Drug companies and researchers aren’t actively pursuing new treatments that would boost the immunity of HIV non-responders, the tens of thousands of people for whom drugs now don’t work.
Published in STAT January 8, 2019
HIV/AIDS
How to Kill HIV: Target Its “Influencers”
writingApplying network theory to HIV’s structure has revealed the most valuable—and vulnerable—parts of the virus.
Published in Scientific American May 2, 2019
New insights into an old foe: TB
writing(This article is part of a series of articles on tuberculosis that I wrote for the Summer 2008 issue of NYU Physician.)
WHITE PLAGUE. KING’S EVIL. WASTING disease. Phthisis. Consumption. Tuberculosis 
(TB) is an old disease with many names and guises. But it wasn’t until last year that scientists discovered how old this ancient scourge really is. Egyptian mummies, skeletal remains, and genetic analysis had all suggested that TB had been around for at least a few thousand years. But in a block of rock mined from a quarry in Western Turkey, anthropologists discovered the fossil of a young male dating back some 500,000 years and infected, unexpectedly, with tuberculosis. They announced in December 2007 that the young man had lesions on the inside of his skull, the imprint of brain membranes that the disease has been ravaging humans for much longer than anyone had ever suspected.
An estimated 2 billion people — nearly one-third of the world’s population — are thought to harbor Mycobacterium tuberculosis (M. tb), the bacterium that causes TB. It grows slowly, lurking in the lungs for years, and outwits the body’s immune system, in part by waiting for the host’s defenses to weaken. In most people, that opportunity never arises, and they show no symptoms of the disease. But once M. tb takes hold, it literally consumes the body from within, eating through lung tissues and the blood vessels that run through it. Every time someone with a full-blown infection speaks, sings, coughs, or sneezes, the bacteria expelled linger in the air for hours, ready to invade the next victim.
This is why TB has so often been a disease of the poor, because it is at its most deadly in overcrowded, unsanitary conditions. In 2006, TB infected 9.2 million people worldwide, claiming the lives of 1.5 million people, most in the developing world. In some parts of South Africa, as many as 70 percent of those with TB are also infected with HIV, because TB is opportunistic.
Worst case: HIV + TB
writing(This article is part of a series of articles on tuberculosis that I wrote for the Summer 2008 issue of NYU Physician.)
When HIV joins forces with TB, the results can be horrific. The neck bulges with lumps as big as an orange, filled with pus-like fluid teeming with the germs that cause TB. Occasionally, these bacteria travel through the blood and lymph vessels, forming lesions in the liver, spleen, and beyond. In chest X-rays, it looks as if the lung were studded with small nodules the size of millet seeds.
This gruesome scenario is rarely seen when TB is the sole affliction. But as HIV ravages the immune system, TB quickly and effortlessly spreads through the body. HIV’s compounding effect on TB has long been known, but recently scientists have discovered that this pernicious partnership works both ways. TB, in turn, eases the path of HIV, dismantling the system that keeps the virus under control in the lungs, allowing it to mutate and multiply.
“If you have HIV and TB, then TB will kill you much more rapidly,” notes Michael Weiden, M.D., associate professor of medicine and environmental medicine. In fact, TB is the leading cause of death among people who are HIV-positive, accounting for one-third of AIDS deaths worldwide.
Fighting drug-resistant TB in New York City
writing(This article is part of a series of articles on tuberculosis that I wrote for the Summer 2008 issue of NYU Physician.)
For a few weeks last summer, Americans were riveted by news that Andrew Speaker, then a 31-year-old Atlanta native, may have been flying on commercial airplanes, exposing hundreds of people to a virtually untreatable type of tuberculosis (TB).
They could be forgiven for having thought of TB as strictly a third-world disease. In 2006, 13,767 people in the U.S. had TB — the lowest prevalence in the country recorded since 1953 — while elsewhere 1.5 million people died of the disease.
Speaker was diagnosed in early May 2007, but against medical advice he flew to Greece for his wedding later that month. Tracked down in Rome on his honeymoon, he was told he had extensively drug-resistant tuberculosis (XDR-TB) and was asked to stay put.
Instead he and his wife, Sarah, flew to Prague and Montreal and then drove to New York City. On May 24, officials from the Centers for Disease Control and Prevention directed Speaker to report to Bellevue Hospital, where he was served with a federal warrant that isolated him for medical evaluation, the first such order issued in 44 years.
Bellevue is no stranger to TB. The hospital’s Chest Service, established in 1903 to treat the disease, has contributed a great deal of knowledge about its pathophysiology, clinical behavior, and treatment. In the late 1980s and early 1990s, Bellevue endured a long bout with this familiar foe, grappling with nearly 4,000 cases in New York City, many of them homeless people addicted to drugs and infected with HIV.
“I came here and I found everything was all TB and AIDS,” recalls William Rom, M.D., M.P.H., director of the Chest Service.
Hope grows for new TB test
writing(This article is part of a series of articles on tuberculosis that I wrote for the Summer 2008 issue of NYU Physician.)
To confirm that you have TB, the doctor will ask you to cough up at least a teaspoonful of phlegm, or sputum. You’ll have to come back to the hospital twice more to provide samples, and technicians will painstakingly culture the slow-growing bacteria from the sputum.
A few weeks after that third visit — by which point you may have exposed others — the doctor should be able to tell you whether you have TB.
This crude sputum diagnostic test is 100 years old. “The situation is fairly horrendous,” says Dr. Suman Laal, Ph.D., associate professor of pathology and mircrobiology.
There are a few expensive alternatives: fluorescent microscopy, automated culture systems, and tests for the bacterial DNA. But 90 percent of the disease is concentrated in the poorest parts of the world, where these options are not feasible.
Clinically, TB symptoms can be difficult to distinguish from those of other bacterial or fungal infections, pneumonia, or certain tumors. Diagnosis with X-rays is subjective and all but useless in people who are HIV-positive, and a commonly used skin test gives false positives in anyone who has been immunized with the BCG vaccine or has been infected with the TB bug’s bacterial cousins.
The ideal test for TB would be fast, cheap, and would deliver a simple Yes or No answer — much like a dipstick pregnancy test. But developing a test like that has proved challenging.
Male circumcision: A new defense against HIV
writing(This article was #15 in Discover Magazine’s top 100 stories of 2007.)
Male circumcision cuts the risk of HIV transmission in men by about 60 percent and should be scaled up in countries hardest hit by the epidemic, the World Health Organization (WHO) announced in March, citing compelling evidence from three large trials in Kenya, Uganda, and South Africa.
Since the 1980s, dozens of smaller studies have suggested that countries with high rates of circumcision, like the Muslim nations of western Africa, have lower rates of AIDS, whereas southern* Africa, where circumcision is rare, has been ravaged by the epidemic. There, a 2006 study suggests, circumcision could prevent about 6 million HIV infections and 3 million deaths over 20 years. Still, the WHO held back its recommendation until 2007, citing the need for randomized clinical trials.
“Circumcision was ignored for ages,” says Daniel Halperin, an AIDS researcher at the Harvard School of Public Health, who laid out the case for circumcision in The Lancet as far back as 1999. “What I mainly criticize the WHO for is that, even with dozens and dozens of powerful studies, they refused to even talk about it.”
Circumcision is thought to prevent infection because the underside of the foreskin is rich in immune cells that are particularly vulnerable to HIV. Small tears in the foreskin during intercourse can also allow the virus to slip into the body.
Circumcision could reduce the odds of an infected man’s transmitting the virus to a female partner by 30 percent or more. For all its benefits, though, the WHO cautions that it should not replace standard methods of prevention like the use of condoms.
Science on trial
writing(This post appeared on Nature Medicine’s Spoonful of Medicine blog on May 1, 2007.)
It’s always frightening when matters of science are settled in a court of law. And a relief
Robert Gallo
when reason prevails.
Last week, an Australian judge declared that yes, HIV does exist and that it causes AIDS.
The criminal case was filed against a HIV-positive man, Andre Chad Parenzee, for knowingly exposing his sexual partners to the virus. In his defense, he maintained that “the existence of HIV has not been proven” and that “there is no scientific evidence that AIDS is caused by a unique infectious agent.”
The case dragged on for months and although it wasn’t covered much outside the US, did create waves in Australia. Robert Gallo, who established the link between HIV and AIDS in 1984, appeared (by videolink) for the prosecution and was grilled by the defense about his research and his notorious squabble with French virologist Luc Montagnier. AIDS denialism has its supporters even among scientists and the dissident Perth Group, led by two Australian doctors, appeared as “expert witnesses” for the defense.
Parenzee had been convicted on three counts of endangering lives and had appealed. Justice John Sulan said last week that the Perth Group witnesses lacked credibility and threw out the appeal.
The two doctors continue to be employed by the Royal Perth Hospital, although AIDS Truth, a loosely banded group of scientists and activists, and other are calling for their dismissal. As I’ve written here before, AIDS denialism has serious consequences in some parts of the world and is not simply an academic debate. It’s time Australian scientists joined these activists in making sure science prevails.
Of men and monkeys
writing(This post appeared on Nature Medicine’s Spoonful of Medicine blog on March 30, 2007. You can see the original post here.)
Sooty mangabey
I realize that my previous blog entry makes it sound as if HIV researchers are a complaining and bitter bunch. Far from it. They do complain, but they are also one of the friendliest and most unpretentious group of researchers anywhere. They can go from discussing how quickly HIV can wipe out the immune system to the latest in footwear and eyewear in a flash.
Last night was the finale of the HIV meeting — and may I just say, these scientists also know how to party.
Earlier in the week, bigwig HIV researcher Bruce Walker hosted his annual keystone bash. Here are a few things that should tell you it was a great party: there was much spilled drink; people sang Happy Birthday to Philip Goulder at midnight (it really was his birthday); everyone with a camera or cellphone snapped incriminating pictures of everyone else; one noted scientist was so falling down drunk that he really did fall down and had to be escorted home; and the police came — twice.
Last night’s was almost a repeat performance, but the police didn’t make an appearance — not that I know of anyway. In between their drunken revelry, these scientists also managed to put on one of the most interesting conferences I’ve ever been to. As per keystone rules, I can’t really write about the specifics, but among the topics I found most interesting were those that delved into why sooty mangabey monkeys infected with SIV, the monkey version of HIV, never progress to a disease like AIDS and on elite controllers, a group of people who, despite being infected with HIV for more than a decade, have undetectable levels of the virus in their blood.
Figuring out what protects the monkeys or the elite controllers could be the key to a good vaccine. And this week’s talks made me feel optimistic that at some point in my lifetime, even if not in the next 15 or 20 years, we’ll know the answer.
Held to ransom
writing(This Opinion column ran on Nature’s news site on March 26, 2007. You can download a pdf of the original post.)
A pharma giant’s decision to withhold new drugs from Thailand will only hurt patients, says Apoorva Mandavilli.
Is there ever a good enough reason to deny life-saving medicines to an entire country’s citizens? I say no. But it seems pharmaceutical giant Abbott begs to differ.
The Chicago-based company decided on 14 March not to introduce in Thailand any of its seven new drugs — including an antibiotic, an important AIDS drug called Kaletra and medicines to treat blood clots, kidney disease and high blood pressure. Without this crucial registration, the drugs cannot be imported to or sold in that country.
It seems to me that Abbott is, in effect, holding millions of Thais’ lives hostage to force their government to respect its patents. This is good business?
The price of drugs varies from place to place.
What’s shocking to me is that the company is making no bones about the fact that its decision is retaliation against Thailand’s decision in January to issue ‘compulsary licenses’ allowing some locals to import or make cheap copies of Abbott’s new version of Kaletra. “This matter is about intellectual property and the integrity of the patent system,” Abbott spokeswoman Melissa Brotz said in a statement.
Lofty words, but I’m reminded more of a schoolyard fight.