Predictors of faster virological suppression in early treated infants with perinatal HIV from Europe and Thailand.

M Chan ,Elena Chiappini ,Russell Goodall ,Niek De Klein ,Ali Judd ,Thomas Klimkait

doi:10.1097/qad.0000000000002172

Abstract

To identify predictors of faster time to virological suppression among infants starting combination antiretroviral therapy (cART) early in infancy. Cohort study of infants from Europe and Thailand included in studies participating in the European Pregnancy and Paediatric HIV Cohort Collaboration. Infants with perinatal HIV starting cART aged less than 6 months with at least 1 viral load measurement within 15 months of cART initiation were included. Multivariable interval-censored flexible parametric proportional hazards models were used to assess predictors of faster virological suppression, with timing of suppression assumed to lie in the interval between last viral load at least 400 and first viral load less than 400 copies/ml. Of 420 infants, 59% were female and 56% from Central/Western Europe, 26% United Kingdom/Ireland, 15% Eastern Europe and 3% Thailand; 46 and 54% started a boosted protease inhibitor-based or nonnucleoside reverse transcriptase inhibitor-based regimen, respectively. At cART initiation, the median age, CD4% and viral load were 2.9 [interquartile range (IQR): 1.4-4.1] months, 34 (IQR: 24-45)% and 5.5 (IQR: 4.5-6.0) log10 copies/ml, respectively. Overall, an estimated 89% (95% confidence interval: 86-92%) achieved virological suppression within 12 months of cART start. In multivariable analysis, younger age [adjusted hazard ratio (aHR): 0.84 per month older; P < 0.001], higher CD4% (aHR: 1.11 per 10% higher; P = 0.010) and lower log10 viral load (aHR: 0.85 per log10 higher; P < 0.001) at cART initiation independently predicted faster virological suppression. We observed a significant independent effect of age at cART initiation, even within a narrow 6 months window from birth. These findings support the earliest feasible cART initiation in infants and suggest that early therapy influences key virological and immunological parameters that could have important consequences for long-term health.

Highlights

The clinical benefits of starting combination antiretroviral therapy early in HIV-infected infants have been demonstrated in several observational studies and trials
We evaluated the following factors: age at combination antiretroviral therapy (cART) initiation, baseline viral load, CD4þ% and cell count, sex, ethnicity, initial cART regimen, infant antiretroviral prevention of mother-tochild transmission (PMTCT) prophylaxis regimen given within 4 weeks of birth, maternal antiretroviral PMTCT regimen used in the prenatal and delivery period, birth abroad, year of birth, year of cART initiation, Centers for Disease Control and Prevention (CDC) C event by cART initiation and geographical region
Patient characteristics Of the 3953 children included in the dataset, 420 (11%) infants met the study inclusion criteria of being perinatally HIV-infected, aged less than 6 months at cART initiation with at least 1 viral load measurement within 15 months of cART start (1998–2013) (Fig. 1)

Summary

Introduction

The clinical benefits of starting combination antiretroviral therapy (cART) early in HIV-infected infants have been demonstrated in several observational studies and trials. The Children with HIV Early Antiretroviral Therapy (CHER) trial showed that starting cART before 12 weeks of age markedly reduces mortality and morbidity in HIVinfected infants [1,2]. These findings were confirmed in the European Infant Collaboration (EIC) observational study [3] and the French perinatal cohort [4]. Few studies have examined factors associated with time to virological suppression in infants starting cART before 6 months of age; most studies have evaluated children initiating cART during the first year of life [19,20,21] or at older ages [22] and results have been variable

Methods

Results

Conclusion