013; 6: 91–93, https://www.ncbi.nlm.nih.gov/pubmed/24353443

“After an additional 4 days, she developed a disabling weakness of her upper limbs and tremors in her hands. The study product was discontinued, and within 2 weeks she was free of all symptoms. One month after restarting the drug, she complained of posture-dependent numbness of her upper limbs.”

• Chan et al., “Potential kidney toxicity from the antiviral drug tenofovir: new indications, new formulations, and a new prodrug”, Curr Opin Nephrol Hypertens. 2018 Mar;27(2):102-112, https://www.ncbi.nlm.nih.gov/pubmed/29278542

“Nephrologists should be aware of the potential kidney and bone toxicity of TDF, as well as unique situations in which the newer prodrug TAF may contribute to kidney injury.”

• Kasonde et al., “Bone mineral density changes among HIV-uninfected young adults in a randomised trial of pre-exposure prophylaxis with tenofovir-emtricitabine or placebo in Botswana.”, PLoS One. 2014 Mar 13;9(3):e90111, https://www.ncbi.nlm.nih.gov/pubmed/24625530

“Use of TDF-FTC was associated with a small but statistically significant decrease in BMD at the forearm, hip and lumbar spine. A high percentage (6.8%) of healthy Batswana young adults had abnormal baseline BMD  Further evaluation is needed of the longer-term use of TDF in HIV-uninfected persons.”

 

• Lu et al., “Tenofovir disoproxil fumarate induces pheochromocytoma cells apoptosis.”, Eur J Pharmacol. 2019 Feb 5;844:139-144, https://www.ncbi.nlm.nih.gov/pubmed/30529468

“Despite the triumph of highly active antiretroviral therapy (HAART) in anti-HIV infection, more than half of the HIV infection individuals receiving antiretroviral therapy acquire HIV-associated neurocognitive disorder (HAND). Previously researches had reported that the HAART neurotoxicity is implicated in HAND-related morbidity.”

“TDF has neural toxicity effect that is relevant to the cell apoptosis, which may be related to the increasing prevalence of HAND.”

 

• Kichloo et al., “Tenofovir and Severe Symptomatic Hypophosphatemia.”, J Investig Med High Impact Case Rep. 2019 Jan-Dec;7:2324709619848796, https://www.ncbi.nlm.nih.gov/pubmed/31142127

“Although the initial results of the clinical trials supported the renal safety of Tenofovir, clinical use of it has caused a low, albeit a significant, risk of renal damage either in the form of AKI or CKD. The pathophysiology has been linked to the effect of this medication on the proximal tubular cell. Although the exact mechanism is unknown, studies have suggested that Tenofovir accumulates in proximal tubular cells which are rich in mitochondria.”

“Here we present a case where Tenofovir treatment resulted in severe hypophosphatemia requiring hospitalization for parentral phosphate repletion.”

• Suzuki et al., “Effect of Tenofovir Disoproxil Fumarate on Incidence of Chronic Kidney Disease and Rate of Estimated Glomerular Filtration Rate Decrement in HIV-1-Infected Treatment-Naïve Asian Patients: Results from 12-Year Observational Cohort.”, AIDS Patient Care STDS. 2017 Mar;31(3):105-112, https://www.ncbi.nlm.nih.gov/pubmed/28282247

“TDF use was associated with CKD [odds ratio (OR), 1.8 …]. The cumulative mean loss in the TDF group, relative to the control, increased over time after 1, 4, and 8 years of TDF exposure (-3.8, -5.5, and -9.0 mL/min/1.73 m2, respectively; p < 0.0001).

The eGFR rapidly declined during the first 3 months of cART, particularly in the TDF group (-26.4 vs. -7.4 mL/min/1.73 m2/year in the control).

In the TDF group, cART introduction was significantly associated with a faster rate of eGFR decline (from -0.44 to -2.11 mL/min/1.73 m2/year; p = 0.010), whereas in the control, the difference was not significant.

For HIV-1-infected Asian patients with low body weight, TDF-containing cART is associated with CKD and faster eGFR decline.”

• Keller et al., „Tenofovir disoproxil fumarate intravaginal ring for HIV pre-exposure prophylaxis in sexually active women: a phase 1, single-blind, randomised, controlled trial”, The Lancer, July 15, 2019, https://www.thelancet.com/journals/lanhiv/article/PIIS2352-3018(19)30145-6/fulltext

“Sexually active women who were HIV negative were randomly assigned (3:1) to a tenofovir disoproxil fumarate ring or placebo ring.”

 “…; eight were asked to discontinue ring use early because of ulcerations (grade 1) near the ring; in the remaining two women, rings were electively removed by study staff on day 20 and day 23.”

 “…, all ulcers resolved after ring removal. No participants in the placebo group developed ulcers.“

“Concentrations of multiple inflammatory cytokines and chemokines were significantly higher at days 14 and 28 compared with baseline in the tenofovir disoproxil fumarate ring group but not the placebo group.”

• Gardner, “HIV treatment and associated mitochondrial pathology: review of 25 years of in vitro, animal, and human studies.”, Toxicol Pathol. 2014 Jul;42(5):811-22, https://www.ncbi.nlm.nih.gov/pubmed/24067671

“In 1988, the suggestion that the first antiretroviral drug, zidovudine, was the potential cause of muscle pathology in HIV-infected persons resulted in structural and biochemical patient studies demonstrating acquired mitochondrial dysfunction. Assessment of subsequent nucleoside analog reverse transcriptase inhibitor (NRTI) antiretroviral drugs has indicated that mitochondria are a common target of NRTI toxicity in multiple tissues, leading to a wide variety of pathology ranging from lipodystrophy to neuropathy. Overwhelmingly, these complications have emerged during post-licensing human studies.”

“Millions of patients have been treated with mitochondrially toxic NRTIs and these drugs remain the backbone of antiretroviral rollout in much of sub-Saharan Africa.”

EU data base of adverse effects with 5400+ cases of severe side effects of TRUVADA (access 4.12.2019),

• EudraVigilance, European Database of suspected adverse drug reaction reports, Truvada, Number of Individual Cases by Reaction Groups by Seriousness, http://www.adrreports.eu/en/search.html