Higher rates of triple-class virological failure in perinatally HIV-infected teenagers compared with heterosexually infected young adults in Europe.
The 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.



We 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.



The 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.



The 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.
MRC Clinical Trials Unit, University College London, London, UK.
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0000-0003-3176-5295
A
Judd
Department of Infection and Population Health, University College London, London, UK.
R
R
Lodwick
Institut de Recerca Pediàtrica Hospital Sant Joan de Déu, Barcelona, Spain.|Departament de Pediatria, Universitat de Barcelona, Barcelona, Spain.|CIBER de Epidemiología y Salud Pública Ciberesp, Barcelona, Spain.
A
A
Noguera-Julian
MRC Clinical Trials Unit, University College London, London, UK.
D M
DM
Gibb
Department of Infectious Diseases and Immunology, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.
K
K
Butler
INSERM, UPMC Univ Paris 06, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136), Sorbonne Universités, Paris, France.
D
D
Costagliola
Department of Infection and Population Health, University College London, London, UK.
C
C
Sabin
Stichting HIV Monitoring, Amsterdam, The Netherlands.
A
A
van Sighem
Division of Infectious Diseases and Hospital Epidemiology, University of Zurich, Zurich, Switzerland.
B
B
Ledergerber
Unit of Infectious and Tropical Diseases, Department of Medical and Surgical Sciences, University "Magna Graecia", Catanzaro, Italy.
C
C
Torti
Department of Infection and Population Health, University College London, London, UK.
A
A
Mocroft
HIV and STD Unit, Infectious Disease Service, Hospital Universitari de Bellvitge. L'Hospitalet, Barcelona, Spain.
D
D
Podzamczer
Istituto Superiore di Sanità, Rome, Italy.
M
M
Dorrucci
Département of Infectious Diseases, Centre Hospitalier Saint-Pierre, Université Libre de Bruxelles, Brussels, Belgium.
S
S
De Wit
Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
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N
Obel
INSERM U1219 - Centre Inserm Bordeaux Population Health, Université de Bordeaux, Bordeaux, France.|ISPED, Centre INSERM U1219-Bordeaux Population Health, Université de Bordeaux, Bordeaux, France.
F
F
Dabis
Department of Infection and Population Health, University College London, London, UK.
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A
Cozzi-Lepri
Clinical Microbiology Department, Complejo Hospitalario Universitario Granada, Instituto de Investigación Biosanitaria ibs.Granada, Granada, Spain.
F
F
García
Department of Dermatology, Venerology and Allergology, Center for Sexual Health and Medicine, St. Josef Hospital, Ruhr-Universität Bochum, Bochum, Germany.
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NH
Brockmeyer
INSERM CESP U1018, AP-HP Public Health Department, Université Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre Paris, France.
J
J
Warszawski
HIV and Paeds Infectious Diseases Department, Hospital 12 de Octubre, Madrid, Spain.
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MI
Gonzalez-Tome
Infectious Diseases Clinics, University Hospital, Modena, Italy.
C
C
Mussini
Department Hygiene, Epidemiology & Medical Statistics, Medical School, National & Kapodistrian University of Athens, Athens, Greece.
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G
Touloumi
Medical University Innsbruck, Innsbruck, Austria.
R
R
Zangerle
EA 7327, Faculté de Médecine site Necker, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.|APHP, Unité Fonctionnelle de Thérapeutique en Immuno-Infectiologie, Hôpitaux Universitaires Paris Centre site Hôtel Dieu, Paris, France.
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J
Ghosn
San Raffaele Scientific Institute, Vita-SaLute University, Milan, Italy.
A
A
Castagna
Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany.
G
G
Fätkenheuer
Second Medical Department, Infectious Diseases Unit, Goethe-University Hospital, Frankfurt, Germany.
C
C
Stephan
INSERM CESP U1018, Université Paris-Sud, Université Paris-Saclay, Paris, France.|AP-HP Public Health Department, Le Kremlin-Bicêtre, Paris, France.
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L
Meyer
Centre for Health and Infectious Disease Research, University of Copenhagen, Copenhagen, Denmark.
M A
MA
Campbell
INSERM U1219 - Centre Inserm Bordeaux Population Health, Université de Bordeaux, Bordeaux, France.|ISPED, Centre INSERM U1219-Bordeaux Population Health, Université de Bordeaux, Bordeaux, France.|CHU de Bordeaux, Pole de sante publique, Service d'information medicale, Bordeaux, France.
G
G
Chene
Department of Infection and Population Health, University College London, London, UK.
A
A
Phillips
D000293:Adolescent; D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D024882:Drug Resistance, Viral; D005060:Europe; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D008297:Male; D044382:Population Groups; D013997:Time Factors; D017211:Treatment Failure; D055815:Young Adult
D044966:Anti-Retroviral Agents
Europe; perinatal HIV infection; virological failure; young people