Scaling-up antiretroviral treatment in resource-poor countries: prioritization and choices

Abstract

Ongoing scale-up of HIV programs in an era of leveling funds for health require that each dollar is spent efficiently and effectively. From 2004 to 2009, the number of people on antiretroviral treatment (ART) grew from 700 000 to 5.2 million, with a 30% increase realized in 2009 alone [1]. At the same time, for every person starting therapy two others get infected, and the unmet need continues to grow. At the end of 2009, there were 9 million HIV-infected people who were eligible for ART but had not yet started treatment [2]. The Joint United Program on HIV/AIDS (UNAIDS) estimates that in 2009 US$ 15.9 billion was available for HIV/AIDS control globally, US$ 10 billion short of what was needed. There is also a recognized need to re-prioritize other areas of health, notably maternal and child care [3] and to reach universal health coverage [4]. Medium and long-term solutions require significant investment in health systems, increasing the money for health and maximizing health outcomes from available money [4]. As the level of international health financing stabilizes, high-HIV prevalence countries must increase HIV funding from domestic budgets [5], and continue to demonstrate the value for money of their AIDS response strategy to secure sustained donor funding [6,7]. Against this background of changing global health funding and priorities, HIV programs need to monitor and maintain the 5.2 million people currently on therapy, expand treatment initiations to people in earlier stages of infection according to WHO's 2010 guidance [8], and transition to less toxic but more expensive (tenofovir-based) antiretroviral regimens that may be more effective for chronic treatment [9]. Clear evidence on what works is vital for prioritizing program activities and budget allocations. The study by Phillips and colleagues [10] is timely to address the important question of the role of viral load monitoring in preventing the spread of antiretroviral drug resistance. Against the hypothesis that delaying the roll-out of viral load monitoring would result in a worldwide escalation of viral resistance, their modeling suggests that postponing the introduction of routine viral load monitoring will have limited consequences for resistance transmission: 12.4% of new HIV infections are predicted to have primary antiretroviral resistance in 2020 if clinical monitoring is used throughout, compared with 5.4 and 6.1% if viral load-guided switching were introduced in 2010 or 2015, respectively. Phillips and colleagues' findings strengthen the policy consensus and WHO recommendation – so far based on individual patient outcomes and cost-effectiveness in the shorter term [11,12] – that resource-poor countries need not delay ART roll-out because of limitations in laboratory capacity [13]. This is good news, especially for the next few years when HIV programs in many low-income settings are forced to ration new treatment initiations [14], and other ART-supportive activities such as patient adherence support remain underfunded [15]. In high HIV prevalence African countries where a viral load test costs $45–80 and overall delivery of first-line ART $600 per patient-year [12,16,17], omitting viral load monitoring (at one or two tests per year) would allow 8–27% more patients to initiate first-line therapy. In addition, routine viral load testing is associated with an average 40% increased rate of early switching to – more expensive – second-line regimens [18]. In the Phillips' model, introduction of viral load monitoring increased the proportion of patients on second-line regimens by four-fold after 10 years [10]. While improving health outcomes by a small extent [11,12], viral load testing might therefore indirectly increase the average cost per patient by 20–40% or more [19]. Reports by National AIDS programs to the WHO and UNAIDS show large variations in patient monitoring strategies, in rates of switching to second-line regimens, as well as in expenditures per patient [1,2,20]. Several middle-income countries such as Brazil use 3-monthly CD4 and viral load monitoring and a large number of first-line and second-line regimens. Low-income country Malawi, in contrast, implements the WHO-recommended Public Health approach [13], relying on clinical patient monitoring alone and providing a minimum set of WHO-recommended antiretroviral regimens [17]. The marked reductions in AIDS deaths documented in Malawi within years of its ART roll-out since 2004 [20,21] illustrate what can be achieved under a highly simplified medicinal and patient monitoring approach. Delaying the introduction of routine viral load monitoring is in keeping with UNAIDS' Treatment 2.0 strategy [22], an extension on WHO's Public Health approach that aims to further simplify delivery and improve effectiveness of ART. An improved profile of antiretroviral regimens (one pill a day containing a regimen that is forgiving of suboptimal adherence and nontoxic, thus minimizing the need for laboratory monitoring) should allow decentralized community-based treatment delivery. The strategy also promotes an enhanced focus on HIV testing, and on linking treatment delivery with behavioral change communication, to maximize prevention effects. Whereas the antiretroviral regimens envisaged for Treatment 2.0 remain to be developed, ongoing evaluation of the program performance and health impact of public health ART approaches such as in Malawi and Uganda [23] should critically inform global policies. In 2011, Malawi will adopt the WHO recommendation to initiate ART at a CD4 threshold of 350 cells/μl, and transition to tenofovir-based first-line regimens – while for the moment maintaining its practice of minimum patient laboratory monitoring [17]. As patients accumulate years on ART, notably when started at higher CD4 cell counts, longer-term health outcomes and viral resistance surveillance [2,24] will also prove or disprove model predictions – which remain a main guidance at the moment. In the long term, ART programs should aim to expand routine viral load monitoring to prevent viral resistance and preserve the effectiveness of antiretroviral regimens. This will become more affordable and more cost-effective as prices of viral load tests and of second-line antiretroviral drugs continue to decrease. In the short term, while high-prevalence countries continue prioritizing the roll-out of HIV testing and counseling and ART initiations, supportive interventions could focus on effective antiretroviral procurement and distribution to minimize health system-induced treatment interruptions, and on patient adherence support to improve retention and survival on first-line regimens [2,24–26].