Second-Line Protease Inhibitor-Based Haart after Failing Non-Nucleoside Reverse Transcriptase Inhibitor-Based Regimens in Asian HIV-Infected Children

Abstract

Background The WHO recommends boosted protease inhibitor (bPI)-based highly active antiretroviral therapy (HAART) after failing non-nucleoside reverse transcriptase inhibitor (NNRTI) treatment. We examined outcomes of this regimen in Asian HIV-infected children. Methods Children from five Asian countries in the TREAT Asia Pediatric HIV Observational Database (TApHOD) with ≥24 weeks of NNRTI-based HAART followed by ≥24 weeks of bPI-based HAART were eligible. Primary outcomes were the proportions with virologic suppression (HIV-RNA <400 copies/ml) and immune recovery (CD4% ≥25% if age <5 years and CD4 count ≥500 cells/mm3 if age ≥5 years) at 48 and 96 weeks. Results Of 3422 children, 153 were eligible; 52% were female. At switch, median age was 10 years, 26% were in WHO stage 4. Median weight-for-age z-score (WAZ) was −1.9 (n=121), CD4% was 12.5% (n=106), CD4 count was 237 (n=112) cells/mm3, and HIV-RNA was 4.6 log10copies/ml (n=61). The most common PI was lopinavir/ritonavir (83%). At 48 weeks, 61% (79/129) had immune recovery, 60% (26/43) had undetectable HIV-RNA and 73% (58/79) had fasting triglycerides ≥130mg/dl. By 96 weeks, 70% (57/82) achieved immune recovery, 65% (17/26) virologic suppression, and hypertriglyceridemia occurred in 66% (33/50). Predictors for virologic suppression at week 48 were longer duration of NNRTI-based HAART (p=0.006), younger age (p=0.007), higher WAZ (p=0.020), and HIV-RNA at switch <10,000 copies/ml (p=0.049). Conclusion In this regional cohort of Asian children on bPI-based second-line HAART, 60% of children tested had immune recovery by one year, and two-thirds had hyperlipidemia, highlighting difficulties in optimizing second-line HAART with limited drug options.

Outcomes of second‐line antiretroviral therapy among children living with HIV: a global cohort analysis

“…At two years of follow‐up, we observed improvements in CD4 counts similar to what have been reported in previous studies conducted primarily in Asia [14,16,18‐21]. While it is reassuring to observe immune recovery after switch to second‐line ART, we noted a large proportion of children with severe immune deficiency and AIDS progression at the time of switch to second‐line ART in some settings.…”

“…Responses to first‐line ART among children have been evaluated in large randomized trials and observational studies [4‐12]. Studies evaluating outcomes on second‐line ART in children; however, have been limited by small sample sizes in both resource‐rich and resource‐limited settings [6,13‐21]. Of the four published studies on second‐line ART with larger sample sizes, ranging from 111 to 277 children, three were conducted in Thailand or the Asia‐Pacific region [18‐20], and one followed Ugandan children who were switched to a lopinavir/ritonavir (LPV/r)‐based second‐line regimen [21].…”

“…Studies evaluating outcomes on second‐line ART in children; however, have been limited by small sample sizes in both resource‐rich and resource‐limited settings [6,13‐21]. Of the four published studies on second‐line ART with larger sample sizes, ranging from 111 to 277 children, three were conducted in Thailand or the Asia‐Pacific region [18‐20], and one followed Ugandan children who were switched to a lopinavir/ritonavir (LPV/r)‐based second‐line regimen [21]. These studies observed improvements in CD4 counts after switch to a second‐line regimen, with an increase of 267 cells/mm 3 in mean CD4 counts after 48 weeks of follow‐up in the Ugandan study [21], and 463 cells/mm 3 in median CD4 counts after 3.3 years of follow‐up in the largest study conducted in Asia [20].…”

“…These studies observed improvements in CD4 counts after switch to a second‐line regimen, with an increase of 267 cells/mm 3 in mean CD4 counts after 48 weeks of follow‐up in the Ugandan study [21], and 463 cells/mm 3 in median CD4 counts after 3.3 years of follow‐up in the largest study conducted in Asia [20]. No deaths were observed over 48 weeks of follow‐up among the Ugandan children on second‐line ART, and less than 2% of children died in the studies of Asian children on second‐line ART [18‐21].…”

The changing epidemiology of the global paediatric HIV epidemic: keeping track of perinatally HIV‐infected adolescents

“…Within a cohort of ART-naïve younger children from Cambodia and Thailand, 28% already had hypertriglyceridemia and 45% had low HDL [52]. In the TApHOD cohort, among children switched to PI-based second-line ART at a median of 10 years of age, 32% had hypercholesterolemia, 73% had hypertriglyceridemia, 18% had HDL, and 49% had elevated triglyceride to HDL ratios at 48 weeks of follow-up [53]. It remains unclear what this abnormal lipid metabolism will mean for PHIVA and their risk of cardiovascular disease.…”