Reducing CD4 Monitoring in Children on Antiretroviral Therapy With Virologic Suppression

Abstract

Background Ongoing CD4 monitoring in patients on antiretroviral therapy (ART) with viral suppression has been questioned. We evaluated the probability of CD4 decline in children with viral suppression and CD4 recovery after 1 year on ART. Methods We included children from 8 South African cohorts with routine HIV-RNA monitoring if: (1) they were “responders” (HIV-RNA <400 copies/ml and no severe immunosuppression after ≥1 year on ART [time 0]) and (2) ≥1 HIV-RNA and CD4 measurement within 15 months of time 0. We determined the probability of CD4 decline to WHO-defined severe immunosuppression for 3 years after time 0 if viral suppression was maintained. Follow-up was censored at the first of: day before first HIV-RNA measurement >400 copies/ml; day before a >15 month gap in testing; date of death, loss to follow-up, transfer out or database closure. Results Among 5984 children (median age at time 0: 5.8 years [IQR:3.1-9.0]), 270 experienced a single CD4 decline to severe immunosuppression within 3 years of time 0 with probability of 6.6% (95%CI:5.8-7.4). A subsequent CD4 measurement within 15 months of the first low measurement was available for 63% of children with CD4 decline and 86% showed CD4 recovery. The probability of CD4 decline was lowest (2.8%) in children ≥2 years with no/mild immunosuppression and on ART for <18 months at time 0. This group comprised 40% of children. Conclusion This finding suggests that it may be safe to stop routine CD4 monitoring in children aged ≥2 years and rely on virologic monitoring alone.

CD4 changes among virologically suppressed patients on antiretroviral therapy: a systematic review and meta‐analysis

“…Overall, 13,504 adults and 6793 children on ART were included for review. Most studies were carried out among adults (11 studies) in high-income settings (8 studies); however, around two-thirds of all data (13,776 patients) came from four studies carried out in Africa: South Africa [3,13], Kenya [15] and Uganda [5] (Table 1). The duration of follow-up ranged from 8 to 120 months [3].…”

A case for reduced frequency of CD4 count monitoring for children on combination antiretroviral therapy with consistently undetectable HIV viral load

“…We suggest that future PENTA guidelines take these data and those of previously published paediatric studies [2,3] into account and recommend annual CD4 count monitoring in virally suppressed children and young people.…”

“…Paediatric European Network for Treatment of AIDS (PENTA) guidelines currently recommend monitoring CD4 T-cell counts every 3-4 months in all children and young people with HIV infection [1]. The clinical utility of monitoring CD4 count this frequently in the context of fully suppressed HIV viral load (VL) has been questioned [2][3][4]. When available, VL is the most useful correlate of adherence and/or combination antiretroviral therapy (cART) failure.…”

“…When available, VL is the most useful correlate of adherence and/or combination antiretroviral therapy (cART) failure. Two published paediatric studies in South Africa and Asia suggest that there is a low risk of CD4 decline in virally suppressed children [2,3]. While transient drops in CD4 count do occur in virally suppressed patients, they rarely contribute to clinical decision-making [4,5].…”

The risk factors for suboptimal CD4 recovery in HIV infected population: an observational and retrospective study in Shanghai, China

“…According to published data (8,(14)(15)(16)(17)(18), predictors for suboptimal CD4 recovery are as follows: CD4 < 200 cell/μL at the initiation of ART, older age, co-infected with hepatitis C virus, HIV-2, human T-cell leukaemia virus, regimen of ART, persistent immune activation, loss of the regenerative potential of the immune system and concomitant medical conditions. However, limited studies mainly focused on the risk factors for incomplete immunologic recovery in China, which is a resource-limited place.…”