Accepted by Scopus and Clarivate Analytics to be indexed in Science Citation Index Expanded, JCR, Current Contents and Biological Abstracts

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

Author List
C Foster
S Kaye
C Smith
NE Mackie

Abstract

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/mm3 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.

Article Category

HIV cure research

Article Type

Original research

Posted Date

30-06-2015

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