Track D report by Lorraine SHERR
Summary: New guidelines suggest that HAART be started earlier. This session highlights three issues in regards to starting HAART: medical, community, and financial. There are a number of medical issues relating to starting HAART at a CD4 count of 350. These include a tension between the availability of rigorous studies and medical best practice as well as challenges of following these guidelines in resource-scarce settings. Both physicians (Dr. Deeks and Dr. Mugyenyi) advocate for following the best scientific evidence and well as providing an informed expert opinion that might provide patients with the best diagnosis and treatment options regardless of whether the context is resource rich or resource poor settings. Others (M. Harrington) argue that an informed expert opinion is not enough and that informed consent and rigorous evidence are much more crucial in decisions to adhere to these new guidelines. There are a number of community issues related to starting HAART earlier. Communities need time to adjust to new guidelines. A key theme arising in these discussions around community issues was the importance of political will and community mobilization as tools to ensure that patients receive treatment in a way that adheres to the best scientific evidence. Finally, there are a number of financial challenges relating to providing HAART earlier. Given the economic climate, finding the funding to provide more drugs to more people for longer periods of time is challenging. Such financial challenges can only be met through adhering to the global commitment to increase funding in all countries to meet the target of 15%. Furthermore, these financial commitments require the political will of country leaders, donors, as well as lobbying of people at the grass-roots level.
Track B report by Vivek JAIN
July 20: TUBS01: Starting HAART: When to take the first step?:
This was a lively and engaging session with an interesting format that allowed for exploration of this central issue from a variety of viewpoints. The video is recommended for those interested in this topic. The three session moderators sat on sofa chairs and “interviewed” each of the 4 guests one at a time, posing vexing questions relevant to the multi-faceted issue of when ART should be started. Guests responded to questions, gave perspectives, and interacted with each other in a spirited manner. Selected quotations from the speakers are included in this summary.
Steven Deeks (USA) gave his perspective which is strongly in favor of ART initiation at early opportunities in most patients. He offered his patient-based approach, initiating ART in all patients with CD4<350 and for patients with CD4>350, starting discussions about how to proceed. He gives all available information and data to patients, ultimately asking them to make a choice on therapy. In his view, initiating ART potentially exposes patients to toxicities, both short and long term. However, delaying ART allows a pathogenic virus to replicate, potentially causing irreversible damage to the immune system and adversely affecting outcomes and quality of life. Whereas most toxicities can be managed, immune system damage may not be reversible, and thus in his mind all patients would likely benefit from therapy. He added that if our goal as clinicians is to offer a full lifespan of treatment to our patients (decades of ART), delaying therapy until a CD4 of 350 may save 2-4 years, yet still involve giving 30-40 years of ART, a small overall time savings. However, irreversible immune system damage, immune activation, and the establishment of chronic inflammation may all occur while waiting to initiate ART.
When asked whether we should wait for a randomized trial (such as START) to prove a benefit to ART at high CD4 counts, Deeks noted that while waiting, a pathogenic virus is being allowed to continue replicating, and in that meantime, a maximally data-informed clinical opinion should be offered to patients to decide what to do. Noting this, he was asked whether he would recommend people enroll in the START trial, to which Deeks said he would indeed.
Next to be interviewed was Peter Mugyenyi (Uganda). The moderators first asked whether discussion of treatment at high CD4 counts, given that most patients in Africa are initiated at below CD4 100, is a purely theoretical one. Mugyenyi delivered impassioned and memorable remarks, stating that “there is no separate science for the rich and the poor” and that “simply because there is poverty, you do not use inferior recommendations.” Moderators asked whether the widespread use of d4T in Africa impacts the when-to-start question, to which Mugyenyi answered that it is “totally unacceptable to continue using a toxic drug like this” on a widespread basis, noting it is a human rights issue and that there were alternatives we could be using.
Most of Mugyenyi’s interview, however, centered on the vexing issue of the cost barrier to expanding treatment access across Africa. He first put this in perspective, noting the large advancements that have been made in Africa since 2000, but then passionately speaking on the urgent need for world leaders, politicians, activists, and health care professionals to jointly push for continued and increasing funding for ART. He noted the “daily frustrations of knowing what needs to be done” but facing the “heartbreak of not being able to deliver it.” Much of the discussion centered on this theme. He noted that all countries should be striving to deliver care consistent with WHO guidelines, particularly for adults with TB, pregnant women, and children, but that much work must be done to secure future continued funding, especially as the numbers of those needing treatment rise. Regarding the START trial, he called for more African sites to be involved in this trial.
Activist Michael Harrington (USA) was interviewed next, surely the most controversial portion of the session. He reinforced earlier viewpoints stating that access should be ensured to treat all with CD4<350, all pregnant women and all with TB. Furthermore we should complete randomized trials to help inform the decision about starting therapy at higher CD4s. He noted that the new US guidelines reflected ambivalence about treating higher CD4 count patients, and said that while there were fears the new US guidelines would impact enrollment in the START trial, this hasn’t occurred.
Then the session entered controversial territory. When asked why he felt most US patients were starting therapy at CD4<200 even in the modern era he stated “[the US’s] healthcare system is a mockery in the developed world”, and that (in reference to waiting lists for the USA’s AIDS drug assistance program, ADAP) there was a “mini-genocide” going on.
When asked about the global response and global treatment needs he echoed Mugyenyi’s comments that our world priority needs to be initiating treatment in the 10 million people who need ART but are not on it, mobilizing donors, performing rigorous randomized trials, and pushing for less toxic medicines. When asked if enough is being done on these fronts, Harrington questioned “what will it take to get Obama to give what he needs to give?” and how and why is he “receiving advice from genocidairres (sic)”. He branded the global health initiative of the Obama administration as “woefully inadequate”, and emphasized that the US has a unique role to play in the global responsibility for HIV care.
The final panelist to be interviewed was Ambassador Eric Goosby (USA). Despite sustaining personal critiques as well as critiques of the government administration which he is a part of, Goosby professionally and eloquently stated that he agrees there are, as Mugyenyi had said earlier, heartbreaking choices about therapy being made every day. While he said that “science should not be changed because there is not enough money”, he acknowledged that “triage decisions” are being made in settings with limited resources, and that these problems need to be addressed aggressively. When asked if there is the will and the money to achieve universal access to treatment at CD4 350, he said that the resources are currently not all there, largely due to global economic stressors, but that the commitment is strong, certainly by the US and also by other countries. When asked to respond to Harrington’s sharp comments about the Obama administration, Goosby replied that not only does he agree that we need more resources, but that President Obama knows this, and is deeply committed to this cause. He expressed confidence that as global economic recovery proceeds, the US’s contributions will continue to escalate.
When Harrington challenged these views once again, noting in particular that the US government had undertaken bailouts of multiple financially troubled systems but “won’t bail out global health”, Goosby responded noting the impressive statistics of US contributions that make up over 50% of the global response, 45-90% in PEPFAR countries, and 70-90% in Sub-Saharan Africa.
While this summary does not detail all issues touched upon by the speakers, it provides a partial glimpse into what was an engaging, highly educational, poignant, and interesting session. The interview format, in particular, allowed for clear expression of multiple viewpoints, and allowed for lively yet professional interaction between the guests. As mentioned, the video of this session is highly recommended for all interested in When To Start ART.
LAPC report by Nathan FORD
This session was set up as ‘judge and jury’ presentation to interrogate the risks and benefits of earlier initiation of antiretroviral therapy – a question which according to Nathan Geffen of the Treatment Action Campaign is “One of the most important questions facing HIV research today.”
Dr Peter Mugyeni from the Joint Clinical Reseach Centre in Uganda made the point that if the evidence showed clear patient benefit from earlier initiation then that should be the goal. “There is no separate science for the rich and a separate science for the poor. The research results apply to both.”
When asked whether this was possible using the older drugs that have greater toxicities (such as stavudine), he made it clear that this was not a question of evidence but a question of human rights. “I think this situation is totally unacceptable that people continue to use a drug that we know is toxic.”
Mugyeni went on to call for a renewed energy in the funding effort for HIV. “In Africa we must acknowledge that in 2003-4 there was absolutely nothing. Then Pepfar and GFATM came on board, and showed how we can succeed in Africa by treating a big number of people. This is the kind of spirit that we need now to reactivate. Although we have a world recession AIDS has not gone into recession. On the contrary it has continued to increase.”
The main barrier to earlier initiation, according to Mugyeni and other panelists, is not a lack of scientific evidence but a lack of resources because starting patients earlier means, in the immediate term, treating more people. When asked about the issue of earlier initiation in the face of limited resources, Mugyeni made clear the dilemma health provides faced. “We know what needs to be done. Therefore it is a heartbreaking condition to know what is right for your patients, to know what should be done, and not to be able to deliver it. We are treating only when they are very sick and as a result we have very high mortality.”
More funding is needed, but major donors, notably the US government, have so far been unwilling to support country efforts to move to earlier initiation. Mark Harrington, of the Treatment Action Group, was asked what he thought about the US Government’s current commitment to HIV Funding. He responded by frankly questioning the advice that was being given: “How can a president who is so progressive and came in so much hope let himself get advice from intellectual genocidaires like Ezekiel Emanuel [a key Whitehouse advisor] and Mead Over [from the Centre for Global Development].”
Ambassador Eric Goosby, US Global AIDS co-ordinator echoed the sentiments expressed by Dr Mugyeni “The science is the science. It shouldn’t be changed because there isn’t enough money or because there is a policy difference by a particular administration.” However, he went on to argue that in the face of limited resources, tough decisions needed to be made: “The question over how one decided a triage mechanism should in my opinion go to the sickest patients.” He went on to say that “The resources are currently not there. To expand to the 350 mark, we are looking at 2-3 times the number of patients. That stresses the system significantly.”
Ambassador Eric Goosby concluded with a note of optimism, stating that he had “great confidence that as the economy returns, the resources will go up.” Mark Harrington, however, wasn’t buying it. He said many of the people currently deciding what should happen to global health funding “are the people who didn’t want to do universal access in the fist place. They are using this as an excuse to get out of universal access. They have found the political will to bail out the banks, the housing industry, the automobile industry, but have not done so for AIDS. I do not see the political will.”
Audience members questioned the short sightedness of not supporting early initiation, stressing that a policy of waiting until people become sick with TB or require hospitalization is no way to improve efficiency in the AIDS response.