In his blog post
, Sean Strub raises serious concerns about three central issues. The first is the on-going debate about when to start ARV treatment. The second involves proposed new studies seeking to improve HIV testing utilization and linkage to care. The third regards the benefits that ARV treatment can have on preventing new HIV infections. There is a good deal that needs to be refuted and/or clarified in order to have an open discussion on these issues.
First, on the issue of when to start ARV therapy, I should begin with some background history. In 1989, a recommendation was made to start AZT monotherapy at <500 CD4 cells and well before the development of AIDS. That recommendation was made with little supporting data. After a year or so, it was clear that the recommendation was wrong. People who started AZT early actually did worse than those who started later. That mistake cost many people their lives. Unfortunately, the same mistake was made repeatedly - with dual therapy (AZT/ddI or ddC) in the early 90s, with AZT and 3TC a bit later. Each time, the recommendation to start early was proven wrong.
When HAART came out in 1996, the US Public Health Service ARV guidelines panel reviewed the scant information on when to start HAART. Once again, many of the scientists on the panel pushed hard for a recommendation of "hitting hard, hitting early" - starting at <500 CD4. But this time, the AIDS treatment activists on the panel - myself, Mark Harrington and the late Martin Delaney of Project Inform - all argued strongly that the recommendation should be to start later, at <200 CD4 cells or at signs of HIV symptoms. Our view was that we had no data whatsoever about early use of HAART - not one single study had been done. And we had made the mistake too many times before. These drugs were approved faster than any drugs in the history of drug development, thanks, in part to our activism. But that meant we had much less data by which to determine how to use them effectively. At that time, we had no information about the development of drug resistance, the need for high levels of adherence, or about most of the side effects from the drugs including lipodistrophy and body changes. And, we argued that if the US PHS put out a guideline recommending starting at 500 t-cells, there would be no way to ethically study the when to start question.
We lost the initial battle. The first HAART guideline recommended early treatment. And over the course of the next three years, we learned about the adherence challenges and the many serious side effects. Many, many people started treatment earlier than necessary and with inferior drugs. And, the definitive clinical trial was never done. Three years later, we were effective in getting the guidelines revised to a recommendation of starting at <200 t-cells or HIV symptoms.
But much has happened since then. There is now a significant amount of very compelling data from cohort and other studies around the world showing that earlier treatment has a positive impact on survival and in delaying not only AIDS-related illnesses but other illnesses that are the result of living with overly active immune system that is constantly battling viral replication, including heart disease, cancers, premature aging, as well as exacerbation of hepatitis C and TB progression. Although this data does not take the form of the more preferable "when to start" randomized clinical trial, it is increasingly compelling. Enough so that doctors and people living with HIV can make a very reasonable decision to use ARVs much earlier than we would have a few years ago. And because the drug regimens are now easier to take and with fewer side effects, the downside of starting earlier has decreased. Starting early isn't the only path, but it is a reasonable path. A change in the PHS guidelines in 2005 reflects this, recommending treatment at <350 CD4 cells. Now, the PHS is changing its guidelines once again to recommend starting at <500 CD4 cells. Again this is based on the data described above. Many doctors and researchers even believe that people should start therapy no matter what their t-cell count is. And they believe this because they think their patients will live longer and better lives for it.
The START study that Sean mentions would answer the question of when to start. Personally, I would prefer that the government (both the U.S. and the San Francisco Dept. of Health) wait until data from the START study is available before changing their recommendations. I think that public health officials have a responsibility to be more conservative in their recommendations, which should be based on the results of randomized clinical trials whenever possible. The emergence of other long-term side effects is one important reason to ensure that the START study is completed. The guideline recommendations will seriously hinder START enrollment in the US.
However, doctors and patients should have the ability to make more aggressive decisions about starting treatment if they feel, after analyzing the available data, that this is the best course of action. Similarly, I think Project Inform has every right to make its own policy decisions based on review of what is currently known. It is not fair nor just to accuse any of those involved in these decisions - guideline panelists, physicians, advocacy groups or people living with HIV - with some sort of underhanded conspiracy to coerce people onto early treatment for the sake of prevention or any other purpose. The data is there and starting early is justified. Again, it is not the sole approach, but it is a very viable one.
Despite Sean's assertions, the NIH-sponsored study that will seek to improve uptake of HIV testing and linkage to care - unfortunately labeled the "test and treat" study - is NOT placing people who test positive on treatment regardless of CD4 cell count. The study seeks to improve testing rates, link people to care, and offer treatment to those who meet current treatment guidelines. This is not a study testing the impact of earlier use of ARVs for prevention purposes. It is a study looking for ways to improve testing uptake and use of care. Up to 33% of people in the U.S. find out they have HIV by developing AIDS. This is a figure that has not improved in over 15 years. This is criminal. And this is not only a US problem. All over the world, testing uptake is horrible. This study is looking at ways to fix this. Treatment will be offered and recommended. Let's hope those who need it are able to access and accept treatment and use it properly. For some, it will save their lives.
The final issue involves the impact that ARV treatment can have in preventing new HIV infections. The data from Vancouver, from San Francisco and most importantly, from a large study of sero-discordant couples in Africa is showing that people taking ARVs are much less likely to transmit HIV. We still have much to learn, but it is very possible that ARV treatment may be the most effective HIV prevention tool we have and will have for many years to come. This is ground breaking news. Nowhere in Sean's piece does he acknowledge the potential good here. I don't want to transmit my HIV to anyone. Prevention is a challenge for all of us - positive or negative. If there is a way to help me make sure that I can't infect someone else, I want it. And I think most people living with HIV feel the same way.
Of course, treatment-centered prevention doesn't replace the need for condom distribution and other prevention interventions. But those interventions on their own have shown very limited effectiveness both in the US and around the world. Condoms won't end the AIDS epidemic. And there is no vaccine on the horizon for years and years to come. If we have a new tool that can effectively prevent HIV transmission, then we need to learn how to use it. And we all have a responsibility to figure out how to use this information in ways that can both protect from harm those of us having to take ARVs as well as protect others so that they never have to take them.
Of course, the threat of stigma and discrimination remains one of the greatest challenges we face in successful implementation HIV treatment and prevention efforts. We have always faced the danger of discrimination in our attempts to live with HIV openly and with dignity. The courage of people living with HIV to overcome these dangers as they seek out information, care and treatment has been and continues to be one of the most inspiring stories in the history of public health. We all need to be able to access treatment and live freely without fear. "Treatment as prevention" approaches do not alter this, but, rather make the need to overcome discrimination all the more important. Can we scale up HIV testing within a context of protecting human rights? We must do this whether we are using ARVs for prevention or not. Should patient confidentiality and choice be protected? We have advocated this course since 1981 as the only way we can expect people living with HIV to successfully engage in care. So, treatment as prevention doesn't really raise new issues in this regard.
There is a lot to learn. There are a whole slew of unanswered questions and challenges. Does earlier treatment put me at risk for more side effects or drug resistance? We don't know. A better first line combination regimen would go far to alleviate these risks, especially in resource-poor countries. That is within our grasp right now with some good advocacy and political commitment.
Personally, I have been on ARVs for 15 years now. If I had started three years earlier (given the drugs we have today), would it have made a difference? I don't know. But I plan and hope to be on ARVs for many years to come, so that three years doesn't seem like such a big deal to me right now.
Should EVERYONE start early, of course not. But maybe many of us can and will. And in doing so, maybe we can see a real decline in new HIV infections in New York and San Francisco and Johannesburg and Moscow and Bangkok. That would make me very happy.
Discussion about treatment-centered prevention approaches are taking place not because of some vast conspiracy to mistreat people living with HIV, but because the science is beginning to show us that treatment can prevent HIV. New scientific understanding of HIV and treatment is what has driven and transformed the response to HIV ever since the virus was first discovered. That is what is driving this discussion. In 1996, all of a sudden we had new tools to save our lives. But we didn't know how to use them. But we learned. That is what is happening now. And it's very exciting.