Impact of low‐level viraemia on virological failure among Asian children with perinatally acquired HIV on first‐line combination antiretroviral treatment: a multicentre, retrospective cohort study

Abstract

Introduction The clinical relevance of low‐level viraemia (LLV) and virological outcomes among children living with HIV (CLHIV) remains controversial. This study aimed to determine the impact of LLV on virological failure (VF) among Asian CLHIV on first‐line combination antiretroviral therapy (cART). Methods CLHIV aged <18 years, who were on first‐line cART for ≥12 months, and had virological suppression (two consecutive plasma viral load [pVL] <50 copies/mL) were included. Those who started treatment with mono/dual antiretroviral therapy, had a history of treatment interruption >14 days, or received treatment and care at sites with a pVL lower limit of detection >50 copies/mL were excluded. LLV was defined as a pVL 50 to 1000 copies/mL, and VF as a single pVL >1000 copies/mL. Baseline was the time of the second pVL < 50 copies/mL. Cox proportional hazards models were performed to assess the association between LLV and VF. Results From January 2008 to September 2016, 508 CLHIV (55% female) were eligible for the study. At baseline, the median age was 9.6 (IQR: 7.0 to 12.3) years, cART duration was 1.4 (IQR: 1.3 to 1.8) years, 97% of CLHIV were on non‐nucleoside reverse transcriptase inhibitor‐based regimens, and the median CD4 was 25% (IQR: 20% to 30%). Over a median follow‐up time of 6.0 (IQR: 3.1 to 8.9) years from baseline, 86 CLHIV (17%) had ever experienced LLV, of whom 32 (37%) had multiple LLV episodes. Female sex, living in Malaysia (compared to Cambodia), having family members other than biological parents/grandparents as a primary caregiver, and baseline CD4 < 25% increased risk of LLV. Overall, 115 children (23%) developed VF, corresponding to a rate of 4.0 (95%CI: 3.4 to 4.9) per 100 person‐years of follow‐up (PYFU). VF was greater among children who had ever experienced LLV compared with those who maintained virological suppression throughout the study period (8.9 vs. 3.3 per 100 PYFU; p < 0.001). In multivariable analyses, ever experiencing LLV was associated with increased risk of subsequent VF (adjusted hazard ratio: 3.01; 95%CI: 1.97 to 4.60). Conclusions LLV increased the risk of subsequent VF among Asian CLHIV who had previously been suppressed on first‐line cART. Adherence interventions and additional targeted pVL monitoring may be warranted among children with LLV to facilitate early detection of VF.

Prevalence and predictors of virological failure in pediatric patients on HAART in sub-Saharan Africa: a systematic review and meta-analysis

“…In this review, the non-availability of biological parents as primary caregivers has been associated with an increased risk of VF [ 34 , 37 , 40 ]. This finding is in consonant with a multicenter retrospective cohort study in the Asian-Pacific [ 59 ]. Having family members other than biological parents/grandparents as primary caregivers increased the risk of subsequent VF among Asian children living with HIV.…”

“…The findings of this review are at variance with what has been documented in studies in other developing countries outside the sub-Saharan region. In Thailand, Cambodia, and India, the mean VF ranged from 3.3 to 27% in children treated for HIV 1 using the WHO standard first-line ART for a period not less than six months [ 55 - 59 ]. This highlights a higher success rate in the management of HIV compared to rates obtained in sub-Saharan Africa.…”

Incidence and predictors of virological failure among children receiving first-line anti-retroviral treatment in public comprehensive specialized hospitals found in Northeast Ethiopia: a retrospective follow-up study

“…Different studies reported the prevalence of VF, being 19.2% in South Africa (12), 25.5 in Cameroon (13), 64% in Senegal (14), 37% in Kenya (15), 23% in Asia (16), 29.2% in Iran (17), and 26% in the Netherlands (18). Cross-sectional studies conducted in resourcelimited countries have reported a risk of VF ranging from 11% to 66% (19)(20)(21), and a 3-year probability of VF in Ghana was found to be 31% (22).…”

HIV Virologic Failure among Patients with Persistent Low‐Level Viremia in Nairobi, Kenya: It Is Time to Review the >1000 Virologic Failure Threshold

“…Some studies have reported PLLV as an independent indicator of VF while others disagree, especially about the significance of low-level low-range viremia. Notably, clinical implications differ among patients with PLLV ≤ 199 copies/ml and patients with higher viremia 200-<1000 copies/ml, with the latter being associated with VF [ 4 , 5 , 8 – 11 ]. The increasing evidence on the negative impacts of PLLV, especially persistent VL between 20 and 999, has led some organizations in resource-rich settings (RRS) to adopt guidelines lowering the ≥1000-copies/ml threshold of VF set by WHO.…”