The role of targeted viral load testing in diagnosing virological failure in children on antiretroviral therapy with immunological failure

Objectives To determine the improvement in positive predictive value of immunological failure criteria for identifying virological failure in HIV‐infected children on antiretroviral therapy (ART) when a single targeted viral load measurement is performed in children identified as having immunological failure. Methods Analysis of data from children (<16 years at ART initiation) at South African ART sites at which CD4 count/per cent and HIV‐RNA monitoring are performed 6‐monthly. Immunological failure was defined according to both WHO 2010 and United States Department of Health and Human Services (DHHS) 2008 criteria. Confirmed virological failure was defined as HIV‐RNA >5000 copies/ml on two consecutive occasions <365 days apart in a child on ART for ≥18 months. Results Among 2798 children on ART for ≥18 months [median (IQR) age 50 (21–84) months at ART initiation], the cumulative probability of confirmed virological failure by 42 months on ART was 6.3%. Using targeted viral load after meeting DHHS immunological failure criteria rather than DHHS immunological failure criteria alone increased positive predictive value from 28% to 82%. Targeted viral load improved the positive predictive value of WHO 2010 criteria for identifying confirmed virological failure from 49% to 82%. Conclusion The addition of a single viral load measurement in children identified as failing immunologically will prevent most switches to second‐line treatment in virologically suppressed children.     

Early HIV viral load determination after initiating first‐line antiretroviral therapy for indentifying patients with high risk of developing virological failure: data from a cohort study in a resource‐limited setting

Objectives To evaluate the performance of a single determination of HIV viral load (VL) 6–12 months after starting antiretroviral therapy (ART) for identifying patients who will subsequently develop virological failure. Methods We selected HIV‐infected patients with at least two VL determinations after 6 months of ART from an HIV cohort study in India. Patients were divided in two groups depending on whether the first VL was below (Group 1) or above (Group 2) 1000 copies/ml. Cut‐off for virological failure was defined according to World Health Organization recommendation (>5000 copies/ml). Results The study included 584 patients and 560.1 person‐years of follow‐up. Of all virological failures, 83% were diagnosed at the first VL determination. The cumulative incidence of virological failure after 1 and 2 years since the first VL was 0.9% [95% confidence interval (CI), 0.3–2.7] and 1.7% (95% CI, 0.6–5), respectively, for Group 1, and 58.2% (95% CI, 47–69.7) and 63.1% (95% CI, 49.8–76.4), respectively, for Group 2. Compared with Group 1, patients from Group 2 had a hazard ratio for virological failure of 78.3 (95% CI, 27.8–220.2). Conclusions A single VL determination after 6 months of ART was able to identify patients with high risk of virological failure.