Treatment interruption after 2-year antiretroviral treatment initiated during acute/early HIV in infancy

Abstract

Objective Treatment interruption (TI) has been safe and durable in some pediatric studies but none have compared TI to continued antiretroviral treatment (ART) following ART initiation in early HIV. The objective of this study was to compare outcomes in TI versus continued ART among early-treated infants. Design Randomized trial (OPH-03; NCT00428116) Methods The trial included HIV-infected infants who initiated ART at <13 months of age, received ART for 24 months, and, if eligible (CD4>25%, normal growth), were randomized to TI vs. continued ART. Children in the TI group re-started ART if they met WHO ART-eligibility criteria. During 18-months post-randomization, primary outcomes were incidence of serious adverse events (SAEs) and growth. CD4, viral load, morbidity, and growth were compared. Results Of 140 infants enrolled, 121 started ART, of whom 75 completed ≥24 months ART and 42 were randomized (21 per arm). ART was initiated at median age 5 months and randomization at 30 months. Among 21 TI children, 14 met ART re-start criteria within 3 months. Randomization was discontinued by DSMB due to low TI durability. At 18 months post-randomization, growth and SAEs were comparable between arms; hypercholesteremia incidence was higher in the continued arm (p=0.03). CD4% and VL did not differ between arms (CD4% 35% and median VL undetectable (<150 c/ml) in both arms, p=0.9 for each comparison). No infants had post-treatment viral control. Conclusion Short TI did not compromise 18-month CD4%, viral control, growth, or morbidity compared to continued ART among infants who started ART in early HIV infection.

Differences in virologic and immunologic response to antiretroviral therapy among HIV-1-infected infants and children

“…Recruitment and enrollment procedures have been described in detail elsewhere[33, 34], but in brief:.in the infant cohort [Optimizing Pediatric HIV Therapy (OPH), NCT00428116], HIV-infected, ART-naive infants less than 13 months old were identified at routine HIV-1 testing in prevention of mother-to-child transmission of HIV (PMTCT) clinics and pediatric wards between 2007–2010. All infants were started on ART and followed monthly for growth and clinical outcomes for two years before being randomized to treatment interruption or continued treatment[35]; for this analysis, only pre-randomization data were used. HIV viral load was assessed at baseline and every three months throughout follow-up, while CD4 counts and CD4% were assessed every six months.…”

Impact of the time to achieve viral control on the dynamics of circulating HIV-1 reservoir in vertically infected children with long-term sustained virological suppression: A longitudinal study

“…This counterpart to this scenario is that most HIV-1 infected infants do not have the opportunity to start ART soon after birth, drugs are inaccessible for many patients, and there are side effects associated with prolonged ART use [ 13 ]. Simplified ART regimens, including break periods or interruption schedules, are being studied in order to improve treatment adherence and reduce the toxic effects associated with the drugs [ 14 , 15 ]. These new therapeutic approaches that include HIV-1 infected patients with low to undetectable plasma viral load (pVL) require ongoing monitoring of the HIV-1 reservoir size.…”

The value of confirmatory testing in early infant HIV diagnosis programmes in South Africa: A cost-effectiveness analysis

“…Lack of detectable anti-HIV antibody, HIV RNA, or HIV DNA may reflect either absence of true infection or the impact of effective ART, which makes withdrawal of treatment the only mechanism available for clinicians wishing to determine the true HIV status of an infant on ART. However, treatment interruptions are not currently recommended, due to concerns about viral rebound and disease progression [ 77 , 78 ]. Unconfirmed EID test results therefore cause diagnostic dilemmas for the provider, whilst families may experience confusion and uncertainty about the health system, discouraging future engagement in care [ 79 ].…”