Establishment and Replenishment of the Viral Reservoir in Perinatally HIV-1-infected Children Initiating Very Early Antiretroviral Therapy

Martínez‐Bonet, Marta; Puertas, María C.; Fortuny, Clàudia; Ouchi, Dan; Mellado, María José; Rojo, Pablo; Noguera-Julián, Antoni; Muñoz‐Fernández, María Ángeles; Martínez-Picado, Javier

doi:10.1093/cid/civ456

Cited by 100 publications

(106 citation statements)

References 35 publications

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“…More recently, an assay that dispenses with the extraction step has been proposed (70). Recent technical progress has permitted the development of HIV DNA quantification by digital droplet PCR (ddPCR), which does not require an external quantification standard (71)(72)(73)(74)(75)(76)(77). However, some false-positive signals have been observed with ddPCR, which can be a problem when this method is used for diagnosis (76).…”

Section: Dna Load In Resting Cd4mentioning

confidence: 99%

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Total HIV-1 DNA, a Marker of Viral Reservoir Dynamics with Clinical Implications

et al. 2016

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SUMMARYHIV-1 DNA persists in infected cells despite combined antiretroviral therapy (cART), forming viral reservoirs. Recent trials of strategies targeting latent HIV reservoirs have rekindled hopes of curing HIV infection, and reliable markers are thus needed to evaluate viral reservoirs. Total HIV DNA quantification is simple, standardized, sensitive, and reproducible. Total HIV DNA load influences the course of the infection and is therefore clinically relevant. In particular, it is predictive of progression to AIDS and death, independently of HIV RNA load and the CD4 cell count. Baseline total HIV DNA load is predictive of the response to cART. It declines during cART but remains quantifiable, at a level that reflects both the history of infection (HIV RNA zenith, CD4 cell count nadir) and treatment efficacy (residual viremia, cumulative viremia, immune restoration, immune cell activation). Total HIV DNA load in blood is also predictive of the presence and severity of some HIV-1-associated end-organ disorders. It can be useful to guide individual treatment, notably, therapeutic de-escalation. Although it does not distinguish between replication-competent and -defective latent viruses, the total HIV DNA load in blood, tissues, and cells provides insights into HIV pathogenesis, probably because all viral forms participate in host cell activation and HIV pathogenesis. Total HIV DNA is thus a biomarker of HIV reservoirs, which can be defined as all infected cells and tissues containing all forms of HIV persistence that participate in pathogenesis. This participation may occur through the production of new virions, creating new cycles of infection and disseminating infected cells; maintenance or amplification of reservoirs by homeostatic cell proliferation; and viral transcription and synthesis of viral proteins without new virion production. These proteins can induce immune activation, thus participating in the vicious circle of HIV pathogenesis.

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Section: Dna Load In Resting Cd4mentioning

confidence: 99%

“…The decline in total blood HIV DNA in patients adherent to cART has been extensively studied in both adults and children (57,77,78,82,(95)(96)(97)(98)(99)(100)(101)(102)(103)(104)(105)(106)(107)(108)(109). This decline varies among patients.…”

Section: Decline In Total Hiv Dna During Cartmentioning

confidence: 99%

Total HIV-1 DNA, a Marker of Viral Reservoir Dynamics with Clinical Implications

et al. 2016

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“…First, columnbased DNA extraction protocols are inefficient and inconsistent. A direct cell lysis protocol using diverse detergents and/or proteinase K improves the efficiency of nucleic acid recovery; therefore, it is possible to reduce cell input to study cell populations with lower cell numbers accurately (1,3,(12)(13)(14)(15). Second, qPCR limits assay accuracy at low copy numbers by exponentially amplifying noise.…”

Section: Pcr-based Assays To Measure the Latent Reservoirmentioning

confidence: 99%

“…Several assays have been developed to study 2-LTR circles using primers flanking the 2-LTR circle junction. These assays have been performed in qPCR on PBMCs (24, 28) and CD4 + T cells (29), as well as ddPCR on PBMCs (10, 13, 25, 30, 31) and CD4 + T cells (14,32,33). HIV cell-associated RNA in unstimulated cells.…”

Section: Pcr-based Assays To Measure the Latent Reservoirmentioning

confidence: 99%

Measuring the latent reservoir in vivo

Massanella¹,

Richman²

2016

Journal of Clinical Investigation

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“…Importantly, it was recently argued by Klein et al (95) that children are ideal candidates for immunotherapeutic interventions to achieve viral remission. The arguments presented by the authors are based on the fact that perinatally infected children for whom antiretroviral (ARV) treatment is initiated early on have a small latent virus reservoir (96,97) and normal development of the memory B cell and T cell compartments (98,99). The potential for viral eradication in children was recently illustrated by the "Mississippi baby."…”

Section: Hiv Vaccine Responses In Infants and Adultsmentioning

confidence: 99%

Contrasting Adult and Infant Immune Responses to HIV Infection and Vaccination

Martinez

Permar

Fouda

2016

Clin Vaccine Immunol

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Extensive studies have demonstrated that infant immune responses are distinct from those of adults. Despite these differences, infant immunization can elicit protective immune responses at levels comparable to or, in some cases, higher than adult immune responses to many vaccines. To date, only a few HIV vaccine candidates have been tested in infant populations, and none of them evaluated vaccine efficacy. Recent exciting studies showing that HIV-infected infants can develop broad neutralizing antibody responses and that some HIV vaccine regimens can elicit high levels of potentially protective antibodies in infants provide support for the development and testing of HIV vaccines in pediatric populations. In this review, we discuss the differences in adult and infant immune responses in the setting of HIV infection and vaccination.

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Establishment and Replenishment of the Viral Reservoir in Perinatally HIV-1-infected Children Initiating Very Early Antiretroviral Therapy

Cited by 100 publications

References 35 publications

Total HIV-1 DNA, a Marker of Viral Reservoir Dynamics with Clinical Implications

Total HIV-1 DNA, a Marker of Viral Reservoir Dynamics with Clinical Implications

Measuring the latent reservoir in vivo

Contrasting Adult and Infant Immune Responses to HIV Infection and Vaccination

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