HIV and the Plight of 23 Million Africans

 

Few had ever heard of the virus that causes HIV the morning in the 1980s that I attended a medical conference at the university.  The  doctors present learned that a rare tumor, Kaposi’s sarcoma, was affecting members of the gay community. Until then, the cancer had chiefly affected old Italian men. Young people were also developing an often lethal pneumonia caused by an organism called Pneumocystis. The microbe responsible for the infection had previously lived quietly in most bodies for a millennium. Problems swallowing were caused by white splotches of yeast that covered the walls of the esophagus in some people. Infections of this sort had occasionally been seen in people who had kidney transplants and were taking drugs that suppressed their immune system, but why healthy young people?

In 1983, Luc Montagnier and other scientists in France and in the U.S. proved that a cytopathic retrovirus isolated from the lymph node of a patient with incipient HIV was the responsible virus. The microbe was invading, controlling, and ultimately destroying T lymphocytes, the immune cells that restrain many of the organisms that live in our bodies. When the T cells are gone our immune system loses its ability to control the microbes and many attack at the same time. In its advanced state the infection is called AIDS, acquired immunodeficiency syndrome.

We 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 who had received multiple transfusions, developed AIDS 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. It called the first five years of the AIDS epidemic “a drama of national failure played out against a background of needless death.”  Addicts who injected drugs and shared syringes were also sharing the virus, and needle exchange programs were initiated. Condoms were encouraged. Gay bath houses were attacked by police. Physicians were not allowed to test people for HIV without permission.

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, acute infectious illnesses were usually caused by a single microscopic organism. When a pneumonia was cured, a person could stop taking antibiotics. In people with AIDS, antibiotics often suppressed but failed to eliminate the creatures responsible for a disease. The infected individuals were at risk for a recurrence and needed antibiotics for life. Also, when we identified an organism that caused an infection (like Pneumocystis), we weren’t out of the woods. The creature had attacked because the immune system wasn’t effective. Additional infections and other problems were brewing. 

Within a few years, medical detectives in the Cameroon found chimp feces that contained simian immunodeficiency virus (SIV) whose DNA was identical to the DNA of the most common strain of human immunodeficiency virus (HIV). Many experts believed the source of the epidemic was a chimpanzee that was infected with the simian immunodeficiency virus. In parts of Africa where the creatures were a source of protein, “bush meat,” the virus presumably jumped to man when a human was injured by a monkey he or she 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. 

As deduced and explained in the Timberg book, Tinderbox-- sometime in the early decades of the century, an infected individual moved to Leopoldville (now Kinshasa). In 1920, the town was the capitol 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.  When the Congo became an independent country, volunteers from Haiti flew in to provide medical care and assistance. One of them presumably caught HIV. He or she eventually went home, and spread the virus in Haiti. A few years later, an unknowing carrier visited the U.S. and Europe and passed it on.

After they identified the likely cause of the disease, scientists learned how the virus methodically infects a cell. HIV is an RNA virus. It uses a special enzyme it brought with it (reverse transcriptase) to create a DNA version of itself. The new DNA becomes part of the DNA in the nucleus. It in essence becomes a gene that is passed to a cell’s offspring. The new DNA then directs cells to keep making HIV viruses.  The viral DNA becomes part of the T cell’s nuclear DNA.  Like a gene it directs the cell to keep making HIV viruses, and it is passed to the T cell’s offspring.  Our alphabet has 26 letters, and we use them to make words. The DNA in the nucleus of cells uses a four-nucleotide alphabet. In each cell, there are 20,000 chains of these nucleotides, which are genes. They only occupy up to 3 percent of a cell’s DNA, but they are the blueprint, the instructions, that tell the cubicles what to make and do.

R., a gay 35-year-old carpenter who was married to a gay woman and had a daughter, was renting an apartment I owned in the San Francisco Bay Area. I came by to check on something 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 found he had Pneumocystis pneumonia and advanced AIDS. Treatment was started, but he got worse and needed to be intubated. A respirator kept him alive for a week and R. recovered. He was able to leave the hospital, but at the time everyone knew AIDS was a death sentence. After he came home, R. 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 to 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 counterattack against HIV started when scientists at Burroughs Wellcome screened  a number of nucleoside compounds they had synthesized years earlier in the hope they would be useful in treating cancer.  They didn't affect malignancies and they were returned to the shelves.  

Now they screened the same compounds to see if they would affect  the HIV virus. One of the compounds, (AZT), inhibited HIV. 

“The company sent samples to the FDA.  Researchers had to be sure the drug was safe and that it would, in some way, stop the growth of the  HIV virus---even if it didn’t eliminate the condition.  At the time, controlled trials of new drugs, when overseen by the FDA, sometimes took eight to 10 years. After 16 weeks, Burroughs Wellcome announced that they were stopping the

 trial because  there was strong evidence that the

 chemical appeared to be working. 

The company reasoned that it wouldn’t be ethical to

 continue the trial and deprive one group of a potentially life-saving treatment.  The results were heralded as a “breakthrough” and “the light at the end of the tunnel” by the company.  The FDA approved the first AIDS medication on March 19, 1987, in a record 20 months.

AZT became was a Burroughs Wellcome best-seller and generated about $4 billion in sales before its patent expired.

During the years that the drug was covered by a patent,  treatment would usually cost the average patient with full-blown AIDS about $8,000 a year. Company officials defended its high price by saying that its research costs were expensive and that the drug would have a limited market. Further, they said, they feared that the AZT phenomenon would be short-lived and other antiviral drugs would be developed.”  See; med-hints--Antivirals that control HIV and cure hepatitis C.  (1)

 A few years later Raymond Schinazi, an Emory University professor, and chemistry professor Dennis Liotta developed emtricitabine and lamivudine. The drugs that were defective nucleosides and they prevented invading HIV from turning its RNA into DNA. As Schinazi explained, “Everyone was intrigued but skeptical about our work. No one realized the importance of what we had found.” Schinazi pushed Emory University to file patent applications. That’s what universities were supposed to do. The drugs were a commodity and the law encouraged owners to reap a profit. When the university licensed the drugs to a pharmaceutical company, Emory was paid $540 million.  In the late 1980s and in the 1990s, manufacturers started cranking out (and selling) a number of other anti-HIV drugs and by 1992-3 industry had a three drug cocktail that turned HIV into a chronic condition. 

 By 1996, a three-drug regimen was shown to continue successfully suppressing the HIV virus, and in advanced nations the disease could be controlled. But the companies that owned each drug’s patent charged what they thought they could get away with and the commodities were too pricey 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. The patents in question benefited first-world pharmaceutical manufacturers.  Back then, most nations allowed people and companies to patent unique, non-obvious inventions and new medications. India had a different approach. Their patent law was enacted in 1966 when Nehru’s daughter Indira Gandhi was prime minister. At one point, she met with the head of the Indian drug maker Cipla. He convinced her to allow inventors to patent the process—the way the drug was manufactured, but not the drug itself. That became and remained the law in India until the country became a member of the WTO—the World Trade Organization. If the country wanted to be able to trade with the U.S. and Europe, they had to sign on. After India joined the international group, the country was forced to change their patent law so drugs themselves could be patented.

In September 2000, years before the rules changed, Yusuf Hamied, the CEO of Cipla, was invited to the European Commission in Brussels. He participated in high-level talks with health ministers and heads of large pharmaceutical companies. Cipla had been founded in 1935 by Hamied’s father, and it was a major pharmaceutical company. The meeting was supposed to discuss access to medicines in the developing world. After the leaders of various gathered 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 was willing to supply needed medicines to pregnant women so they would not infect their unborn child. Poor nations could be taught how to create pharmaceutical factories.  The proposal was serious and significant, but it was ignored. In the early 2000s, according to Denis Broun, MD, of Unitaid, the powers that be believed “treatment for AIDS was something for the rich. It was unthinkable for Africans.” Yusuf Hamied believed Africa was being taken for a ride.  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, Hamied told him, is the cost of the active pharmaceutical ingredients. If you can get them cheaply, the end product is cheap. Hamied offered to have his company, Cipla, 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 for the drug 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,” and he put the price of generics on the front page of the Times. 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 medications.  When they arrived at the country’s airport, they were impounded and the doctor who came to pick them up was arrested. He refused to leave the airport without his drugs and the authorities eventually relented. He distributed the medications, and other nations joined Uganda. 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 medications. The U.S. insisted that the fund could only buy branded medications or they would pull out.  In 2003, South Africa’s competition commission ruled that GlaxoSmithKline 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, and the company took a 5 percent 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 right-wing evangelical Christian who had exploited racial prejudices in his election campaigns and had called homosexuals “weak, morally sick wretches.”  Bono, by contrast, had publicly supported Greenpeace, Amnesty International, and had joined Jubilee 2000, a 40-country movement that advocated canceling 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 U.S. 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 2,103 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,’ and he was in tears. He 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 toward 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 over five years to combat the disease. Since its creation in 2003, the “President’s Emergency Plan for AIDS Relief (PEPFAR)” has received more than $70 billion in congressional funds, and in fiscal 2017, the nation contributed $6.56 billion.  Bush’s embrace of the under $300 number caught the drug industry by surprise. They fought back and within days the administration had changed its approach. Rather than generic anti-retroviral drugs, the U.S. government money would be used to buy high-priced branded medications.  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.” Clinton was not president and was not seeking office, and he decided to ignore the politics of the situation. In late November 2006, he 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. Two million children in Africa had been infected by their mother and only 10 percent were receiving drugs. Without treatment, 80 percent would be dead by age five.

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 constructing the factories and producing the medicines was 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.” “Orders for large quantities of generic drugs were critical to bringing African prices for anti-retroviral treatment below $100 per person per year.”  “After that the cost difference between branded and generic anti-retrovirals, 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 (the president’s emergency plan for AIDS relief) eventually committed themselves to buying generics, and the number of people treated exploded.”

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 percent of people who carried the virus knew they were infected.  The U.N. thinks they can end the epidemic if 90 percent of those infected know they are infected. Then 90 percent of those infected 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.  The CDC (Centers for Disease Control) thinks that 1.1 million Americans are currently infected, and 40,000 inhabitants will acquire HIV each year. Between 83 and 88 percent of those infected have been diagnosed, and 85 percent of the people regularly take medicine that controls the virus, but only half take enough pills in the right dose.  The drugs that turn HIV into a chronic controllable condition are commodities, products, and people with “decent” health insurance are often required to pay two-thirds of their cost. That comes to about $20,000 a year, or $360,000 in a lifetime. In the appropriate age and income situations, Medicare and Medicaid supply the medications and the nonprofit Ryan White Foundation helps people who can’t afford the drugs.  I don’t think most insurance pays for the drugs that prevent HIV. Gilead marketed a combination of two antivirals that significantly reduced the risk of sexually acquired HIV-1 infections. In 2019, the medications had a list price of $24,000 a year and were bringing in annual revenues of close to $3 billion. There were assistance programs for the poor. I’m not sure how hard it was to get the drugs for free, but when an $8-a-month generic form of the drugs was introduced in Australia in 2019, the number of new cases of HIV “dramatically declined.” 

(1)            https://www.natap.org/2005/HIV/092005_02.htm

https://time.com/4705809/first-aids-drug-azt//

https://www.latimes.com/archives/la-xpm-1989-09-19-mn-111-story.html

Understanding Modern Health Care by Steve Fredman M.D.

Fire in the Blood  an online documentary movie by Dylan Mohan Gray.  youtube