Children with perinatal HIV respond well to the switch to second-line treatment
In all regions, children show significant immune recovery after switching to second-line treatment, but still too many children switch late.
Children living with perinatal HIV who switch to second-line antiretroviral (ART) treatment respond well to their new treatment and have low- to moderate-levels of loss to follow-up (LTFU), reveals a new global study.
Yet a large number of children were switched to second-line ART when they already had severe immune deficiency or an AIDS diagnosis, suggesting that recognition of treatment failure and transition to a new regime is too often late.
The findings come from the Collaborative Initiative for Paediatric HIV Education & Research (CIPHER) global cohort collaboration and represent the largest ever observational analysis of outcomes associated with switching to second-line treatment regimes in children infected with HIV from birth or breastfeeding. The analysis looks at CD4 counts and weight-for-age scores (known as WAZ) at one and two years of follow-up after children switched to second-line ART. They also looked at changes in CD4 counts and WAZ scores, death rates and LTFU.
85,389 children from 11 participating paediatric networks started a “standard” first-line ART regimen between 1993 and 2015 and were followed until a switch to second-line treatment. Children from sub-Saharan Africa accounted for almost 70% of the study population, with 13% from Europe, 12% from Asia, 3% from Latin America and 2% from North America.
Around 4% (n=3,555) initiated a second-line regimen at an average age of 8.4 years-old, after being on ART for an average of 2.8 years. In North America, the average time to switch was shorter at 2 years, while in southern Africa it was 2.8 years, 3.7 years in the rest of sub-Saharan Africa, 3.5 years in Latin America, 2.9 years in Europe, and 2.7 years in Asia.
Average CD4 counts increased across all regions from the switch to second-line treatment over two years. The change was most pronounced in regions where CD4 counts were very low at baseline. For example, the average CD4 count increased in Latin America from 239 to 641 cells/mm3 after two years; from 315 to 911 cells/mm3 in Asia; and 577 to 764 cells/mm3 in southern Africa and 235 to 698 cells/mm3 in the rest of Africa. In North America, where CD4 counts were already in the upper range, the change was more stable.
As noted by the low CD4 counts in many regions, poor immune status was common at second-line treatment switch. In sub-Saharan Africa, not counting southern Africa, 59% of children were severely immunocompromised at switch, followed by 56% in Asia, 55% in Latin America, 27% in Europe, 26% in southern Africa, and 12.5% in North America.
There was little improvement in observed weight scores of children switching treatment regimens – analysed by region, type of treatment regime, CD4 count and age at switch. The most pronounced change was observed among children who were at an extremely low weight at switch, but this was still small after two years.
The cumulative incidence of LTFU at two years was low at less than 5% in all regions except Southern Africa and the rest of sub-Saharan Africa, where it was 7.1% and 7.4%.
Children who switch to second-line treatment are already very sick. The authors call for better recognition and management of treatment failure in children to improve health outcomes in this group.