Pediatric HIV: the Potential of Immune Therapeutics to Achieve Viral Remission and Functional Cure

被引:12
作者
Berendam, Stella J. [1 ]
Nelson, Ashley N. [1 ]
Goswami, Ria [1 ]
Persaud, Deborah [2 ]
Haigwood, Nancy L. [3 ]
Chahroudi, Ann [4 ,5 ,6 ]
Fouda, Genevieve G. [1 ]
Permar, Sallie R. [1 ]
机构
[1] Duke Univ, Duke Human Vaccine Inst, Sch Med, 2 Genome Court MSRBII, Durham, NC 27710 USA
[2] Johns Hopkins Univ, Sch Med, 720 Rutland Ave,Ross Bldg 1170, Baltimore, MD 21205 USA
[3] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Pathobiol & Immunol Div, Beaverton, OR 97006 USA
[4] Emory Univ, Dept Pediat, Sch Med, Atlanta, GA 30322 USA
[5] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA
[6] Childrens Healthcare Atlanta, Emory Childrens Ctr Childhood Infect & Vaccines, Atlanta, GA 30322 USA
关键词
Pediatric HIV; Immune-based therapeutics; Viral remission; Functional cure; BROADLY NEUTRALIZING ANTIBODIES; DEPENDENT CELLULAR CYTOTOXICITY; ACTIVE ANTIRETROVIRAL THERAPY; CD8(+) T-CELLS; MONOCLONAL-ANTIBODIES; VIROLOGICAL CONTROL; INFECTION; RESPONSES; DNA; INFANTS;
D O I
10.1007/s11904-020-00495-1
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
Purpose of Review In the absence of antiretroviral therapy (ART), more than 50% of perinatally HIV-infected children die by 2 years of age. Early ART from infancy is therefore a global recommendation and significantly improves immune health, child survival, and disease outcome. However, even early treatment does not prevent or eradicate the latent reservoir necessitating life-long ART. Adherence to life-long ART is challenging for children and longstanding ART during chronic HIV infection led to higher risks of non-AIDS co-morbidities and virologic failure in infected children. Thus, HIV-infected children are an important population for consideration for immune-based interventions to achieve ART-free remission and functional cure. This review summarizes how the uniqueness of the early life immune system can be harnessed for the development of ART-free remission and functional cure, which means complete virus control in absence of ART. In addition, recent advances in therapeutics in the HIV cure field and their potential for the treatment of pediatric HIV infections are discussed. Recent Findings Preclinical studies and clinical trials demonstrated that immune-based interventions target HIV replication, limit size of virus reservoir, maintain virus suppression, and delay time to virus rebound. However, these studies have been performed so far only in carefully selected HIV-infected adults, highlighting the need to evaluate the efficacy of immune-based therapeutics in HIV-infected children and to design interventions tailored to the early life maturing immune system. Immune-based therapeutics alone or in combination with ART should be actively explored as potential strategies to achieve viral remission and functional cure in HIV-infected pediatric populations.
引用
收藏
页码:237 / 248
页数:12
相关论文
共 112 条
  • [1] Abrams D, 2009, NEW ENGL J MED, V361, P1548, DOI 10.1056/NEJMoa0903175
  • [2] [Anonymous], 2017, PREGN WOM INF CHILDR
  • [3] [Anonymous], 2019, GUID US ANT AG PED H
  • [4] AVERT, 2019, WOM GIRLS HIV AIDS
  • [5] Early ART Results in Greater Immune Reconstitution Benefits in HIV-Infected Infants: Working with Data Missingness in a Longitudinal Dataset
    Azzoni, Livio
    Barbour, Russell
    Papasavvas, Emmanouil
    Glencross, Deborah K.
    Stevens, Wendy S.
    Cotton, Mark F.
    Violari, Avy
    Montaner, Luis J.
    [J]. PLOS ONE, 2015, 10 (12):
  • [6] Key factors in mTOR regulation
    Bai, Xiaochun
    Jiang, Yu
    [J]. CELLULAR AND MOLECULAR LIFE SCIENCES, 2010, 67 (02) : 239 - 253
  • [7] Safety and antiviral activity of combination HIV-1 broadly neutralizing antibodies in viremic individuals
    Bar-On, Yotam
    Gruell, Henning
    Schoofs, Till
    Pai, Joy A.
    Nogueira, Lilian
    Butler, Allison L.
    Millard, Katrina
    Lehmann, Clara
    Suarez, Isabelle
    Oliveira, Thiago Y.
    Karagounis, Theodora
    Cohen, Yehuda Z.
    Wyen, Christoph
    Scholten, Stefan
    Handl, Lisa
    Belblidia, Shiraz
    Dizon, Juan P.
    Vehreschild, Joerg J.
    Witmer-Pack, Maggi
    Shimeliovich, Irina
    Jain, Kanika
    Fiddike, Kerstin
    Seaton, Kelly E.
    Yates, Nicole L.
    Horowitz, Jill
    Gulick, Roy M.
    Pfeifer, Nico
    Tomaras, Georgia D.
    Seaman, Michael S.
    Faetkenheuer, Gerd
    Caskey, Marina
    Klein, Florian
    Nussenzweig, Michel C.
    [J]. NATURE MEDICINE, 2018, 24 (11) : 1701 - +
  • [8] Universal antiretroviral therapy for HIV-infected children: a review of the benefits and risks to consider during implementation
    Barlow-Mosha, Linda
    Musiime, Victor
    Davies, Mary-Ann
    Prendergast, Andrew J.
    Musoke, Philippa
    Siberry, George
    Penazzato, Martina
    [J]. JOURNAL OF THE INTERNATIONAL AIDS SOCIETY, 2017, 20
  • [9] Metabolic complications and treatment of perinatally HIV-infected children and adolescents
    Barlow-Mosha, Linda
    Eckard, Allison Ross
    McComsey, Grace A.
    Musoke, Philippa M.
    [J]. JOURNAL OF THE INTERNATIONAL AIDS SOCIETY, 2013, 16
  • [10] Therapeutic efficacy of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys
    Barouch, Dan H.
    Whitney, James B.
    Moldt, Brian
    Klein, Florian
    Oliveira, Thiago Y.
    Liu, Jinyan
    Stephenson, Kathryn E.
    Chang, Hui-Wen
    Shekhar, Karthik
    Gupta, Sanjana
    Nkolola, Joseph P.
    Seaman, Michael S.
    Smith, Kaitlin M.
    Borducchi, Erica N.
    Cabral, Crystal
    Smith, Jeffrey Y.
    Blackmore, Stephen
    Sanisetty, Srisowmya
    Perry, James R.
    Beck, Matthew
    Lewis, Mark G.
    Rinaldi, William
    Chakraborty, Arup K.
    Poignard, Pascal
    Nussenzweig, Michel C.
    Burton, Dennis R.
    [J]. NATURE, 2013, 503 (7475) : 224 - +