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Treatment of HIV/AIDS in resource-limited settings: Exploring the idea of universal test and treat

Issue: August 2013

ByCharles van der Horst, MD, FACP

ByMichael Herce, MD, MPH

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On July 1, WHO released new consolidated guidelines for the use of antiretroviral drugs to treat and prevent HIV infection. The guidelines take the laudable step of advocating for expanded access to ART for an estimated 25 million people — or nearly three in four people living with HIV globally.

The new recommendations reflect a global trend toward, although notably stop short of, endorsing the “test-and-treat” approach — a public health strategy advancing immediate ART initiation at the time of HIV diagnosis for all patients with HIV. With the new guidelines, WHO now recommends starting ART immediately in key HIV-positive demographic groups, including all pregnant women and uninfected partners of serodiscordant couples, to decrease HIV transmission; all children aged younger than 5 years due to more rapid progression of pediatric HIV disease; and all persons dually infected with HIV and either hepatitis B or tuberculosis.

For patients with HIV who do not fall into one of the affected groups, the new guidelines set a CD4+ count of 500 cells/mm3 as the threshold for ART initiation. Data from randomized controlled trials and large cohort studies have demonstrated the clear benefit to individual health of ART initiation at CD4+ counts below 350 cells/mm3 and support starting ART in patients with CD4+ counts between 350 cells/mm3 and 500 cells/mm3.

The time is now

Although the new guidelines have made a successful case to further expand ART access, have they gone far enough in light of mounting evidence showing the individual and public health benefits of early ART? Haven’t we reached a watershed moment in the global HIV response when the test-and-treat strategy should be the universal recommendation? We believe so, and argue that the time to endorse the test-and-treat approach is now.

Recent studies have demonstrated the survival advantage and reduced morbidity conferred by starting ART in individuals with a CD4+ count above 500 cells/mm3. The NA-ACCORD cohort study revealed an increased risk of death of 94% among patients who deferred therapy until their CD4+ count dropped below 500 cells/mm3 compared with persons starting ART above this threshold. ACTG A5217 showed that initiating ART within 6 months of HIV-1 seroconversion delayed progression to AIDS-defining clinical and immunologic events. Secondary analyses of HPTN 052 data make a similar case, arguing that immediate ART markedly reduces the risk for TB and other WHO clinical stage 3 and 4 conditions.

Although randomized controlled trial data are still needed to conclusively establish the benefit of immediate ART on individual health outcomes, particularly in resource-poor settings, the public health benefits of such an approach are clear. HPTN 052 definitively demonstrated a 96% reduction in the risk of HIV-1 transmission within serodiscordant couples resulting from early ART initiation. A study from South Africa has corroborated the population-level implications of this finding, suggesting that individual HIV acquisition risk decreases with increasing ART coverage within communities.

Michael Herce

Charles van
der Horst

Among the most widely cited potential barriers to the test-and-treat approach are the cost of immediate lifelong ART and the capacity of developing health systems to meet the increased demand for treatment, especially in settings still aspiring to provide access to ART consistent with 2010 WHO recommendations. Indeed, investment in antiretroviral drugs alone will not be enough to introduce the test-and-treat strategy to overburdened health systems in resource-limited settings. We believe that commensurate resource allocation to improve clinical infrastructure, expand the health care workforce and strengthen local governance should be made by national governments and bilateral and multilateral donors to enable the successful implementation of the test-and-treat strategy. If adequately funded, the test-and-treat approach holds promise to simplify national HIV treatment guidelines, reduce health worker training requirements and promote task shifting of HIV care, potentially offsetting some of the projected increased health system expenditures associated with expanded ART access.

Cost-saving approach

Simple costing analyses may overemphasize short-term costs and mask the relative long-term savings and other benefits afforded by the test-and-treat approach. Cost-effectiveness analyses using HPTN 052 data reveal that early ART may be a very cost-effective strategy over time in resource-constrained settings. Incremental gains in cost-effectiveness may be achieved from future reductions in HIV incidence and through efficiencies generated by a strategy relying on a simple HIV rapid test as the gateway to ART rather than the outcome of more resource-intense clinical or laboratory evaluations.

Even if countries are quick to adopt the test-and-treat approach, it is unlikely that all newly diagnosed people living with HIV will consent to treatment immediately, partly allaying concerns about the start-up costs of the strategy. In HPTN 052, for example, 17% of HIV-positive study participants declined ART at 1 year despite routine test result notification and follow-up. External to the health system, upfront costs of test and treat may be recuperated by the increased productivity and resultant contributions to gross domestic product of a healthy workforce. Patients with HIV who have a CD4+ count of 500 cells/mm3 or greater were estimated to work nearly 1 week per month more than counterparts with a CD4+ count less than 200 cells/mm3 — providing a level of productivity essentially equivalent to their HIV-uninfected peers.

Questions remain about how effective the test-and-treat strategy will be in practice, especially given observed high patient dropout, along the HIV treatment cascade, increasing levels of drug resistance globally and low uptake of HIV counseling and testing in many settings.

Ethical questions loom as well. Without adequate investments in health system strengthening in resource-limited settings, the test-and-treat strategy may unintentionally displace sicker patients with lower CD4+ counts in need of immediate treatment in favor of healthier patients with easier access to health care. Answers to some of these questions should emerge with the findings of HPTN 071, an ongoing community cluster randomized trial from Zambia and South Africa.

Path to HIV elimination

Despite these concerns, however, there is reason for well-founded optimism. The results of mathematical modeling suggest that the test-and-treat approach could achieve dramatic reductions in HIV incidence, prevalence and mortality in just 10 years. Over decades, the Granich model predicts that once highly HIV prevalent settings could be transformed into ones with low HIV prevalence — below 1% — placing countries firmly on the path to HIV elimination.

We believe full implementation of the test-and-treat strategy is necessary to both decrease transmission of HIV/AIDS and improve the health and livelihoods of people living with HIV in line with established international targets. Achieving this goal, however, will require bold HIV policy guidance and resource mobilization to match the lofty rhetoric of an AIDS-free generation.

Disclosure: van der Horst and Herce report no relevant financial disclosures.