We used a model-based analysis and South African data to project the average impact of alternative ART strategies over the next 5 years. We applied these strategies to different cohorts, which were intended to be representative of patients who were eligible for ART in 2007, patients who will be eligible for ART from 2008−2012, and patients who have been waiting for ART for varying periods of time. We aggregated the results of these cohorts to create a comparative analysis of population-based scenarios for ART scale-up.
The findings suggest that the potential loss of life associated with the failure to provide ART to all who need it, in South Africa alone, is enormous. A scenario that maintains current treatment capacity with no addition of treatment resources over the long term (zero growth) will result in over 1.2 million more deaths in South Africa—a country with a population of 48 million people [34
]—by 2012, compared with a scenario that provides the resources to ensure universal access to ART by 2011 (rapid growth). The current projected time line for ART scale-up in South Africa (2.1 million receiving treatment by 2012, or a moderate-growth scenario) will likely result in nearly 1.5 million deaths through 2012, over 200,000 more than would be seen with rapid growth [35
ART guidelines are generally country-specific and vary widely [36
]. Some countries, for example, Malawi, do not recommend CD4 count monitoring, and ART initiation is based on WHO stage-3 or stage-4 disease, or CD4 count, if available [37
]. Patients are now being enrolled in trials to examine the long-term impact of clinical monitoring versus laboratory monitoring while on ART, because earlier reports from programs that used clinical guidelines alone suggest substantial survival benefits, even without CD4 count monitoring [12
]. These reports are consistent with the results reported here, however, without access to CD4 monitoring, the number of deaths through 2012 may increase by as many as 986,000, compared with similar scale-up scenarios in which CD4 monitoring is available. Indeed, these results emphasize that the addition of any ART regimen will greatly improve survival; however, they also highlight that the benefits of ART will be maximized with the addition of CD4 counts, as is current South Africa policy.
This analysis has several limitations. It does not compare different strategies for the operational delivery of ART (an essential component to effective scale-up), nor does it include unintended negative consequences of ART. Importantly, we also do not discuss the opportunity costs of investment in expanded ART. One South African projection estimates that full HIV treatment coverage by 2010—including the costs of antiretroviral drugs, nutritional support, and non-antiretroviral drugs—will cost 16.9−21.4 billion Rand in South Africa (US$2.54−3.22 billion) [38
]. Although we have not addressed societal trade-offs in this paper, this analysis offers a quantitative assessment of the opportunity cost—in lives lost—of failing to make these investments in HIV care.
Beyond economic requirements, other complicated infrastructure issues cannot be overlooked and must play a role in any ART implementation. These include facilities, personnel, equipment, and political will. A goal of rapid scale-up must also be accompanied by a commitment to adequate monitoring of therapy, to avoid depletions of stock and interruptions in drug delivery, and to ensure patient adherence so that drug resistance does not occur. Recent findings on the role of extensively drug-resistant tuberculosis (XDR-TB) suggest that the implementation of a large-scale ART program in South Africa will require improvements in tuberculosis control programs as well, to maximize the survival benefits conferred by ART [39
]. The rising prevalence of drug-resistant strains of tuberculosis, coupled with the high mortality rate among HIV-infected patients with XDR-TB, risks considerably undermining the benefits of ART in South Africa [39
]. Infrastructure improvements for the care of individuals with HIV infection and tuberculosis are particularly important, given the possibility that XDR-TB may be transmitted in healthcare settings, thus putting HIV patients who seek medical care at greater risk of infection with this virulent tuberculosis strain [39
As with all model-based analyses, data were derived from multiple sources, which contributes to some uncertainty in the model projections. In most cases, data are specifically from South Africa. However, when South African data were unavailable, we used the closest appropriate surrogate data. To ensure that the model outcomes adequately reflect the South African context, we provided validation from the South African natural history and treatment literature. The estimates of mean CD4 count in the population were made under the assumption of an HIV epidemic in steady state. We have addressed this assumption via sensitivity analyses, examining the parameters that might be most influential in the overall results. The analysis of prioritization made ART available first to those who had been waiting longest. On average, this meant prioritizing those with the lowest CD4 count (mean CD4 count when receiving ART after a wait of 1 year was 139 cells/μL, compared with a CD4 count of 210 cells/μL for those who received ART immediately), though this might not be true in every case.
Though the goal is ambitious, ART scale-up efforts to date have been impressive. The number of people receiving ART in low-income and middle-income countries worldwide increased more than five fold between 2001 and 2005, from 240,000 to 1.3 million [1
]. This level of achievement was previously thought to be impossible. Deliberate, purposeful, and expedient scale-up—together with careful analysis of the outcomes associated with different pro-grammatic approaches—will make the difference in saving hundreds of thousands, or millions, of lives.