When Global ART Budgets Cannot Cover All Patients, Who Should Be Eligible?

Abstract

Background:

Widely-expected cuts to budgets for global HIV/AIDS response force hard prioritization choices.

Setting:

We examine policies for ART eligibility through the lens of the most relevant ethical approaches.

Methods:

We compare earlier ART eligibility to later ART eligibility in terms of saving the most lives, life-years, and quality-adjusted life years, special consideration for the sickest, special consideration for those who stand to benefit the most, special consideration for recipients’ own health needs, and special consideration to avoid denying ART permanently.

Results:

We argue that, in most low and middle income countries with generalized HIV/AIDS epidemic, ethically, ART for sicker patients should come before ART eligibility for healthier ones immediately upon diagnosis (namely, before “universal test and treat”). In particular, reserving all ART for sicker patients would usually save more life years, prioritize the sickest, and display other properties that some central ethical approaches find imporatnt and that concern none—so ethically, it is “cross-theoretically dominant,” as we put it.

Conclusion:

In most circumstances of depressed financing in low and middle income countries with generalized HIV/AIDS epidemic, reserving all ART for sicker patients is more ethical than the current international standard.

Decreases in development assistance for HIV/AIDS funding in recent years place pressure on programs in low- and middle- income HIV-endemic countries.¹ Projections suggest that growth in domestic spending will not fully compensate for these reductions in aid.^{2, 3} If current funding trends continue, as is widely expected, HIV/AIDS funding shortages in countries eligible for development assistance are likely to worsen.^{4, 5}

Even before funding reductions, nearly half of people living with HIV globally were not accessing ART.⁶ Further budgetary constraints literally spell death for scores of additional people. We strongly counsel a large boost in global health funding.

Unless such budgetary boost materializes, health ministries and providers may judge that HIV service cuts are unavoidable and force painful prioritization decisions. It would be best to consider in advance: what should give way in such an event—old strategies for HIV/AIDS policy, or new ones?

Per WHO recommendations, several low- and middle-income HIV-endemic countries have adopted an approach termed “universal test and treat” or “treatment as prevention”.⁷ This approach, which we shall call “immediate eligibility for ART”, makes patients eligible for ART immediately upon diagnosis, regardless of CD4 count and disease progression. In contrast, “later ART eligibility” shall mean eligibility only for patients with lower CD4 cell counts (e.g. ≤500 cells/mm³, ≤350 cells/mm³,…) who are typically at later stages of disease.

Properly followed, immediate ART eligibility protects the recipient against some health damage from initial stages of HIV infection, which later ART eligibility does not.^{8, 9} Immediate eligibility is especially efficacious for reducing HIV transmission, as shown in stable serodiscordant couples mutually aware of their serostatus.^{9, 10}

We wholeheartedly endorse providing ART to all patients where possible. But where this is far from being possible, we shall argue that immediate ART eligibility becomes difficult to justify due to its human opportunity cost. Under any budget insufficient to cover everyone, money spent on immediate ART eligibility reduces funds left to expand access at later disease stages. Even when there are enough antiretrovirals left to fulfill advanced patients’ nominal eligibility, there isn’t enough for interventions like building clinics nearer to undertreated, late-stage patients, improving transportation to clinics, and running ad campaigns.¹¹ The resulting utilization gap among advanced patients translates, we shall see, into fewer lives saved and sicker patients abandoned. In fact, we shall add, later ART eligibility “ethically dominates” immediate ART eligibility. By that, we mean that it has traits that at least one leading relevant ethical approach finds important and that none finds concerning. These traits only intensify the later the ART threshold being considered, questioning a central tenet of global HIV response in the last decade.

a. Saving the most lives for the budget

The high efficacy of early ART is not matched by equally high cost effectiveness. The latter is smaller per annum than that of late ART, which saves more quality-adjusted life years, life-years, and lives at current (and reduced) budgets. Comparing cost-effectiveness of immediate ART eligibility to ART initiation at CD4≤500 cells/mm³ (per current guidelines in South Africa) found the latter to be nearly twice as cost-effective, costing $96 per life-year saved vs. $186.¹² Cost-effectiveness increases for even later eligibility thresholds as well.^{13, 14} For any dollar amount in the relevant range, later ART averts greater HIV-related mortality and morbidity.

There are several explanations for this difference in cost effectiveness. Providing ART early necessitates additional years of costly ART¹⁵ —and where antiretrovirals are much cheaper (e.g. Brazil) our findings may not apply. While in principle these additional years on ART could have been expensive yet cost-effective, healthier patients are less likely to consistently adhere to treatment.¹⁶

Another explanation is that while immediate ART is highly efficacious against onward transmission of HIV,¹⁰ so is late ART.¹⁰ Indeed, with the exception of initial weeks of primary infection (during which patients rarely reach clinics), viral load and infectiousness increase steadily as HIV progresses.¹⁷ So when rates of unprotected sex are similar, later ART administration averts a higher risk of transmission per patient per period than earlier ART does.

A third explanation is that while earlier ART might save some patients for long enough to carry them through the budget crunch, so could later ART. There is no telling which would carry through more.

The greater tendency of later ART to save more quality-adjusted life years, life-years, and lives for the relevant budgetary constraints is a decisive advantage according to some leading ethical approaches,¹⁸ a nondecisive advantage according to others,^{19, 20} and a disadvantage according to none.

b. Special consideration for the sickest

Some immediate-eligibility advocates may answer that equity considerations beyond cost-effectiveness matter for ethical priority setting in health.^{20, 21} We propose that the ethical approaches mentioned in these contexts and applicable to our dilemma must also support later ART eligibility, albeit for reasons beyond its greater cost effectiveness.

First, several philosophers arguing against complete reliance on cost effectiveness propose that priority setting should strive especially to help those at highest risk—in this case, the sickest.^{19, 22} Indeed, nations and donors do not disburse HIV budgets exclusively to the most cost-effective interventions, leaving nothing for those already infected, e.g. ART or, nowadays, research towards a cure.¹² That may indicate commitment to the sickest. Furthermore, a common pragmatic argument for funding ART is that even if HIV prevention is more cost-effective, rescuing infected patients may move donors and voters more, enlarging the budget for both ART and prevention.

But priority to the sickest supports later ART eligibility more than it does immediate ART eligibility. Patients with lower CD4 counts have typically suffered pain, disability and strife, and are at significantly increased risk of infection with fatal opportunistic diseases,²³ with much lower likelihood of immune system recovery.²⁴ Initiating ART at later stages therefore reduces risk in individuals at greater risk on average than does immediate ART eligibility. Pragmatically, rescuing these patients is likely to move donors and voters more than assisting asymptomatic recently diagnosed patients.

Inasmuch as the value underlying priority to the sickest is priority to high-risk patients, it also supports priority to advanced patients’ sex partners over sex partners of patients shortly after diagnosis. Sex partners of the former are at greater risk of infection (setting aside acute infectiousness following infection, usually too brief for even immediate ART eligibility to catch on time).

It may seem strange to claim, as we do, that reserving ART eligibility to later stages targets people at higher average risk of morbidity and mortality from HIV. After all, universal test and treat was conceived with no aspiration to bar anyone from eligibility, only to extend ART to all. But universal eligibility is not universal access. For true universal health coverage, access is what matters. In practice, where current budgets can pull only half of infected patients through the cascade of care and are unlikely to cover all anytime soon, any budgets dedicated to treating asymptomatic newly-infected patients come at the expense of drug availability and other means to enhance access for those with more advanced infection.

The tendency of later ART eligibility to prioritize the needs of the sickest or those otherwise at higher risk matters to some ethical approaches,^{19, 22} and concerns none.

c. Special consideration for those who stand to benefit the most

Some nonconsequentialist philosophers make another argument against deciding by cost effectiveness alone. They hold that allocators should prioritize those recipients who stand to benefit most. Even if benefiting others with smaller stakes would generate more good in the aggregate, dramatic personal stakes command high or even abslute priority compred to far smaller stakes.²⁵

In our context, these philosophers might advocate added weight to later-stage patients (and perhaps their sex partners), for whom stakes in immediate treatment are highest. Patients at later stages of HIV infection tend to benefit from ART more than ones at earlier stages, for whom waiting several more years is unhealthy, but rarely terminal. For patients at lower starting CD4 counts, improvements in CD4 counts are associated with a much larger reduction in risk of clinical progression and AIDS-events than for patients at higher counts.^{24, 26} Even for patients at very low CD4 counts, ART can significantly alleviate AIDS-related cancers and infections.^27–29 In short, nearly all HIV-infected patients would benefit from ART, but except at the very end of life, benefits tend to be higher in the pool targeted by late eligibility.

While some philosophers reject such prioritization,^{30, 31} none thinks that higher stakes should count against anyone. Moreover, those who deny the relevance of high personal stakes tend to support instead exclusive focus on cost-effectiveness³¹ or priority to the worse off,³⁰ which would also support later eligibility for ART.

d. Special consideration for recipients’ own health needs

Prevention of transmission comprises a large portion of the impact of both immediate ART and later ART. However, while immediate ART’s impact consists primarily in preventing transmission, later ART’s impact lies to a higher portion in rescuing later-stage patients—ART recipients themselves. This difference may matter ethically. For some nonconsequentialist philosophers, the moral claim of a person in direct need of a resource—in our case, someone who needs ART—is greater than the claim of a person who needs for someone else—in our case, her sexual partner—to receive the resource.³²

This argument does not deny the latter person’s claim altogether. It merely implies that, in comparing claims to limited ART, other things being equal, aiding her—to a similar overall degree—commands somewhat less weight than aiding an HIV-positive patient directly dependent on treatment. If this argument works, then proper weighting for the greater claims enhances the overall ethical advantage of later ART eligibility.

This is a further way in which later ART eligibility is preferable to immediate ART eligibility by some ethical approaches, with others remaining neutral or irrelevant. No ethical approach prioritizes indirect beneficiaries.

e. Special consideration to avoid denying ART permanently

When funds are insufficient to fund the ART or other resources necessary for fulfilling a late-stage patient’s nominal ART eligibility, because healthier patients’ ART used up the entire budget, this is a death sentence. But a person denied immediate ART eligibility remains eligible under late eligibility criteria for initiation at lower CD4 levels. That deferral is far from ideal for her health but, given acute resource scarcity, more acceptable than spelling death. Some ethicists consider condemning a person to certain death an independent evil, far and beyond its contribution to worse population health.³³ No ethicist considers open horizons ethically problematic.

It is true that, should HIV funding later decline further, even late eligibility could stop, condemning currently-new patients to death at that later point. But patients who are now already on the brink of death would die whatever happens to funding later.

f. Conclusion

In the last decade, global HIV response has committed to starting ART increasingly early in disease progression. However, several leading ethical approaches find aspects of later eligibility important, and none find any to be concerning. Thus, regardless of which of these ethical approaches is right, it is clear that later ART is more ethical.

Even with activist effort to increase HIV response budgets, it is unfortunately safe to project that funding for some HIV care systems will continue to fall far short of providing ART to all later-stage patients in need. So long as this remains the case, and later-ART eligibility remains superior across leading ethical approaches to immediate eligibility, insistence on immediate ART eligibility is unethical. It wastes more lives and life-years, and fails to target patients for whom straits are direr, personal stakes are higher, needs are more direct, and immediate assistance is more critical.

Future work could specify how much later in the progression of disease ART eligibility should come, given e.g. each country’s degree of scarcity; and whether patients should ever lose ART eligibility once on treatment. But we hope to have established that some variant of later eligibility is superior to the currently-recommended immediate eligibility.

It may be tempting to replace this detailed discussion by inviting stakeholders to make this decision. But the question would then become: How should these stakeholders decide? And besides, who are the main stakeholders—all infected patients, or only those for whom the stakes are highest, namely, progressive patients? Finally, would stakeholders appraised of their personal stakes decide impartially?

We cannot rule out the possibility that every one of the ethical approaches we mentioned is mistaken, such that no attraction of later ART eligibility is genuine. However, these are all leading approaches to health resource allocation, and some are usually understood as each other’s only serious rivals (e.g. when maximizing lives saved is rejected as the ethical goal, that’s typically done precisely in the name of priority to sicker patients, or direct personal stakes, etc.). In our case these considerations converge to support later ART eligibility, lending robustness to our thesis. Reliance on what we have called “cross-theoretical dominance” can sometimes circumvent the moral uncertainty arising from disagreement between leading ethical approaches, it can provide higher confidence margins than relying on any single one of these leading approaches.

Nor can we rule out that ART at later disease stages is inferior to some public health interventions. Some might recommend shifting budgets instead to voluntary male circumcision, for instance, or to non-HIV interventions. All we are saying is that, in the competition between immediate eligibility and later eligibility for ART, later eligibility is morally superior, by the lights of all leading rival ethical approaches bearing on this question.