When the first sun rose
it found us awake and waiting
Long before they came to this hill
Our footsteps shaped the landscape, tamed the buffalo
we rode the wind, we silenced the hurricane
Look at us
we have been here before
-- Don Mattera
I am the quest
Giver of Life
Alpha without Omega
I am Africa
-- Don Mattera
The XIII International Conference on AIDS, with its theme "Break the Silence," was the first in history held in the Southern Hemisphere, on a continent with millions infected, orphaned, sick or dying. It is a home for countries where, in the words of the Vice President of Malawi, one of the Sub-Saharan democracies most impacted, "it is not a question of losing a generation but of losing the nation." The message is simple -- Africa is dying.
The questions that were asked in Africa are important to us all -- they are the same questions we need answered here. When is it necessary to start drugs? Which drugs are the most effective to use? How can we minimize the use of antiretrovirals without compromising the health of people with HIV? What do we do when the drugs fail people? And one more question -- the biggest in the world, but unique to the poor countries on earth: How can we get access to these drugs?
The ambiance of the South African host city of Durban made those of us from the United States realize constantly that we were on a continent unfamiliar to most Americans. Durban is in KwaZuluNatal, where instead of hello we heard "Sawubona -- Welcome to the Kingdom of the Zulu." Occasionally we heard people make tongue clicks -- sounds that have tones as distinct as our vowels. Flat-topped Jacaranda trees often surrounded us. In front of the convention center sat small-headed Baobad trees with fat-bottoms. Lounging on the green lawns of the University of Natal, in whose dormitories many of the delegates stayed, were exotic birds with long curved blue beaks. There were vistas overlooking the busy seaport. Trees whose leaves looked like long green dreadlocks spread out like a jester's hat that made us smile whenever we saw them. Dozens of monkeys waited on pathways in the hopes of food.
The real work of this conference began with an invitation to the community indaba sessions. Indaba means meeting or getting together. Hundreds of delegates from around the world, including many from the United States, attended these sessions that attempted to teach activists how best to use the presentations, how best to understand the science. Africans like Dr. Salim Karim Abdool (the scientific chair of the conference) led off these sessions.
Everything told us we were in an international setting -- even the clothing. Brand names like Inkulu, Indali, Groot Uitverkooping. There were Kani jeans. What do they all mean? Probably pretty much what Hilfiger or The Gap means in the USA. And the ways of thinking were as diverse as the clothing.
Thousands of delegates gathered on the first night at the Kingsmead Cricket Stadium -- a huge field near the conference center. The ceremony began with a black woman singing a cappella that life had changed and would never be like it used to be. Behind her, people wrapped in white shrouds stood silently, representing the dead. On a stage in the background sang a chorus of hundreds of people dressed in red, purple and yellow. Across the foreground ran crowds of young men dressed as warriors followed by children dressed like lion cubs. The drums beat, people started to scream and moved faster and faster, and the ground shook with the sound as if we were having an earthquake. If music, noise and crowds could end an epidemic, AIDS would be over.
Then, amidst the music stood Thabo Mbeki, the President of South Africa. He spoke with a quiet passion. "We are a country and a continent driven by hope and not despair and resignation to a cruel fate. Those who have nothing would perish if the forces that govern our universe deprived them of the capacity to hope for a better tomorrow.
Every year in the developing world, 12.2 million children under five years old die, most of them from causes that could be prevented for just a few U.S. cents per child. They die largely because of world indifference, but most of all; they die because they are poor.
For most people in the world today, every step of life, from infancy to old age, is taken under the twin shadows of poverty and inequity, and under the double burden of suffering and disease. For many, the prospect of a longer life may seem more like a punishment than a gift."
President Mbeki outlined the country's AIDS action plan and called upon the world community to help. He said that in the context of a world driven by a value system based on financial profit, he assumes that the notion of " human solidarity remains a valid precept governing human behavior."
The conference then ran for a week, covering topics familiar to everyone who attends similar gatherings of scientists and doctors, issues around treatment and prevention. The difference in the South African conference was a noticeable effort to make material relevant to poor countries. Here are a few of the general subjects covered in great detail during the thousands of sessions.
First, if how long we can use antiviral cocktails is limited by both how many side effects they have and also how long it takes before the virus gets resistant to them, then it makes sense to use them as late as possible (and as infrequently as necessary!). This is also the cheapest way to use the drugs, which means that countries without lots of money can spend the least amount necessary.
This is a big change from the idea of "Hit Hard Hit Early" and there are two clear reasons for the change: First, the notion of "eradication" first proposed at the International AIDS conference in Vancouver four years ago has eluded science. It was the hope of eradication that drove most people toward the idea of starting antiretrovirals as soon as it was clear a person was HIV-positive.
There are several theories on why the drugs fail to eradicate the virus after many years of use. The drugs are clearly not powerful enough as data shows there is still virus being made by cells at a very low level. This may be the reason eradication failed, or it may be because there are cells programmed to produce virus at some future time that take a very long time before they "turn on" and start making virus. (These are the so-called "latent" cells.)
Either way, without the prospect of eradicating the virus to drive taking pills, and with the growing evidence that drugs cause cumulative side effects like lipodystrophy syndrome, its just common sense to use them only when necessary.
There is no evidence whatsoever -- from any study -- that using antiretrovirals early helps keep people healthier longer or alive longer. In fact, there are many reasons to believe that the opposite is true: the longer you are on antiretrovirals, the greater the chances the virus will become resistant to them, and the more likely that there will be side effects that force you to stop using the drugs and, without question, compromise quality of life. The only clinical trials, the only experiments with real people that tested the cocktails for how effective they are in delaying disease progression and death were in people with very advanced disease. This means that we simply do not know that using drugs early is helpful.
Many people believe that as long as you have enough T-cells to fight illnesses, it makes no sense to use antiretrovirals. It would seem that in general, people with more than 350 T-cells only rarely get any opportunistic infections and, for this reason, starting antiretrovirals before this point, unless one has an opportunistic infection, makes little sense.
From the African perspective, this information is good news, because it means that if antiretrovirals are used, they should be used in late-stage illness. That means less cost and minimized management of side effects.
There are two types of HIV drugs that have FDA approvals: reverse transcriptase inhibitors (RTIs) and protease inhibitors (PIs). RTIs stop HIV from teaching a cell how to make more HIV. PIs stop an infected cell that already knows how to make HIV from making HIV that functions. RTIs come in two types: nucleoside analogues (nukes) and non-nucleoside reverse transcriptase inhibitors (NNRTIs).
Nukes stop HIV by operating as decoy instructions so the virus gives the cell bad information on how to make more HIV. NNRTIs ruin HIV's ability to teach the cell anything. PIs ruin the part of an infected cell's machinery that helps make new virus particles.
There are now a total of six nukes, five protease inhibitors and three NNRTIs approved by the FDA. We are expecting many more drugs over the next two years, most of them variations on one or another from one of the basic types of drugs we already have.
Now with respect to the question: which drugs are most powerful? Unfortunately, we are not 100% sure yet. But the conference gave us some new information that helps.
First, for people who have not yet used antiretrovirals: You cannot know if one cocktail is more or less powerful than another cocktail without trying them out head to head in a trial. This means that for the most part, we really do not know exactly which cocktails are the most powerful. However, one study showed that most of the standard drug cocktails are equivalent when used in people who have never taken antiretrovirals, in terms of keeping people alive and delaying disease progression. It was also shown that carefully choosing a cocktail to make sure that a person can comply with taking the pills on time and to make sure that a person has virus that will respond to the particular cocktail leads to better outcomes. Unfortunately, for most of the world, tests of what drugs might work best are not affordable.
There was some new data presented that has implications for people just starting drugs, whether here or in Africa.
First, it would appear from the latest data that the powerful nuke Ziagen, the trade name for abacavir, used with two other nukes, did just as well over a six-month period as a protease-plus-two-nuke combination (the standard against which all cocktails are measured). This is important because the first cocktails that stopped HIV for a long period of time were based upon protease inhibitors. If a cocktail can be made without using these powerful protease inhibitors, then they can be saved for later!
This would also lead us to believe that the new "one-pill cocktail" which will be called "Trivir" might be successful. (Trivir is a mix of AZT, 3TC and Ziagen, all of which are nukes.) A one-pill cocktail would also have great benefits, as current 25 plus-pill-a-day regimens have made adherence extremely challenging. And because it is made of all nukes, it saves protease and NNRTI-based cocktails as a second bite at the apple for later! This pill would be pretty easy to store, so all in all it would be a great drug for developing countries.
We have also figured out that surprisingly, three old nukes, 3TC plus d4T plus ddI, used together is almost as good a cocktail as a protease inhibitor regimen at getting down virus and getting up T-cells. This may not be true for people with very high amounts of virus, but given how inexpensive it is to make these three drugs (CIPLA, a drug company in India makes them all quite inexpensively, and can produce a cocktail for about sixty-three cents a day instead of the thirty-three dollars a day the average cocktail costs here in the USA) this might be a logical cocktail for countries that cannot afford fancy drugs. And it buys time.
Finally there were several presentations of the use of the nuke ddI plus hydroxyurea. (Hydroxyurea is a very old drug that seems to make ddI work much better. It is not an antiretroviral.) There is a lot of controversy about the use of this combination, although it is certainly inexpensive and seems to do a pretty good job on people without very high amounts of virus. Many poor countries are trying out this regimen.
However, a word of caution here: there has been no study comparing this new drug cocktail with the famous double protease cocktail of ritonavir plus crixivan, or ritonavir plus fortovase. It may well be that these "double protease" combinations are just as good as the new drug. There was data presented that shows the crixivan-ritonavir combo may be more powerful than the saquinavir (or fortovase)-ritonavir combo.
A technique called "Markov modeling" was used to evaluate the long-term outcomes of different antiretroviral strategies. The amazing result was that using ddI alone first and HAART much later is better than using HAART right away.
The point of therapy is to give people the longest and best quality of life. Given the side effects of the new medicines and the fact that there is a rate at which the virus gets resistant to them, a plan that uses a less powerful regimen at the beginning is a better plan than starting the heavy artillery when you don't need it yet.
Poor countries have not yet used many drugs. But sometimes there can be a benefit from not being the first. To begin with, most people in Africa and Asia are drug naive. This means that the chances a person with HIV will not have a virus that responds to a therapy is at present very low. It also means that poor countries have a public health duty to try to make sure people do not use drugs in a way that leads to widespread drug-resistant virus. Not taking drugs on time is the biggest cause of drug resistance. For this reason, simplification of regimens is extremely important.
Glaxo has begun testing the two-pill-a-day drug that will be called "Trivir." In India, a similar event took place, with a company called CIPLA producing a drug called "Duovir," which is the same as "Combivir" only much less expensive. Such combinations of drugs into one pill can help make sure people can take their medicines on time and this is the biggest single way to keep the virus from getting through the drug blockade. Studies of Trivir were presented and we fully expect this drug will be made available over the next two years or less.
Data was presented showing that during longer "drug holidays" some of the side effects of drugs might be reversed, like high cholesterol and other fats in your blood. Nobody should try these ideas out on their own. But everyone should pay attention, for not only will these methods make it possible for more people in the world to get medicines -- it might lead to a much better way for all of us to take the medicines that we already have.
What is more promising is the news about new drugs. There are 37 new antiretrovirals in development. Some we can expect in the next couple years, but the majority wont be developed for a much longer time. A few of them are truly amazing; several are efforts that look excellent to stop the virus from getting into cells. These are called "fusion inhibitors." They will be useful for people who have used up all their options. Others are called nucleotide analogues that look like they will be a kind of "nuke" that people who have used up their nukes can still use. Other types of drugs that are being studied are protease inhibitors (PIs) that work in a person who has PI-resistant virus, and NNRTIs that work even on virus that has grown resistant to NNRTIs. In short, there are many drugs in the pipeline that are improvements on what we have now.
But there is no substitute for two realities: Using the drugs we have wisely. And having access to them in the first place.
Companies, countries, politicians, rich men and women, and people of good will around the world are trying to find ways to get medicines to everyone who needs them.
"We need and there is increasing evidence of African resolve to fight this war. Others will not save us if we do not primarily commit ourselves. Let us, however, not underestimate the resources required to conduct this battle. A constant theme in all our messages has been that in this interdependent and globalized world, we have indeed again become the keepers of our brother and sister."
As you read these notes, an U.S. Congresswoman named Barbara Lee (D.-California) got a bill through the House and Senate to give hundreds of millions of dollars for Africa. It is a beginning. With your help, it will not be the end. There are those who say you do not care about Africa. That you do not care about poor people in far away places.
Break the silence.
David Scondras is the founder and chairperson of Search For A Cure.
Search For A Cure is a not for profit organization providing education, promoting access & advocating the basic human right to safe and effective treatment for all people living with HIV/AIDS. In 1996, Search For A Cure created the nationally recognized, free HIV treatment series Reasons For Hope, now published in over 50 community-based gay and lesbian newspapers across the U.S. Contact Search For A Cure at 617-536-2474, fax 617-266-0051, and e-mail firstname.lastname@example.org.