Research Article: Clinical decision tools are needed to identify HIV-positive patients at high risk for poor outcomes after initiation of antiretroviral therapy

Date Published: April 18, 2017

Publisher: Public Library of Science

Author(s): Margaret L. McNairy, Elaine J. Abrams, Miriam Rabkin, Wafaa M. El-Sadr

Abstract: Margaret McNairy and colleagues highlight the need for clinical decision tools to help identify HIV patients who would benefit from tailored services to avoid poor outcomes such as death and loss to follow-up.

Partial Text: Over the past decade, the scale-up of HIV programs in resource-limited settings has been remarkable, with over 17 million persons initiating lifesaving antiretroviral therapy (ART) by the end of 2015 [1]. However, in order to reduce HIV-related morbidity and mortality and decrease the number of new infections, it is critical to double the number of HIV-positive patients on treatment by 2020 [2]. It is equally important for health outcomes among children and adults on ART to be optimized [2,3]. To achieve these two goals—i.e., a massive increase in the number of patients on ART as well as an enhancement in the quality of care—the global health community has recognized the need for tailored HIV services to meet the unique needs of different patient groups, often referred to as differentiated models of service delivery [4].

Patients at high risk for poor outcomes, on the other hand, also require a service model that is tailored to their unique needs. The first group of such patients consists of those at high risk for early death after ART initiation. Adults with advanced HIV disease have been noted to have mortality rates up to 5-fold higher in the first 6 months after treatment initiation compared with after 1 year [10,11]. Mortality rates also remain high in the first year of treatment among more recent cohorts with less advanced disease [12]. In a study of 19 cohorts with advanced disease from sub-Saharan Africa, the mortality rate in the first 4 months after ART initiation was 19.1 deaths per 100 person years (PY), decreasing to 1.3 deaths/100 PY beyond 1 year of follow-up [11]. Similarly, in a multicountry study of over 37,000 HIV-infected children, the mortality rate in the first 6 months was 9.1 deaths/100 PY versus 4.5 deaths/100 PY at 24 months [13]. This high early mortality is particularly evident among patients with HIV-related tuberculosis, cryptococcal meningitis, or malnutrition [14–16]. For children, poor growth, advanced disease, and young age are also predictive of early death [13,16].

While multiple studies have identified individual risk factors associated with early death and loss to follow-up among HIV-positive patients in resource-limited settings, work is needed to translate univariable and multivariable models into validated and easy-to-use risk scores to predict an individual’s risk of death and loss to follow-up after ART initiation [11,28–31]. In contrast to the use of CD4+ count or WHO HIV disease staging to identify high-risk patients for disease progression, a composite risk score may provide more specific information on the magnitude of risk for each patient by integrating additional variables such as weight, history, or the presence of a specific opportunistic infection and other parameters. Risk scores also may identify patients who may not have advanced HIV disease but are at high risk of poor outcomes because of a combination of socioeconomic or demographic variables such as limited income, un- or underemployment, and a fragile social support network. For example, while most providers are likely to intuit that a patient with a CD4+ count < 50 cells/mm3 or with concurrent tuberculosis is at high risk for early mortality even after initiation of ART, there is more ambiguity in determining the risk of early mortality for a patient with a CD4+ count of 250 cells/mm3 who lives alone and is unemployed. While the development of simple risk scores to identify patients at high risk for poor outcomes could be of substantial value, further efforts are needed to define interventions and care models to minimize the risk of these poor outcomes. Interventions to mitigate early mortality after ART initiation for patients with advanced HIV disease may include hospitalization of severely ill patients, providing prophylaxis or pre-emptive therapy for opportunistic infections, and/or more intensive clinical visit schedules. The WHO guidelines recommend for such patients the rapid initiation of ART, screening and prompt treatment for coexisting TB or cryptococcus, and provision of isoniazid preventive therapy, if indicated, as well as intensive follow-up for patients with CD4+ count < 200 cells/mm3 or WHO stage III/IV disease [5]. The Reduction of Early Mortality in HIV-Infected Adults and Children Starting Antiretroviral Therapy (REALITY) trial conducted in Zimbabwe, Kenya, Malawi, and Uganda found that enhanced prophylaxis at the time of ART initiation with ongoing cotrimoxazole prophylaxis, 12 weeks of isoniazid/pyridoxine, 5 days of azithromycin, and a single dose of albendazole was associated with a 25% reduction in early mortality among adults and children with CD4+ counts < 100 cells/mm3 [38]. The Reduction of Early Mortality among HIV-Infected Subjects Starting Antiretroviral Therapy (REMSTART) trial conducted in Tanzania and Zambia, in which patients at clinics were assigned to a combination strategy that included screening for cryptococcal disease coupled with 4 weeks of home visits for monitoring response and ART adherence support, resulted in a 28% decrease in mortality when compared to the standard of care [39]. For patients at high risk of loss to follow-up, structural and behavioral interventions such as accelerated ART initiation, phone messaging and texting for appointment reminders, tailored community support, and transport vouchers may be necessary to enhance retention in care [40]. Over the past decade, the scale-up of HIV services has saved millions of lives, but a substantial proportion of patients continue to suffer poor health outcomes, particularly in the first year of treatment. Clinical decision tools, including risk scores, are urgently needed to promptly identify such patients and to guide them to appropriately tailored services that offer them individual benefits while at the same time contributing to the efficient use of health system resources. Source:


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