Abstract
ObjectivesThe aim of the study was to determine the time to, and risk factors for, triple‐class virological failure (TCVF) across age groups for children and adolescents with perinatally acquired HIV infection and older adolescents and adults with heterosexually acquired HIV infection.MethodsWe analysed individual patient data from cohorts in the Collaboration of Observational HIV Epidemiological Research Europe (COHERE). A total of 5972 participants starting antiretroviral therapy (ART) from 1998, aged < 20 years at the start of ART for those with perinatal infection and 15–29 years for those with heterosexual infection, with ART containing at least two nucleoside reverse transcriptase inhibitors (NRTIs) and a nonnucleoside reverse transcriptase inhibitor (NNRTI) or a boosted protease inhibitor (bPI), were followed from ART initiation until the most recent viral load (VL) measurement. Virological failure of a drug was defined as VL > 500 HIV‐1 RNA copies/mL despite ≥ 4 months of use. TCVF was defined as cumulative failure of two NRTIs, an NNRTI and a bPI.ResultsThe median number of weeks between diagnosis and the start of ART was higher in participants with perinatal HIV infection compared with participants with heterosexually acquired HIV infection overall [17 (interquartile range (IQR) 4–111) vs. 8 (IQR 2–38) weeks, respectively], and highest in perinatally infected participants aged 10–14 years [49 (IQR 9–267) weeks]. The cumulative proportion with TCVF 5 years after starting ART was 9.6% [95% confidence interval (CI) 7.0−12.3%] in participants with perinatally acquired infection and 4.7% (95% CI 3.9−5.5%) in participants with heterosexually acquired infection, and highest in perinatally infected participants aged 10–14 years when starting ART (27.7%; 95% CI 13.2−42.1%). Across all participants, significant predictors of TCVF were those with perinatal HIV aged 10–14 years, African origin, pre‐ART AIDS, NNRTI‐based initial regimens, higher pre‐ART viral load and lower pre‐ART CD4.ConclusionsThe results suggest a beneficial effect of starting ART before adolescence, and starting young people on boosted PIs, to maximize treatment response during this transitional stage of development.
Highlights
One of the major challenges for children and young people with perinatal HIV infection is the maintenance of long-term adherence to treatment regimens to suppress virus and prevent resistant virus from developing [1]
≥ 1 year of age according to age-specific immunological thresholds (1–3 years, CD4 count ≤ 1000 cells/lL or CD4% ≤ 25%; 3–5 years, CD4 count ≤ 750 cells/lL or CD4% ≤ 25%; >5 years, CD4 count ≤ 350 cells/lL), and in any child with a World Health Organization (WHO) stage 3/4 or Centers for Disease Control and Prevention (CDC) category B/C event, largely to prevent progression to AIDS and death and to potentially optimize the ultimate CD4 count in adulthood [3]
We showed how the risk of triple-class virological failure (TCVF) of the three original drug classes in children increased with older age at the start of antiretroviral therapy (ART) [4]
Summary
One of the major challenges for children and young people with perinatal HIV infection is the maintenance of long-term adherence to treatment regimens to suppress virus and prevent resistant virus from developing [1]. We showed how the risk of triple-class virological failure (TCVF) of the three original drug classes in children increased with older age at the start of ART [4]. The main analysis of that study used a broad definition of TCVF which included outdated treatment regimens, including unboosted PIs. A restricted analysis (including two NRTIs with either an NNRTI or a bPI) suggested that the overall rate of failure in children was over twice as high as in adults with heterosexually acquired HIV infection (hazard ratio 2.2; 95% confidence interval (CI) 1.6, 3.0; P < 0.0001). We further explored the difference in TCVF rates between perinatally infected children and young adults aged 15 to 29 years with heterosexual infection, and in particular looked at the effect of age at the start of ART on risk of TCVF
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