Very early combination antiretroviral therapy in infants

Rainwater-Lovett, Kaitlin; Luzuriaga, Katherine; Persaud, Deborah

doi:10.1097/coh.0000000000000127

Cited by 61 publications

(39 citation statements)

References 39 publications

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“…This is consistent with the premise that early ART rapidly removes the antigenic stimulation needed to sustain an HIV-specific antibody response. 18–22 However, almost a third of those children with negative antibody responses had a history of viremia in the 50–1000 copies/ml range. It will be important to study the initial development of HIV-specific antibodies of different types in early treated infants to determine whether it is primary ontogeny of these responses that is affected or whether the influence occurs later leading to decline of responses over time.…”

Section: Discussionmentioning

confidence: 99%

Young age at start of antiretroviral therapy and negative HIV antibody results in HIV-infected children when suppressed

Kuhn

Schramm²,

Shiau

et al. 2015

Aids

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Background Negative results on standard HIV antibody tests have been described among HIV-infected children suppressed on antiretroviral therapy (ART) started early in life. Here we describe the frequency and predictors of this phenomenon in a well-characterized cohort of treated children. Methods We selected samples from 103 HIV-infected children who started ART ≤ 14 months of age and from 122 children who started ≤ 6 months of age followed as part of two sequential clinical trials in Johannesburg, South Africa. Children had attained viral suppression on ART and had received ART for between 3 and 6.4 years (mean 4.3 years) when tested for HIV antibody using a standard ELISA (Genescreen™ HIV1/2 version 2; Bio-rad). Results Only children ≤6 months of age when ART was started had negative antibody results when tested after suppression on ART several years later. Negative or low-positive antibody results were observed in 40.0%, 37.0% and 27.8% of children starting ART <2 months of age, or starting during month 2 or 3, respectively. This dropped to 5.9%, 3.5%, and 5.3% if ART was started during month 4, 5, and 6, respectively. Higher CD4 percentage prior to ART initiation and no recorded intermittent viremia also predicted negative antibody results. Conclusion Testing negative on standard HIV antibody tests occurs fairly commonly among HIV-infected children who started ART ≤ 3 months of age and are virally-suppressed. It would be prudent in clinical practice to avoid HIV antibody tests among virally-suppressed, early-treated children to prevent unnecessary confusion.

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Section: Discussionmentioning

confidence: 99%

Young age at start of antiretroviral therapy and negative HIV antibody results in HIV-infected children when suppressed

Kuhn

Schramm²,

Shiau

et al. 2015

Aids

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“…This strongly suggests early treatment initiation results in small proviral reservoir size, possibly by skewing seeding of short-lived cells and permitting continual decay of HIV-infected cells [23]. Low proviral DNA concentrations do not ensure long-term remission, however, as perinatally-infected children experience plasma viral rebound within days of ART discontinuation irrespective of their proviral DNA load (reviewed in [24]). Therefore, small proviral reservoir size may not result in permanent virologic remission, but it may provide an optimal platform for studies aimed at purging the reservoir with other immunotherapeutic interventions.…”

Section: Biomarkers Of Hiv Persistencementioning

confidence: 99%

Advances and hope for perinatal HIV remission and cure in children and adolescents

Rainwater-Lovett

Uprety

Persaud

2016

Current Opinion in Pediatrics

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Purpose of review The known timing of HIV infection in perinatal transmission combined with the capacity for early antiretroviral therapy (ART) initiation and immune reconstitution can provide unique insights into HIV persistence. The scientific basis for a pediatric-specific research agenda aimed at HIV remission and cure is discussed. Recent findings Accumulating evidence supports a favorable biomarker profile for immunotherapeutic interventions in early treated, perinatally-infected individuals. HIV DNA concentrations in infected cells of early treated infants decrease over the first few years of life and, after >10 years of ART, the overwhelming majority of non-induced proviral genomes are replication-deficient. With early ART initiation, approximately half of perinatally-infected individuals become seronegative. Studies of untreated infants and vaccine trials indicate infected infants can generate HIV-specific humoral responses. Taken together, this evidence suggests early treatment results in low levels of replication-competent provirus, an absence of HIV-specific immunity, and the capacity to generate immune responses to potential immunotherapeutic interventions. Summary Perinatally HIV-infected individuals require lifelong ART due to the prompt establishment of viral latency in long-lived resting memory CD4+ T cells that rekindle viremia upon treatment cessation. However, intense research efforts are ongoing to perturb HIV latency towards reservoir clearance for virologic remission and cure in which perinatally-infected individuals can discontinue ART.

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“…Current treatment strategies focus on timely initiation of cART regimens capable of maximally suppressing viral replication in order to prevent disease progression. There are emerging reports that very early cART is associated with very small proviral reservoirs and restricted HIV-specific immune responses in perinatal infection [18–20]. However, when to start (Box 2) and what ART regimen to start a patient on (Table 3) vary from country to country.…”

Section: Hivmentioning

confidence: 99%