Viral load versus CD4+ monitoring and 5-year outcomes of antiretroviral therapy in HIV-positive children in Southern Africa

Abstract

Objectives Many paediatric antiretroviral therapy (ART) programmes in Southern Africa rely on CD4 counts to monitor ART. We assessed the benefit of replacing CD4 by viral load (VL) monitoring. Design Mathematical modelling study. Methods Simulation model of HIV progression over 5 years in children on ART, parameterised by data from seven South African cohorts. We simulated treatment programmes with 6-monthly CD4 count or 6- or 12-monthly VL monitoring. We compared mortality, second-line ART use, immunological failure and time spent on failing ART. In further analyses we varied the rate of virological failure, and assumed that the rate is higher with CD4 than with VL monitoring. Results About 7% of children were predicted to die within 5 years, independent of the monitoring strategy. Compared with CD4 monitoring, 12-monthly VL monitoring reduced the 5-year risk of immunological failure from 1.6% to 1.0% and the mean time spent on failing ART from 6.6 to 3.6 months; 1% of children with CD4 compared to 12% with VL monitoring switched to second-line ART. Differences became larger when assuming higher rates of virological failure. When assuming higher virological failure rates with CD4 than with VL monitoring, up to 4.2% of children with CD4 compared to 1.5% with VL monitoring experienced immunological failure; the mean time spent on failing ART was 27.3 months with CD4 monitoring and 6.0 months with VL monitoring. Conclusions VL monitoring did not affect 5-year mortality, but reduced time on failing ART, improved immunological response and increased switching to second-line ART.

The need for second-line antiretroviral therapy in adults in sub-Saharan Africa up to 2030: a mathematical modelling study

“…A large proportion of the children who have started with a standard NNRTI-based regimen may need second-line ART in adolescence. 13,23 The current recommendations suggest that children <3 years should start with a PI-based first line regimen 2 , making it complicated to find suitable and affordable regimens for those patients who experience treatment failure. 10 …”

“…12 The structure is similar to models we have developed before, 10,11,13 and a detailed description is given in the Supplementary Appendix, Text S1. We simulated cohorts of 10,000 adults (>15 years) who progress from ART initiation through a sequence of health states that combine the patient’s virological, immunological, clinical and retention status and the type of treatment regimen (first- or second-line) (Supplementary Appendix, Text S1, Table S1.1).…”

Differences in virologic and immunologic response to antiretroviral therapy among HIV-1-infected infants and children

“…In contrast to poor viral suppression with ART, infants generally have better immune status on ART than older children[17–19]; this may be due to their high thymic output[20] and higher age-specific CD4 counts and CD4%[21–23], or to greater damage to the CD4 T-cell population among older children who have lived with untreated HIV for an extended period[24–25]. As ART response is primarily assessed using CD4 monitoring in developing country settings[26–29], treatment failure among infants in particular may be masked by their comparatively good CD4 counts and percentages[26,29,30]. …”

Drug resistance testing through remote genotyping and predicted treatment options in human immunodeficiency virus type 1 infected Tanzanian subjects failing first or second line antiretroviral therapy

“…Other studies have demonstrated that absence of virological monitoring and a delayed switch of therapy lead to a high degree of accumulation of DRMs [22] and an increased mortality [23]. Since 2013, WHO have included virological testing as the preferred monitoring strategy [10], which may eventually enable affordable viral load testing in resource-limited settings and shift the cost/benefit balance in favour of implementing virological monitoring on a broader scale.…”