Taking HIV "Treatment is Prevention" to New Heights

Somewhat missing from the headlines in recent days is a landmark HIV study the solidifies the concept that treatment is prevention. The back story to that important catch phrase is that, in the recent past, there was a real policy debate over where emphasis should be placed: on treatment or on prevention. One's answer to that question would have multiple cascading effects on which anti-HIV strategies were planned, evaluated, and promoted. 

All that changed with the publication of HPTN 052 which demonstrated a 96% reduction in sexual transmission of HIV in mostly hetorosexual serodiscordant couples when the HIV-infected member was on HIV therapy. This trial was revolutionary in that it showed that the HIV treatment vs. prevention debate rested on a false dichotomy. Its results changed the way HIV prevention was viewed and provided yet another reason to initative therapy as soon as possible in the HIV infected. Caveats to the generalizability of this study existed however and included the high number of heterosexual couples and a high use of condoms (94%). Despite these caveats, HPTN 052 was pathbreaking.

Buttressing and expanding HPTN 025 is the PARTNER study, recently published in JAMA. This study's aim was to assess the ability of antiretroviral therapy on the transmission of HIV in serodiscordant couples who regularly engaged in condomless sex. The results, which solidify the treatment as prevention, paradigm are stunning.

The trial included about 2/3 heterosexual couples and 1/3 men-who-have-sex with men (MSM) couples. Condom-less sex occurred between couples a median of 37 times per year. Strikingly, just 11 transmission events occurred with nearly 60,000 condom-less sex acts. The thing about the 11 HIV infections was they were not genetically linked to the other study partner, meaning these infections derived from an additional partner not in the study--a great example of the exception proving the rule. 

This study shows just how potent antiretroviral therapy is. It is not only life-saving for those who take it but extremely effective at extinguishing contagiousness. As we wait for a vaccine, antiretroviral therapy (treatment as well as pre-exposure prophylaxis) is the cornerstone to keeping HIV contained.

Is 21st Century Civilization Immune? A Review of the Novel Immunity

Taylor Antrim's Immunity, a novel set in a post-pandemic world, provides an interesting view of how such a world could look, operate, and devolve. Even as a work of fiction, there are aspects of Antrim's insights--some of with which I agree, some with which I disagree--that merit discussion in their own right.

In the universe of Immunity, the TX virus, a genetic recombinant of influenza and Lassa Fever that emerged in Texas, has circled the globe in a murderous spree. By killing 4% of the world's population the pandemic threw the governments of the world into a quarantine-laden panic. At the time of the events depicted in the novel, the pandemic is over but occasional flare-ups continue to occur, prompting draconian controls, in the name of "public health", on the population. The plot of the novel centers on a young former socialite who has is struggling to flourish in this setting that is rife with unsavory individuals and public health "police" who are ready to pounce with just one errant cough or elevated temperature reading on the ubiquitous thermal scanners that this world is rife with.

The unsavory characters range from the protagonist's conspiracy-minded father (who is eerily reminiscent of people who I debated during the West African Ebola outbreak), to "propagators" who purposely try to infect unsuspecting citizens by coughing on them, to the overtly exploitative who find a perverse pleasure in sacrificing others to their whims. The various strands of the events in Immunity culminate in an intersection of biotechnology and surveillance that leaves the reader wondering what really happened and what will happen next. 

What I take to be the theme of Immunity is what is worthy of discussion. Antrim's point seems to be on stressing how the well-off are not only the first to be granted immunity through biotechnology but that they are, in a higher sense, immune from the vicissitudes of the rumblings in the infectious disease world. Through hyperbolic characters, Antrim shows that the realm of the rich and famous is easily adaptable to a world in which a deadly virus has destroyed the lives of everyone else. I suspect Antrim is making a political point about the relative resiliency of various socioeconomic segments of the population and is using the TX virus as a background. However, the fact that the world still turns after 4% of the population has died is itself a fact that highlights species-level resiliency that transcends socioeconomics.

My own thoughts on this theme are somewhat different. Humans today live in a civilization that is itself largely immune from the challenges of outbreaks that occurred just 50 years ago. Today, worldwide extreme poverty -- in real terms -- is at its lowest. Smallpox has been vanquished with polio and guinea worm about to follow suit. Even Ebola, because of major advances that have occurred in the basic understanding of the clinical illness as well as in vaccine technology since the last outbreak, has been substantially defanged.

In many ways civilization's progress can be roughly gauged by the conquest of various infectious diseases. This species-wide resilience humans possess (which I discussed in my recent Atlantic piece) is the result of both the immune systems and the fruits of humans minds that have largely rendered nature's beasts, in all their shapes and sizes, threats from a bygone era...if we are willing to confront them with the appropriate response.

Nice Work if You Can Get It: Paid Stool Donors

A long-time friend of mine yesterday said that, unlike many, he hasn't gained any weight since high school: a span of two decades in which weight gain is the norm for many people. I immediately replied that he must have a good conglomeration of bacteria in his intestines that are partly responsible for his feat through their metabolism of what he eats. In fact, he eats so much with little effect on his weight that his nickname was "Worm" because a tapeworm was thought to be responsible for his physiological feat.

The conversation yesterday ultimately devolved into how his stool will be highly sought after once fecal transplantation and microbiome alteration for obesity and weight management are more fully developed. 

The microbiome will be the key to understanding many diseases -- infectious and non-infectious alike -- and fine-tuning the microbiome will be a full-fledged medical speciality. With respect obesity, more and more evidence is accumulating that the microbiomes of obese patients are distinct from the non-obese. Animal studies have shown that antibiotic treatment, which by definition alters the microbiome, can cause test animals to gain weight. Transferring of the stool from obese to non-obese animals can also induce obesity. In short, multiple strains of converging evidence all provide ample evidence supporting the hypothesis that the microbiome and obesity are strongly connected. 

Fecal transplantation is the current crude mechanism for altering the microbiome and is being used for refractory or recurrent C.diff (Clostridium difficile) infection. Right now the FDA is exercising "discretionary enforcement" allowing the innovative treatment to flourish (I hope they continue to exercise such discretion forever).  Results have been stellar and there are efforts underway to capture the magic of the stool transplant and bottle it in a pill.

Until pills become the means of microbiome alteration, fecal transplantation will be the major mechanism for microbiome improvement. This scenario leads to the need for stool donors. These donors must have their stool screened for potential pathogens and themselves must not be obese (a fecal transplant from an overweight donor can induce obesity in the recipient).  

All this discussion leads to my suggestion that my friend become a paid stool donor -- which he took as a means of saving the world (with his stool). He is eager to get to work and looks forward to being in his "office".

Burkholderia Exploits the Desire for Soft Stool

One of the tell-tale smells of the hospital is the aroma of poop. The smell of poop abounds in all its varieties: infected and non-infected, formed or liquid, and any other variety you could imagine. Part of the reason for this fragrance has to do with what happens to one in the hospital: the food, the antibiotics, the infections (e.g. C.diff), and the "bowel regimens". 

Bowel regimens involve a cocktail of various medications that promote softening of the stool, act as a laxative, or both. These medications are often prescribed for ordinary constipation but also to counteract the actions of painkillers like morphine which predictably constipate patients.

An alert from the CDC issued this week, however, warns of a possible infection risk that is associated with a widely used product: the stool softener liquid docusate. The bacteria possibly associated with this product, Burkholderia cepacia complex, is one that is well-known to infectious disease physicians as a major cause of lung infections in those with cystic fibrosis. However in these cases, which appear to be confined to a single state, the patients involved do not have cystic fibrosis but are mostly critically ill ICU patients on mechanical ventilators. Because these patients are critically ill and this bacteria is difficult to treat, I suspect the mortality rate may be high.

This warning includes the recommendation that liquid docusate products not be used in critically ill patients or the immunosuppressed (other formulations of the drug are unaffected and can be used).

This outbreak underscores the well-established fact that hospitals aren't always the safest places to be. Product contamination-related outbreaks can have major consequences and be difficult to contain as products can be distributed widely and, if medical products are involved, are administered to sick patients. 

I don't think the bowel regimen will be going anywhere soon so the faster this outbreak is dissected and controlled the better.

Did the Microbe Make Me Do It? A Review of Infectious Madness

In recent years there has been a growing accumulation of evidence of the role infectious diseases may have in the development of neuropsychiatric illness. A new book, Infectious Madness: The Surprising Science of How We "Catch" Mental Illness by Harriet Washington, provides an extensive overview of the evidence behind this linkage.

While I don't agree with everything suggested in the book, it is indisputable that several converging lines of evidence exist in this realm. The role of the enteric nervous system, its interaction with the microbiome, and attributes of specific pathogens (e.g. influenza, Toxoplasma, and group A streptococcus) are all fascinating and illustrate the potential role specific infections can have on mental functioning. 

For anyone who has taken care of a person sick with an infection, it is clear that mentation and cognitive ability are adversely effected in a global manner. Also, infections such as rabies and viral encephalitis are obvious examples familiar to all. However, Washington moves beyond these canonical examples by providing an overview of infections that possibly provoke specific mental disorders such as schizophrenia and anorexia. Toxoplasmosis is probably the most interesting pathogen that is known to alter behavior in rodents and, intriguingly, possibly behind the attraction to cat pee flavored wine.

While I am (and remain) a staunch defender of free will and do not believe that a microbe can determine behavior, Washington provides ample evidence of microbe-induced alterations in neural circuitry, brain neurochemistry, and hormonal balance and mental illness that can no longer be dismissed as mere coincidence. Perhaps many mental illnesses are varieties of encephalitis?