One morning in the 1980s I attended a conference at the medical center, and heard about a tumor, Kaposi’s sarcoma, a cancer of old Italian men. It was affecting members of the gay community. Pneumocystis, a microbe that had lived harmlessly in most lungs for a millennium, was causing pneumonia in young men. Similar infections had previously attacked the lungs of kidney transplant recipients whose immune system was suppressed. Some had trouble swallowing and white dots of yeast covered their esophagus. Previously healthy young men and women developed a bizarre assortment of diseases. Many were quite ill, occupied many of our hospital beds, and were receiving multiple medications. For almost a decade everyone who contracted HIV eventually died.
In 1983 scientists in France and in the U.S. at almost the same time isolated the responsible virus. The microbe was colonizing, taking over, and ultimately destroying T lymphocytes, a vital constituent of the system that keeps a lid on many of the organisms that live in the body. As the virus destroys more and more of our defenders, the immune system loses its ability to control the indigenous microbes.
We soon learned of cases of the disease in 33 countries. Actor Rock Hudson died with AIDS and the Hollywood community rallied. Our blood supply was tainted. Ryan White, a kid with hemophilia had the condition and was not allowed to attend classes. A journalist who worked for the San Francisco Chronicle published a book called: “And the Band Played On.” The Gay community was particularly afflicted and decimated, and the book told of their struggle and “governmental indifference and political infighting”. Condoms were encouraged and needle exchange programs were initiated. Gay bath houses were attacked by the police in many cities. Laws were passed that forbade physicians from testing people for HIV without permission.
After the HIV virus wiped out most of a person’s T lymphocytes, their immune system was unable to control the bugs that normally inhabit a body and their disease had morphed into the full blown acquired immunodeficiency syndrome—AIDS.
The HIV virus, we later learned, is not highly contagious. You could shake hands or hug someone who had the virus growing in their body. Two principles of medicine, however, were turned on their head: In otherwise healthy people, infectious illnesses were usually caused by a single micro organism. When it was eradicated the person could stop taking antibiotics. In people with AIDS antibiotics often suppressed but failed to eliminate the creatures responsible for a disease. These individuals commonly required lifelong low doses of antibiotics to prevent a recurrence.
Also, when we identified the organism causing an infection (like Pneumocystis) we weren’t out of the woods. The creature had attacked the body because the immune system reached a low point. Additional problems were brewing.
Within a few years medical detectives in the Cameroon found chimp feces that contained Simian Immune Virus (SIV) with DNA that was identical to the DNA of the most common type of Human Immune Virus (HIV). The source of the epidemic was a chimpanzee infected with the simian immune virus.
In the early 20th century chimps were wild game– “bush meat” in parts of Africa. When wounded, the animals struggled. Presumably on one occasion a human was injured by a chimp he was killing. Blood containing the Simian Virus entered the hunter’s body and the virus survived and thrived. Later the pathogen was sexually passed to one person after another. Sometime in the early decades of the century an infected individual moved to Leopoldville, (now Kinshasa). In 1920 the town was the capital of the Belgian Congo and was full of migrants. Scientists figure that by the time the colony became an independent country (1960) an estimated 1,000 to 2,000 people were living with HIV. A physician of the day probably encountered many sick souls who had developed diarrhea, fever and wasting. There’s no reason to believe that anyone at the time suspected their symptoms were the result of a new virus.
As the Congo, now a new country, was getting started, UN aid workers and volunteers from Haiti were flown in to provide medical care and assistance. One of them presumably caught HIV, eventually went home, and the virus spread quietly in Haiti for a few years. Then unknowing carriers visited the U.S. and Europe and passed it on.1
After they identified the cause of the disease, scientists learned how the RNA virus methodically infects a cell and, uses a special enzyme it brought with it, (reverse transcriptase), to make a DNA version of itself. The DNA then integrates–becomes part of the host chromosome–becomes a gene.
- BRIEF GENETIC TUTORIAL (again–sorry)
- Our alphabet has 26 letters and we use them to make words.
- The DNA of living organisms uses 4 letter alphabet. They “letters” are molecules called nucleotides.
- Genes are strands of nucleotides. They tell a cell what to do and make and they occupy up to 3 percent of a body’s DNA. We aren’t sure what the other 97 percent of the DNA is there for.
- Every cell in a person’s body has 3 billion pairs of DNA nucleotides.
- They exist in groups called chromosomes. Each cell has 23 pairs of chromosomes.
- The nucleus of every cell in the body contains all 20,000 genes. Some are turned on and some aren’t.
- To summarize: The HIV virus knows how to create a DNA version of itself. That DNA becomes a gene and it commands the cell to make more HIV viruses.
R., a gay 35 year old carpenter, was renting an apartment I owned in the SF Bay area. I came by one afternoon and heard coughing from the house. R. let me in and told me he didn’t feel well and was having trouble breathing. His condition worried me and I suggested he visit a hospital. He went and the doctors made a diagnosis of Pneumocystis Pneumonia. He had AIDS. Treatment was started but he got worse and needed to be intubated. A tube was inserted through his mouth, passed his vocal cord, and into the main breathing tube. A respirator kept him alive for a week. It took a few weeks before R. recovered and was able to leave the hospital, but he knew AIDS was a death sentence. After he came home he moved out of the apartment, bought a house, fixed it up for his family and invited my wife and me over for Sunday afternoon Tea. He told us that he had long wanted have a home of his own before he died. He looked good, seemed relaxed, and was proud of what he had recently accomplished. We never saw him again.
The counter attack against HIV started when scientists at Burroughs-Wellcome synthesized compounds that might hinder the activity of the reverse transcriptase enzyme. In 1985 they sent eleven promising compounds to researchers at the National Cancer Institute, and people at the NCI identified a chemical that worked in the test tube. The drug was given to people with HIV, and their lives were prolonged.
25 months later the FDA approved the drug, and it was marketed by GlaxoSmithKline. The company sold 225 million dollars worth in 1989.
In the late 1980s and in the 1990s manufacturers started cranking out (and selling) anti HIV drugs. Some of the agents targeted protease, an enzyme that plays a role in the production of more viruses. The first Protease inhibitors became available in 1996.
Drugs that work against the enzyme that turns HIV RNA into DNA, (like turning a photograph into a negative) were created by Emory university professors. They discovered 2 important drugs (emtricitabine and lamivudine.) “Everyone was intrigued but skeptical about our work—no one realized the importance of what we had found,” Schinazi (the physician who developed the drug) said. He “pushed Emory University to file patent applications.” They did and less than ten years later the University was paid $540 million…a lot of money but considerably less than big Pharma often pays to control a significant medication. .
Two of the drugs that most effectively prevent and suppress the HIV virus were created in Prague Czechoslovakia by Anotonin Holy. An intuitive researcher, Holy had been sneaking promising chemical creations through the iron curtain to a colleague in Belgium named Erik De Clercq for 20 years. At the time a number of rules and regulations restricted trade between the Communist countries and the West. But Czechs were able to export the hops that Belgians used to make beer and they could import powdered Belgian milk. Somehow the chemicals got through. In 1981 De Clercq visited Prague. Holy took his friend to dinner and stuffed his coat with vials of newly developed compounds.
In the mid 1980’s the Bristol Myers head of virology was John Martin. A respected researcher, he had developed the herpes fighting drug, guancyclovir when he was in his 20s and was working for Searle. At the time pharmaceutical leaders were starting to pay attention to HIV and researchers were developing compounds. At one point Martin heard about a promising new group of antivirals that were discovered by a researcher in Czechoslovakia. Called “acyclic nucleotide phosphonates” they were just chemicals in a test tube. No one knew if they were safe or effective. But for some reason De Clercq in Belgium thought they were special. So Martin visited Prague and met Holy. As the two strolled through the city’s narrow streets and cobblestone alleys they got to know and like one another. Holy wasn’t a complainer. His lab facilities were limited but he managed to do his work and he had no desire to leave the country of his birth. When Martin returned to the U.S., a CIA officer tried to convince Martin to turn Holy into an “asset” and Martin declined.
In July 1989 Gorbachev allowed the nation’s of the Soviet Bloc to break away from Russia. The iron curtain fell, and commerce and travel between the East and the West became relatively easy. About that time Bristol Myers merged with Squibb and the company’s leadership and goals changed. The following year Michael Riordan the long suffering, optimistic CEO of Gilead, a failing startup, convinced Martin to jump ship and become one of his company’s new leaders. Martin (perhaps a little uncertain about his role in the new mega company) agreed and brought two of his best researchers with him. At the time a number of pharmaceutical manufacturers were trying to fabricate drugs that suppressed the HIV virus, but Gilead was not one of them. The chemicals Holy had created had been tested in Belgium and they effectively neutralized the HIV virus. But they needed tweeking before they would be ready for human consumption. Bristol Myers had planned to license and modify them. Gilead wasn’t a player.
Then in mid 1991, with the head of Squibb calling the shots, the newly formed mega company decided they weren’t interested in Holy’s chemicals. They didn’t want to take the risks and make the investment necessary to perhaps develop another HIV medication. Realizing Squibb’s error, Martin phoned Holy and convinced him to sign a licensing agreement with Gilead. In July 1991 Holy, Martin, and De Clercq met in a restaurant near the Eiffel Tower and signed a deal on a napkin. Holy’s nucleotide became the basis of several of the most potent medications that are currently used to prevent and treat HIV, and Gilead was finally an important player.
In 1995, influenced in part by well healed pharmaceutical companies, the World Trade Organization was formed. It required members “to honor 20 year patents on drugs”. Poor countries were given until 2005 to comply with the mandate. (Half the big drug makers are headquartered outside the U.S.).
In 1996 a three drug regimen was shown to successfully suppress the HIV virus. The disease could be controlled in advanced nations. But the companies that owned each drug’s patent charged what they thought they could get away with. The medications were too pricy for most people in the developing world.
As Nobel Prize winner Joseph Stiglitz explained: Patents are created for each nation’s needs. They give the inventor a monopoly for a number of years. When they are appropriately designed they promote innovation and societal well being. When they are not appropriately designed people die and innovation is suppressed.
Most nations allow people and companies to patent unique, non obvious inventions. When it came to medications, India had a different approach. The country gained its independence from England in 1947. In 1966 Nehru’s daughter, Indira Gandhi became prime minister. At some point she met with the head of the Indian drug maker—Cipla. He convinced her to allow inventors to patent the process –the way they manufactured a drug. But the drug itself could NOT be patented in India. That was the law in India before the country joined the WTO—the World Trade Organization. After India joined they changed their patent law. Drugs could now be patented.
In September 2000 Yusuf Hamied, the CEO of Cipla, was invited to the European Commission in Brussels for high level talks with health ministers and heads of large pharmaceutical companies. The meeting was supposed to discuss access to medicines, especially those that suppressed AIDS, in the developing world. At the large gathering, after the leaders of various companies made their remarks, Hamied spoke. Saying he represented the developing world and an opportunity, he offered to provide the three anti retroviral drugs that suppressed HIV at a cost of $800 a year; and/or to set up factories in other nations; and to provide needed medicines to pregnant women so they would not infect their unborn child. Founded in 1935 by Hamied’s father, Cipla is a major pharmaceutical company. His proposal was serious and significant. But his offer was ignored.
In the early 2000’s, according to Denis Broun M.D. of Unitaid, the powers- -that–be believed “Treatment for AIDS was something for the rich. It was unthinkable for Africans.” Yusuf Hamied felt the whole of Africa was being taken for a ride.1
A year after the Brussels meeting James Love, an AIDS activist called Hamied and asked how cheaply he could produce the three drugs that suppressed the virus. The key to pricing in medicine (according to Hamied) is the cost of the active pharmaceutical ingredients. If you can get them cheaply, the end product is cheap. Hamied told Love that Cipla would pay the cost of manufacturing a generic regimen. He would only charge for the material. Nevirapine would cost 65 cents a day. 3TC, lamivudine, 35 cents. And there would be no charge for d4T, Stavudine. The materials were too cheap. In other words the three drug regimen would cost $350 a year.
Donald McNeill of the New York Times felt the offer “was a watershed event.” He put the price of generics on the front page of the NY times, and papers around the world spread the news.
Shortly thereafter Peter Mugyenyi, a Uganda physician and director of the continent’s largest research and treatment center, decided to take matters into his own hands. “I knew where drugs were, and as a doctor it was my job to save my patients lives.” He contacted Cipla in India, and in defiance of patent laws ordered the drugs.
When the medications arrived at the airport they were impounded and the doctor was arrested. He refused to leave the airport without his medications. Eventually the authorities relented. Other nations acted. To many it seemed like the blockade for inexpensive drugs in Africa was broken.
In 2002 Kofi Annan, the diplomat from Ghana who was the Secretary-General of the United Nations, proposed a Global Fund to buy the drugs. The U.S. insisted that the fund could only buy branded medications or they would pull out.
Poor countries couldn’t and wouldn’t comply with the WHO directive. HIV was a killing their people. 143 countries favored relaxation of patent protection.
“In 2003 South Africa’s competition commission ruled that Glaxo Smith Kline and another company had violated the country’s anti competitive act. Glaxo was charging excessively high prices and was refusing to license their patents to generic manufacturers in return for reasonable royalties. The company eventually agreed to allow three generic manufacturers to make and sell three of its AIDS drugs,3 and the company took a 5% fee.
Prior to 2003, the U.S hung tough. Then the Irish singer Bono got together with one of the day’s more influential Republican senators, Jesse Helms, and attitudes changed. When they met the Senator was 80 and walked with a four-pronged cane. He was a rightwing evangelical Christian who had exploited racial prejudices in his election campaigns and had called homosexuals “weak, morally sick wretches”.
Bono, by contrast, had publically supported Greenpeace, Amnesty International, and had joined Jubilee 2000, a 40 country movement that advocated cancelling third world debt for the millennium. At one point the Jubilee campaign asked Bono to get the Baptist Nigerian President to write a letter to Baptist churches across southern US states. He was supposed to explain the Biblical principles behind debt cancellation.
The Baptist leaders listened, and Bono suddenly had access to a lot of strongly Christian Republicans. That’s why he was able to meet and speak with Jesse Helms. Helms had been very tough on the concept of foreign HIV drug assistance. “He’s a religious man”, Bono said, “so I told him that 2103 verses of scripture pertain to the poor, and Jesus speaks of judgment only once – It’s not about being gay or sexual morality, but about poverty. I quoted that verse of Matthew chapter 25: ‘I was naked and you clothed me.’ He was in tears. And later publicly acknowledged that he was ashamed…”
After the meeting vice president “Dick Cheney walked into the Oval office, and told President Bush that, ‘Jesse Helms wants us to listen to Bono’s idea.” That led to negotiations and Bush’s 2003 plan.
That January in his State of the Union message President Bush announced his policy towards HIV had changed. His words: “Today on the continent of Africa nearly 30 million people have the AIDS virus, and across that continent only 50,000 are receiving the medicine they need. Many hospitals tell people: “you have AIDS. Go home and die.” In an age of miraculous medicines no person should have to hear those words.”– “Anti retroviral drugs can extend life for many years. And the cost of those drugs has dropped from $12,000 a year to under $300 a year. Seldom has history offered a greater opportunity to do so much for so many. “
Bush would ask congress to spend $15 billion dollars over 5 years to combat the disease. Since its creation in 2003, the “President’s Emergency Plan for AIDS Relief (PEPFAR)” received more than $70 billion in congressional funds …$6.56 billion in fiscal 2017. The Trump budget plans to cut the amount the government contributes in 2019 by a billion dollars.
The under $300 number caught the drug industry by surprise, and they fought back. Within days the administration changed its approach. Rather than generic anti retro-virals the U.S. government money would be used to buy high priced branded drugs, and fewer lives would be saved.
As Bill Clinton later put it, “If you ran the numbers there was no way the money was enough to save the number who had to be saved in a hurry… it would never be enough unless they bought generics.”
Many of the drug manufacturers are headquartered outside the U.S. One hundred and twenty three nations (probably goaded by large corporations) signed an intellectual property rights agreement.-TRIPS, that “came into effect” in January 1995. It allows members “to promote access to medicines for all.” Clinton decided to ignore the politics of the situation and do the right thing. At the time India was a member of the World Trade Organization but patents issued before 2005 were still valid.9
In late November 2006 Bill Clinton announced an agreement between his foundation, two Indian drug makers: Cipla and Ranbaxy; Aspen Pharmacare, of South Africa, and Matrix Laboratories of Dubai. The companies agreed to make pills for children that combined three HIV drugs and cost $60 a year. 2 million children in Africa had been infected by their mother and only 10 percent were receiving drugs. Without treatment 80% would be dead by age 5.
The companies also apparently agreed that “The cost of anti-retroviral drugs (in general) was going to drop to $140 a year, and pills would cost 36 to 38 cents a day.” The cost of making the medicines would be paid for by a $35 million grant from an international drug-buying consortium and $15 million from the Clinton Foundation. The funds guaranteed the volume of drugs purchased would be “high enough to justify the lower prices.” “The large quantity orders for generics was critical to bringing prices for anti retroviral treatment in Africa below $100 per person per year.”
“After that the difference between branded and generic anti-retro-virals, and the scale of human tragedy in Africa made it impossible for donor funds to spend vast sums of money on expensive drugs. The global fund and Pepfar eventually committed themselves to buying generics, and the number of people treated exploded.”1
In 2017, per the U.N., 19.5 million people, more than half those infected, were being treated, but 2 million additional people had acquired the disease. Over 25 million HIV carriers lived in Sub Sahara Africa. That year worldwide 75% of people who carried the virus knew they were infected.4
The UN thinks they can end the epidemic if 90% of those infected know they are infected. Then 90% of those infected would need to take anti retroviral drugs that effectively lower the measurable blood level of HIV 90 percent of the time. Seven countries have achieved the 90/90/90 goal.
In 2019 the U.S. is still pretty far from getting HIV under control. One in six men who has sex with other men will eventually acquire HIV. Half are Latino or black. In 2015 there were about 6500 AIDS-related deaths in the U.S.
The CDC (Center for Disease Control) thinks that 1.1 million people are currently infected and 40,000 inhabitants will acquire HIV each year. 83-88% of those infected have been diagnosed, and 85% of the people regularly take medicine that controls the virus; only half take enough pills in the right dose.
People with “decent” health insurance are commonly required to pay two thirds of the cost.5 The estimated average annual cost of HIV drugs is about $20,000 ($360,000 lifetime.) In the appropriate age and income situations Medicare and Medicaid supply the meds. The non-profit Ryan White Foundation helps when people can’t afford the drugs. And there are federal programs for some populations.
Pharmaceutical companies have managed to keep the price of drug combinations relatively high by combining one or two relatively cheap anti-retro-virals with an expensive newer drug that is still patented. Some contend that people are more likely to take one pill that contains several drugs than they are to take a few capsules.
Most new infections can be prevented with a daily pill that contains two of the more effective anti-viral drugs, but it is not always covered by insurance.8
Anthony Fauci of the NIH is quoted as saying: “if we had a vaccine this effective-wow”. He was talking about a drug containing polymer that is implanted in a person’s body and slowly elutes significant quantities of a medication that suppresses HIV.
But we haven’t learned how to eliminate the HIV virus from a body. The HIV DNA has become one of the genes of too many T cells.
- Tinderbox. By Craig Timberg and Daniel Halperin. Penguin Press. 2012—.
Fire in the Blood. Documentary Movie. Written and directed by Dylan Mohan Gray. 2013.
https://www.nytimes.com/2006/11/30/world/asia/01aidscnd.htm l http://www.cnn.com/2003/ALLPOLITICS/10/23/clinton / http://news.bbc.co.uk/2/hi/americas/3209741.stm https://www.nejm.org/doi/full/10.1056/NEJMp1710914
Treating and Preventing HIV with Generic Drugs–Barriers in the U.S. Erika G. Martin, Ph.D., M.P.H.,and Bruce R. Schackman, Ph.D.
3. The Truth About Drug Companies by Marcia Angell. Random House. 2005
4. https://www.nejm.org/doi/full/10.1056/NEJMp1804306 . (CDC website.)
5.http://www.gtp.autm.net/story/view/76
7. https://www.sciencedaily.com/releases/2019/07/190702112844.htm
8. A 2010 therapeutic manual for doctors listed drugs that block the virus at several transitional sites. We had more than 10 reverse transcriptase inhibitors, 9 protease inhibitors, 2 entry inhibitors and an integrase inhibitor. All drugs had side effects. People who couldn’t tolerate one reverse transcriptase inhibitor often had no problem taking a different one. When a combination of medications was used, the viral biochemical assembly line was blocked in more than one location, and viral resistance was uncommon. Refractory HIV however, commonly developed when a person stopped and started the medications. That happens when people can’t afford their co-pay, when they live in a remote part of the world and don’t have access, or if they merely decide to take a “drug holiday”.