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Review
. 2015 Jan;10(1):4-11.
doi: 10.1097/COH.0000000000000127.

Very early combination antiretroviral therapy in infants: prospects for cure

Kaitlin Rainwater-Lovett  1 , Katherine Luzuriaga, Deborah Persaud
Affiliations
Review

Very early combination antiretroviral therapy in infants: prospects for cure

Kaitlin Rainwater-Lovett et al. Curr Opin HIV AIDS. 2015 Jan.

Abstract

Purpose of review: A single case of sustained HIV control in the absence of antiretroviral therapy or HIV-specific immune responses ensued following 18 months of combination antiretroviral therapy initiated at 30 h of age in a perinatally HIV-infected child (the Mississippi child). This case provides proof-of-concept that delay in HIV viremic rebound may ensue following very early treatment (VET) in perinatal infection, likely through marked reduction of latent replication-competent HIV reservoirs.

Recent findings: The latent HIV reservoir remains the critical barrier to remission. Several studies indicate that the earlier effective combination antiretroviral therapy is initiated, the smaller the size of the HIV reservoir. The unique ability of perinatally infected neonates to initiate VET at the time of birth maximizes the potential benefits of limiting latent reservoir size and permitting reservoir decay, likely lengthening the duration of remission and limiting the capacity for re-establishment of viremia.

Summary: This article covers the rationale and feasibility of VET to achieve sustained virologic remission in perinatal infection. Recent studies highlighting the effects of VET on biomarkers of HIV persistence in perinatal HIV infection are reviewed as well as implications and challenges for cure research in pediatric populations.

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Conflict of interest statement

Conflicts of interest

There are no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Reservoir size and duration of HIV remission is directly affected by the time from HIV infection to initiation of cART. Susceptible CD4+ T cells (green) become infected with HIV (yellow) and transition to either productively infected CD4+ T cells (pink) or latently infected CD4+ T cells (blue). Reactivated CD4+ T cells (purple) from latency re-establish viremia. ART, antiretroviral therapy; cART, combination antiretroviral therapy.
FIGURE 2
FIGURE 2
Summary of potential HIV remission biomarkers in perinatally infected children who initiated very early cART. Solid lines represent time since cART initiation with duration in text. Dotted line connected to time line indicates age at cART initiation. Dashed line for Mississippi case indicates period off combination antiretroviral therapy. * No replication-competent HIV detected. c/m, copies per million cells; c/ml, copies per milliliter blood; cART, combination antiretroviral therapy; ELISA, enzyme immunoassay; IUPM, infectious units per million resting CD4+ T cells; Neg, negative; np, assay not performed; Undet, undetectable; WB, western blot.
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References

    1. UNAIDS. AIDS by the numbers. [Accessed 4 December 2013]; http://www.unaids.org/en/resources/documents/2013/name,88096,en.asp.

    1. Persaud D, Gay H, Ziemniak C, et al. Absence of detectable HIV-1 viremia after treatment cessation in an infant. N Engl J Med. 2013;369:1828–1835. This case report describes the first known case of sustained absence of viremia without combination antiretroviral therapy in a perinatally infected child, the ‘Mississippi Child’ likely by very early antiretroviral treatment.

    1. Persaud D, Deveikis A, Gay H, et al. Very early combination anti-retroviral therapy in perinatal HIV infection: two case studies. 21st Conference on Retroviruses and Opportunistic Infections; 3–6 March 2014; Boston, MA, USA. 2014. abstract 75LB.
    1. Henrich TJ, Hanhauser E, Marty FM, et al. Antiretroviral-free HIV-1 remission and viral rebound after allogeneic stem cell transplantation: report of 2 cases. Ann Intern Med. 2014;161:319–327. - PMC - PubMed

    1. Yukl SA, Boritz E, Busch M, et al. Challenges in detecting HIV persistence during potentially curative interventions: a study of the Berlin patient. PLoS Pathog. 2013;9:e1003347. This study highlights the extensive blood and tissue sampling required for cure-related research and challenges in interpretation of the findings.

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