HIV-1 co-receptor tropism and disease progression in children and young adults with perinatally acquired HIV-1 infection. The HICCUP Study

OBJECTIVES: Retrospective analysis of evolution of HIV tropism and association with disease progression in perinatal HIV-1 infection (PaHIV). METHODOLOGY: Eligible patients with PaHIV were grouped as slow, rapid or long-term non-progressors (LTNP). The V3 region of gp120 was sequenced from stored plasma samples and tropism determined by geno2pheno algorithm (FPR 5.75%). Logistic regression with generalised estimating equations assessed factors associated with R5 virus. Time to tropism change was assessed using standard survival methods. RESULTS: At baseline (n=48) median age was 12 years (IQR 9.3–14.8), 52% were female, 79% were Black African, 96% were non-B subtypes and 81% (39/48) had R5-using virus. Median follow-up was 7.7 years (308.6 person-years), with a median of five (range 1–14) samples per subject (total 252). Analysing all samples, R5 virus was associated with higher current CD4 cell count (median 520 cells/mm(3) R5 vs 202 for X4, P=0.0005), LTNP (35% vs 11%, P=0.05), non-Black ethnicity (74% vs 89%, P=0.05) and female gender (55% vs 28%, P=0.005). Twelve of 38 (31%) with R5 virus at baseline switched to X4/dual-using virus, with an estimated 5-year risk of switch of 24.4% (95% CI 9.7–39.2%) predicted by lower current CD4 cell count (unadjusted HR 0.62/50 cells higher, 95% CI 0.47–0.81, P=0.0006). Eleven of 19 (58%) with X4/dual-using virus subsequently had R5 virus at one or more time points. CONCLUSION: Maraviroc was a treatment option for 81% at 12 years, falling to 56% at 18 years, with lower CD4 cell count predictive of co-receptor switching. Paediatric studies of CCR5 antagonists should be expedited to ensure they are an early treatment option before tropism switching occurs.