How Will PEPFAR Reach 4 Million AIDS Patients on Treatment by 2014: Expanded Access or Earlier Recruitment? Millions of Years of Life Hang in the Balance

December 8, 2009

On December 1 the White House announced a new five-year strategy for PEPFAR which aims to increase the number of patients PEPFAR directly supports on antiretroviral therapy from the current 2.4 million to 4 million by 2014. This quite specific policy objective is the subject of this post, which further develops the analysis in my December 1 post: Should Poor Countries Follow WHO’s New Advice on When to Start AIDS Treatment?

PEPFAR managers can meet the new goal of increasing the number of people on treatment to 4 million by 2014 in two ways that cost about the same: they can recruit earlier, that is, start HIV infected people on treatment before they are very sick as counseled by the new WHO guidelines; OR they can expand access, that is, direct the drugs to people who have been infected longer and are therefore sicker. The second choice seems to be the more humane and equitable: give the medicine to the patients who need it most. However, because the prognosis of these patients is generally less good than that of people more recently infected, recruiting patients earlier in their illness actually averts more deaths.

Here’s why: like the figure in my December 1 post, the figure below plots various contours to show tradeoffs between the annual rate of uptake of new patients (on the vertical axis) and the starting CD4 count at ART initiation (on the horizontal axis). The two points indicated with arrows are two ways that PEPFAR and its partners could reach PEPFAR’s 2014 target of four million patients on ART. The blue line which shows the combination that would reach 4 million is almost exactly overlaid by a red line that is a cost contour. According to these calculations, reaching the 4 million mark will require a five-year budget of $12 billion.

The benefit of this $12 billion of treatment financing for the recipient countries is the reduction in the number of deaths through 2014 that would occur without any increase in patients and the number that will occur as a result of additional patient enrollment. Since about 7.5 million deaths are estimated to occur in these countries through 2014 if enrollment remains at the current level of 2.4 million, the number of averted deaths is 7.5 million less the number of deaths to occur if 4 million patients are enrolled. With a policy that favors access, that number of deaths will be about 5 million (indicated by the steep green line) while with a policy favoring early recruitment, total deaths through 2014 drops to 3.5 million (the orange line).

Both the green line representing 5 million total deaths and the orange line representing 3.5 million deaths intersect with the line showing the 4 million patient PEPFAR target and, in about the same locations, with the line showing the $12 billion budget. This means that PEPFAR and its partners could use the same budgetary resources and meet the same goal for patients on treatment in either way. Increasing annual uptake to 18 percent of those in need while holding constant the starting CD4 at 130 would mean expanding the current practice of identifying AIDS patients when they are sick, typically by testing people who have sought health care for their opportunistic illnesses. Deaths would be reduced from 7.5 mmillion to 5 million for a saving of 2.5 million.

A policy favoring early recruitment, would adopt a passive approach to the recruitment of sick people from health centers and instead recruit much more aggressively through programs that test and counsel healthy people. If by applying the latter approach, the average starting CD4 count can be increased to 250, the 23 PEPFAR countries modeled here will experience about 3.5 million deaths through 2014, or about 1.5 million fewer AIDS deaths than would be the case with the expanded access policy. Thus, if the objective were to use the 4 million patient enrollment target and the associated budget to avert as many deaths as possible through 2014, PEPFAR and its partners should favor the lower access with early recruitment policy (towards the lower right of the chart) over one of higher access with continued late recruitment (to the upper left). By the measure of averted deaths, early recruitment would be the more cost-effective policy.

However, this cost-effectiveness comparison is not sufficient to propose a blanket PEPFAR policy of preferring early recruitment over increased access. First, in comparison to the ideal of universal access, even an improved annual uptake rate of 18 percent denies treatment each year to 82 percent of those who are eligible for it. While other sources of financing in these countries, including the Global Fund for AIDS TB and Malaria, national governments, domestic and international NGOs and the patients themselves might together directly support another million or two patients, perhaps increasing the uptake rate from 18 to 30 or even 40 percent, this would still leave many patients unserved. Furthermore, the choice to allocate resources to earlier recruitment rather than increased access implies prioritizing relatively healthy HIV positive patients for treatment over those with low CD4 counts who are in more desperate straits. These considerations are likely to convince many policy makers to prioritize access over early recruitment, regardless of the increased number of deaths.

These are tough choices with no easy answers, not unlike battlefield triage. While PEPFAR may have a view about which point on the 4 million patient contour to aim for, I believe it would be unethical for any donor to impose the choice of any given point on this contour on other governments. The difficulty of this choice, and of choices along other tradeoff envelopes, underlines the importance of another theme of PEPFAR’s new strategy – “partnership” in decision-making with the host country.

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1. Jeremiah Norris Says:
   December 9th, 2009 at 11:28 am

   Mead,

   A good analysis and much needed, too. It does, though, generally isolate PEPFAR from other ongoing AIDS activities wherein all the good that is being done in the former can be undone by the latter.

   On November 30, WHO recommended that countries no longer use Stavudine due to irreversible long-term side effects. WHO did not, however, issue a recall notice for this therapy, which has been the backbone of its treatment recommendation policy since December 2003.

   Of the some 178 ARVs now on WHO’s Prequalification Programme, Stavudine composes 41 therapies, or 23% of the total in the Programme.

   On December 9, MSF was quoted in a published article as saying that in an African township which has been in its treatment program for more than seven years, “16 percent of patients fail lst line therapies within five years.” The price for 2nd line therapies “increases costs by seventeen fold.”

   MSF doesn’t say which therapies these patients have been using. But at least through 2007, all Stavudine products were manufactured in India.

   The Univesity of Maryland’s Virology Institute stated that India’s triple dose combination, which contained Stavudine, resulted in 44% failure rates after two years of treatment in Brazil.

   While PEPFAR is much more concerned about the quality, safety and efficacy of ARV products, the same cannot be said for either WHO or the Global Fund. WHO issues a Disclaimer on its recommended ARVs, saying they are not warranted for safety and/or efficacy if used in the treatment of AIDS. And the Global Fund has a procurement option permitting Members to procure products not approved by a regulatory authority.

   There is a tsunami of unfunded liabilities coming due, notwithstanding PEPFAR’s performance over the next five years.

   Best,
   Jerry Norris
   Hudson Institute

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